Paul J. Wang: Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief with some of the key highlights from this month's issue. In our first paper, Danielle Haanschoten, Hein Wellens and Associates aim to examine survival benefit of prophylactic implantable cardioversion defibrillator (ICD) implantation in early selected high-risk patients with primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). A randomized, multicenter, controlled trial compared ICD versus conventional medical therapy in high-risk primary PCI patients based on one of the following factors: Left ventricular ejection fraction (LVF) less than 30% within four days of STEMI, primary ventricular fibrillation, Killip class 2 or greater and/or TEMI flow less than three after PCI. ICD was implanted 30 to 60 days after MI, myocardial infarction, primary endpoint was all cause mortality three years of follow-up. The trial was prematurely ended after inclusion of 266 patients, 38% of the calculated sample size. Additional survival assessments was performed in February 2019 for the primary endpoint. A total of 266 patients, 78.2% male with a mean age of 60.8 years were enrolled. 131 were randomized to the ICD arm and 135 patients to the control arm. All cause mortality was significantly lower in the ICD group, five versus 13, hazard ratio of 0.37 after three years follow-up. Appropriate ICD therapy occurred in nine patients at three years follow-up, 5 within the first eight months after implantation. After median long-term follow-up of nine years, total mortality (18% versus 38%, hazard ratio of 0.58) and cardiac mortality (hazard ratio of 0.52) was significantly lower in the ICD group. Non-cardiac death was not significantly different between the groups. LVEF increased 10% or more in the 46.5% of patients during follow-up and the extent of improvement was similar in both study groups. The authors concluded that in this prematurely terminated and thus underpowered randomized trial early prophylactic ICD implantation demonstrated lower total and cardiac mortality in high-risk STEMI patients treated with primary PCI.   In our next paper Felipe Bisbal, Eva Benito and Associates aim to test the efficacy of ablating, cardiac magnetic resonance, CMR detected atrial fibrosis plus pulmonary vein isolation (PVI). This was an open label, parallel group, randomized controlled trial. Patients with symptomatic drug refractory AF paroxysmal or persistent undergoing first or repeat ablation were randomized one-to-one basis to receive PVI plus CMR-guided fibrosis ablation, the CMR group or PVI alone, the PVI alone group. The primary endpoint was a rate of recurrence greater than 30 seconds at 12 months of follow-up using a 12-lead ECG and Holter monitoring at 3, 6 and 12 months. The analysis was conducted by intention to treat. In total 155 patients, 71% male, age 59, CHADS2-VASc 1.3, 54% paroxysmal AF were allocated to the PVI group alone (n=76) or CMR group(n=79). First ablation was performed in 80% and 71% in the PVI alone and CMR groups respectively. The mean atrial fibrosis burden was 12%, only approximately 50% of patients had fibrosis outside the pulmonary vein area. 100% and 99% of patients received the assigned intervention in the PVI alone and CMR group. Primary outcome was achieved in 21 patients (27.6%) in the PVI alone group and 22 patients (27.8%) in the CMR group (Odds ratio 0.01, P=0.976). There was no differences in the rate of adverse events, three in the CMR group and two in the PVI alone group. The authors concluded that a pragmatic ablation approach targeting CMR detected atrial fibrosis plus PVI was not more effective than PVI alone in an unselected population undergoing AF ablation with low fibrosis burden.   In the next paper, Vivek Reddy and Associates tested a novel neuromodulation therapy of stimulation of epicardial cardiac nerves passing along the posterior surface of the right pulmonary artery. 15 subjects admitted for defibrillator implantation (ejection fraction≤35%) on standard heart failure medications were enrolled. Through femoral arterial access, high fidelity pressure catheters were placed in the left ventricle and aortic root. After electro anatomic rendering of the pulmonary artery and branches, either a circular or basket electrophysiology catheter was placed in the right pulmonary artery to allow electrical intravascular stimulation at 20 hertz, 4 ms pulse width, and less than or equal to 20 milliamperes. Changes in the maximum positive dP/dt, the dP/dtMax indicated change in ventricular contractility. Of 15 enrolled patients, five were not studied due to equipment failure or abnormal pulmonary artery anatomy. In the remaining patients dP/dtMax increased significantly by 22.6%. There was also a significant increase in maximum negative dP/dt, dP/dtMin, mean arterial pressure, systolic pressure, diastolic pressure, and left ventricular systolic pressure. There was no significant change in heart rate or left ventricular diastolic pressure. In this first-in-human study, the authors demonstrated that in humans with stable heart failure, left ventricular contractility could be accentuated without an increase in heart rate or left ventricular filling pressures.   In our next paper, Jorge Romero, Luigi Di Biase, and Associates, in their study investigated the incremental benefit of left atrial appendage electrical isolation (LAAEI) in patients undergoing catheter ablation for nonparoxysmal atrial fibrillation (AF). Propensity score-matched analysis was performed using a prospective registry database from 2010 to 2014. All patients in the LAAEI group were matched based on baseline characteristics, echocardiographic parameters, and procedural ablation techniques. Authors identified 1842 patients who underwent catheter ablation for nonparoxysmal atrial fibrillation. Propensity score matching yielded 1092 patients, 546 with LAAEI, and 546 without LAAEI. At five years follow-up, overall freedom from all arrhythmia recurrence, off-antiarrhythmic drugs, in patients who underwent LAAEI was 68.9% versus 50.2% in those who underwent standard ablation (p

Paul J. Wang: Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief with some of the key highlights from this month's issue. In our first paper, Danielle Haanschoten, Hein Wellens and Associates aim to examine survival benefit of prophylactic implantable cardioversion defibrillator (ICD) implantation in early selected high-risk patients with primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). A randomized, multicenter, controlled trial compared ICD versus conventional medical therapy in high-risk primary PCI patients based on one of the following factors: Left ventricular ejection fraction (LVF) less than 30% within four days of STEMI, primary ventricular fibrillation, Killip class 2 or greater and/or TEMI flow less than three after PCI. ICD was implanted 30 to 60 days after MI, myocardial infarction, primary endpoint was all cause mortality three years of follow-up. The trial was prematurely ended after inclusion of 266 patients, 38% of the calculated sample size. Additional survival assessments was performed in February 2019 for the primary endpoint. A total of 266 patients, 78.2% male with a mean age of 60.8 years were enrolled. 131 were randomized to the ICD arm and 135 patients to the control arm. All cause mortality was significantly lower in the ICD group, five versus 13, hazard ratio of 0.37 after three years follow-up. Appropriate ICD therapy occurred in nine patients at three years follow-up, 5 within the first eight months after implantation. After median long-term follow-up of nine years, total mortality (18% versus 38%, hazard ratio of 0.58) and cardiac mortality (hazard ratio of 0.52) was significantly lower in the ICD group. Non-cardiac death was not significantly different between the groups. LVEF increased 10% or more in the 46.5% of patients during follow-up and the extent of improvement was similar in both study groups. The authors concluded that in this prematurely terminated and thus underpowered randomized trial early prophylactic ICD implantation demonstrated lower total and cardiac mortality in high-risk STEMI patients treated with primary PCI. In our next paper Felipe Bisbal, Eva Benito and Associates aim to test the efficacy of ablating, cardiac magnetic resonance, CMR detected atrial fibrosis plus pulmonary vein isolation (PVI). This was an open label, parallel group, randomized controlled trial. Patients with symptomatic drug refractory AF paroxysmal or persistent undergoing first or repeat ablation were randomized one-to-one basis to receive PVI plus CMR-guided fibrosis ablation, the CMR group or PVI alone, the PVI alone group. The primary endpoint was a rate of recurrence greater than 30 seconds at 12 months of follow-up using a 12-lead ECG and Holter monitoring at 3, 6 and 12 months. The analysis was conducted by intention to treat. In total 155 patients, 71% male, age 59, CHADS2-VASc 1.3, 54% paroxysmal AF were allocated to the PVI group alone (n=76) or CMR group(n=79). First ablation was performed in 80% and 71% in the PVI alone and CMR groups respectively. The mean atrial fibrosis burden was 12%, only approximately 50% of patients had fibrosis outside the pulmonary vein area. 100% and 99% of patients received the assigned intervention in the PVI alone and CMR group. Primary outcome was achieved in 21 patients (27.6%) in the PVI alone group and 22 patients (27.8%) in the CMR group (Odds ratio 0.01, P=0.976). There was no differences in the rate of adverse events, three in the CMR group and two in the PVI alone group. The authors concluded that a pragmatic ablation approach targeting CMR detected atrial fibrosis plus PVI was not more effective than PVI alone in an unselected population undergoing AF ablation with low fibrosis burden. In the next paper, Vivek Reddy and Associates tested a novel neuromodulation therapy of stimulation of epicardial cardiac nerves passing along the posterior surface of the right pulmonary artery. 15 subjects admitted for defibrillator implantation (ejection fraction≤35%) on standard heart failure medications were enrolled. Through femoral arterial access, high fidelity pressure catheters were placed in the left ventricle and aortic root. After electro anatomic rendering of the pulmonary artery and branches, either a circular or basket electrophysiology catheter was placed in the right pulmonary artery to allow electrical intravascular stimulation at 20 hertz, 4 ms pulse width, and less than or equal to 20 milliamperes. Changes in the maximum positive dP/dt, the dP/dtMax indicated change in ventricular contractility. Of 15 enrolled patients, five were not studied due to equipment failure or abnormal pulmonary artery anatomy. In the remaining patients dP/dtMax increased significantly by 22.6%. There was also a significant increase in maximum negative dP/dt, dP/dtMin, mean arterial pressure, systolic pressure, diastolic pressure, and left ventricular systolic pressure. There was no significant change in heart rate or left ventricular diastolic pressure. In this first-in-human study, the authors demonstrated that in humans with stable heart failure, left ventricular contractility could be accentuated without an increase in heart rate or left ventricular filling pressures. In our next paper, Jorge Romero, Luigi Di Biase, and Associates, in their study investigated the incremental benefit of left atrial appendage electrical isolation (LAAEI) in patients undergoing catheter ablation for nonparoxysmal atrial fibrillation (AF). Propensity score-matched analysis was performed using a prospective registry database from 2010 to 2014. All patients in the LAAEI group were matched based on baseline characteristics, echocardiographic parameters, and procedural ablation techniques. Authors identified 1842 patients who underwent catheter ablation for nonparoxysmal atrial fibrillation. Propensity score matching yielded 1092 patients, 546 with LAAEI, and 546 without LAAEI. At five years follow-up, overall freedom from all arrhythmia recurrence, off-antiarrhythmic drugs, in patients who underwent LAAEI was 68.9% versus 50.2% in those who underwent standard ablation (p

Circulation: Arrhythmia and Electrophysiology November 2020 Issue

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation, Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief with some of the key highlights from this month's issue. In our first paper, Bruce Wilkoff and associates evaluated antibacterial envelope cost effectiveness compared to standard of care infection prevention strategies in the US healthcare system. Decision tree model was used to compare costs and outcomes of the antimicrobial envelope used adjunctive to standard of care infection prevention versus standard of care alone over a lifelong time horizon. The analysis was performed from an integrated payer provider network perspective. Infection rates, antimicrobial envelope effectiveness, infection treatment costs and patterns, infection related mortality and utility estimates were obtained from the WRAP-IT study. Life expectancy and long-term costs associated with device replacement, follow-up, and healthcare utilization were sourced from the literature. Costs and quality life adjusted years were discounted at 3%. An upper willingness-to-pay threshold of $100,000 per quality adjusted life year was used to determine cost-effectiveness in alignment with the American College of Cardiology and American Heart Association practice guidelines and as supported by the World Health Organization and contemporary literature. The base case incremental cost-effectiveness ratio (ICER) of the antibacterial envelope compared with standard-of-care was $112,603 per quality-adjusted life year. The ICER remained lower than the threshold in 74% of iterations in the probabilistic sensitivity analysis and was most sensitive to the following model inputs: infection-related mortality, life expectancy, and infection cost. The authors concluded that the absorbable antibacterial envelope was associated with a cost-effectiveness ratio below contemporary benchmarks in the WRAP-IT patient population, suggesting that the envelope provides value for the US healthcare system by reducing the incidence of CIED infection. In our next paper, Peter Loh and associates in this study aim to investigate the feasibility and safety of single pulse irreversible electroporation (IRE) pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). Ten patients with symptomatic paroxysmal or persistent AF underwent single pulse IRE pulmonary vein isolation under general anesthesia. Three-dimensional reconstruction and electroanatomical voltage mapping of the left atrium and pulmonary veins were performed using a conventional circular mapping catheter. Pulmonary vein isolation was performed by delivering nonarcing, nonbarotraumatic 6 ms, 200 Joule direct current IRE applications via a custom nondeflectable 14-polar circular IRE ablation catheter with a variable hoop diameter (16–27 millimeters). A deflectable sheath was used to maneuver the ablation catheter. A minimum of 2 IRE applications with slightly different catheter positions were delivered per vein to achieve circular tissue contact, even if pulmonary vein potentials were abolished after the first application. Bidirectional pulmonary vein isolation was confirmed with the circular mapping catheter and a post ablation voltage map. After a 30-minute waiting period, adenosine testing was used to reveal dormant pulmonary vein conduction. All 40 pulmonary veins could be successfully isolated with a mean of 2.4 IRE applications per pulmonary vein. Mean delivery peak voltage and peak current were 2154 volts and 33.9 amperes. No pulmonary vein reconnections occurred during the waiting period and adenosine testing. No periprocedural complications were observed. The authors concluded that in 10 patients in this first in-human study, acute bidirectional electrical pulmonary vein isolation could be achieved safely using single pulse IRE ablation. In our next paper, Christian Sohns and associates studied the relationship between left ventricular ejection fraction (LVEF) New York Heart Association (NYHA) class on presentation and the end points of mortality and heart failure (HF) admissions in the CASTLE-AF study population. Furthermore, predictors for LVEF improvement were examined. The CASTLE-AF patients with coexisting heart failure and AF (n=363) were randomized in a multicenter prospective controlled fashion to ablation (n=179) versus pharmacological therapy (n=184). Left ventricular function in NYHA class were assessed at baseline after randomization and at each follow-up visit. In the ablation arm, a significantly higher number of patients experienced an improvement in their LVEF to greater than 35% at the end of the study (odds ratio, 2.17; P

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation, Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief with some of the key highlights from this month's issue. In our first paper, Bruce Wilkoff and associates evaluated antibacterial envelope cost effectiveness compared to standard of care infection prevention strategies in the US healthcare system. Decision tree model was used to compare costs and outcomes of the antimicrobial envelope used adjunctive to standard of care infection prevention versus standard of care alone over a lifelong time horizon. The analysis was performed from an integrated payer provider network perspective. Infection rates, antimicrobial envelope effectiveness, infection treatment costs and patterns, infection related mortality and utility estimates were obtained from the WRAP-IT study. Life expectancy and long-term costs associated with device replacement, follow-up, and healthcare utilization were sourced from the literature. Costs and quality life adjusted years were discounted at 3%. An upper willingness-to-pay threshold of $100,000 per quality adjusted life year was used to determine cost-effectiveness in alignment with the American College of Cardiology and American Heart Association practice guidelines and as supported by the World Health Organization and contemporary literature. The base case incremental cost-effectiveness ratio (ICER) of the antibacterial envelope compared with standard-of-care was $112,603 per quality-adjusted life year. The ICER remained lower than the threshold in 74% of iterations in the probabilistic sensitivity analysis and was most sensitive to the following model inputs: infection-related mortality, life expectancy, and infection cost. The authors concluded that the absorbable antibacterial envelope was associated with a cost-effectiveness ratio below contemporary benchmarks in the WRAP-IT patient population, suggesting that the envelope provides value for the US healthcare system by reducing the incidence of CIED infection. In our next paper, Peter Loh and associates in this study aim to investigate the feasibility and safety of single pulse irreversible electroporation (IRE) pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). Ten patients with symptomatic paroxysmal or persistent AF underwent single pulse IRE pulmonary vein isolation under general anesthesia. Three-dimensional reconstruction and electroanatomical voltage mapping of the left atrium and pulmonary veins were performed using a conventional circular mapping catheter. Pulmonary vein isolation was performed by delivering nonarcing, nonbarotraumatic 6 ms, 200 Joule direct current IRE applications via a custom nondeflectable 14-polar circular IRE ablation catheter with a variable hoop diameter (16–27 millimeters). A deflectable sheath was used to maneuver the ablation catheter. A minimum of 2 IRE applications with slightly different catheter positions were delivered per vein to achieve circular tissue contact, even if pulmonary vein potentials were abolished after the first application. Bidirectional pulmonary vein isolation was confirmed with the circular mapping catheter and a post ablation voltage map. After a 30-minute waiting period, adenosine testing was used to reveal dormant pulmonary vein conduction. All 40 pulmonary veins could be successfully isolated with a mean of 2.4 IRE applications per pulmonary vein. Mean delivery peak voltage and peak current were 2154 volts and 33.9 amperes. No pulmonary vein reconnections occurred during the waiting period and adenosine testing. No periprocedural complications were observed. The authors concluded that in 10 patients in this first in-human study, acute bidirectional electrical pulmonary vein isolation could be achieved safely using single pulse IRE ablation. In our next paper, Christian Sohns and associates studied the relationship between left ventricular ejection fraction (LVEF) New York Heart Association (NYHA) class on presentation and the end points of mortality and heart failure (HF) admissions in the CASTLE-AF study population. Furthermore, predictors for LVEF improvement were examined. The CASTLE-AF patients with coexisting heart failure and AF (n=363) were randomized in a multicenter prospective controlled fashion to ablation (n=179) versus pharmacological therapy (n=184). Left ventricular function in NYHA class were assessed at baseline after randomization and at each follow-up visit. In the ablation arm, a significantly higher number of patients experienced an improvement in their LVEF to greater than 35% at the end of the study (odds ratio, 2.17; P

Circulation: Arrhythmia and Electrophysiology October 2020 Issue

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-chief, with some of the key highlights from this month's issue. In our first paper, Zak Loring and associates examined 3,139 patients undergoing atrial fibrillation (AF) ablation, between 2016 and 2018 in the Get With The Guidelines-Atrial Fibrillation Registry from 24 US centers. Patients undergoing AF ablation were predominantly male (63.9%) and Caucasian (93.2%) with a median age of 65. Hypertension was the most common comorbidity (67.6%), and persistent atrial fibrillation patients had more comorbidities than paroxysmal AF patients. Drug refractory, paroxysmal AF was most common ablation indication (class I, 53.6%) followed by drug refractory, persistent AF (class I, 41.8%). Radio-frequency, RF ablation, with contact force sensing was the most common ablation modality (70.5%) and 23.7% of patients underwent cryoballoon ablation. Pulmonary vein isolation was performed in 94.6% of de novo ablations. The most common adjunctive lesion included left atrial roof or posterior/inferior lines and cavotricuspid isthmus ablation. Complications were uncommon (5.1%) and were life-threatening in 0.7% of cases. In our next paper, Brian Howard and associates hypothesize that pulse field ablation (PFA) would reduce pulmonary vein stenosis risk and collateral injury compared to irrigated radiofrequency ablation (IRF). IRF and PFA deliveries were randomized in eight dogs with two superior pulmonary veins (PVs), ablated with using one technology and two inferior PVs ablated with the other technology. IRF energy (25-30 watts) or PFA with delivered (16 pulse trains) at each PV in a proximal and in a distal site. Contrast computed tomography (CT scans) were collected at 0, 2, 4 and 8, and 12 week, including termination time points to monitor PV cross-sectional area at each PV ablation site. Maximum average change in normalized cross-sectional area at 4 weeks was 46.1%±45.1% post IRF compared to -5.5±20.5% for PFA (P≤ to 0.001). Necropsy showed expansive PFA lesions without stenosis in the proximal PV sites compared to more confined and often incomplete lesions after IRF. At the distal PV sites only IRF ablations were grossly identified based on focal fibrosis. Mild pulmonary chronic parenchymal hemorrhage was noted in three left superior pulmonary vein lobes after IRF. Damage to vagus nerves, as well as evidence of esophagus dilation, occurred at sites associated with IRF. In contrast, no lung, vagal nerve, or esophageal injury was observed at PFA sites. In our next paper, Mohamed Diab and associates aimed to assess the safety of ablation for atrial fibrillation (AF) with trans-esophageal (TEE) screening on intracardiac echocardiography (ICE) imaging of the appendage in direct oral anticoagulant (DOAC) compliant patients. They studied 900 patients with a medium CHA2DS2-VASc score of two. Interquartile range one to three. All consecutive patients presenting with AF or atrial flutter on DOAC were included. All were on DOACs (333 Rivaroxaban, 285 Dabigatran, 281 Apixaban and one Edoxaban). Thromboembolic complications occurred in four patients (0.3%), two ischemic strokes, one transient ischemic attack without residual deficit and one splenic infarct, all with no further complications. Bleeding complications incurred in 5 patients (0.4%), including 2 pericardial effusions (1 intraoperative, 1 after 30 days, both drained), and 3 groin hematomas (1 due to needing heparin for venous thrombosis, none requiring intervention). No patients required emergent surgeries. In our next paper, Alexios Hadjis and associates aim to explore the role of complete diastolic pathway activation mapping on ventricular tachycardia (VT) recurrence. They studied 85 consecutive patients who underwent VT ablation using and guided by high-density mapping. During activation mapping, the presence of electrical activity in all segments of diastole defined the evidence of having had recorded the whole diastolic interval. Patients were categorized as having recorded the full diastolic pathway, partial diastolic pathway or no diastolic pathway map performed. Recurrences of VT were defined as appropriate IC therapies or on the basis of EC documented arrhythmia. Complete recording of the diastolic pathway was achieved in 36 of 85 (42.4%). Partial recording of the diastolic pathway of clinical VT was achieved in 24 of 85 (28.2%). No recording of the diastolic pathway of clinical VT was feasible in 25 of 85 patients (29.4%). At a mean of 12.8 months, freedom from VT recurrences was 67% in the overall cohort. At a mean of 12.8 months, freedom from VT recurrence was 88% in patients who had full diastolic activity recorded, 50% of partial diastolic activity recorded and 55% in those who underwent substrate modification (P=0.02). The authors concluded that mapping of the entire diastolic pathway was associated with a higher freedom from VT occurrence compared to partial diastolic pathway recording and substrate modification. The use of multielectrode mapping catheters in recording diastolic activity may help predict those VTs employing intramural circuits and further optimize ablation strategies. In our next paper, Hui-Nam Pak and associates investigated whether electrical posterior box isolation (POBI) may improve rhythm outcome of catheter ablation in patients in whom persistent atrial fibrillation changes to paroxysmal atrial fibrillation after antiarrythmic drug medication and cardioversion. They prospectively randomized 114 patients, 75% male, 59.8 years old to circumferential pulmonary vein ablation (CPVI) alone (n=57) and an additional POBI group (n=57). Primary endpoint was AF recurrence after a single procedure, and secondary endpoints were recurrence pattern, cardioversion rate and response to antiarrhythmic drugs (AAD). After a mean follow-up of 23.8 months, the clinical recurrence rate did not significantly differ between the CPVI alone and additional POBI group (31.6% versus 28.1%; P=0.682). The recurrence rate as atrial tachycardias, 5.3% versus 12.3% (P=0.14) and cardioversion rates, 5.3% versus 10.5% (P=0.25) were not significantly different between the CPVI and POBI group. At the final follow-up, sinus rhythm was maintained without antiarryhthmic drug in 52.6% of CPVI group and 59.6% of the POBI group (P=0.45). No significant difference was found in major complications between the two groups, 5.3% versus 1.8% (P=0.618). But the total ablation time was significantly longer in the POBI group (4187 seconds versus 5337 seconds; P

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-chief, with some of the key highlights from this month's issue. In our first paper, Zak Loring and associates examined 3,139 patients undergoing atrial fibrillation (AF) ablation, between 2016 and 2018 in the Get With The Guidelines-Atrial Fibrillation Registry from 24 US centers. Patients undergoing AF ablation were predominantly male (63.9%) and Caucasian (93.2%) with a median age of 65. Hypertension was the most common comorbidity (67.6%), and persistent atrial fibrillation patients had more comorbidities than paroxysmal AF patients. Drug refractory, paroxysmal AF was most common ablation indication (class I, 53.6%) followed by drug refractory, persistent AF (class I, 41.8%). Radio-frequency, RF ablation, with contact force sensing was the most common ablation modality (70.5%) and 23.7% of patients underwent cryoballoon ablation. Pulmonary vein isolation was performed in 94.6% of de novo ablations. The most common adjunctive lesion included left atrial roof or posterior/inferior lines and cavotricuspid isthmus ablation. Complications were uncommon (5.1%) and were life-threatening in 0.7% of cases. In our next paper, Brian Howard and associates hypothesize that pulse field ablation (PFA) would reduce pulmonary vein stenosis risk and collateral injury compared to irrigated radiofrequency ablation (IRF). IRF and PFA deliveries were randomized in eight dogs with two superior pulmonary veins (PVs), ablated with using one technology and two inferior PVs ablated with the other technology. IRF energy (25-30 watts) or PFA with delivered (16 pulse trains) at each PV in a proximal and in a distal site. Contrast computed tomography (CT scans) were collected at 0, 2, 4 and 8, and 12 week, including termination time points to monitor PV cross-sectional area at each PV ablation site. Maximum average change in normalized cross-sectional area at 4 weeks was 46.1%±45.1% post IRF compared to -5.5±20.5% for PFA (P≤ to 0.001). Necropsy showed expansive PFA lesions without stenosis in the proximal PV sites compared to more confined and often incomplete lesions after IRF. At the distal PV sites only IRF ablations were grossly identified based on focal fibrosis. Mild pulmonary chronic parenchymal hemorrhage was noted in three left superior pulmonary vein lobes after IRF. Damage to vagus nerves, as well as evidence of esophagus dilation, occurred at sites associated with IRF. In contrast, no lung, vagal nerve, or esophageal injury was observed at PFA sites. In our next paper, Mohamed Diab and associates aimed to assess the safety of ablation for atrial fibrillation (AF) with trans-esophageal (TEE) screening on intracardiac echocardiography (ICE) imaging of the appendage in direct oral anticoagulant (DOAC) compliant patients. They studied 900 patients with a medium CHA2DS2-VASc score of two. Interquartile range one to three. All consecutive patients presenting with AF or atrial flutter on DOAC were included. All were on DOACs (333 Rivaroxaban, 285 Dabigatran, 281 Apixaban and one Edoxaban). Thromboembolic complications occurred in four patients (0.3%), two ischemic strokes, one transient ischemic attack without residual deficit and one splenic infarct, all with no further complications. Bleeding complications incurred in 5 patients (0.4%), including 2 pericardial effusions (1 intraoperative, 1 after 30 days, both drained), and 3 groin hematomas (1 due to needing heparin for venous thrombosis, none requiring intervention). No patients required emergent surgeries. In our next paper, Alexios Hadjis and associates aim to explore the role of complete diastolic pathway activation mapping on ventricular tachycardia (VT) recurrence. They studied 85 consecutive patients who underwent VT ablation using and guided by high-density mapping. During activation mapping, the presence of electrical activity in all segments of diastole defined the evidence of having had recorded the whole diastolic interval. Patients were categorized as having recorded the full diastolic pathway, partial diastolic pathway or no diastolic pathway map performed. Recurrences of VT were defined as appropriate IC therapies or on the basis of EC documented arrhythmia. Complete recording of the diastolic pathway was achieved in 36 of 85 (42.4%). Partial recording of the diastolic pathway of clinical VT was achieved in 24 of 85 (28.2%). No recording of the diastolic pathway of clinical VT was feasible in 25 of 85 patients (29.4%). At a mean of 12.8 months, freedom from VT recurrences was 67% in the overall cohort. At a mean of 12.8 months, freedom from VT recurrence was 88% in patients who had full diastolic activity recorded, 50% of partial diastolic activity recorded and 55% in those who underwent substrate modification (P=0.02). The authors concluded that mapping of the entire diastolic pathway was associated with a higher freedom from VT occurrence compared to partial diastolic pathway recording and substrate modification. The use of multielectrode mapping catheters in recording diastolic activity may help predict those VTs employing intramural circuits and further optimize ablation strategies. In our next paper, Hui-Nam Pak and associates investigated whether electrical posterior box isolation (POBI) may improve rhythm outcome of catheter ablation in patients in whom persistent atrial fibrillation changes to paroxysmal atrial fibrillation after antiarrythmic drug medication and cardioversion. They prospectively randomized 114 patients, 75% male, 59.8 years old to circumferential pulmonary vein ablation (CPVI) alone (n=57) and an additional POBI group (n=57). Primary endpoint was AF recurrence after a single procedure, and secondary endpoints were recurrence pattern, cardioversion rate and response to antiarrhythmic drugs (AAD). After a mean follow-up of 23.8 months, the clinical recurrence rate did not significantly differ between the CPVI alone and additional POBI group (31.6% versus 28.1%; P=0.682). The recurrence rate as atrial tachycardias, 5.3% versus 12.3% (P=0.14) and cardioversion rates, 5.3% versus 10.5% (P=0.25) were not significantly different between the CPVI and POBI group. At the final follow-up, sinus rhythm was maintained without antiarryhthmic drug in 52.6% of CPVI group and 59.6% of the POBI group (P=0.45). No significant difference was found in major complications between the two groups, 5.3% versus 1.8% (P=0.618). But the total ablation time was significantly longer in the POBI group (4187 seconds versus 5337 seconds; P

Circulation: Arrhythmia and Electrophysiology September 2020 Issue

Paul J. Wang: Welcome to the monthly podcast, On the BEAT, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor in Chief, with some of the key highlights from this month's issue. Albert Feeny and Associates used unsupervised machine learning of electrocardiogram [ECG] waveforms to identify cardiac resynchronization therapy [CRT] subgroups to differentiate outcomes beyond QRS duration and left bundle branch block. They retrospectively analyzed 946 CRT patients with conduction delay. Principal component analysis [PCA] dimensionality reduction obtained a 2-dimensional representation of pre-CRT 12-lead QRS waveforms. K-means clustering of the 2-dimensional PCA representation of 12-lead QRS waveforms identified two patient subgroups [QRS PCA groups]. Vectorcardiographic QRS area was also calculated. They examined two primary outcomes: (1) composite endpoint of death, left ventricular assist device, or heart transplant, and (2) degree of echocardiographic left ventricular ejection fraction [LVEF] change after CRT. Compared to QRS PCA group 2 (n = 425), Group 1 (n=521) had a lower risk for achieving the composite endpoint (hazard ratio of 0.44, P &lt; 0.001) and experienced greater mean LVEF improvement (11.1% versus 4.8%, P &lt; 0.001), even among left bundle branch block patients with QRS duration, 150 milliseconds or greater (hazard ratio 0.45, P &lt; 0.001; mean LVF change 12.5% versus 7.3%, P=0.001). A stratification scheme combining QRS area and QRS PCA group identified left bundle branch block patients with similar outcomes as non left bundle branch block patients (hazard ratio 1.32, mean difference LVEF change 0.8%). That stratification scheme also identified left bundle branch block patients with QRS duration less than 150 ms is comparable outcomes to left bundle branch patients with QRS duration 150 ms or greater (hazard ratio 0.93, mean difference in LVF change -0.2%). The authors concluded that unsupervised machine learning of ECG waveforms identified CRT subgroups with relevance beyond left bundle branch block and QRS duration. In our next paper, Julie Shade, Rheeda Ali and Associates combined machine learning [ML] and personalized computational modeling to predict, prior to pulmonary vein isolation [PVI], which patients are most likely to experience atrial fibrillation [AF] recurrence after PVI. The single center retrospective proof of concept study included 32 patients with documented paroxysmal AF who underwent PVI and had pre-procedural late gadolinium enhanced magnetic resonance imaging [LGE MRI]. For each patient, a personalized computational model of the left atrium simulated AF induction via rapid pacing features were derived from pre-PVI LG MRI images and from results of simulations [SIM] AF. The most predictive features used to input to a quadratic discrimination analysis ML classifier, which was trained, optimized, and evaluated with a 10-fold nested cross validation to predict the probability of AF recurrence post PVI. In the cohort, the ML classifier predicted probability of AF recurrence with an average validation, sensitivity, and specificity of 82% and 89% respectively, and a validation AUC of 0.82. Dissecting the relative contributions of simulations SIM AF and raw images to the predictive capability of the ML classifier, they found that only when features from simulation SIM AF were used to train the ML classifier, its performance retained similar (validation AUC equals 0.81). However, when only features classified from raw images were used for training, the validation AUC significantly decreased (0.47). In our next paper, Sarah Vermij and Associates examined sodium channel NaV 1.5 localization and function mutations in the gene and coding the sodium channel NaV 1.5 caused various cardiac arrhythmias. The authors use novel single-molecule localization [S-M-L-M] and computational modeling to define nanoscale features of NaV 1.5 localization and distribution at the lateral membrane [L-M], the LM groove, and T-tubules in cardiomyocytes from wild-type (N=3), dystrophin-deficient (mdx; N=3) mice, and mice expressing C-terminally truncated NaV 1.5 (ΔSIV; N=3). The authors assessed T-tubules sodium current by recording whole-cell sodium currents in control (N=5) in detubulated (N=5) wild-type cardiomyocytes. The authors found that NaV 1.5 organizes as distinct clusters in the groove and T-tubules which density, distribution, and organization partially depend on SIV and dystrophin. They found that overall reduction in NaV 1.5 expression expressed in mdx and ΔSIV cells result in a non-uniform distribution with NaV 1.5 being specifically reduced at the groove ΔSIV and increased in T-tubules of mdx cardiomyocytes. A T-tubules sodium current could, however, not be demonstrated. The authors concluded that NaV 1.5 mutations may site-specifically affect NaV 1.5 localization and distribution at the lateral membrane and T-tubules, depending on site-specific interacting proteins. In our next paper, Sharan Sharma, Mohit Turagam, and associates studied strategies to improve patient comfort related to pericardial access. They conducted a multi-centered retrospective study, including 104 patients who underwent epicardial ventricular tachycardia [VT] ablation and Lariat left atrial appendage occlusion. They compared 53 patients who received post-procedural intrapericardial liposomal bupivacaine (LB)+oral colchicine (LB group) and 51 patients who received colchicine alone (non-LB group). Lyposomal bupivacaine was associated with significant lowering of median pain scale at 6 hours (1.0 versus 8.0, P

Paul J. Wang: Welcome to the monthly podcast, On the BEAT, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor in Chief, with some of the key highlights from this month's issue. Albert Feeny and Associates used unsupervised machine learning of electrocardiogram [ECG] waveforms to identify cardiac resynchronization therapy [CRT] subgroups to differentiate outcomes beyond QRS duration and left bundle branch block. They retrospectively analyzed 946 CRT patients with conduction delay. Principal component analysis [PCA] dimensionality reduction obtained a 2-dimensional representation of pre-CRT 12-lead QRS waveforms. K-means clustering of the 2-dimensional PCA representation of 12-lead QRS waveforms identified two patient subgroups [QRS PCA groups]. Vectorcardiographic QRS area was also calculated. They examined two primary outcomes: (1) composite endpoint of death, left ventricular assist device, or heart transplant, and (2) degree of echocardiographic left ventricular ejection fraction [LVEF] change after CRT. Compared to QRS PCA group 2 (n = 425), Group 1 (n=521) had a lower risk for achieving the composite endpoint (hazard ratio of 0.44, P &lt; 0.001) and experienced greater mean LVEF improvement (11.1% versus 4.8%, P &lt; 0.001), even among left bundle branch block patients with QRS duration, 150 milliseconds or greater (hazard ratio 0.45, P &lt; 0.001; mean LVF change 12.5% versus 7.3%, P=0.001). A stratification scheme combining QRS area and QRS PCA group identified left bundle branch block patients with similar outcomes as non left bundle branch block patients (hazard ratio 1.32, mean difference LVEF change 0.8%). That stratification scheme also identified left bundle branch block patients with QRS duration less than 150 ms is comparable outcomes to left bundle branch patients with QRS duration 150 ms or greater (hazard ratio 0.93, mean difference in LVF change -0.2%). The authors concluded that unsupervised machine learning of ECG waveforms identified CRT subgroups with relevance beyond left bundle branch block and QRS duration. In our next paper, Julie Shade, Rheeda Ali and Associates combined machine learning [ML] and personalized computational modeling to predict, prior to pulmonary vein isolation [PVI], which patients are most likely to experience atrial fibrillation [AF] recurrence after PVI. The single center retrospective proof of concept study included 32 patients with documented paroxysmal AF who underwent PVI and had pre-procedural late gadolinium enhanced magnetic resonance imaging [LGE MRI]. For each patient, a personalized computational model of the left atrium simulated AF induction via rapid pacing features were derived from pre-PVI LG MRI images and from results of simulations [SIM] AF. The most predictive features used to input to a quadratic discrimination analysis ML classifier, which was trained, optimized, and evaluated with a 10-fold nested cross validation to predict the probability of AF recurrence post PVI. In the cohort, the ML classifier predicted probability of AF recurrence with an average validation, sensitivity, and specificity of 82% and 89% respectively, and a validation AUC of 0.82. Dissecting the relative contributions of simulations SIM AF and raw images to the predictive capability of the ML classifier, they found that only when features from simulation SIM AF were used to train the ML classifier, its performance retained similar (validation AUC equals 0.81). However, when only features classified from raw images were used for training, the validation AUC significantly decreased (0.47). In our next paper, Sarah Vermij and Associates examined sodium channel NaV 1.5 localization and function mutations in the gene and coding the sodium channel NaV 1.5 caused various cardiac arrhythmias. The authors use novel single-molecule localization [S-M-L-M] and computational modeling to define nanoscale features of NaV 1.5 localization and distribution at the lateral membrane [L-M], the LM groove, and T-tubules in cardiomyocytes from wild-type (N=3), dystrophin-deficient (mdx; N=3) mice, and mice expressing C-terminally truncated NaV 1.5 (ΔSIV; N=3). The authors assessed T-tubules sodium current by recording whole-cell sodium currents in control (N=5) in detubulated (N=5) wild-type cardiomyocytes. The authors found that NaV 1.5 organizes as distinct clusters in the groove and T-tubules which density, distribution, and organization partially depend on SIV and dystrophin. They found that overall reduction in NaV 1.5 expression expressed in mdx and ΔSIV cells result in a non-uniform distribution with NaV 1.5 being specifically reduced at the groove ΔSIV and increased in T-tubules of mdx cardiomyocytes. A T-tubules sodium current could, however, not be demonstrated. The authors concluded that NaV 1.5 mutations may site-specifically affect NaV 1.5 localization and distribution at the lateral membrane and T-tubules, depending on site-specific interacting proteins. In our next paper, Sharan Sharma, Mohit Turagam, and associates studied strategies to improve patient comfort related to pericardial access. They conducted a multi-centered retrospective study, including 104 patients who underwent epicardial ventricular tachycardia [VT] ablation and Lariat left atrial appendage occlusion. They compared 53 patients who received post-procedural intrapericardial liposomal bupivacaine (LB)+oral colchicine (LB group) and 51 patients who received colchicine alone (non-LB group). Lyposomal bupivacaine was associated with significant lowering of median pain scale at 6 hours (1.0 versus 8.0, P

Circulation: Arrhythmia and Electrophysiology July 2020 Issue

Circulation: Arrhythmia and Electrophysiology August 2020 Issue

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor in chief, with some of the key highlights from this month's issue.   In our first paper, Vivek Reddy and associates studied a novel, 7.5, French lattice tip catheter with the compressible 9 mm nitinol tip that is able to deliver either focal radio frequency ablation [RFA] or pulsed field ablation [PFA], 2 to 5 second lesions. In a 3 center, single-arm, first in human trial, the catheter was used with a custom mapping system to treat paroxysmal or persistent atrial fibrillation. Toggling between energy sources, point by point, pulmonary vein [PV] encirclement was performed using biphasic pulsed field ablation, posteriorly, and either temperature controlled irrigated RFA or pulse field ablation, anteriorly (RF/PF or PF/PF) respectively. Linear lesions were created with either PFA or RFA. The 76 patient cohort included 55 paroxysmal and 21 persistent atrial fibrillation [AF] patients undergoing either RF/PF [pulse field ablation] 40 patients or PF/PF ablation in 36 patients, pulmonary vein isolation therapy duration was 22.6 minutes per patient with a mean of 50.1 RF/PF ablation lesions per patient. Linear lesions included 14 mitral, 34 left atrial roof and 44 cavo-tricuspid isthmus lines with therapy duration times of 5.1, 1.8 and 2.4 min/patient respectively. All lesion sets were acutely successful using 4.7 minutes of fluoroscopy. There were no device-related complications, including no strokes. Post-procedure esophagogastroduodenoscopy revealed minor mucosal thermal injury in two of the 36 RF/PF and zero of the 24 PF/PF patients. Post-procedure brain MRI revealed DWI positive flair, negative and DWI positive flare positive asymptomatic lesions in 5 and 3 of the 51 patients respectively.   In our next paper, Moussa Saleh and associates examined whether chloroquine, hydroxychloroquine plus or minus azithromycin lead to a prolongation of the QT interval, possibly increasing the risk of torsades de pointes and sudden death in a hospitalized population of patients with COVID-19. 201 patients were treated for COVID-19 with chloroquine/hydroxychloroquine. 10 patients or 5% received chloroquine, and 191 or 95% received hydroxychloroquine and 119 or 59% also received azithromycin. The primary outcome of Torsades de pointes was not observed in the entire population. Baseline QTC interval did not differ between patients treated with chloroquine or hydroxychloroquine monotherapy versus those treated with combination group chloroquine/hydroxychloroquine and azithromycin (440 ms versus 439.9 ms). The maximum QT during treatment was significantly longer in the combination versus the monotherapy group, 470 ms versus 453 ms (P = 0.004). Seven patients (3.5%) required discontinuation of these medications due to QTC prolongation. No arrhythmic deaths were reported.   In our next paper, Mikko Tulppo and associates examine whether the association between leisure time physical activity and the risk of sudden death and non-sudden cardiac death in coronary artery disease patients. 1,946 patients with angiographically verified coronary artery disease were classified into four groups: inactive, irregularly active, active exercise regularly two to three times per week, and highly active, exercise four times or more weekly. During follow-up, median 6.3 years, 52 sudden cardiac death and 49 non-sudden cardiac deaths occurred. Inactive patients had increased risk for sudden cardiac death compared to active patients, hazard ratio 2.45. Leisure time was not associated with sudden cardiac death in patients with Canadian cardiovascular class one, 18 events in 1,107 patients. Among patients with Canadian cardiovascular society, class two or higher, 34 events in 839 patients. An increased risk for sudden cardiac death encountered in highly active patients, hazard ratio 7.46 (P &lt; 0.001). In inactive patients hazard ratio 3.64 as compared to active patients. A linear association was observed between leisure time, physical activity and non-sudden cardiac death. Those with high leisure time physical activity had the lowest risk for non sudden cardiac death.   In our next paper, Jacob Koruth and associates examined the preclinical feasibility and safety of a 9mm lattice tip catheter with focal biphasic pulse field [PF] based thoracic vein isolation and linear ablation combined focal biphasic pulse field and radio-frequency [RF] focal ablation and vocal biphasic pulse field delivered directly on top of the esophagus. They treated two cohorts of six swine with pulse fields at low dose and high dose followed for four weeks and two weeks, respectively to isolate 25 thoracic veins and to create five right atrial low dose PF, six mitral high dose PF, and six roof lines with combined RF and high dose PF. Baseline and follow-up voltage mapping, venus potentials, ostial diameters and phrenic nerve viability were assessed. High dose PF in RF lesions were delivered in 4 and 1 swine from the inferior vena cava onto a forcefully deviate esophagus. 100% of thoracic veins, 25 out of 25, were successfully isolated with 12.4 applications per vein with a mean pulse field times of less than 90 seconds per vein. Durable isolation improved from 61.5% in the low dose pulse field to 100% with a high dose pulse field (P = 0.04). And all linear lesions were successfully completed without incurring venous stenosis or phrenic injury. High dose pulse field sections had higher trans mortality rates than low dose pulse field (98.3% versus 88.1%, P = 0.03). Despite greater thickness, 2.5 versus 1.3 mm, pulse field lesions demonstrated homogeneous fibrosis without epicardial fat, nerve or vessel involvement. In comparison, combined RF plus high dose PF sections revealed similar transmurality, but expectedly more necrosis, inflammation and epicardial fat, nerve and vessel involvement. Significant ablation related esophageal and necrosis inflammation and fibrosis were seen in all RF sections as compared to no PF sections.   In our next paper, Hagai Yavin and associates investigated the effects of a novel, lattice tip catheter designed for focal radiofrequency ablation [RFA] or pulse field ablation in 25 swine. In 14 animals, they examined in step one (n = 14) the feasibility to create atrial line of block and described as acute effects on the phrenic nerve and esophagus. In step two (n = 7), they examined the subacute effects of pulse field ablation on block durability, phrenic nerve, and esophagus 2 or more weeks. In 4 animals in step three, they compare the effects of pulse field ablation and RFA on the esophagus using a mechanical deviation model, approximating the esophagus through the right atrium in 4 and direct ablation honest lumen in 4. The effects of endocardial PFA and RFA on the phrenic nerve were also compared (n = 10). Histological analysis were performed. Pulse field ablation produced acute block in 100% of lines achieved with 2.1 applications per centimeter line. Histological analysis following a mean of 35 days showed 100% transmurality (thickness range 0.4 to 3.4 mm) with a lesion width of 19.4 mm. Pulse field ablation selectively affected cardiomyocytes, but spared blood vessels and nervous tissue. Pulse field ablation applied from the posterior atrium to the approximated esophagus produced transmural lesions without esophageal injury. Pulse field ablation applied within the esophageal lumen produced mild edema compared to radiofrequency ablation (13 applications) which produced epithelial ulcerations. Pulse field ablation resulted in no or transient stunning of the phrenic nerve, less than 5 minutes without histological changes while radiofrequency ablation produced paralysis.   In our next paper, Elad Anter and associates investigated the optimal methods to identify arrhythmogenic substrate of scar related VT. They examine how often sites of activation slowing during sinus rhythm co localize with ventricular tachycardia VT circuit. In a multicenter study in patients with infarct-related VT, the left ventricle was mapped during activation from three directions, sinus rhythm, or atrial pacing, right ventricular and left ventricular LV pacing at 600 ms. Ablation was applied selectively to the cumulative area of slow activation defined as a sum of all regions with activation time of 40 ms or greater per 10 mm. Hemodynamically tolerated ventricular tachycardias or VT were mapped with activation or entrainment. The primary outcome was a composite of appropriate ICD therapies and cardiovascular death. In 85 patients, the left ventricle was mapped during activation from 2.4 directions. The direction of LV activation influenced the location and magnitude of activation slowing. The spacial overlap of activation slowing between sinus rhythm and right ventricular RV pacing was 84.2%, between sinus rhythm and LV pacing was 61.4%, and between right ventricular and left ventricular pacing, 71.3% (P &lt; 0.05) between all comparisons. Mapping during sinus rhythm identified only 66.2% of the entire area of activation slowing and 58% of critical isthmus sites. Activation from other directions, right ventricular or left ventricular stimulation unmasked an additional 33% of slowly conducting zones and 25% critical isthmus sites. The area of maximal activation slowing often corresponded to the site where the wavefront first interacted with the infarct. During a follow-up period of 3.6 years, the primary end point incurred in 14 out of 85 or 16.5% of patients. The authors concluded that the spatial distribution of activation slowing is dependent on the direction of LV activation with the area of maximal slowing corresponding to the site where the wavefront first interacts with the infarct.   In our next paper, Georg Gussak and associates identified a novel form of abnormal calcium wave activity in normal and failing dog atrial myocytes, which occurs during the action potential and is absent during diastole. The goal of this study was to determine if triggered calcium waves affect cellular electrophysiological properties. The authors use simultaneous recordings of intracellular calcium, and action potentials for the measurement of maximum diastolic potential and action potential duration during triggered calcium waves in isolated dog atrial myocytes. Computer simulations then explored electrophysiological behavior arising from triggered calcium waves at the tissue scale. At 3.3 to five Hertz, triggered calcium waves occurred during the action potential and outlasted several action potential cycles. Maximum diastolic potential was reduced and actual potential duration was significant prolonged during trigger calcium waves. All electrophysiological responses that triggered calcium waves were abolished by using SCA 0400 and ORM 10103, indicating that sodium calcium exchange current caused depolarization. The time constant recovery from inactivation of calcium current was 40 to 70 ms in atrial myocytes, depending on the holding potential. This current could be responsible for action potential (AP) activation during repolarization induced by triggered waves. Modeling studies demonstrate the characteristic properties of triggered calcium waves are potentially arrhythmogenic by promoting both conduction block and reentry arising from the repolarization induced by triggered calcium waves. The authors concluded that triggered calcium waves activate inward sodium calcium exchange and dramatically reduce atrial maximum diastolic potential and prolonged action potential duration establishing the substrate for reentry that could contribute to initiation and maintenance of atrial arrhythmias.   In our next paper Faisal Merchant and Omid Sayadi and associates evaluate the ability of a real-time, closed loop system to record and analyze repolarization alternans from multiple intracardiac leads and deliver dynamically R-wave triggered pacing stimuli during the absolute refractory period. They examined the ability of this system to control repolarization alternans and reduce arrhythmia susceptibility, in vivo. R-wave trigger pacing can induce repolarization alternans, the magnitude of which can be modulated by varying the amplitude, pulse width, or size of the pacing vector. Using a swine model (n = 9), the authors demonstrated that to induce 1 microvolt change in the alternans voltage on the body surface, coronary sinus or left ventricle, requires a delivery charge of 0.04, 0.05 and 0.06 microcoulombs, respectively, while to induce one unit change of the case score requires a delivery charge of 0.93, 0.32 and 0.33 microcoulombs, respectively. For all body surface and intracardiac leads a Delta alternans voltage and Delta K score between baseline and R-wave triggered pace peaks increases consistently with an increase in the pacing pulse amplitude, pulse width and vector spacing. Additionally, the author showed that the proposed method can be used to suppress spontaneously occurring alternans (n = 7), in the presence of myocardial ischemia. Suppression of repolarization alternans by pacing during the absolute refractory period results in a significant reduction in arrhythmia susceptibility, evidenced by lower S rank score during program ventricular stimulation compared to baseline prior to ischemia.   In a perspective outlining the cardiovascular effects of chloroquine and hydroxychloroquine, Ohad Oren and associates describe their belief that the use of chloroquine and hydroxychloroquine in COVID-19 should be limited to randomized, controlled trials. For critically ill patients, unable to enroll in a trial, selective in-hospital use could be considered with careful clinical monitoring in keeping with the FDA's emergency use authorization. The authors suggested that studies evaluating chloroquine and hydroxychloroquine should systematically collect baseline demographic data, results from electrocardiographic and echocardiographic monitoring prior to and during treatment and rates of adverse cardiovascular events in both the near and long-term.   In a research letter, Federico Migliore and Alessandro Zorzi and associates found a 28% decrease in the number of urgent pacemaker implantations during the six weeks after the first COVID-19 case, from 122 to 88 (P = 0.02), compared to the six weeks before the first COVID-19 case. The proportion of female patients requiring urgent pacemaker implantation after the COVID-19 outbreak decreased from six out of 122 (49%) to 30 out of 88 (34%) (P = 0.03).   In a special report Stephanie Kochav and associates described 4 cases of cardiac arrhythmias in COVID-19, including AV block, atrial fibrillation, polymorphic ventricular tachycardia, and pulseless electrical activity arrest.   In a year in review, Suraj Kapa and associates discuss a number of the many advances in our understanding of arrhythmia mechanisms, diagnosis, and new therapies in the past year. Data suggests that secretoneurin may be a marker for patients at risk of ventricular arrhythmias, while natriuretic peptide receptor C may have a role in atrial fibrosis. In atrial specific 2-pore potassium channel TASK-1 may be a therapeutic target for atrial fibrillation. Sensory neurons may play a key role in sleep apnea related to atrial fibrillation. Bariatric surgery is associated with improved atrial fibrillation outcome. Artificial intelligence applied to electrocardiography has yielded estimates of age, gender, and overall health. We've seen new tools for collection of patient centered outcomes following catheter ablation. There's been significant advances in the ability to identify ventricular tachycardia termination sites through high density mapping of deceleration zones. We've learned that right ventricular dysfunction may be a predictor of survival benefit after ICD implantation in non ischemic cardiomyopathy patients. We've seen further insights in the role of his bundle pacing on improving outcomes. As our understanding of cardiac laminopathies advance, we have new tools to predict arrhythmic event rates in gene carriers. And finally, we've seen numerous advances in the treatment of arrhythmias in patients with congenital heart disease.   That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, Vivek Reddy and associates studied a novel, 7.5, French lattice tip catheter with the compressible 9 mm nitinol tip that is able to deliver either focal radio frequency ablation [RFA] or pulsed field ablation [PFA], 2 to 5 second lesions. In a 3 center, single-arm, first in human trial, the catheter was used with a custom mapping system to treat paroxysmal or persistent atrial fibrillation. Toggling between energy sources, point by point, pulmonary vein [PV] encirclement was performed using biphasic pulsed field ablation, posteriorly, and either temperature controlled irrigated RFA or pulse field ablation, anteriorly (RF/PF or PF/PF) respectively. Linear lesions were created with either PFA or RFA. The 76 patient cohort included 55 paroxysmal and 21 persistent atrial fibrillation [AF] patients undergoing either RF/PF [pulse field ablation] 40 patients or PF/PF ablation in 36 patients, pulmonary vein isolation therapy duration was 22.6 minutes per patient with a mean of 50.1 RF/PF ablation lesions per patient. Linear lesions included 14 mitral, 34 left atrial roof and 44 cavo-tricuspid isthmus lines with therapy duration times of 5.1, 1.8 and 2.4 min/patient respectively. All lesion sets were acutely successful using 4.7 minutes of fluoroscopy. There were no device-related complications, including no strokes. Post-procedure esophagogastroduodenoscopy revealed minor mucosal thermal injury in two of the 36 RF/PF and zero of the 24 PF/PF patients. Post-procedure brain MRI revealed DWI positive flair, negative and DWI positive flare positive asymptomatic lesions in 5 and 3 of the 51 patients respectively. In our next paper, Moussa Saleh and associates examined whether chloroquine, hydroxychloroquine plus or minus azithromycin lead to a prolongation of the QT interval, possibly increasing the risk of torsades de pointes and sudden death in a hospitalized population of patients with COVID-19. 201 patients were treated for COVID-19 with chloroquine/hydroxychloroquine. 10 patients or 5% received chloroquine, and 191 or 95% received hydroxychloroquine and 119 or 59% also received azithromycin. The primary outcome of Torsades de pointes was not observed in the entire population. Baseline QTC interval did not differ between patients treated with chloroquine or hydroxychloroquine monotherapy versus those treated with combination group chloroquine/hydroxychloroquine and azithromycin (440 ms versus 439.9 ms). The maximum QT during treatment was significantly longer in the combination versus the monotherapy group, 470 ms versus 453 ms (P = 0.004). Seven patients (3.5%) required discontinuation of these medications due to QTC prolongation. No arrhythmic deaths were reported. In our next paper, Mikko Tulppo and associates examine whether the association between leisure time physical activity and the risk of sudden death and non-sudden cardiac death in coronary artery disease patients. 1,946 patients with angiographically verified coronary artery disease were classified into four groups: inactive, irregularly active, active exercise regularly two to three times per week, and highly active, exercise four times or more weekly. During follow-up, median 6.3 years, 52 sudden cardiac death and 49 non-sudden cardiac deaths occurred. Inactive patients had increased risk for sudden cardiac death compared to active patients, hazard ratio 2.45. Leisure time was not associated with sudden cardiac death in patients with Canadian cardiovascular class one, 18 events in 1,107 patients. Among patients with Canadian cardiovascular society, class two or higher, 34 events in 839 patients. An increased risk for sudden cardiac death encountered in highly active patients, hazard ratio 7.46 (P &lt; 0.001). In inactive patients hazard ratio 3.64 as compared to active patients. A linear association was observed between leisure time, physical activity and non-sudden cardiac death. Those with high leisure time physical activity had the lowest risk for non sudden cardiac death. In our next paper, Jacob Koruth and associates examined the preclinical feasibility and safety of a 9mm lattice tip catheter with focal biphasic pulse field [PF] based thoracic vein isolation and linear ablation combined focal biphasic pulse field and radio-frequency [RF] focal ablation and vocal biphasic pulse field delivered directly on top of the esophagus. They treated two cohorts of six swine with pulse fields at low dose and high dose followed for four weeks and two weeks, respectively to isolate 25 thoracic veins and to create five right atrial low dose PF, six mitral high dose PF, and six roof lines with combined RF and high dose PF. Baseline and follow-up voltage mapping, venus potentials, ostial diameters and phrenic nerve viability were assessed. High dose PF in RF lesions were delivered in 4 and 1 swine from the inferior vena cava onto a forcefully deviate esophagus. 100% of thoracic veins, 25 out of 25, were successfully isolated with 12.4 applications per vein with a mean pulse field times of less than 90 seconds per vein. Durable isolation improved from 61.5% in the low dose pulse field to 100% with a high dose pulse field (P = 0.04). And all linear lesions were successfully completed without incurring venous stenosis or phrenic injury. High dose pulse field sections had higher trans mortality rates than low dose pulse field (98.3% versus 88.1%, P = 0.03). Despite greater thickness, 2.5 versus 1.3 mm, pulse field lesions demonstrated homogeneous fibrosis without epicardial fat, nerve or vessel involvement. In comparison, combined RF plus high dose PF sections revealed similar transmurality, but expectedly more necrosis, inflammation and epicardial fat, nerve and vessel involvement. Significant ablation related esophageal and necrosis inflammation and fibrosis were seen in all RF sections as compared to no PF sections. In our next paper, Hagai Yavin and associates investigated the effects of a novel, lattice tip catheter designed for focal radiofrequency ablation [RFA] or pulse field ablation in 25 swine. In 14 animals, they examined in step one (n = 14) the feasibility to create atrial line of block and described as acute effects on the phrenic nerve and esophagus. In step two (n = 7), they examined the subacute effects of pulse field ablation on block durability, phrenic nerve, and esophagus 2 or more weeks. In 4 animals in step three, they compare the effects of pulse field ablation and RFA on the esophagus using a mechanical deviation model, approximating the esophagus through the right atrium in 4 and direct ablation honest lumen in 4. The effects of endocardial PFA and RFA on the phrenic nerve were also compared (n = 10). Histological analysis were performed. Pulse field ablation produced acute block in 100% of lines achieved with 2.1 applications per centimeter line. Histological analysis following a mean of 35 days showed 100% transmurality (thickness range 0.4 to 3.4 mm) with a lesion width of 19.4 mm. Pulse field ablation selectively affected cardiomyocytes, but spared blood vessels and nervous tissue. Pulse field ablation applied from the posterior atrium to the approximated esophagus produced transmural lesions without esophageal injury. Pulse field ablation applied within the esophageal lumen produced mild edema compared to radiofrequency ablation (13 applications) which produced epithelial ulcerations. Pulse field ablation resulted in no or transient stunning of the phrenic nerve, less than 5 minutes without histological changes while radiofrequency ablation produced paralysis. In our next paper, Elad Anter and associates investigated the optimal methods to identify arrhythmogenic substrate of scar related VT. They examine how often sites of activation slowing during sinus rhythm co localize with ventricular tachycardia VT circuit. In a multicenter study in patients with infarct-related VT, the left ventricle was mapped during activation from three directions, sinus rhythm, or atrial pacing, right ventricular and left ventricular LV pacing at 600 ms. Ablation was applied selectively to the cumulative area of slow activation defined as a sum of all regions with activation time of 40 ms or greater per 10 mm. Hemodynamically tolerated ventricular tachycardias or VT were mapped with activation or entrainment. The primary outcome was a composite of appropriate ICD therapies and cardiovascular death. In 85 patients, the left ventricle was mapped during activation from 2.4 directions. The direction of LV activation influenced the location and magnitude of activation slowing. The spacial overlap of activation slowing between sinus rhythm and right ventricular RV pacing was 84.2%, between sinus rhythm and LV pacing was 61.4%, and between right ventricular and left ventricular pacing, 71.3% (P &lt; 0.05) between all comparisons. Mapping during sinus rhythm identified only 66.2% of the entire area of activation slowing and 58% of critical isthmus sites. Activation from other directions, right ventricular or left ventricular stimulation unmasked an additional 33% of slowly conducting zones and 25% critical isthmus sites. The area of maximal activation slowing often corresponded to the site where the wavefront first interacted with the infarct. During a follow-up period of 3.6 years, the primary end point incurred in 14 out of 85 or 16.5% of patients. The authors concluded that the spatial distribution of activation slowing is dependent on the direction of LV activation with the area of maximal slowing corresponding to the site where the wavefront first interacts with the infarct. In our next paper, Georg Gussak and associates identified a novel form of abnormal calcium wave activity in normal and failing dog atrial myocytes, which occurs during the action potential and is absent during diastole. The goal of this study was to determine if triggered calcium waves affect cellular electrophysiological properties. The authors use simultaneous recordings of intracellular calcium, and action potentials for the measurement of maximum diastolic potential and action potential duration during triggered calcium waves in isolated dog atrial myocytes. Computer simulations then explored electrophysiological behavior arising from triggered calcium waves at the tissue scale. At 3.3 to five Hertz, triggered calcium waves occurred during the action potential and outlasted several action potential cycles. Maximum diastolic potential was reduced and actual potential duration was significant prolonged during trigger calcium waves. All electrophysiological responses that triggered calcium waves were abolished by using SCA 0400 and ORM 10103, indicating that sodium calcium exchange current caused depolarization. The time constant recovery from inactivation of calcium current was 40 to 70 ms in atrial myocytes, depending on the holding potential. This current could be responsible for action potential (AP) activation during repolarization induced by triggered waves. Modeling studies demonstrate the characteristic properties of triggered calcium waves are potentially arrhythmogenic by promoting both conduction block and reentry arising from the repolarization induced by triggered calcium waves. The authors concluded that triggered calcium waves activate inward sodium calcium exchange and dramatically reduce atrial maximum diastolic potential and prolonged action potential duration establishing the substrate for reentry that could contribute to initiation and maintenance of atrial arrhythmias. In our next paper Faisal Merchant and Omid Sayadi and associates evaluate the ability of a real-time, closed loop system to record and analyze repolarization alternans from multiple intracardiac leads and deliver dynamically R-wave triggered pacing stimuli during the absolute refractory period. They examined the ability of this system to control repolarization alternans and reduce arrhythmia susceptibility, in vivo. R-wave trigger pacing can induce repolarization alternans, the magnitude of which can be modulated by varying the amplitude, pulse width, or size of the pacing vector. Using a swine model (n = 9), the authors demonstrated that to induce 1 microvolt change in the alternans voltage on the body surface, coronary sinus or left ventricle, requires a delivery charge of 0.04, 0.05 and 0.06 microcoulombs, respectively, while to induce one unit change of the case score requires a delivery charge of 0.93, 0.32 and 0.33 microcoulombs, respectively. For all body surface and intracardiac leads a Delta alternans voltage and Delta K score between baseline and R-wave triggered pace peaks increases consistently with an increase in the pacing pulse amplitude, pulse width and vector spacing. Additionally, the author showed that the proposed method can be used to suppress spontaneously occurring alternans (n = 7), in the presence of myocardial ischemia. Suppression of repolarization alternans by pacing during the absolute refractory period results in a significant reduction in arrhythmia susceptibility, evidenced by lower S rank score during program ventricular stimulation compared to baseline prior to ischemia. In a perspective outlining the cardiovascular effects of chloroquine and hydroxychloroquine, Ohad Oren and associates describe their belief that the use of chloroquine and hydroxychloroquine in COVID-19 should be limited to randomized, controlled trials. For critically ill patients, unable to enroll in a trial, selective in-hospital use could be considered with careful clinical monitoring in keeping with the FDA's emergency use authorization. The authors suggested that studies evaluating chloroquine and hydroxychloroquine should systematically collect baseline demographic data, results from electrocardiographic and echocardiographic monitoring prior to and during treatment and rates of adverse cardiovascular events in both the near and long-term. In a research letter, Federico Migliore and Alessandro Zorzi and associates found a 28% decrease in the number of urgent pacemaker implantations during the six weeks after the first COVID-19 case, from 122 to 88 (P = 0.02), compared to the six weeks before the first COVID-19 case. The proportion of female patients requiring urgent pacemaker implantation after the COVID-19 outbreak decreased from six out of 122 (49%) to 30 out of 88 (34%) (P = 0.03). In a special report Stephanie Kochav and associates described 4 cases of cardiac arrhythmias in COVID-19, including AV block, atrial fibrillation, polymorphic ventricular tachycardia, and pulseless electrical activity arrest. In a year in review, Suraj Kapa and associates discuss a number of the many advances in our understanding of arrhythmia mechanisms, diagnosis, and new therapies in the past year. Data suggests that secretoneurin may be a marker for patients at risk of ventricular arrhythmias, while natriuretic peptide receptor C may have a role in atrial fibrosis. In atrial specific 2-pore potassium channel TASK-1 may be a therapeutic target for atrial fibrillation. Sensory neurons may play a key role in sleep apnea related to atrial fibrillation. Bariatric surgery is associated with improved atrial fibrillation outcome. Artificial intelligence applied to electrocardiography has yielded estimates of age, gender, and overall health. We've seen new tools for collection of patient centered outcomes following catheter ablation. There's been significant advances in the ability to identify ventricular tachycardia termination sites through high density mapping of deceleration zones. We've learned that right ventricular dysfunction may be a predictor of survival benefit after ICD implantation in non ischemic cardiomyopathy patients. We've seen further insights in the role of his bundle pacing on improving outcomes. As our understanding of cardiac laminopathies advance, we have new tools to predict arrhythmic event rates in gene carriers. And finally, we've seen numerous advances in the treatment of arrhythmias in patients with congenital heart disease. That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.

Circulation: Arrhythmia and Electrophysiology June 2020 Issue

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. In our first paper, Bruce Wilkoff and associates examine the impact of cardiac implantable electronic device [CIED] infections on mortality, quality of life, healthcare utilization, and cost in the U.S. Healthcare system. They found that the majority CIED infection was associated with increased all-cause mortality, 12-month risk-adjusted hazard ratio 3.41, P &lt; 0.001. An effect that sustained beyond 12 months.   The quality of life was reduced, P = 0.004, and did not normalize for six months. Disruptions in CIED therapy were observed in 36% of infections for a median duration of 184 days. The authors reported that the mean hospital costs were $55,547.   In our next paper, Songwen Chen, Xiaofeng Lu and associates examine the ability to eliminate premature ventricular complexes [PVCs] originating from the proximal left anterior fascicle, safely from the right coronary sinus. The authors mapped the the right coronary sinus and left ventricle in 20 patients with left anterior fascicle PVCs. They found that the earliest activation site with Purkinje potential during both PVC and sinus rhythm was localized at proximal left anterior fascicle in eight patients, the proximal group, or non-proximal left anterior fascicle in 12 groups, the non-proximal group. The Purkinje potentials proceeded PVC-QRS at the earliest activation site in proximal group 32.6 milliseconds was significantly earlier than that in non-proximal group, 28.3 milliseconds P = 0.025. Similar difference in the Purkinje potentials proceeding sinus QRS at the earliest activation site was also observed between proximal and non-proximal group, 35.1 milliseconds versus 25.2 milliseconds, P &lt; 0.001.   In proximal group, the distance between the earliest activation site to the left His-bundle into the right coronary sinus were shorter than that of the non-proximal group 12.3 millimeters versus 19.7, P = 0.002, and 3.9 millimeters versus 15.7 millimeters, P &lt; 0.001, respectively. The authors found no difference in the distance between the right coronary sinus to proximal left anterior fascicle between the two groups. PVCs were successfully eliminated from the right coronary sinus in all proximal group, but at left ventricular earliest activation site for the non-proximal group, the radiofrequency application time, ablation time and procedure time of non-proximal group were longer than that proximal group.   Electrocardiographic analysis showed that when compared to non-proximal group, the PVCs proximal group had a narrower QRS duration, smaller S wave in leads one, V five,and V six; lower R waves in leads one, aVL, aVR, V one, V two, and V four and smaller q wave in leads three and aVF. The QRS duration difference [PVC-QRS and sinus rhythm QRS] &lt; 15 milliseconds predicted the proximal left anterior fascicle origin with high sensitivity and specificity.   In our next paper, Benjamin Steinberg and associates examined the factors that are associated with large improvements in health-related quality of life in patients with atrial fibrillation. The authors assessed factors associated with a one-year increase in quality of life, measured by AFEQT of one standard deviation that is greater and equal to 18 points, three times clinically important difference among patients in the ORBIT-AF one registry. They found that 28% of patients had such a health-related quality improvement compared with patients not showing large health-related quality of life improvement. They were similar age, (median 73 versus 74 years of age), equally likely to be female, (44% versus 48%), but more likely to have newly diagnosed atrial fibrillation [AF] at baseline (18% versus 8%, P = 0.0004) prior antiarrhythmic drug use (52% versus 40%, P = 0.005), baseline antiarrhythmic drug use (34.8% versus 26.8%, P = 0.045), and more likely to undergo AF related procedures during follow-up (AF ablation 6.6% versus 2.0%, cardioversion 12.2% versus 5.9%). In multivariate analysis, a history of alcohol abuse has a ratio 2.4 and increased baseline diastolic blood pressure has a ratio 1.23 per 10 point increase and greater than 65 millimeters of mercury were associated with large improvements in health-related quality of life at one year. Whereas patients with prior stroke, chronic obstructive pulmonary disease and peripheral artery disease were less likely to improve.   In our next paper, Eiichi Watanabe and associates studied safety and resource consumption of exclusive remote follow-up in pacemaker patients for two years. Consecutive pacemaker patients committed to remote pacemaker management were randomized to either remote follow-up or conventional in-office follow-up at twice yearly intervals.   Remote follow-up patients were only seen if indicated by remote monitoring, all returned to hospital after two years. In 1,274 randomized patients (50.4% female, age 77 years), 558 remote follow-up or 550 conventional in office follow-up patients reached either the primary end point or 24 months follow-up. The primary end point, a composite of death, stroke, or cardiovascular events requiring surgery occurred in 10.9% and 11.8% respectively in the two groups (P = 0.0012) for non-inferiority. The median number of in-office follow-ups was 0.5 in the remote follow-up group and 2.01 in the conventional in-office follow-up per patient year (P &lt; 0.001). Only 1.4% of remote follow-ups triggered an unscheduled in-office follow-up, and only 1.5% of scheduled in-office follow-ups were considered actionable.   In our next paper, Sarah Strand and associates use fetal magnetocardiography from the University of Wisconsin biomagnetism laboratory to study 39 fetuses with pathogenic variants in long QT syndrome, LQTS genes. 27 carried the family variant, 11 had de novo variants, and one was indeterminant. De novo variants, especially de novo SCN5A variants were strongly associated with a severe rhythm phenotype and perinatal death. Nine or 82% showed signature LQTS rhythms, six showed torsade de pointes, five were still born, and 9% died in infancy. Those that died exhibited novel fetus rythms, including AV block with 3:1 conduction ratio, QRS alternans in 2:1 AV block, long cycle length, torsade de pointes, and slow monomorphic ventricular tachycardia. Premature ventricular contractions were also strongly associated with torsade de pointes and perinatal death. Fetuses with familiar variants showed a lower incidence of signature LQTS rhythm, six out of 27 or 22%, including torsade de pointes, and 3 out of 27 or 11% all were live born. The authors concluded that the malignancy of de novo LQTS variants was remarkably high and demonstrate that these mutations are a significant cause of stillbirth.   In our next paper, Corina Schram-Serban and associates compare the severity of extensiveness of conduction disorders between obese patients and non-obese patients measured at high resolution scale. They studied 212 patients undergoing cardiac surgery (male:161, mean 63 years of age), who underwent epicardial mapping of the right atrium, Bachmann's bundle, and left atrium during sinus rhythm. Conduction delay [CD] was defined as interelectrode conduction time seven to 11 milliseconds and conduction block [CB] as conduction time ≥ 12 milliseconds. In obese patients, the overall incidence of conduction delay was 3.1% versus 2.6% (P = 0.002), conduction block 1.8% versus 1.2%, and continuous CDCB 2.6% versus 1.9% higher in the obese patients, conduction delay (P = 0.012) and continuous CDCB lines are longer. There were more conduction disorders at Bachman's bundle, and this area has a higher incidence of conduction delay 4.4% versus 3.3% (P = 0.002), conduction block 3.1% versus 1.6% (P &lt; 0.001), continuous conduction block conduction delay 4.6% versus 2.7% and longer conduction delay or conduction delay conduction block lines. Severity of conduction block is also higher, particularly in the Bachmann bundle and pulmonary vein areas. In addition, obese patients have a higher incidence of early de novo postoperative atrial fibrillation. Body mass index and the overall amount of conduction block were independent predictors for the incidents of early postoperative atrial fibrillation.   In our next paper, Ricardo Cardona-Guarache and associates describe five patients with concealed, left-sided nodoventricular in four patients and nodofascicular in one patient accessory pathways. They proved the participation of accessory pathway in tachycardia by delivering His-synchronous premature ventricular complexes that either delayed the subsequent atrial electrogram or terminated the tachycardia, and by observing an increase in ventricular atrial interval coincident with left bundle branch block in two patients. The accessory pathways were not atrioventricular pathways because the septal ventricular atrial interval during tachycardia was less than 70 milliseconds in 3, 1 had spontaneous AV dissociation, and in 1 the atria were dissociated from the circuit with atrial overdrive pacing.   Entrainment from the right ventricle showed ventricular fusion in 4 out of 5 cases. A left-sided origin of accessory pathways was suspected after failed ablation of the right inferior extension of the AV node in 3 cases and by observing VA increase in left bundle branch block in 2 cases. The nodofascicular in 3 of the 4 nodoventricular accessory pathways were successfully ablated from within the proximal coronary sinus guided by recorded potentials at the roof of the coronary sinus, and nodoventricular accessory pathway was ablated via a transseptal approach near the coronary sinus os.   In our next paper, Pierre Qian and associates examined whether an open irrigated microwave catheter ablation can achieve deep myocardial lesions endocardially and epicardially through fat while acutely sparing nearby coronary arteries. Epicardial ablations via subxiphoid access in pigs were performed at 90 to 100 Watts at four minutes at sites near coronary arteries and produced mean lesion depth of 10 millimeters, width 18 millimeters, and length 29 millimeters through median epicardial fat thickness of 1.2 millimeters. Endocardial ablations at 180 Watts achieved depths of 10.7 millimeters, width of 16.6 millimeters, and length of 20 millimeters. Acute coronary occlusion or spasm was not observed at median separation distance of 2.7 millimeters.   In our next paper, Jad Ballout and associates examined 21 consecutive patients with cardiogenic shock and refractory ventricular arrhythmias undergoing bailout ablation due to inability to wean off of mechanical support. Mean age was 61 years, 86% were males, median left ventricular injection fraction 20%, 81% ischemic cardiomyopathy. The type of mechanical support in place prior to the procedure was intra-aortic balloon pump in 14 patients, Impella in 2, ECMO in 2, ECMO and intra-aortic balloon pump in 2, and ECMO and Impella in 1. In the cardio voltage maps with myocardial scar in 90% (19 patients), the clinical ventricular tachycardias VTs were inducible in 13% (62 patients), whereas 6 patients had PVC induced ventricular fibrillation, VT (29%), and VT could not be induced in 2 patients (9%). Activation mapping was possible in all 13 patients with inducible clinical VTs, substrate modification was performed in 15 patients with scar in 79%. After ablation and scar modification, the arrhythmia was noninducible in 19 patients (91%). Seventeen (81%) were eventually weaned off mechanical support successfully with the majority of patients being discharged home and surviving beyond one year. However, 6 (29%) died during the index admission with persistent cardiogenic shock.   In a research letter, Parveen Garg and associates examined the multi-ethnic study of atherosclerosis [MESA] incident atrial fibrillation a population with 50% African-American or Hispanic. After adjusting for age, race, ethnicity, sex education, income, clinic site, height, body, mass index, cigarette, smoking, diabetes, systolic and diastolic blood pressure, and hypertensive medications, physical activity, alcohol consumption, lipid parameter to lipid lowering therapy, the baseline lipoprotein A level greater or equal to 30 milligram per deciliter was inversely associated with developing atrial fibrillation compared those with lower levels (hazard ratio 0.84). However, the mechanism of this paradoxical association is unclear.   In another research letter, Yoshihide Takahashi and associates reported that 49 patients undergoing ablation of persistent atrial fibrillation had at least one focal site and rotational activation in 57%. Of these, 19 patients underwent a repeat ablation for recurrent atrial fibrillation. AF was mapped in 17 patients and 131 focal activation sites were ablated. There were 105 displayed focal activation sites during the de novo ablation and 89 focal activation sites during the repeat ablation. During the de novo ablation, rotation activation was observed in 19 sites. Of the 19 sites, 12 (63%) displayed rotational activity, also with the repeat ablation. The author suggested focal or rotational activation sites can be classified into two types, ones critical for AF recurrence and the ones that are bystander.   That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time.   This program is copyright American Heart Association, 2020.   Correction: In the study by Pierre Qian and associates, the epicardial ablations via subxiphoid access were performed in sheep, not pigs, as previously stated.

Paul J. Wang: Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. In our first paper, Bruce Wilkoff and associates examine the impact of cardiac implantable electronic device [CIED] infections on mortality, quality of life, healthcare utilization, and cost in the U.S. Healthcare system. They found that the majority CIED infection was associated with increased all-cause mortality, 12-month risk-adjusted hazard ratio 3.41, P &lt; 0.001. An effect that sustained beyond 12 months. The quality of life was reduced, P = 0.004, and did not normalize for six months. Disruptions in CIED therapy were observed in 36% of infections for a median duration of 184 days. The authors reported that the mean hospital costs were $55,547. In our next paper, Songwen Chen, Xiaofeng Lu and associates examine the ability to eliminate premature ventricular complexes [PVCs] originating from the proximal left anterior fascicle, safely from the right coronary sinus. The authors mapped the the right coronary sinus and left ventricle in 20 patients with left anterior fascicle PVCs. They found that the earliest activation site with Purkinje potential during both PVC and sinus rhythm was localized at proximal left anterior fascicle in eight patients, the proximal group, or non-proximal left anterior fascicle in 12 groups, the non-proximal group. The Purkinje potentials proceeded PVC-QRS at the earliest activation site in proximal group 32.6 milliseconds was significantly earlier than that in non-proximal group, 28.3 milliseconds P = 0.025. Similar difference in the Purkinje potentials proceeding sinus QRS at the earliest activation site was also observed between proximal and non-proximal group, 35.1 milliseconds versus 25.2 milliseconds, P &lt; 0.001. In proximal group, the distance between the earliest activation site to the left His-bundle into the right coronary sinus were shorter than that of the non-proximal group 12.3 millimeters versus 19.7, P = 0.002, and 3.9 millimeters versus 15.7 millimeters, P &lt; 0.001, respectively. The authors found no difference in the distance between the right coronary sinus to proximal left anterior fascicle between the two groups. PVCs were successfully eliminated from the right coronary sinus in all proximal group, but at left ventricular earliest activation site for the non-proximal group, the radiofrequency application time, ablation time and procedure time of non-proximal group were longer than that proximal group. Electrocardiographic analysis showed that when compared to non-proximal group, the PVCs proximal group had a narrower QRS duration, smaller S wave in leads one, V five,and V six; lower R waves in leads one, aVL, aVR, V one, V two, and V four and smaller q wave in leads three and aVF. The QRS duration difference [PVC-QRS and sinus rhythm QRS] &lt; 15 milliseconds predicted the proximal left anterior fascicle origin with high sensitivity and specificity. In our next paper, Benjamin Steinberg and associates examined the factors that are associated with large improvements in health-related quality of life in patients with atrial fibrillation. The authors assessed factors associated with a one-year increase in quality of life, measured by AFEQT of one standard deviation that is greater and equal to 18 points, three times clinically important difference among patients in the ORBIT-AF one registry. They found that 28% of patients had such a health-related quality improvement compared with patients not showing large health-related quality of life improvement. They were similar age, (median 73 versus 74 years of age), equally likely to be female, (44% versus 48%), but more likely to have newly diagnosed atrial fibrillation [AF] at baseline (18% versus 8%, P = 0.0004) prior antiarrhythmic drug use (52% versus 40%, P = 0.005), baseline antiarrhythmic drug use (34.8% versus 26.8%, P = 0.045), and more likely to undergo AF related procedures during follow-up (AF ablation 6.6% versus 2.0%, cardioversion 12.2% versus 5.9%). In multivariate analysis, a history of alcohol abuse has a ratio 2.4 and increased baseline diastolic blood pressure has a ratio 1.23 per 10 point increase and greater than 65 millimeters of mercury were associated with large improvements in health-related quality of life at one year. Whereas patients with prior stroke, chronic obstructive pulmonary disease and peripheral artery disease were less likely to improve. In our next paper, Eiichi Watanabe and associates studied safety and resource consumption of exclusive remote follow-up in pacemaker patients for two years. Consecutive pacemaker patients committed to remote pacemaker management were randomized to either remote follow-up or conventional in-office follow-up at twice yearly intervals. Remote follow-up patients were only seen if indicated by remote monitoring, all returned to hospital after two years. In 1,274 randomized patients (50.4% female, age 77 years), 558 remote follow-up or 550 conventional in office follow-up patients reached either the primary end point or 24 months follow-up. The primary end point, a composite of death, stroke, or cardiovascular events requiring surgery occurred in 10.9% and 11.8% respectively in the two groups (P = 0.0012) for non-inferiority. The median number of in-office follow-ups was 0.5 in the remote follow-up group and 2.01 in the conventional in-office follow-up per patient year (P &lt; 0.001). Only 1.4% of remote follow-ups triggered an unscheduled in-office follow-up, and only 1.5% of scheduled in-office follow-ups were considered actionable. In our next paper, Sarah Strand and associates use fetal magnetocardiography from the University of Wisconsin biomagnetism laboratory to study 39 fetuses with pathogenic variants in long QT syndrome, LQTS genes. 27 carried the family variant, 11 had de novo variants, and one was indeterminant. De novo variants, especially de novo SCN5A variants were strongly associated with a severe rhythm phenotype and perinatal death. Nine or 82% showed signature LQTS rhythms, six showed torsade de pointes, five were still born, and 9% died in infancy. Those that died exhibited novel fetus rythms, including AV block with 3:1 conduction ratio, QRS alternans in 2:1 AV block, long cycle length, torsade de pointes, and slow monomorphic ventricular tachycardia. Premature ventricular contractions were also strongly associated with torsade de pointes and perinatal death. Fetuses with familiar variants showed a lower incidence of signature LQTS rhythm, six out of 27 or 22%, including torsade de pointes, and 3 out of 27 or 11% all were live born. The authors concluded that the malignancy of de novo LQTS variants was remarkably high and demonstrate that these mutations are a significant cause of stillbirth. In our next paper, Corina Schram-Serban and associates compare the severity of extensiveness of conduction disorders between obese patients and non-obese patients measured at high resolution scale. They studied 212 patients undergoing cardiac surgery (male:161, mean 63 years of age), who underwent epicardial mapping of the right atrium, Bachmann's bundle, and left atrium during sinus rhythm. Conduction delay [CD] was defined as interelectrode conduction time seven to 11 milliseconds and conduction block [CB] as conduction time ≥ 12 milliseconds. In obese patients, the overall incidence of conduction delay was 3.1% versus 2.6% (P = 0.002), conduction block 1.8% versus 1.2%, and continuous CDCB 2.6% versus 1.9% higher in the obese patients, conduction delay (P = 0.012) and continuous CDCB lines are longer. There were more conduction disorders at Bachman's bundle, and this area has a higher incidence of conduction delay 4.4% versus 3.3% (P = 0.002), conduction block 3.1% versus 1.6% (P &lt; 0.001), continuous conduction block conduction delay 4.6% versus 2.7% and longer conduction delay or conduction delay conduction block lines. Severity of conduction block is also higher, particularly in the Bachmann bundle and pulmonary vein areas. In addition, obese patients have a higher incidence of early de novo postoperative atrial fibrillation. Body mass index and the overall amount of conduction block were independent predictors for the incidents of early postoperative atrial fibrillation. In our next paper, Ricardo Cardona-Guarache and associates describe five patients with concealed, left-sided nodoventricular in four patients and nodofascicular in one patient accessory pathways. They proved the participation of accessory pathway in tachycardia by delivering His-synchronous premature ventricular complexes that either delayed the subsequent atrial electrogram or terminated the tachycardia, and by observing an increase in ventricular atrial interval coincident with left bundle branch block in two patients. The accessory pathways were not atrioventricular pathways because the septal ventricular atrial interval during tachycardia was less than 70 milliseconds in 3, 1 had spontaneous AV dissociation, and in 1 the atria were dissociated from the circuit with atrial overdrive pacing. Entrainment from the right ventricle showed ventricular fusion in 4 out of 5 cases. A left-sided origin of accessory pathways was suspected after failed ablation of the right inferior extension of the AV node in 3 cases and by observing VA increase in left bundle branch block in 2 cases. The nodofascicular in 3 of the 4 nodoventricular accessory pathways were successfully ablated from within the proximal coronary sinus guided by recorded potentials at the roof of the coronary sinus, and nodoventricular accessory pathway was ablated via a transseptal approach near the coronary sinus os. In our next paper, Pierre Qian and associates examined whether an open irrigated microwave catheter ablation can achieve deep myocardial lesions endocardially and epicardially through fat while acutely sparing nearby coronary arteries. Epicardial ablations via subxiphoid access in pigs were performed at 90 to 100 Watts at four minutes at sites near coronary arteries and produced mean lesion depth of 10 millimeters, width 18 millimeters, and length 29 millimeters through median epicardial fat thickness of 1.2 millimeters. Endocardial ablations at 180 Watts achieved depths of 10.7 millimeters, width of 16.6 millimeters, and length of 20 millimeters. Acute coronary occlusion or spasm was not observed at median separation distance of 2.7 millimeters. In our next paper, Jad Ballout and associates examined 21 consecutive patients with cardiogenic shock and refractory ventricular arrhythmias undergoing bailout ablation due to inability to wean off of mechanical support. Mean age was 61 years, 86% were males, median left ventricular injection fraction 20%, 81% ischemic cardiomyopathy. The type of mechanical support in place prior to the procedure was intra-aortic balloon pump in 14 patients, Impella in 2, ECMO in 2, ECMO and intra-aortic balloon pump in 2, and ECMO and Impella in 1. In the cardio voltage maps with myocardial scar in 90% (19 patients), the clinical ventricular tachycardias VTs were inducible in 13% (62 patients), whereas 6 patients had PVC induced ventricular fibrillation, VT (29%), and VT could not be induced in 2 patients (9%). Activation mapping was possible in all 13 patients with inducible clinical VTs, substrate modification was performed in 15 patients with scar in 79%. After ablation and scar modification, the arrhythmia was noninducible in 19 patients (91%). Seventeen (81%) were eventually weaned off mechanical support successfully with the majority of patients being discharged home and surviving beyond one year. However, 6 (29%) died during the index admission with persistent cardiogenic shock. In a research letter, Parveen Garg and associates examined the multi-ethnic study of atherosclerosis [MESA] incident atrial fibrillation a population with 50% African-American or Hispanic. After adjusting for age, race, ethnicity, sex education, income, clinic site, height, body, mass index, cigarette, smoking, diabetes, systolic and diastolic blood pressure, and hypertensive medications, physical activity, alcohol consumption, lipid parameter to lipid lowering therapy, the baseline lipoprotein A level greater or equal to 30 milligram per deciliter was inversely associated with developing atrial fibrillation compared those with lower levels (hazard ratio 0.84). However, the mechanism of this paradoxical association is unclear. In another research letter, Yoshihide Takahashi and associates reported that 49 patients undergoing ablation of persistent atrial fibrillation had at least one focal site and rotational activation in 57%. Of these, 19 patients underwent a repeat ablation for recurrent atrial fibrillation. AF was mapped in 17 patients and 131 focal activation sites were ablated. There were 105 displayed focal activation sites during the de novo ablation and 89 focal activation sites during the repeat ablation. During the de novo ablation, rotation activation was observed in 19 sites. Of the 19 sites, 12 (63%) displayed rotational activity, also with the repeat ablation. The author suggested focal or rotational activation sites can be classified into two types, ones critical for AF recurrence and the ones that are bystander. That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association, 2020. Correction: In the study by Pierre Qian and associates, the epicardial ablations via subxiphoid access were performed in sheep, not pigs, as previously stated.

Circulation: Arrhythmia and Electrophysiology May 2020 Issue

Paul J. Wang: Welcome to the monthly podcast On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue.   In our first paper, David Okada and associates assess the ability of a novel machine learning approach for quantifying 3D spatial complexity of gray scale patterns on late gadolinium-enhanced cardiac magnetic resonance images to predict ventricular arrhythmias in patients with ischemic cardiomyopathy.   They examined 122 consecutive ischemic cardiomyopathy patients with left ventricular ejection fraction of 35%, without prior history of reentrant ventricular arrhythmias. These patients underwent late gadolinium-enhanced cardiac magnetic resonance imaging. From raw gray scale data, the authors generated graphs encoding the 3D geometry of the left ventricle. They then assess the global regularity of signal intensity patterns using Fourier-like analysis and generated a substrate spatial complexity profile for each patient. A machine learning statistical algorithm was employed to discern which substrate spatial complexity profiles correlated with ventricular arrhythmic events. That is appropriate ICD firings and arrhythmic sudden cardiac death.   At five years of follow-up from the statistical machine learning results, a complexity score ranging from zero to one was calculated for each patient that was tested using multivariate Cox regression models. At five years of follow-up, 40 patients had ventricular arrhythmia events. The machine learning algorithm classified with overall 81% accuracy and correctly classified 86% of those without ventricular arrhythmia. Overall negative predictive value was 91%. Average complexity score was significantly higher in patients with ventricular arrhythmia events versus those without P

Paul J. Wang: Welcome to the monthly podcast On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. In our first paper, David Okada and associates assess the ability of a novel machine learning approach for quantifying 3D spatial complexity of gray scale patterns on late gadolinium-enhanced cardiac magnetic resonance images to predict ventricular arrhythmias in patients with ischemic cardiomyopathy. They examined 122 consecutive ischemic cardiomyopathy patients with left ventricular ejection fraction of 35%, without prior history of reentrant ventricular arrhythmias. These patients underwent late gadolinium-enhanced cardiac magnetic resonance imaging. From raw gray scale data, the authors generated graphs encoding the 3D geometry of the left ventricle. They then assess the global regularity of signal intensity patterns using Fourier-like analysis and generated a substrate spatial complexity profile for each patient. A machine learning statistical algorithm was employed to discern which substrate spatial complexity profiles correlated with ventricular arrhythmic events. That is appropriate ICD firings and arrhythmic sudden cardiac death. At five years of follow-up from the statistical machine learning results, a complexity score ranging from zero to one was calculated for each patient that was tested using multivariate Cox regression models. At five years of follow-up, 40 patients had ventricular arrhythmia events. The machine learning algorithm classified with overall 81% accuracy and correctly classified 86% of those without ventricular arrhythmia. Overall negative predictive value was 91%. Average complexity score was significantly higher in patients with ventricular arrhythmia events versus those without P

Circulation: Arrhythmia and Electrophysiology April 2020 Issue

Paul J. Wang: Welcome to the monthly podcast On the Beat for circulation, arrhythmia, and electrophysiology. I'm Dr. Paul Wang, Editor In Chief, with some of the key highlights from this month's issue.   Elizabeth Wang and Associates examined the relationship between acute precipitants of atrial fibrillation and long-term recurrence of atrial fibrillation, AF, from a multi-institutional, longitudinal electronic medical record database. Among 10,723 patients with newly diagnosed Afib, age 67.9 years, 41% women, the authors found that 19% had an acute AF precipitant, the most common of which were cardiac surgery in 22%, pneumonia in 20% and non-cardiothoracic surgery in 15%. The cumulative incidence of AF recurrence at five years was 41% among individuals with a precipitant, compared to 52% in those without a precipitant. Adjusted hazard ratio 0.75 P &lt; 0.001. The lowest risk of recurrence among those with precipitants with postoperative atrial fibrillation, five-year incidence 32% in cardiac surgery and 39% in non-cardiothoracic surgery. Regardless of the initial precipitant, recurrent atrial fibrillation was associated with an increased adjusted risk of heart failure, hazard ratio of 2.74 P &lt; 0.001, Stroke, hazard ratio 1.57 P &lt; 0.001 and mortality, hazard ratio 2.96 P &lt; 0.001. Thus, the authors found that atrial fibrillation after acute precipitant frequently recurs and the recurrence is associated with substantial long-term morbidity and mortality.   In the next paper, Jacob Koruth and associates examine the effect of pulse field ablation on the esophagus in a novel in-vivo porcine esophageal injury model. The authors studied 10 animals under general anesthesia while the lower esophagus was deflected towards the inferior vena cava using an esophageal deviation balloon and ablation was formed from within the inferior vena cava at areas of esophageal contact. Six animals received eight pulse field ablation applications per site and four animals received six clusters of irrigated radio frequency ablation applications at 30 Watts for 30 seconds. All animals survived to 25 days, sacrificed, and the esophagus was submitted for a pathological examination including 10 discreet histological sections of the esophagus. The authors found that zero out of six pulse field ablation animals demonstrated esophageal lesions while esophageal injury occurred in all four radio frequency ablation animals, P = 0.005. A mean of 1.5 mucosal lesions per animal, length 21.8 millimeters with 4.9 millimeters were observed, including one esophageal pulmonary fistula, and deep esophageal ulcers in the other animals. Histological examination demonstrated tissue necrosis surrounded by an acute and chronic inflammation and fibrosis. The necrotic radio frequency ablation lesions involved multiple esophageal tissue layers with evidence of arteriolar medial thickening and fibrosis of peri-esophageal nerves, abscess formation and full thickness esophageal wall disruption were seen in the areas of perforation or fistula.   In our next paper, Peter Noseworthy and associates examine whether the ability of deep learning algorithms to detect low left ventricular ejection fraction using the 12 lead electrocardiogram varies by race or ethnicity. The authors used a retrospective cohort analysis and included 97,829 patients with paired electrocardiograms and echocardiograms and used a convolutional neural network to identify patients with a left ventricular ejection fraction less than or equal to 35% from the 12 lead electrocardiogram. The convolutional neural network was previously derived in a homogeneous population, 96.2% non Hispanic white, N = 44,959 which demonstrated consistent performance to detect low left ventricular ejection fraction across a range of racial ethnic subgroups in a separate cohort of 52,870 patients (Non-Hispanic white 44,524 patients with an AUC of 0.93; Asian 557 with an AUC of 0.96; Black/African American N = 651 with an AUC of 0.937; in Hispanic/Latino N = 331 AUC of 0.937; in Native American/Alaskan N = 223 AUC of 0.938). In secondary analysis, a separate neural network was able to discern racial subgroup category, Black/African American AUC 0.84 and white non-Hispanic AUC 0.75 in a five-class classifier. In a network trained only in non-Hispanic whites, from the original derivation cohort, performed similarly well across a range of racial ethnic subgroups in the testing cohort with at least an AUC of 0.93 in all racial ethnic subgroups. The authors concluded that while ECG characteristics vary by race, this did not impact the ability of a convolutional neural network to predict low left ventricular ejection fraction from the ECGs. They recommend reporting of performance against diverse ethnic, racial, age, and gender groups for all new artificial intelligent tools.   In our next paper, Benjamin Shoemaker and associates examine the association between atrial fibrillation or AF genetic susceptibility and recurrence after de novo AF ablation, using a comprehensive polygenic risk score for AF in the 10 centers from the AF genetics consortium. AF genetic susceptibility was measured using a previously described a polygenic risk score, N = 929 snips. The overall arrhythmia recurrence rate between 3 and 12 months was 44% in 3,259 patients. Patients with a higher AF genetic susceptibility were younger and have fewer clinical risk factors for atrial fibrillation. Persistent atrial fibrillation has a ratio of 1.39, left atrial size has a ratio of 1.32, and left ventricular ejection fraction per 10% has a ratio of 0.88, were associated with increased risk of occurrence. In unit varied analysis, the authors found that AF genetic susceptibility had a hazard ratio of 1.08 P = 0.07 and in multivariate analysis hazard ratio 1.06 with a P value 0.13.   In our next paper, Mohit Turagam and associates reported the outcomes of the first inhuman value trial, which uses low intensity collimated ultrasound or LICU guided anatomical mapping in robotic ablation to isolate the pulmonary veins for atrial fibrillation ablation. In 52 paroxysmal atrial fibrillation patients, ultrasound M-mode based left atrial anatomies were successfully created and ablation was performed under robotic control along an operated defined lesion path. The operatives found that acute pulmonary vein isolation was achieved in 98% of pulmonary veins using LICU only in 77% of pulmonary veins and requiring touch-up with a standard radio frequency ablation catheter in 23% of the pulmonary veins. The touch up rate decreased to 5.8% in patients undergoing LICU ablation with an enhanced software. Freedom from atrial relational recurrence was 79.6% at 12 months or 92.3%, 12 out of 13 patients with the enhanced software. Major adverse events occurred in three patients or 5.8%. One had transient diaphragmatic paralysis, one vascular access complication and one had transient ST segment elevation from air-embolism without sequelae.   In our next paper, Miguel Rodrigo and associates mapped electrical patterns of disorganization and reasons of reentrant activity in atrial fibrillation, or AF, from the body surface using electrocardiographic imaging. The author examined the bi-atrial intracardiac electrograms of 47 patients at ablation (30 persistent, 29 males, age 63 years) obtained using 64-pole basket catheters while simultaneously recording 57-lead body surface electrocardiogram. The authors found the body surface mapping showed greater atrial fibrillation organization near intracardiac detected drivers and elsewhere, both in phase singularity density in numbers of drivers, they found that complexity defined as a number of stable AF reentrant sites was concordant between the noninvasive and invasive methods. The subset receiving targeted ablation, AF complexity, showed lower values in those in whom AF terminated than in those in whom AF did not terminate, P &lt; 0.01. The authors concluded that AF complexity, assessed noninvasively, correlates well with organized, disorganized regions detected by intracardiac mapping.   In our next paper, Krystien Lieve and Veronica Dusi and associates examined whether heart rate reduction immediately after exercise is regulated by autonomic reflexes, particularly vagal tone and may be associated with symptoms and ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia, CPVT. In a retrospective observational study, the authors studied 187 patients mean age 36 years, 68 or 36% symptomatic before diagnosis, pre-exercise stress test heart rate and maximal heart rate were equal amongst symptomatic and asymptomatic patients. Patients that were symptomatic prior to diagnosis had a greater delta HRR one prime after a maximum exercise, 43 versus 25, P &lt; 0.001. Corrected for age, gender, and relatedness, patients in the upper tertile for Delta HRR one prime had an odd ratio of 3.4 of being symptomatic before diagnosis, P &lt; 0.001. In addition, Delta HRR one prime was higher in patients with complex ventricular arrhythmias at exercise stress test, off antiarrhythmic drugs. After diagnosis, patients with a Delta HRR one prime in the upper tertile of its distribution, had significantly more rhythmic events as compared to patients and other tertiles, P=0.045. The authors concluded that CPVT patients with a larger heart rate reduction following exercise are more likely to be symptomatic and have complex ventricular arrhythmias during first exercise stress test off antiarrhythmic drugs.   In our next paper, Balvinder Handa and associates examined whether low spatial resolution, sequentially acquired data can be used to examine the global fibrillation organization, characterizing dominant propagating patterns and identifying rotational drivers. The authors employed ranger causality analysis, an econometric tool for quantifying causal relationships between complex time series, which was developed as a novel fibrillation mapping tool and adapted to low spatial resolution sequentially acquired data. Ventricular fibrillation, or VF, optical mapping was performed and Langendorff-perfused Sprague Dawley rat hearts, N = 18. And novel algorithms were developed using Granger causality analysis to quantify causal dependence of neighboring signals and plot Granger causality analysis vectors, quantify global organization using causality pairing index, a measure of neighboring causal signal pairs, and localize rotational drivers by quantifying the circular interdependence of neighboring signals with the circular interdependence value. Granger causality analysis based mapping tools were optimized for low spatial resolution by down sampled optical mapping data validated against high resolution phase mapping analysis and further tested in previous VF optical mapping recordings of coronary perfused donor heart LV wedge preparations, N = 12, and adaptive for sequentially acquired intracardiac electric Grande during human persistent atrial relation mapping, N=16. The authors found that global VF organization quantified by causality pairing index showed a negative correlation at progressively lower resolutions in organized VF with high causality pairing index values. Ranger causality analysis vector mapping characterize dominant propagating patterns and localized stable rotational drivers with the circular interdependence value showing a significant difference in driver versus non driver regions, P = 0.0002. These findings were further confirmed in human VF in persistent atrial fibrillation, a positive correlation was found between causality peri-index and presence of stable rotational drivers. 50% of patients had rotational drivers with a low incidence of 0.9 rotational drivers per patient. In a special report, Piotr Futyma and associates report on the use of bipolar radiofrequency ablation of ventricular arrhythmias originating in the vicinity of the His bundle. Bryce Alexander and associates report in a research letter the patient acceptance of cybersecurity upgrade in ICDs.   That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time.   This program is copyright American Heart Association 2020.

Paul J. Wang: Welcome to the monthly podcast On the Beat for circulation, arrhythmia, and electrophysiology. I'm Dr. Paul Wang, Editor In Chief, with some of the key highlights from this month's issue. Elizabeth Wang and Associates examined the relationship between acute precipitants of atrial fibrillation and long-term recurrence of atrial fibrillation, AF, from a multi-institutional, longitudinal electronic medical record database. Among 10,723 patients with newly diagnosed Afib, age 67.9 years, 41% women, the authors found that 19% had an acute AF precipitant, the most common of which were cardiac surgery in 22%, pneumonia in 20% and non-cardiothoracic surgery in 15%. The cumulative incidence of AF recurrence at five years was 41% among individuals with a precipitant, compared to 52% in those without a precipitant. Adjusted hazard ratio 0.75 P &lt; 0.001. The lowest risk of recurrence among those with precipitants with postoperative atrial fibrillation, five-year incidence 32% in cardiac surgery and 39% in non-cardiothoracic surgery. Regardless of the initial precipitant, recurrent atrial fibrillation was associated with an increased adjusted risk of heart failure, hazard ratio of 2.74 P &lt; 0.001, Stroke, hazard ratio 1.57 P &lt; 0.001 and mortality, hazard ratio 2.96 P &lt; 0.001. Thus, the authors found that atrial fibrillation after acute precipitant frequently recurs and the recurrence is associated with substantial long-term morbidity and mortality. In the next paper, Jacob Koruth and associates examine the effect of pulse field ablation on the esophagus in a novel in-vivo porcine esophageal injury model. The authors studied 10 animals under general anesthesia while the lower esophagus was deflected towards the inferior vena cava using an esophageal deviation balloon and ablation was formed from within the inferior vena cava at areas of esophageal contact. Six animals received eight pulse field ablation applications per site and four animals received six clusters of irrigated radio frequency ablation applications at 30 Watts for 30 seconds. All animals survived to 25 days, sacrificed, and the esophagus was submitted for a pathological examination including 10 discreet histological sections of the esophagus. The authors found that zero out of six pulse field ablation animals demonstrated esophageal lesions while esophageal injury occurred in all four radio frequency ablation animals, P = 0.005. A mean of 1.5 mucosal lesions per animal, length 21.8 millimeters with 4.9 millimeters were observed, including one esophageal pulmonary fistula, and deep esophageal ulcers in the other animals. Histological examination demonstrated tissue necrosis surrounded by an acute and chronic inflammation and fibrosis. The necrotic radio frequency ablation lesions involved multiple esophageal tissue layers with evidence of arteriolar medial thickening and fibrosis of peri-esophageal nerves, abscess formation and full thickness esophageal wall disruption were seen in the areas of perforation or fistula. In our next paper, Peter Noseworthy and associates examine whether the ability of deep learning algorithms to detect low left ventricular ejection fraction using the 12 lead electrocardiogram varies by race or ethnicity. The authors used a retrospective cohort analysis and included 97,829 patients with paired electrocardiograms and echocardiograms and used a convolutional neural network to identify patients with a left ventricular ejection fraction less than or equal to 35% from the 12 lead electrocardiogram. The convolutional neural network was previously derived in a homogeneous population, 96.2% non Hispanic white, N = 44,959 which demonstrated consistent performance to detect low left ventricular ejection fraction across a range of racial ethnic subgroups in a separate cohort of 52,870 patients (Non-Hispanic white 44,524 patients with an AUC of 0.93; Asian 557 with an AUC of 0.96; Black/African American N = 651 with an AUC of 0.937; in Hispanic/Latino N = 331 AUC of 0.937; in Native American/Alaskan N = 223 AUC of 0.938). In secondary analysis, a separate neural network was able to discern racial subgroup category, Black/African American AUC 0.84 and white non-Hispanic AUC 0.75 in a five-class classifier. In a network trained only in non-Hispanic whites, from the original derivation cohort, performed similarly well across a range of racial ethnic subgroups in the testing cohort with at least an AUC of 0.93 in all racial ethnic subgroups. The authors concluded that while ECG characteristics vary by race, this did not impact the ability of a convolutional neural network to predict low left ventricular ejection fraction from the ECGs. They recommend reporting of performance against diverse ethnic, racial, age, and gender groups for all new artificial intelligent tools. In our next paper, Benjamin Shoemaker and associates examine the association between atrial fibrillation or AF genetic susceptibility and recurrence after de novo AF ablation, using a comprehensive polygenic risk score for AF in the 10 centers from the AF genetics consortium. AF genetic susceptibility was measured using a previously described a polygenic risk score, N = 929 snips. The overall arrhythmia recurrence rate between 3 and 12 months was 44% in 3,259 patients. Patients with a higher AF genetic susceptibility were younger and have fewer clinical risk factors for atrial fibrillation. Persistent atrial fibrillation has a ratio of 1.39, left atrial size has a ratio of 1.32, and left ventricular ejection fraction per 10% has a ratio of 0.88, were associated with increased risk of occurrence. In unit varied analysis, the authors found that AF genetic susceptibility had a hazard ratio of 1.08 P = 0.07 and in multivariate analysis hazard ratio 1.06 with a P value 0.13. In our next paper, Mohit Turagam and associates reported the outcomes of the first inhuman value trial, which uses low intensity collimated ultrasound or LICU guided anatomical mapping in robotic ablation to isolate the pulmonary veins for atrial fibrillation ablation. In 52 paroxysmal atrial fibrillation patients, ultrasound M-mode based left atrial anatomies were successfully created and ablation was performed under robotic control along an operated defined lesion path. The operatives found that acute pulmonary vein isolation was achieved in 98% of pulmonary veins using LICU only in 77% of pulmonary veins and requiring touch-up with a standard radio frequency ablation catheter in 23% of the pulmonary veins. The touch up rate decreased to 5.8% in patients undergoing LICU ablation with an enhanced software. Freedom from atrial relational recurrence was 79.6% at 12 months or 92.3%, 12 out of 13 patients with the enhanced software. Major adverse events occurred in three patients or 5.8%. One had transient diaphragmatic paralysis, one vascular access complication and one had transient ST segment elevation from air-embolism without sequelae. In our next paper, Miguel Rodrigo and associates mapped electrical patterns of disorganization and reasons of reentrant activity in atrial fibrillation, or AF, from the body surface using electrocardiographic imaging. The author examined the bi-atrial intracardiac electrograms of 47 patients at ablation (30 persistent, 29 males, age 63 years) obtained using 64-pole basket catheters while simultaneously recording 57-lead body surface electrocardiogram. The authors found the body surface mapping showed greater atrial fibrillation organization near intracardiac detected drivers and elsewhere, both in phase singularity density in numbers of drivers, they found that complexity defined as a number of stable AF reentrant sites was concordant between the noninvasive and invasive methods. The subset receiving targeted ablation, AF complexity, showed lower values in those in whom AF terminated than in those in whom AF did not terminate, P &lt; 0.01. The authors concluded that AF complexity, assessed noninvasively, correlates well with organized, disorganized regions detected by intracardiac mapping. In our next paper, Krystien Lieve and Veronica Dusi and associates examined whether heart rate reduction immediately after exercise is regulated by autonomic reflexes, particularly vagal tone and may be associated with symptoms and ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia, CPVT. In a retrospective observational study, the authors studied 187 patients mean age 36 years, 68 or 36% symptomatic before diagnosis, pre-exercise stress test heart rate and maximal heart rate were equal amongst symptomatic and asymptomatic patients. Patients that were symptomatic prior to diagnosis had a greater delta HRR one prime after a maximum exercise, 43 versus 25, P &lt; 0.001. Corrected for age, gender, and relatedness, patients in the upper tertile for Delta HRR one prime had an odd ratio of 3.4 of being symptomatic before diagnosis, P &lt; 0.001. In addition, Delta HRR one prime was higher in patients with complex ventricular arrhythmias at exercise stress test, off antiarrhythmic drugs. After diagnosis, patients with a Delta HRR one prime in the upper tertile of its distribution, had significantly more rhythmic events as compared to patients and other tertiles, P=0.045. The authors concluded that CPVT patients with a larger heart rate reduction following exercise are more likely to be symptomatic and have complex ventricular arrhythmias during first exercise stress test off antiarrhythmic drugs. In our next paper, Balvinder Handa and associates examined whether low spatial resolution, sequentially acquired data can be used to examine the global fibrillation organization, characterizing dominant propagating patterns and identifying rotational drivers. The authors employed ranger causality analysis, an econometric tool for quantifying causal relationships between complex time series, which was developed as a novel fibrillation mapping tool and adapted to low spatial resolution sequentially acquired data. Ventricular fibrillation, or VF, optical mapping was performed and Langendorff-perfused Sprague Dawley rat hearts, N = 18. And novel algorithms were developed using Granger causality analysis to quantify causal dependence of neighboring signals and plot Granger causality analysis vectors, quantify global organization using causality pairing index, a measure of neighboring causal signal pairs, and localize rotational drivers by quantifying the circular interdependence of neighboring signals with the circular interdependence value. Granger causality analysis based mapping tools were optimized for low spatial resolution by down sampled optical mapping data validated against high resolution phase mapping analysis and further tested in previous VF optical mapping recordings of coronary perfused donor heart LV wedge preparations, N = 12, and adaptive for sequentially acquired intracardiac electric Grande during human persistent atrial relation mapping, N=16. The authors found that global VF organization quantified by causality pairing index showed a negative correlation at progressively lower resolutions in organized VF with high causality pairing index values. Ranger causality analysis vector mapping characterize dominant propagating patterns and localized stable rotational drivers with the circular interdependence value showing a significant difference in driver versus non driver regions, P = 0.0002. These findings were further confirmed in human VF in persistent atrial fibrillation, a positive correlation was found between causality peri-index and presence of stable rotational drivers. 50% of patients had rotational drivers with a low incidence of 0.9 rotational drivers per patient. In a special report, Piotr Futyma and associates report on the use of bipolar radiofrequency ablation of ventricular arrhythmias originating in the vicinity of the His bundle. Bryce Alexander and associates report in a research letter the patient acceptance of cybersecurity upgrade in ICDs. That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.

 Circulation: Arrhythmia and Electrophysiology March 2020 Issue

Paul J. Wang: Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, Ling Kuo and associates examine the association between left atrial high-resolution late gadolinium enhancement on cardiac magnetic resonance and electrogram abnormalities in patients with atrial fibrillation or AF. They found that in 40 AF patients age 63.2 years with a mean of 1312 electrogram points per patient. Lower bipolar voltage was associated with higher signal intensity Z score in patients who had undergone previous ablation coefficient equals -0.049 P &lt; 0.001 but not in ablation-naive patients, coefficient = -0.004, P = 0.7. Left atrial high-resolution late gadolinium enhancement activation delay was associated with signal intensity z-score in patients with previous ablation, signal intensity Z score coefficient = 0.004, P &lt; 0.001 but not in ablation-naive patients. In contrast, increased left atrial high-resolution late gadolinium enhancement fractionation was associated with signal intensity z-score coefficient 0.012, P = 0.03, and left atrial high-resolution late gadolinium enhancement coefficient 0.035, P &lt; 0.001 only in ablation-naive patients. The authors concluded that the association of left atrial late gadolinium enhancement with voltage is modified by ablation in ablation naive patients. Atrial late gadolinium enhancement is associated with electrogram fractionation even in the absence of voltage abnormality. In our next paper, Laila Staerk and associates examine the associations between 85 protein biomarkers and incident atrial fibrillation or AF in patients 50 years of age or greater, from the Framingham Heart Study Offspring and Third Generation cohorts. Out of 3378 participants, 54% women, mean age 61.5 years, 401 developed AAF over a mean follow-up of 12.3 years. They observed a lower hazard of incident atrial fibrillation associated with mean higher levels of incident like growth factor hazard ratio per one standard deviation increment in protein level equals 0.84, and higher hazard ratio of incident atrial fibrillation associated with higher mean levels of both insulin-like growth factor-binding protein and N-terminal pro-B-hormone type a natriuretic peptide. In our next paper, Eoin Donnellan and associates examine changes in atrial fibrillation or AF type following bariatric surgery in 220 morbidly obese patients body mass index ≥40 kilograms per meter square. They observed a reduction in body mass index following bariatric surgery from 49.7 to 37.2 kilograms per meter square. Weight loss was greatest in the gastric bypass group with a mean percentage loss of 25% compared to 19% in patients underwent sleeve gastrectomy, and 16% following gastric banding. P &lt; 0.0001 reversal of AF type occurred in 71% of patients following gastric bypass, 56% of patients who underwent sleeve gastrectomy and 50% of patients following gastric banding, P = 0.004. They found that on Cox proportional hazards analysis percent weight loss was significantly associated with AFib reversal, P = 0.0002. In our next paper, Thomas Pezawas and associates examine the role of diastolic function assessment to predict arrhythmic death. They prospectively enrolled 120 patients with ischemic, 60 patients with dilated cardiomyopathy, and 30 patients with normal left ventricular ejection fraction. After an average of 7.0 years, arrhythmic death or resuscitated cardiac arrest was observed in 28 (or 13.3%) and 33 (or 15.7%) of patients respectively. Non-arrhythmic death was found in 41 (or 19.5%) of patients. On Kaplan Meier analysis patients with dysfunction grade III had the highest risk of arrhythmic death or resuscitated cardiac arrest, P &lt; 0.001. This finding was independent from the degree of left ventricular ejection fraction and was observed in patients with ejection fraction ≤ 35%, P = 0.001 and with a left ejection fraction &gt; 35%, P = 0.014. Non-arrhythmic mortality was highest and patients with dysfunction grade III. This was true for patients with left ventricular ejection fraction ≤to 35%, or &gt; 35%. In an adjusted model for relevant confounding factors, grade III dysfunction was associated with a 3.5-fold, increased risk of arrhythmic death or resuscitated cardiac arrest in the overall study population hazard ratio of 3.52, P &lt; 0.001. In our next paper, because asthma and atrial fibrillation share an underlying inflammatory pathophysiology, Matthew Tattersall and associates hypothesize that persistent asthmatics would be at higher risk for developing atrial fibrillation or AF and this association would it be attenuated by adjust for baseline markers of systemic inflammation. The authors examined 6,615 patients mean age 62.0 years, 47% male, 27% African American, 12% Chinese, 22% Hispanic. In the MESA, or multiethnic study of atherosclerosis study, a prospective longitudinal study of adults free of cardiovascular disease at baseline, AF incident rates were 0.11 events per ten person-years for non-asthmatics, 0.11 events per ten person-years for intermittent asthmatic, and 0.19 events per ten person-years for persistent asthmatic. Log rank P value = 0.008. In risk factor adjusted models, persistent asthmatic had a greater risk of incident atrial fibrillation has a ratio of 1.49 P = 0.03. Interleukin six tumor necrosis factor and D-dimer predicted incident atrial fibrillation, but the relationship between asthma and incident AFib was not attenuated by adjustment for any inflammation marker. In our next paper, Deepak Pasupula and associates examine the survival trends in out-of-hospital cardiac arrest patients before and after the introduction of the 2010 AHA CPR guidelines in the United States. They sought to assess survival trends in out-of-hospital cardiac arrest patients before and after the introduction of the 2010 AHA CPR guidelines. Using the retrospective observational study from the National Emergency Department sample, they found that the change in the 2010 AHA CPR guidelines was associated with only small improvement in Emergency Department survival and survival-to-discharge trends among US out-of-hospital cardiac arrest patients, and only one out of six out-of-hospital cardiac arrest patients survive to discharge. They studied 1,282,520 patients presenting to the emergency department after out-of-hospital cardiac arrest, meaning age 65.8 years, 62% males. The average survival after emergency department care increased only 1%, 22% before 2010 in 23% after 2010, P &lt; 0.001, and there was no significant change in the discharge rate. In our next paper, Julian Stewart and associates examine the changes in cardiac output, inappropriate sinus tachycardia, postural tachycardia syndrome, vasovagal syncope in the presence of symptomatic excessive heart rate. They studied 12 healthy controls, nine inappropriate sinus tachycardia, 30 vasovagal syncope and 30 postural tachycardia syndrome patients, selected randomly by disorder. Subjects were instrumented for electrocardiography, beat-to-beat blood pressure, respiratory rate, CO-Model flow algorithm, and central blood volume from impedance cardiography. At baseline heart rates, diastolic and mean arterial pressure in inappropriate sinus and tachycardia postural tachycardia syndrome were higher versus controls. Upright mean heart rate increased most in postural tachycardia syndrome. Then in inappropriate sinus tachycardia, in vasovagal syncope with diverse changes in cardiac output, systemic or vascular resistance, and central blood volume. Each patient grouping was separately and collectively analyzed for heart rate change following transition from in-phase to anti-phase as heart rate increased. Heart rates transition =115 for inappropriate sinus tachycardia, 123 for postural orthostatic tachycardia syndrome and 124 for vasovagal syncope. P=ns. Controls never reached the transitional heart rate. The authors concluded that excessive heart rate independently and equivalently reduces upright cardiac output in inappropriate sinus tachycardia, vasovagal and postural tachycardia syndrome patients. In our next paper, Adam Graham, Michele Orini, and associates examined the accuracy of non-invasive ECG imaging or ECGI in localizing the origin of arrhythmias during catheter ablation of ventricular tachycardia and structurally abnormal hearts. In 18 patients, 29 ventricular tachycardias were examined. The distance between the site of origin and sites of earliest activation in ECGI were 22.6 millimeters with a first quartile of 13.9, and third quartile of 36.2 millimeters. ECGI mapped ventricular sites of origin onto the correct AHA segment with a higher accuracy than a validated 12-lead ECG algorithm, 83.3% versus 38.9%, P=0.015. In a research letter, Shadi Yaghi and associates report about the ability of left atrial appendage morphology to improve prediction of stagnant flow and stroke risk in atrial fibrillation. In an interesting review article, Charles Swerdlow and associates provide an in depth look at how impedance may provide insights into lead performance. That's it for this month. We hope that you will find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.

Paul J. Wang: Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, Ling Kuo and associates examine the association between left atrial high-resolution late gadolinium enhancement on cardiac magnetic resonance and electrogram abnormalities in patients with atrial fibrillation or AF. They found that in 40 AF patients age 63.2 years with a mean of 1312 electrogram points per patient. Lower bipolar voltage was associated with higher signal intensity Z score in patients who had undergone previous ablation coefficient equals -0.049 P &lt; 0.001 but not in ablation-naive patients, coefficient = -0.004, P = 0.7. Left atrial high-resolution late gadolinium enhancement activation delay was associated with signal intensity z-score in patients with previous ablation, signal intensity Z score coefficient = 0.004, P &lt; 0.001 but not in ablation-naive patients. In contrast, increased left atrial high-resolution late gadolinium enhancement fractionation was associated with signal intensity z-score coefficient 0.012, P = 0.03, and left atrial high-resolution late gadolinium enhancement coefficient 0.035, P &lt; 0.001 only in ablation-naive patients. The authors concluded that the association of left atrial late gadolinium enhancement with voltage is modified by ablation in ablation naive patients. Atrial late gadolinium enhancement is associated with electrogram fractionation even in the absence of voltage abnormality. In our next paper, Laila Staerk and associates examine the associations between 85 protein biomarkers and incident atrial fibrillation or AF in patients 50 years of age or greater, from the Framingham Heart Study Offspring and Third Generation cohorts. Out of 3378 participants, 54% women, mean age 61.5 years, 401 developed AAF over a mean follow-up of 12.3 years. They observed a lower hazard of incident atrial fibrillation associated with mean higher levels of incident like growth factor hazard ratio per one standard deviation increment in protein level equals 0.84, and higher hazard ratio of incident atrial fibrillation associated with higher mean levels of both insulin-like growth factor-binding protein and N-terminal pro-B-hormone type a natriuretic peptide. In our next paper, Eoin Donnellan and associates examine changes in atrial fibrillation or AF type following bariatric surgery in 220 morbidly obese patients body mass index ≥40 kilograms per meter square. They observed a reduction in body mass index following bariatric surgery from 49.7 to 37.2 kilograms per meter square. Weight loss was greatest in the gastric bypass group with a mean percentage loss of 25% compared to 19% in patients underwent sleeve gastrectomy, and 16% following gastric banding. P &lt; 0.0001 reversal of AF type occurred in 71% of patients following gastric bypass, 56% of patients who underwent sleeve gastrectomy and 50% of patients following gastric banding, P = 0.004. They found that on Cox proportional hazards analysis percent weight loss was significantly associated with AFib reversal, P = 0.0002. In our next paper, Thomas Pezawas and associates examine the role of diastolic function assessment to predict arrhythmic death. They prospectively enrolled 120 patients with ischemic, 60 patients with dilated cardiomyopathy, and 30 patients with normal left ventricular ejection fraction. After an average of 7.0 years, arrhythmic death or resuscitated cardiac arrest was observed in 28 (or 13.3%) and 33 (or 15.7%) of patients respectively. Non-arrhythmic death was found in 41 (or 19.5%) of patients. On Kaplan Meier analysis patients with dysfunction grade III had the highest risk of arrhythmic death or resuscitated cardiac arrest, P &lt; 0.001. This finding was independent from the degree of left ventricular ejection fraction and was observed in patients with ejection fraction ≤ 35%, P = 0.001 and with a left ejection fraction &gt; 35%, P = 0.014. Non-arrhythmic mortality was highest and patients with dysfunction grade III. This was true for patients with left ventricular ejection fraction ≤to 35%, or &gt; 35%. In an adjusted model for relevant confounding factors, grade III dysfunction was associated with a 3.5-fold, increased risk of arrhythmic death or resuscitated cardiac arrest in the overall study population hazard ratio of 3.52, P &lt; 0.001. In our next paper, because asthma and atrial fibrillation share an underlying inflammatory pathophysiology, Matthew Tattersall and associates hypothesize that persistent asthmatics would be at higher risk for developing atrial fibrillation or AF and this association would it be attenuated by adjust for baseline markers of systemic inflammation. The authors examined 6,615 patients mean age 62.0 years, 47% male, 27% African American, 12% Chinese, 22% Hispanic. In the MESA, or multiethnic study of atherosclerosis study, a prospective longitudinal study of adults free of cardiovascular disease at baseline, AF incident rates were 0.11 events per ten person-years for non-asthmatics, 0.11 events per ten person-years for intermittent asthmatic, and 0.19 events per ten person-years for persistent asthmatic. Log rank P value = 0.008. In risk factor adjusted models, persistent asthmatic had a greater risk of incident atrial fibrillation has a ratio of 1.49 P = 0.03. Interleukin six tumor necrosis factor and D-dimer predicted incident atrial fibrillation, but the relationship between asthma and incident AFib was not attenuated by adjustment for any inflammation marker. In our next paper, Deepak Pasupula and associates examine the survival trends in out-of-hospital cardiac arrest patients before and after the introduction of the 2010 AHA CPR guidelines in the United States. They sought to assess survival trends in out-of-hospital cardiac arrest patients before and after the introduction of the 2010 AHA CPR guidelines. Using the retrospective observational study from the National Emergency Department sample, they found that the change in the 2010 AHA CPR guidelines was associated with only small improvement in Emergency Department survival and survival-to-discharge trends among US out-of-hospital cardiac arrest patients, and only one out of six out-of-hospital cardiac arrest patients survive to discharge. They studied 1,282,520 patients presenting to the emergency department after out-of-hospital cardiac arrest, meaning age 65.8 years, 62% males. The average survival after emergency department care increased only 1%, 22% before 2010 in 23% after 2010, P &lt; 0.001, and there was no significant change in the discharge rate. In our next paper, Julian Stewart and associates examine the changes in cardiac output, inappropriate sinus tachycardia, postural tachycardia syndrome, vasovagal syncope in the presence of symptomatic excessive heart rate. They studied 12 healthy controls, nine inappropriate sinus tachycardia, 30 vasovagal syncope and 30 postural tachycardia syndrome patients, selected randomly by disorder. Subjects were instrumented for electrocardiography, beat-to-beat blood pressure, respiratory rate, CO-Model flow algorithm, and central blood volume from impedance cardiography. At baseline heart rates, diastolic and mean arterial pressure in inappropriate sinus and tachycardia postural tachycardia syndrome were higher versus controls. Upright mean heart rate increased most in postural tachycardia syndrome. Then in inappropriate sinus tachycardia, in vasovagal syncope with diverse changes in cardiac output, systemic or vascular resistance, and central blood volume. Each patient grouping was separately and collectively analyzed for heart rate change following transition from in-phase to anti-phase as heart rate increased. Heart rates transition =115 for inappropriate sinus tachycardia, 123 for postural orthostatic tachycardia syndrome and 124 for vasovagal syncope. P=ns. Controls never reached the transitional heart rate. The authors concluded that excessive heart rate independently and equivalently reduces upright cardiac output in inappropriate sinus tachycardia, vasovagal and postural tachycardia syndrome patients. In our next paper, Adam Graham, Michele Orini, and associates examined the accuracy of non-invasive ECG imaging or ECGI in localizing the origin of arrhythmias during catheter ablation of ventricular tachycardia and structurally abnormal hearts. In 18 patients, 29 ventricular tachycardias were examined. The distance between the site of origin and sites of earliest activation in ECGI were 22.6 millimeters with a first quartile of 13.9, and third quartile of 36.2 millimeters. ECGI mapped ventricular sites of origin onto the correct AHA segment with a higher accuracy than a validated 12-lead ECG algorithm, 83.3% versus 38.9%, P=0.015. In a research letter, Shadi Yaghi and associates report about the ability of left atrial appendage morphology to improve prediction of stagnant flow and stroke risk in atrial fibrillation. In an interesting review article, Charles Swerdlow and associates provide an in depth look at how impedance may provide insights into lead performance. That's it for this month. We hope that you will find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.

Circulation: Arrhythmia and Electrophysiology February 2020 Issue

Each podcast will include key highlights from the journal's current issue and a report on new research published in the field of arrhythmia and electrophysiology.

This is the worst possible format to read a series of studies and P values. The podcast would be much better spent having interactive discussions with the journal authors for them to describe in their own words the significance and import of each piece of work. The current format is no better than having some kind of artificial intelligence that scrubs abstract for key findings recite them to you. Horrible format and reading. The fact that it enjoys a four star rating boggles my mind. Maybe Dr. Wong has his mother, relatives, and rotating students chime in with reviews.

P values and paper summaries are not interesting

Circulation: Arrhythmia and Electrophysiology On the Beat

Dr Paul Wang: Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, Leroy Joseph and associates examined whether an increase in dietary saturated fat could lead to abnormalities of calcium homeostasis and heart rhythm, by an NADPH oxidase 2, NOX2-dependent mechanism. In mice on high fat diets, they found that saturated fat activates NOX, whereas polyunsaturated fat does not. The high saturated fat diet increased repolarization heterogeneity in ventricular tachycardia, VT inducibility in perfused hearts. Pharmacologic inhibition or genetic deletion of NOX2 prevented arrhythmogenic abnormalities in vivo during high saturated fat diet and resulted in less inducible VT. On the other hand, high saturated fat diet activates calcium calmodulin dependent protein kinase in the heart, which contributes to abnormal calcium handling, promoting arrhythmia. This work suggests that a molecular mechanism links cardiac metabolism to arrhythmia and it suggest that NOX2 inhibitors could be a novel therapy for heart rhythm abnormalities caused by cardiac lipid overload. In our next paper, Misha Regouski and associates examined whether the relationship between endurance exercise and atrial fibrillation, or AF, is dependent on atrial myopathy. They examined six cardiac specific TGFβ1 transgenic and six wild type goats. Pacemakers were implanted in all animals for continuous arrhythmia monitoring and AF inducibility. AF inducibility was evaluated using five separate ten second bursts of atrial pacing. At baseline sustained AF greater than 30 seconds was induced with 10 seconds of atrial pacing in 4 out of 6 transgenic goats, compared to zero out of six wild type controls, P less than 0.05. No spontaneous AF was observed at baseline, three months of progressive endurance exercise up to 90 minutes at 4.5 miles per hour was performed. The authors observed that between two to three months of exercise, three out of six transgenic animals developed self-terminating spontaneous atrial fibrillation compared to zero out of six wild type animals, (P less than 0.05). There was an increase in AF inducibility in both transgenic and wild type animals during the first two months of exercise with partial normalization at three months. These changes in AF susceptibility were associated with a decrease in circulating micro RNA 21 and micro RNA 29 during the first two months of exercise, with partial normalization three months in both transgenic and wild type animals. The authors concluded that endurance exercise appears to increase inducible AF secondary to altered expression of key profibrotic biomarkers that is independent of the presence of an atrial myopathy. In our next paper, Seokhun Yang and associates examined whether there is an association between lifetime exposure to endogenous sex hormone, and incident atrial fibrillation, or AF, in subsequent ischemic stroke. They studied nearly five million natural postmenopausal women aged 40 years or greater without prior history of AF and with breast cancer. The primary end point was incident AF and the secondary end point was subsequent ischemic stroke once AF is developed. During the mean follow up of 6.3 years, shorter total reproductive years (&lt;30 years) was associated with 7% increased risk of AF after adjusting for confounding variables. Adjusted hazard ratio, 1.07. Risk of AF declined progressively with every five-year increment in total reproductive years. P for trend less than 0.001. However, the prolonged, two years or greater use of hormone replacement therapy after menopause was paradoxically associated with a 3% increase in AF risk. (Adjusted ratio 1.03). For the secondary endpoint analysis, the risk of ischemic stroke after AF development significantly decreased with each five-year increment in total reproductive years with less than 30 years as a reference. (Adjusted hazard ratio 0.93, for 30 to 34 years 0.84, for 35 to 39 years is 0.88, for 40 years or greater. P for trend less than 0.001) the authors concluded that women with natural menopause shortened lifetime exposure to endogenous sex hormone, that is, shorter total reproductive years, was significantly associated with a higher risk of AF and subsequent ischemic stroke. In contrast, prolonged exogenous hormone replacement therapy increased the risk of incident AF. In our next paper, Stephan Hohmann and associates examine the accuracy of electrocardiographic imaging, ECGi, in a closed chest porcine model. A total of 109 endocardial and nine epicardial locations were paced in nine pigs. ECGi predicted the correct chamber of origin in 85% of atrial and 92% of ventricular sites. Lateral locations were predicted in the correct chamber more often than septal location. (97% versus 79% P=0.01) Absolute distances in space between true and predicted pacing locations were 20.7 millimeters. In the next paper, Ayelet Shapira-Daniels and associates examine the lesion formation produced by a novel expandable lattice electrode radio frequency, RF catheter with an expanded lattice electrode in a larger surface area. The eight French bi-directional irrigated catheter (Sphere-9 Affera Inc) has a nine-millimeter spherical lattice tip with an effective surface area 10-fold larger than standard linear catheter. In 11 ex vivo bovine hearts unipolar ablation lattice produce deeper lesions at 60, 30 and 126 application duration. 6.7 versus 4.8 millimeters. 8.3 versus 5.3 millimeters and 10.0 versus 6.2 millimeters respectively. (P less than or equal 0.001) In five porcine hearts bipolar ablation was compared between the catheters. T max 60 degrees centigrade versus 40 Watts, 60 seconds bipolar lesions were deeper, 15.8 versus 10.5 millimeters, (P less THA 0.001) and we're more likely to be transmural (80% versus 0% P equals 0.002) in vivo lattice produced deeper lesions, 10.5 versus 6.5 millimeters. (P less than or equal to 0.001) Tissue temperature at seven millimeters was higher with lattice. (P less than 0.001) The steam pop occurrence was lower with lattice. (4% versus 18% P equals 0.01) (in vivo, 0% versus 14.2% P equals 0.13) the authors concluded that this novel RF system produces larger ventricle lesions compared to standard irrigated catheters and at a lower risk of tissue overheating. In our next paper, Jinlin Zhang and associates used an ultra-high-density mapping system to identify the characteristics and precise mechanisms of atrial tachycardia with cycle length alternans. They identified seven atrial tachycardias with alternating cycle length in a total of 478 atrial tachycardias from two institutions mapped with an ultra-high-density mapping system. Activation maps were performed for long cycle length (289 milliseconds; mapping points 21,520) in short cycle length, (251 milliseconds; mapping points, 17,594) separately. The authors classified atrial tachycardias with cycle length alternans into two types. Type one: There existed two potential loops with different routes. Cycle length alternans resulted from an intermittently 2:1 conducting block within the channel of the smaller loop. Type two: Cycling alternans resulted from different conduction velocity through two closely spaced gaps within preexisting linear lesions. Catheter ablation successfully terminated all seven atrial tachycardias. In our next paper Marine Cacheux and associates examine the role of stromal interaction molecule one STIM1, a calcium sensor that regulates cardiac hypertrophy by triggering store operated calcium entry on arrhythmias. Binding to phospholamban STIM1 increases sarcoplasmic reticulum calcium load independent of store operated calcium entry. They hypothesize that STIM1 controls electrophysiological function in arrhythmias in the adult heart. Inducible myocyte restricted STIM1 knockdown was achieved in adult mice. STIM1 knocked down mice (n=23) exhibited poor survival compared to STIM control (n=22). In Cre recombinase control (n=11) with greater than 50% mortality after only eight days of cardiomyocyte restricted STIM1 knock down. STIM1 knock down but not STIM1 control or CRE recombinase control hearts exhibited increased arrhythmias, such as frequent ectopy to pacing induced VTVF. There was decreased conduction velocity, increased action potential duration heterogeneity in STEM one knocked down mice. These features however, were comparable in VTVF positive and VTVF negative hearts. They also uncovered a marked increase in the magnitude of action potential duration alternans during rapid pacing and the emergence of a spatially discordant alternans profile in STIM1 knock down hearts. Unlike conduction velocity slowing and actual potential duration of heterogeneity, the magnitude of action potential alternatives was greater. (80%, P less than 0.05 in VTVF positive versus VTVF negative STIM1 knock down hearts) The authors concluded that an adult murine model with inducible and myocyte specific STIM1 depletion. The regulation of spatially discord alternans was mediated by STIM1. In our next paper Charlotte Houck and associates examined arrhythmia mechanisms and procedural and long-term outcomes in pediatric congenital heart disease patients undergoing catheter ablation. The authors studied 232 patients, (11.7 years, 33.5 kilograms). The most common diagnoses were Ebstein's anomaly (n=44), septal defects (n=39) and single ventricle (n=36). Arrhythmia Mechanisms included atrioventricular reentry tachycardia (n=104 in 90 patients), atrioventricular nodal reentry tachycardia (n=33 in 29 patients). Twin atrioventricular nodal tachycardia (n=3 in two patients), macroreentrant atrial tachycardia (n=59 in 56 patients). Focal atrial tachycardia (n=33 in 25 patients). Ventricular ectopy (n=10 in eight patients) and ventricular tachycardia (n=15 in 13 patients). 56 arrhythmias in 39 patients were undefined, outcomes included complete success (n=189 in 81%), partial success n=7 in 33%), failure. (n=16 in 7%), or empiric ablation (n=20 in 9%). Over 3.6 years, arrhythmia recurred in 49%. In 23 out of 51 repeat procedures, or 45%, a different arrhythmia a substrate was found. Overall adverse event rate was 9.4% although only 1.6% (n=4) were of major severity and 0.8% (n=2) of moderate severity. In our next paper, Babikir Kheiri and associates conducted a systematic review and meta-analysis, randomized controlled trials, to evaluate the efficacy and safety of antiarrhythmic drugs and catheter ablation in the treatment of ventricular tachyarrhythmias in patients with an ICD. They identified 22 randomized controlled trials with 3,828 total patients (age 64.3 79% males). The use of amiodarone was associated with a significant reduced rate of VT recurrence compared to control (hazard ratio 0.34). Sotalol was associated with increased risk of VT recurrence compared to amiodarone (hazard ratio 2.88). Compared to control, amiodarone had a hazard ratio of 0.33, and catheter ablation (hazard ratio 0.52) were associated with significant reduced ICD shocks. Compared with amiodarone, sotalol was associated with significant increase ICD shocks (hazard ratio 2.70). The rate of death was not significantly different between the competing strategies. Also, in this issue, Michele Orini and associates wrote a research letter on further evidence on how to measure local repolarization time using intracardiac unipolar electrograms in the intact human heart. Also in this issue, Christopher Andrews and associates wrote a special report on electro-mechanics of normal human heart in situ. In this issue, Arvindh Kanagasundram and associates wrote a review on sustained monomorphic ventricular tachycardia and non-ischemic heart disease, the arrhythmia substrate correlation that informed the approach to ablation That’s it for this month. We hope that you will find the journal, the go to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.

Dr Paul Wang: Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, Leroy Joseph and associates examined whether an increase in dietary saturated fat could lead to abnormalities of calcium homeostasis and heart rhythm, by an NADPH oxidase 2, NOX2-dependent mechanism. In mice on high fat diets, they found that saturated fat activates NOX, whereas polyunsaturated fat does not. The high saturated fat diet increased repolarization heterogeneity in ventricular tachycardia, VT inducibility in perfused hearts. Pharmacologic inhibition or genetic deletion of NOX2 prevented arrhythmogenic abnormalities in vivo during high saturated fat diet and resulted in less inducible VT. On the other hand, high saturated fat diet activates calcium calmodulin dependent protein kinase in the heart, which contributes to abnormal calcium handling, promoting arrhythmia. This work suggests that a molecular mechanism links cardiac metabolism to arrhythmia and it suggest that NOX2 inhibitors could be a novel therapy for heart rhythm abnormalities caused by cardiac lipid overload. In our next paper, Misha Regouski and associates examined whether the relationship between endurance exercise and atrial fibrillation, or AF, is dependent on atrial myopathy. They examined six cardiac specific TGFβ1 transgenic and six wild type goats. Pacemakers were implanted in all animals for continuous arrhythmia monitoring and AF inducibility. AF inducibility was evaluated using five separate ten second bursts of atrial pacing. At baseline sustained AF greater than 30 seconds was induced with 10 seconds of atrial pacing in 4 out of 6 transgenic goats, compared to zero out of six wild type controls, P less than 0.05. No spontaneous AF was observed at baseline, three months of progressive endurance exercise up to 90 minutes at 4.5 miles per hour was performed. The authors observed that between two to three months of exercise, three out of six transgenic animals developed self-terminating spontaneous atrial fibrillation compared to zero out of six wild type animals, (P less than 0.05). There was an increase in AF inducibility in both transgenic and wild type animals during the first two months of exercise with partial normalization at three months. These changes in AF susceptibility were associated with a decrease in circulating micro RNA 21 and micro RNA 29 during the first two months of exercise, with partial normalization three months in both transgenic and wild type animals. The authors concluded that endurance exercise appears to increase inducible AF secondary to altered expression of key profibrotic biomarkers that is independent of the presence of an atrial myopathy. In our next paper, Seokhun Yang and associates examined whether there is an association between lifetime exposure to endogenous sex hormone, and incident atrial fibrillation, or AF, in subsequent ischemic stroke. They studied nearly five million natural postmenopausal women aged 40 years or greater without prior history of AF and with breast cancer. The primary end point was incident AF and the secondary end point was subsequent ischemic stroke once AF is developed. During the mean follow up of 6.3 years, shorter total reproductive years (&lt;30 years) was associated with 7% increased risk of AF after adjusting for confounding variables. Adjusted hazard ratio, 1.07. Risk of AF declined progressively with every five-year increment in total reproductive years. P for trend less than 0.001. However, the prolonged, two years or greater use of hormone replacement therapy after menopause was paradoxically associated with a 3% increase in AF risk. (Adjusted ratio 1.03). For the secondary endpoint analysis, the risk of ischemic stroke after AF development significantly decreased with each five-year increment in total reproductive years with less than 30 years as a reference. (Adjusted hazard ratio 0.93, for 30 to 34 years 0.84, for 35 to 39 years is 0.88, for 40 years or greater. P for trend less than 0.001) the authors concluded that women with natural menopause shortened lifetime exposure to endogenous sex hormone, that is, shorter total reproductive years, was significantly associated with a higher risk of AF and subsequent ischemic stroke. In contrast, prolonged exogenous hormone replacement therapy increased the risk of incident AF. In our next paper, Stephan Hohmann and associates examine the accuracy of electrocardiographic imaging, ECGi, in a closed chest porcine model. A total of 109 endocardial and nine epicardial locations were paced in nine pigs. ECGi predicted the correct chamber of origin in 85% of atrial and 92% of ventricular sites. Lateral locations were predicted in the correct chamber more often than septal location. (97% versus 79% P=0.01) Absolute distances in space between true and predicted pacing locations were 20.7 millimeters. In the next paper, Ayelet Shapira-Daniels and associates examine the lesion formation produced by a novel expandable lattice electrode radio frequency, RF catheter with an expanded lattice electrode in a larger surface area. The eight French bi-directional irrigated catheter (Sphere-9 Affera Inc) has a nine-millimeter spherical lattice tip with an effective surface area 10-fold larger than standard linear catheter. In 11 ex vivo bovine hearts unipolar ablation lattice produce deeper lesions at 60, 30 and 126 application duration. 6.7 versus 4.8 millimeters. 8.3 versus 5.3 millimeters and 10.0 versus 6.2 millimeters respectively. (P less than or equal 0.001) In five porcine hearts bipolar ablation was compared between the catheters. T max 60 degrees centigrade versus 40 Watts, 60 seconds bipolar lesions were deeper, 15.8 versus 10.5 millimeters, (P less THA 0.001) and we're more likely to be transmural (80% versus 0% P equals 0.002) in vivo lattice produced deeper lesions, 10.5 versus 6.5 millimeters. (P less than or equal to 0.001) Tissue temperature at seven millimeters was higher with lattice. (P less than 0.001) The steam pop occurrence was lower with lattice. (4% versus 18% P equals 0.01) (in vivo, 0% versus 14.2% P equals 0.13) the authors concluded that this novel RF system produces larger ventricle lesions compared to standard irrigated catheters and at a lower risk of tissue overheating. In our next paper, Jinlin Zhang and associates used an ultra-high-density mapping system to identify the characteristics and precise mechanisms of atrial tachycardia with cycle length alternans. They identified seven atrial tachycardias with alternating cycle length in a total of 478 atrial tachycardias from two institutions mapped with an ultra-high-density mapping system. Activation maps were performed for long cycle length (289 milliseconds; mapping points 21,520) in short cycle length, (251 milliseconds; mapping points, 17,594) separately. The authors classified atrial tachycardias with cycle length alternans into two types. Type one: There existed two potential loops with different routes. Cycle length alternans resulted from an intermittently 2:1 conducting block within the channel of the smaller loop. Type two: Cycling alternans resulted from different conduction velocity through two closely spaced gaps within preexisting linear lesions. Catheter ablation successfully terminated all seven atrial tachycardias. In our next paper Marine Cacheux and associates examine the role of stromal interaction molecule one STIM1, a calcium sensor that regulates cardiac hypertrophy by triggering store operated calcium entry on arrhythmias. Binding to phospholamban STIM1 increases sarcoplasmic reticulum calcium load independent of store operated calcium entry. They hypothesize that STIM1 controls electrophysiological function in arrhythmias in the adult heart. Inducible myocyte restricted STIM1 knockdown was achieved in adult mice. STIM1 knocked down mice (n=23) exhibited poor survival compared to STIM control (n=22). In Cre recombinase control (n=11) with greater than 50% mortality after only eight days of cardiomyocyte restricted STIM1 knock down. STIM1 knock down but not STIM1 control or CRE recombinase control hearts exhibited increased arrhythmias, such as frequent ectopy to pacing induced VTVF. There was decreased conduction velocity, increased action potential duration heterogeneity in STEM one knocked down mice. These features however, were comparable in VTVF positive and VTVF negative hearts. They also uncovered a marked increase in the magnitude of action potential duration alternans during rapid pacing and the emergence of a spatially discordant alternans profile in STIM1 knock down hearts. Unlike conduction velocity slowing and actual potential duration of heterogeneity, the magnitude of action potential alternatives was greater. (80%, P less than 0.05 in VTVF positive versus VTVF negative STIM1 knock down hearts) The authors concluded that an adult murine model with inducible and myocyte specific STIM1 depletion. The regulation of spatially discord alternans was mediated by STIM1. In our next paper Charlotte Houck and associates examined arrhythmia mechanisms and procedural and long-term outcomes in pediatric congenital heart disease patients undergoing catheter ablation. The authors studied 232 patients, (11.7 years, 33.5 kilograms). The most common diagnoses were Ebstein's anomaly (n=44), septal defects (n=39) and single ventricle (n=36). Arrhythmia Mechanisms included atrioventricular reentry tachycardia (n=104 in 90 patients), atrioventricular nodal reentry tachycardia (n=33 in 29 patients). Twin atrioventricular nodal tachycardia (n=3 in two patients), macroreentrant atrial tachycardia (n=59 in 56 patients). Focal atrial tachycardia (n=33 in 25 patients). Ventricular ectopy (n=10 in eight patients) and ventricular tachycardia (n=15 in 13 patients). 56 arrhythmias in 39 patients were undefined, outcomes included complete success (n=189 in 81%), partial success n=7 in 33%), failure. (n=16 in 7%), or empiric ablation (n=20 in 9%). Over 3.6 years, arrhythmia recurred in 49%. In 23 out of 51 repeat procedures, or 45%, a different arrhythmia a substrate was found. Overall adverse event rate was 9.4% although only 1.6% (n=4) were of major severity and 0.8% (n=2) of moderate severity. In our next paper, Babikir Kheiri and associates conducted a systematic review and meta-analysis, randomized controlled trials, to evaluate the efficacy and safety of antiarrhythmic drugs and catheter ablation in the treatment of ventricular tachyarrhythmias in patients with an ICD. They identified 22 randomized controlled trials with 3,828 total patients (age 64.3 79% males). The use of amiodarone was associated with a significant reduced rate of VT recurrence compared to control (hazard ratio 0.34). Sotalol was associated with increased risk of VT recurrence compared to amiodarone (hazard ratio 2.88). Compared to control, amiodarone had a hazard ratio of 0.33, and catheter ablation (hazard ratio 0.52) were associated with significant reduced ICD shocks. Compared with amiodarone, sotalol was associated with significant increase ICD shocks (hazard ratio 2.70). The rate of death was not significantly different between the competing strategies. Also, in this issue, Michele Orini and associates wrote a research letter on further evidence on how to measure local repolarization time using intracardiac unipolar electrograms in the intact human heart. Also in this issue, Christopher Andrews and associates wrote a special report on electro-mechanics of normal human heart in situ. In this issue, Arvindh Kanagasundram and associates wrote a review on sustained monomorphic ventricular tachycardia and non-ischemic heart disease, the arrhythmia substrate correlation that informed the approach to ablation That’s it for this month. We hope that you will find the journal, the go to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.

Circulation: Arrhythmia and Electrophysiology November 2019 Issue

Circulation: Arrhythmia and Electrophysiology On the Beat April 2018

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue.                                                  Koji Miyamoto and associates conducted the AD-Balloon Study, which investigates the ideal number of free cycles during second-generation cryoballoon pulmonary vein isolation. In a prospective, multicenter, randomized clinical trial, the authors compared in 110 patients the addition of a three minute freeze after pulmonary vein isolation had been achieved to pulmonary vein isolation alone. Delayed-enhancement magnetic resonance imaging was also performed one to two months after the pulmonary vein isolation to assess the ablation lesions. The freedom from atrial arrhythmias at one year was similar. Log rank test, P equals 0.78 in the two groups, 87.3% in the extra three-minute freeze group, and 89.1% in the pulmonary vein isolation group. There was no significant difference in the frequency of gaps on the pulmonary vein isolation lines in the delayed-enhancement magnetic resonance imaging. The authors conclude that an insurance freeze after achieving pulmonary vein isolation may be unnecessary and time consuming.                                                  In our next study, Robert Sheldon and associates examined the genetic basis of vasovagal syncope. They studied 160 subjects in 9 kindreds comprising 82 fainters and 78 controls. Common genetic variants were genotype for 12 genes for vascular signaling, potassium channels, the serotonin 5-HT1A receptor, the serotonin transporter and catecholamine-O-methyltransferase or COMT. They found that in 9 of 12 variants, there was no significant association between genotype and phenotype. However, the serotonin 5-HT1A receptor, HTR1-A G alleles were associated with syncope in males but not in females. P equals 0.005. The men with serotonin 5-HT1 receptor C alleles had a 9% likelihood of syncope while Gg males had a 77% likelihood of syncope. The SL6A4 promoter L alleles were associated with decreased syncope in males but increase in females. P equals 0.059. The Ll males had a 25% syncope likelihood and Ss males had a 47% syncope likelihood. The COMT A alleles were associated with decreased syncope in males but increased in females. P equals 0.017. The Gg males had a 50% syncope likelihood and A males had a 15% syncope likelihood. The Gg females had 52% syncope likelihood and the Aa females had a 73% syncope likelihood. The authors concluded that there is a sex-dependent effect of alleles of serotonin signaling in vasovagal syncope, supporting the serotonin hypothesis of the physiology of vasovagal syncope.                                                  In the next study, Michael Barkagan and associates sought to examine whether the standard criteria for mitral line block with endocardial and epicardial activation mapping may not distinguish from slow conduction or conduction via epicardial bridging connections. In 56 patients, the authors creates a posterior mitral line using radiofrequency ablation. Mitral block determined by pacing with conduction block defined as trans-isthmus time of 100 milliseconds or greater in reversal of coronary sinus activation during pacing from the left atrial appendage was achieved in 51 out of 56 or 91% of patients. In 11 of 51 or 22% of patients, high-resolution activation mapping, using Rhythmia, of the endocardium and epicardium via the coronary sinus demonstrated residual endocardial in 27% or residual epicardial in 73% connections. Epicardial bridging connections were distant from the line, 2.4 plus or minus 1.6 centimeters, inserting laterally at the proximal-mid coronary sinus and septally at the left atrial ridge. Patients with residual conduction were prone to complex circuits involving the epicardium in 7 of 11 patients. Mitral line block was achieved in 75% by targeting these insertion sites. The trans-isthmus time had limited predictive value for distinguishing block from pseudoblock. The authors concluded the connections are a frequent cause of complex circuits, and their insertion sites can be targeted for ablation.                                                  In our next paper, Santiago Rivera and associates examined the causes of QRS variability in Papillary muscle arrhythmias usually attributed to anisotropy. In 33 patients with papillary muscle arrhythmias prospectively undergoing cardiac resonance imaging, papillary muscle connections away from the papillary muscle base were identified. Arrhythmogenic papillary muscles, N equals 35, exhibited a higher number of papillary muscle connections, 72 versus 18, P equals 0.01. Patients with inconsistent QRS precordial transition and inconsistent QRS access exhibited a 100% prevalence of papillary muscle connections. Those with consistent precordial transition and consistent QRS access showed 40% and 26% prevalence of papillary muscle connections respectively. Inconsistent QRS precordial transition and inconsistent QRS access predicted the presence of papillary muscle connections with 59% or 28% sensitivity and 100% specificity respectively. Those papillary muscles exhibiting clinical recurrence after ablation presented a higher prevalence of papillary muscle connections, 91% versus 60%, P=0.04.                                                  In our next paper, Jason Coult and associates examined the quantitative measures of the electrocardiogram waveform during ventricular fibrillation to assess myocardial physiology and predict cardiac arrest outcomes. They collected five second ventricular fibrillation ECG segments with and without chest compressions prior to 2,755 defibrillation shocks from 1,151 out of hospital cardiac arrest patients. 24 individual measures and 3 combination measures were optimized to predict functionally intact survival using 460 training cases. Measures predicted functionally intact survival in 691 independent test cases with an area under the receiver operating curve (AUC) ranging from 0.56 to 0.75 without chest compressions and 0.53 to 0.75 with compressions, P less than 0.001. Of all measures evaluated, the support vector machine model ranked highest both without chest compressions, AUC equals 0.75, and with compressions, AUC equals 0.75. The authors concluded the waveform measures predict functionally intact survival when calculated during chest compressions, but prognostic performance is generally reduced compared to analysis without compressions. Support vector machine models exhibited similar performance with and without compressions while also achieving the highest area under the curve.                                                  In our last paper, Hailey Jansen, Martin Mackasey and associates examined the effective natriuretic peptides in the specific natriuretic peptide receptor NPR-C on angiotensin II-mediated atrial fibrillation. The authors examined wild-type and NPR-C knockout mice to investigate the effects of angiotensin II administered three milligrams per kilo per day for three weeks on atrial fibrillation susceptibility and atrial function. In wild-type mice, angiotensin II increased susceptibility to atrial fibrillation and associated with a prolonged P wave duration, increased atrial refractory period, and slowed atrial conduction. These effects were exacerbated in angiotensin II-treated NPR-C knockout mice. Angiotensin II prolonged action potential duration and reduced action potential upstroke velocity. Angiotensin II also increased fibrosis in the atria in wild-type mice while angiotensin II-treated NPR-C knockout mice exhibited substantially higher atrial fibrosis. Co-treating wild-type mice with angiotensin II and the NPR-C agonist cANF, those dependently reduced atrial fibrillation inducibility by preventing some of the angiotensin II-induced changes in atrial myocyte electrophysiology and preventing atrial fibrosis. The authors suggested that the NPR-C receptor may represent a new target for the prevention of angiotensin II-induced atrial fibrillation via protective effects on atrial, electrical and structural remodeling.                                                  That's it for this month! We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time! This program is copyright American Heart Association 2019.

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue.                                                 Koji Miyamoto and associates conducted the AD-Balloon Study, which investigates the ideal number of free cycles during second-generation cryoballoon pulmonary vein isolation. In a prospective, multicenter, randomized clinical trial, the authors compared in 110 patients the addition of a three minute freeze after pulmonary vein isolation had been achieved to pulmonary vein isolation alone. Delayed-enhancement magnetic resonance imaging was also performed one to two months after the pulmonary vein isolation to assess the ablation lesions. The freedom from atrial arrhythmias at one year was similar. Log rank test, P equals 0.78 in the two groups, 87.3% in the extra three-minute freeze group, and 89.1% in the pulmonary vein isolation group. There was no significant difference in the frequency of gaps on the pulmonary vein isolation lines in the delayed-enhancement magnetic resonance imaging. The authors conclude that an insurance freeze after achieving pulmonary vein isolation may be unnecessary and time consuming.                                                 In our next study, Robert Sheldon and associates examined the genetic basis of vasovagal syncope. They studied 160 subjects in 9 kindreds comprising 82 fainters and 78 controls. Common genetic variants were genotype for 12 genes for vascular signaling, potassium channels, the serotonin 5-HT1A receptor, the serotonin transporter and catecholamine-O-methyltransferase or COMT. They found that in 9 of 12 variants, there was no significant association between genotype and phenotype. However, the serotonin 5-HT1A receptor, HTR1-A G alleles were associated with syncope in males but not in females. P equals 0.005. The men with serotonin 5-HT1 receptor C alleles had a 9% likelihood of syncope while Gg males had a 77% likelihood of syncope. The SL6A4 promoter L alleles were associated with decreased syncope in males but increase in females. P equals 0.059. The Ll males had a 25% syncope likelihood and Ss males had a 47% syncope likelihood. The COMT A alleles were associated with decreased syncope in males but increased in females. P equals 0.017. The Gg males had a 50% syncope likelihood and A males had a 15% syncope likelihood. The Gg females had 52% syncope likelihood and the Aa females had a 73% syncope likelihood. The authors concluded that there is a sex-dependent effect of alleles of serotonin signaling in vasovagal syncope, supporting the serotonin hypothesis of the physiology of vasovagal syncope.                                                 In the next study, Michael Barkagan and associates sought to examine whether the standard criteria for mitral line block with endocardial and epicardial activation mapping may not distinguish from slow conduction or conduction via epicardial bridging connections. In 56 patients, the authors creates a posterior mitral line using radiofrequency ablation. Mitral block determined by pacing with conduction block defined as trans-isthmus time of 100 milliseconds or greater in reversal of coronary sinus activation during pacing from the left atrial appendage was achieved in 51 out of 56 or 91% of patients. In 11 of 51 or 22% of patients, high-resolution activation mapping, using Rhythmia, of the endocardium and epicardium via the coronary sinus demonstrated residual endocardial in 27% or residual epicardial in 73% connections. Epicardial bridging connections were distant from the line, 2.4 plus or minus 1.6 centimeters, inserting laterally at the proximal-mid coronary sinus and septally at the left atrial ridge. Patients with residual conduction were prone to complex circuits involving the epicardium in 7 of 11 patients. Mitral line block was achieved in 75% by targeting these insertion sites. The trans-isthmus time had limited predictive value for distinguishing block from pseudoblock. The authors concluded the connections are a frequent cause of complex circuits, and their insertion sites can be targeted for ablation.                                                 In our next paper, Santiago Rivera and associates examined the causes of QRS variability in Papillary muscle arrhythmias usually attributed to anisotropy. In 33 patients with papillary muscle arrhythmias prospectively undergoing cardiac resonance imaging, papillary muscle connections away from the papillary muscle base were identified. Arrhythmogenic papillary muscles, N equals 35, exhibited a higher number of papillary muscle connections, 72 versus 18, P equals 0.01. Patients with inconsistent QRS precordial transition and inconsistent QRS access exhibited a 100% prevalence of papillary muscle connections. Those with consistent precordial transition and consistent QRS access showed 40% and 26% prevalence of papillary muscle connections respectively. Inconsistent QRS precordial transition and inconsistent QRS access predicted the presence of papillary muscle connections with 59% or 28% sensitivity and 100% specificity respectively. Those papillary muscles exhibiting clinical recurrence after ablation presented a higher prevalence of papillary muscle connections, 91% versus 60%, P=0.04.                                                 In our next paper, Jason Coult and associates examined the quantitative measures of the electrocardiogram waveform during ventricular fibrillation to assess myocardial physiology and predict cardiac arrest outcomes. They collected five second ventricular fibrillation ECG segments with and without chest compressions prior to 2,755 defibrillation shocks from 1,151 out of hospital cardiac arrest patients. 24 individual measures and 3 combination measures were optimized to predict functionally intact survival using 460 training cases. Measures predicted functionally intact survival in 691 independent test cases with an area under the receiver operating curve (AUC) ranging from 0.56 to 0.75 without chest compressions and 0.53 to 0.75 with compressions, P less than 0.001. Of all measures evaluated, the support vector machine model ranked highest both without chest compressions, AUC equals 0.75, and with compressions, AUC equals 0.75. The authors concluded the waveform measures predict functionally intact survival when calculated during chest compressions, but prognostic performance is generally reduced compared to analysis without compressions. Support vector machine models exhibited similar performance with and without compressions while also achieving the highest area under the curve.                                                 In our last paper, Hailey Jansen, Martin Mackasey and associates examined the effective natriuretic peptides in the specific natriuretic peptide receptor NPR-C on angiotensin II-mediated atrial fibrillation. The authors examined wild-type and NPR-C knockout mice to investigate the effects of angiotensin II administered three milligrams per kilo per day for three weeks on atrial fibrillation susceptibility and atrial function. In wild-type mice, angiotensin II increased susceptibility to atrial fibrillation and associated with a prolonged P wave duration, increased atrial refractory period, and slowed atrial conduction. These effects were exacerbated in angiotensin II-treated NPR-C knockout mice. Angiotensin II prolonged action potential duration and reduced action potential upstroke velocity. Angiotensin II also increased fibrosis in the atria in wild-type mice while angiotensin II-treated NPR-C knockout mice exhibited substantially higher atrial fibrosis. Co-treating wild-type mice with angiotensin II and the NPR-C agonist cANF, those dependently reduced atrial fibrillation inducibility by preventing some of the angiotensin II-induced changes in atrial myocyte electrophysiology and preventing atrial fibrosis. The authors suggested that the NPR-C receptor may represent a new target for the prevention of angiotensin II-induced atrial fibrillation via protective effects on atrial, electrical and structural remodeling.                                                 That's it for this month! We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time! This program is copyright American Heart Association 2019.

Circulation: Arrhythmia and Electrophysiology january 2019 Issue

Paul Wang:         Welcome to the monthly podcast On The Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, Moo-Nyun Jin, Tae-Hoon Kim, and associates examined the 1-year serial changes in cognitive function, with or without atrial fibrillation catheter ablation. They used the Montreal cognitive assessment score in 308 patients undergoing atrial fibrillation ablation, the ablation group and 50 atrial fibrillation patients on medical therapy who met the same indication for atrial fibrillation ablation, the control group at baseline three months and 12 months. Cognitive impairment was defined as a published cutoff score of less than 23 points. Pre-ablation cognitive impairment was a detected in 18.5%. The Montreal cognitive assessment score significantly improved one year after radio frequency ablation. In both the overall ablation group, 24.9 to 26.4 p less than 0.001, and the propensity matched ablation group 25.4 to 26.5, but not in the control group. 25.4 to 24.8 p equals 0.012. Pre-ablation cognitive pyramid odds ratio 13.7, was independently associated with an improvement in one-year post ablation cognitive function. In our next paper, Zian Tseng, James Salazar and associates studied World Health Organization defined sudden cardiac deaths autopsied in the POstmortem Systemic InvesTigation of sudden cardiac death, the POST SCD study to determine whether premortem characteristics could identify autopsy defined sudden arrhythmic death among presumed sudden cardiac deaths. They prospectively identified 615 World Health Organization defined sudden cardiac deaths, of which 144 were witnessed. Autopsy defined sudden arrhythmic death had no extra cardiac or acute heart failure cause of death. Of the 615 presumed sudden critic deaths, 348 or 57% were autopsy defined, sudden arrhythmic deaths. For witness cases, using an emergency medical system model area under the receiver operator curve 0.75, included presenting rhythm of ventricular tech or cardiac fibrillation, pulseless electrical activity, while the comprehensive model, adding medical record data and depression, area under the curve 0.78. If only VTVF witness cases, 48 of those were classified as sudden arrhythmic death. The sensitivity was 0.46, and specificity 0.90. For unwitnessed cases, the emergency medical system model, area under the curve 0.68, included black race, male sex, age, time since last seen normal, while the comprehensive, area into the curve 0.75, added the use of beta blockers, antidepressants, QT prolonging drugs, opiates, illicit drugs and dyslipidemia. If only unwitnessed cases, less than one hour, n equals 59, were classified as sudden arrhythmic deaths, the sensitivities were 0.18, and specificity was 0.95. The authors concluded that models could identify pre-mortem characteristics to better specify autopsy defined sudden arrhythmic deaths, among presumed sudden cardiac arrests. The authors suggest that the World Health Organization definition can be improved by restricting witnessed sudden cardiac deaths to ventricular tachycardia fibrillation or non-pulseless electrical activity rhythms in unwitnessed cases to less than one hour since last normal, at a cost of sensitivity. In our next paper, Rafael Jaimes III and associates performed optical mapping of trends, membrane, voltage and pacing studies on isolated Langendorff-perfused rat hearts to assess the cardiac electrophysiology after mono-2-ethylhexyl phthalate, a phthalate with documented exposure in intensive care patients. The authors found that a 30-minute exposure to mono-2-ethylhexyl phthalate increased the atrioventricular node effector in period 147 milliseconds compared to 170 milliseconds in controls and increased the ventricular effective refractory periods of 117 milliseconds compared to 77.5 milliseconds in controls. Optical mapping revealed prolonged action potential duration at slower pacing cycle lengths. Mono-2-ethylhexyl phthalate exposure also slowed epicardial conduction velocity, 25 centimeters per second compared to 60 centimeters per second in controls. The authors concluded that acute mono-2-ethylhexyl phthalate exposure, at clinically relevant doses, has a significant effect on cardiac electrophysiology in the intact heart. Heightened clinical exposure to plasticized medical products may have cardiac safety implications and lead to cardiac arrhythmias. In our next paper, Stephan Willems and associates report the use of a novel, non-contact imaging and mapping system that uses ultrasound to reconstruct atrial chamber anatomy and measure timing and density of dipolar, ionic activation or charge density across the myocardium to guide ablation of atrial arrhythmias. They conducted a prospective non-randomized study, the UNCOVER AF trial which was conducted at 13 centers across Europe and Canada. In 127 patients with persistent atrial fibrillation who underwent mapping and catheter ablation, acute procedural efficacy of 98% was seen. At 12 months, the single procedure freedom from atrial fibrillation, on or off antiarrhythmic drugs, was 72.5%, with 23% undergoing retreatments following one or two procedures. Freedom from atrial fibrillation was 93.2%. The primary safety outcome was 98% was no device related major adverse events reported. In our next paper, Anne-Floor Quast, Niek Beurskens, and associates describe a novel, completely extracardiac pacing system, with a lead in the anterior mediastinum, outside the pericardium and circulatory system. A total of 166 or 95% out of 174 patients had a viable lead access path through the fourth, fifth, or sixth intercostal space. Access to the targeted implant location using delivery tool was successful in all five cadavers and three humans, without use of fluoroscopy, with an average lead delivery time of 121 seconds. No damage to the lung, pericardium, heart or internal thoracic vessels occurred. Pacing performance in six human subjects showed a voltage threshold of 4.7 volts in a threshold pulse width of 1.8 milliseconds. In our next paper, Yasuhiro Shirai and associates compare the ability to identify ventricular tachycardia isthmuses in ischemic and nonischemic cardiomyopathies. Of 445 patients, 228 with ischemic cardiomyopathy and 217 with nonischemic cardiomyopathy, undergoing VT ablation. Detailed entrainment mapping of at least one tolerated VT was performed in 111 patients, 71 with ischemic cardiomyopathy and 40 with nonischemic cardiomyopathy. Of 89 nonischemic cardiomyopathy VTs, the isthmus could be identified by endocardial entrainment in 55 or 62%, compared to only eight out of 47 or 17% nonischemic cardiomyopathy VTs, p less than 0.01. With combined endocardial and epicardial mapping, the isthmus could be identified in 56 or 63% ischemic cardiomyopathy VTs, and 12 or 26% of nonischemic cardiomyopathy VTs, p less than 0.01, while a similar proportion of patients any critical component, defined as entrance, isthmus or exit, could be identified in 85% of ischemic cardiomyopathy VTs and 79% of nonischemic cardiomyopathy VTs, p equals 0.3. Complete success, no inducible VT at the end of the procedure was 82% versus 65%, p equals 0.04 and a one-year single procedure VT survival, 82% versus 55%, p less than 0.01. Both higher in patients with ischemic cardiomyopathy. The authors concluded that among mappable ischemic cardiomyopathy VTs, critical circuit components can be usually identified on the endocardium. In contrast, among mappable nonischemic cardiomyopathy VTs, although some critical components can be typically identified with the addition of epicardial mapping, the isthmus is less commonly identified, possibly due to midmyocardial location. In our next paper, Miki Yokokawa and associates targeted documented but non-inducible clinical VTs, based on stored, implantable cardioverter defibrillator electrograms. Radio frequency ablation was performed in a consecutive group of 66 postinfarction VTs, in whom clinical VTs were non-inducible during an ablation procedure. In the first 33 patients, the control group, only inducible VTs were targeted. In the second 33 patients, non-inducible clinical VTs were targeted by pace mapping based on stored ICD-electrograms, the ICD electrogram guided ablation group. VT recurred in five patients or 15% in the ICD-electrogram guided approach, and in 13% or 39% in the control group. Freedom from recurrent VT was higher, p equals 0.04, in the ICD-electrogram-guided group, but there was no difference in ventricular fibrillation or total mortality between groups. In our next paper, Albert Feeny and associates examined whether machine learning could predict cardiac resynchronization therapy or CRT response. A training cohort was created from all Johns Hopkins patients and an equal number of randomly sampled Cleveland Clinic patients. All remaining patients comprise the testing cohort. Response was defined as greater than or equal to 10% increase in left ventricular ejection fraction. Machine learning models were developed to predict CRT response using different combinations of classification algorithms in clinical variable sets on the training cohort. 925 patients were included. On the training cohort, the best machine learning model was a naive Bayes classifier using nine variables, QRS morphology, QRS duration, New York Heart Association classification, left ventricular ejection fraction and end-diastolic diameter, sex, ischemic cardiomyopathy, atrial fibrillation, and epicardial LV lead. On the testing cohort, machine learning demonstrated better response prediction than guidelines, area under the curves 0.7 versus 0.65, p equals 0.012, and greater discrimination of event-free survival, concordance index 0.61 versus 0.56, p less than 0.001. The fourth quartile of machine learning model had greatest risk of reaching the composite endpoint, while the first quartile had the least, hazard ratio of 0.34, p less than 0.001. The authors found that machine learning with nine variables incrementally improved prediction of CRT response and survival beyond guidelines, but its performance with not improved by incorporating more variables. In our next paper, Bernhard Kaess, Charlotte Andersson and associates examine the familial clustering of cardiac conduction defects in the Framingham heart study, using multivariable-adjusted logistic regression models to investigate the association of parental AV block, complete bundle branch block, or a pacemaker insertion with occurrence of cardiac conduction abnormalities on offspring. Individuals with at least one effected parent with a conduction defect had at 1.65-fold odds for manifesting AV block, and 1.62-fold odds for developing complete bundle branch block. If at least one parent had any electrocardiographic conduction defect or pacemaker insertion, the offspring had 1.62-fold odds for experiencing any of these conditions. The Danish and nationwide administrative registries of nearly 3 million individuals and about five thousand incident pacemaker implantations, individuals with at least one first degree relative with a history of pacemaker insertion, had a multivariable-adjusted 1.68-fold incident rate ratio of undergoing pacemaker insertion. If the affected relative was less than or equal to 45 years of age, the incident rate ratio was markedly increased to 51.0. In our final paper, a review article, Venkat Nagarajan, Siew Ho Yen, and Sabine Ernst provide a detailed discussion of anatomic landmarks and considerations that will aid in his bundle pacing lead implantation. That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.

Paul Wang:         Welcome to the monthly podcast On The Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor in chief, with some of the key highlights from this month's issue. In our first paper, Moo-Nyun Jin, Tae-Hoon Kim, and associates examined the 1-year serial changes in cognitive function, with or without atrial fibrillation catheter ablation. They used the Montreal cognitive assessment score in 308 patients undergoing atrial fibrillation ablation, the ablation group and 50 atrial fibrillation patients on medical therapy who met the same indication for atrial fibrillation ablation, the control group at baseline three months and 12 months. Cognitive impairment was defined as a published cutoff score of less than 23 points. Pre-ablation cognitive impairment was a detected in 18.5%. The Montreal cognitive assessment score significantly improved one year after radio frequency ablation. In both the overall ablation group, 24.9 to 26.4 p less than 0.001, and the propensity matched ablation group 25.4 to 26.5, but not in the control group. 25.4 to 24.8 p equals 0.012. Pre-ablation cognitive pyramid odds ratio 13.7, was independently associated with an improvement in one-year post ablation cognitive function. In our next paper, Zian Tseng, James Salazar and associates studied World Health Organization defined sudden cardiac deaths autopsied in the POstmortem Systemic InvesTigation of sudden cardiac death, the POST SCD study to determine whether premortem characteristics could identify autopsy defined sudden arrhythmic death among presumed sudden cardiac deaths. They prospectively identified 615 World Health Organization defined sudden cardiac deaths, of which 144 were witnessed. Autopsy defined sudden arrhythmic death had no extra cardiac or acute heart failure cause of death. Of the 615 presumed sudden critic deaths, 348 or 57% were autopsy defined, sudden arrhythmic deaths. For witness cases, using an emergency medical system model area under the receiver operator curve 0.75, included presenting rhythm of ventricular tech or cardiac fibrillation, pulseless electrical activity, while the comprehensive model, adding medical record data and depression, area under the curve 0.78. If only VTVF witness cases, 48 of those were classified as sudden arrhythmic death. The sensitivity was 0.46, and specificity 0.90. For unwitnessed cases, the emergency medical system model, area under the curve 0.68, included black race, male sex, age, time since last seen normal, while the comprehensive, area into the curve 0.75, added the use of beta blockers, antidepressants, QT prolonging drugs, opiates, illicit drugs and dyslipidemia. If only unwitnessed cases, less than one hour, n equals 59, were classified as sudden arrhythmic deaths, the sensitivities were 0.18, and specificity was 0.95. The authors concluded that models could identify pre-mortem characteristics to better specify autopsy defined sudden arrhythmic deaths, among presumed sudden cardiac arrests. The authors suggest that the World Health Organization definition can be improved by restricting witnessed sudden cardiac deaths to ventricular tachycardia fibrillation or non-pulseless electrical activity rhythms in unwitnessed cases to less than one hour since last normal, at a cost of sensitivity. In our next paper, Rafael Jaimes III and associates performed optical mapping of trends, membrane, voltage and pacing studies on isolated Langendorff-perfused rat hearts to assess the cardiac electrophysiology after mono-2-ethylhexyl phthalate, a phthalate with documented exposure in intensive care patients. The authors found that a 30-minute exposure to mono-2-ethylhexyl phthalate increased the atrioventricular node effector in period 147 milliseconds compared to 170 milliseconds in controls and increased the ventricular effective refractory periods of 117 milliseconds compared to 77.5 milliseconds in controls. Optical mapping revealed prolonged action potential duration at slower pacing cycle lengths. Mono-2-ethylhexyl phthalate exposure also slowed epicardial conduction velocity, 25 centimeters per second compared to 60 centimeters per second in controls. The authors concluded that acute mono-2-ethylhexyl phthalate exposure, at clinically relevant doses, has a significant effect on cardiac electrophysiology in the intact heart. Heightened clinical exposure to plasticized medical products may have cardiac safety implications and lead to cardiac arrhythmias. In our next paper, Stephan Willems and associates report the use of a novel, non-contact imaging and mapping system that uses ultrasound to reconstruct atrial chamber anatomy and measure timing and density of dipolar, ionic activation or charge density across the myocardium to guide ablation of atrial arrhythmias. They conducted a prospective non-randomized study, the UNCOVER AF trial which was conducted at 13 centers across Europe and Canada. In 127 patients with persistent atrial fibrillation who underwent mapping and catheter ablation, acute procedural efficacy of 98% was seen. At 12 months, the single procedure freedom from atrial fibrillation, on or off antiarrhythmic drugs, was 72.5%, with 23% undergoing retreatments following one or two procedures. Freedom from atrial fibrillation was 93.2%. The primary safety outcome was 98% was no device related major adverse events reported. In our next paper, Anne-Floor Quast, Niek Beurskens, and associates describe a novel, completely extracardiac pacing system, with a lead in the anterior mediastinum, outside the pericardium and circulatory system. A total of 166 or 95% out of 174 patients had a viable lead access path through the fourth, fifth, or sixth intercostal space. Access to the targeted implant location using delivery tool was successful in all five cadavers and three humans, without use of fluoroscopy, with an average lead delivery time of 121 seconds. No damage to the lung, pericardium, heart or internal thoracic vessels occurred. Pacing performance in six human subjects showed a voltage threshold of 4.7 volts in a threshold pulse width of 1.8 milliseconds. In our next paper, Yasuhiro Shirai and associates compare the ability to identify ventricular tachycardia isthmuses in ischemic and nonischemic cardiomyopathies. Of 445 patients, 228 with ischemic cardiomyopathy and 217 with nonischemic cardiomyopathy, undergoing VT ablation. Detailed entrainment mapping of at least one tolerated VT was performed in 111 patients, 71 with ischemic cardiomyopathy and 40 with nonischemic cardiomyopathy. Of 89 nonischemic cardiomyopathy VTs, the isthmus could be identified by endocardial entrainment in 55 or 62%, compared to only eight out of 47 or 17% nonischemic cardiomyopathy VTs, p less than 0.01. With combined endocardial and epicardial mapping, the isthmus could be identified in 56 or 63% ischemic cardiomyopathy VTs, and 12 or 26% of nonischemic cardiomyopathy VTs, p less than 0.01, while a similar proportion of patients any critical component, defined as entrance, isthmus or exit, could be identified in 85% of ischemic cardiomyopathy VTs and 79% of nonischemic cardiomyopathy VTs, p equals 0.3. Complete success, no inducible VT at the end of the procedure was 82% versus 65%, p equals 0.04 and a one-year single procedure VT survival, 82% versus 55%, p less than 0.01. Both higher in patients with ischemic cardiomyopathy. The authors concluded that among mappable ischemic cardiomyopathy VTs, critical circuit components can be usually identified on the endocardium. In contrast, among mappable nonischemic cardiomyopathy VTs, although some critical components can be typically identified with the addition of epicardial mapping, the isthmus is less commonly identified, possibly due to midmyocardial location. In our next paper, Miki Yokokawa and associates targeted documented but non-inducible clinical VTs, based on stored, implantable cardioverter defibrillator electrograms. Radio frequency ablation was performed in a consecutive group of 66 postinfarction VTs, in whom clinical VTs were non-inducible during an ablation procedure. In the first 33 patients, the control group, only inducible VTs were targeted. In the second 33 patients, non-inducible clinical VTs were targeted by pace mapping based on stored ICD-electrograms, the ICD electrogram guided ablation group. VT recurred in five patients or 15% in the ICD-electrogram guided approach, and in 13% or 39% in the control group. Freedom from recurrent VT was higher, p equals 0.04, in the ICD-electrogram-guided group, but there was no difference in ventricular fibrillation or total mortality between groups. In our next paper, Albert Feeny and associates examined whether machine learning could predict cardiac resynchronization therapy or CRT response. A training cohort was created from all Johns Hopkins patients and an equal number of randomly sampled Cleveland Clinic patients. All remaining patients comprise the testing cohort. Response was defined as greater than or equal to 10% increase in left ventricular ejection fraction. Machine learning models were developed to predict CRT response using different combinations of classification algorithms in clinical variable sets on the training cohort. 925 patients were included. On the training cohort, the best machine learning model was a naive Bayes classifier using nine variables, QRS morphology, QRS duration, New York Heart Association classification, left ventricular ejection fraction and end-diastolic diameter, sex, ischemic cardiomyopathy, atrial fibrillation, and epicardial LV lead. On the testing cohort, machine learning demonstrated better response prediction than guidelines, area under the curves 0.7 versus 0.65, p equals 0.012, and greater discrimination of event-free survival, concordance index 0.61 versus 0.56, p less than 0.001. The fourth quartile of machine learning model had greatest risk of reaching the composite endpoint, while the first quartile had the least, hazard ratio of 0.34, p less than 0.001. The authors found that machine learning with nine variables incrementally improved prediction of CRT response and survival beyond guidelines, but its performance with not improved by incorporating more variables. In our next paper, Bernhard Kaess, Charlotte Andersson and associates examine the familial clustering of cardiac conduction defects in the Framingham heart study, using multivariable-adjusted logistic regression models to investigate the association of parental AV block, complete bundle branch block, or a pacemaker insertion with occurrence of cardiac conduction abnormalities on offspring. Individuals with at least one effected parent with a conduction defect had at 1.65-fold odds for manifesting AV block, and 1.62-fold odds for developing complete bundle branch block. If at least one parent had any electrocardiographic conduction defect or pacemaker insertion, the offspring had 1.62-fold odds for experiencing any of these conditions. The Danish and nationwide administrative registries of nearly 3 million individuals and about five thousand incident pacemaker implantations, individuals with at least one first degree relative with a history of pacemaker insertion, had a multivariable-adjusted 1.68-fold incident rate ratio of undergoing pacemaker insertion. If the affected relative was less than or equal to 45 years of age, the incident rate ratio was markedly increased to 51.0. In our final paper, a review article, Venkat Nagarajan, Siew Ho Yen, and Sabine Ernst provide a detailed discussion of anatomic landmarks and considerations that will aid in his bundle pacing lead implantation. That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.

Circulation: Arrhythmia and Electrophysiology July 2018 Issue

Dr Paul Wong:                   Welcome to the monthly podcast on the beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wong, Editor-in Chief with some of the key highlights from this month's issue.                                                  This month's issue is dedicated to a new exciting topic, His bundle pacing. His bundle pacing is designed to achieve a more physiological human dynamic response than right ventricular pacing alone, which may be needed in patients with AV conduction abnormalities. In our first paper, Marek Jastrzebski and associates examined whether program stimulation may be used to distinguish nonselective His bundle capture from right ventricular myocardial capture. Premature beats were introduced at 10 millisecond steps during intrinsic rhythm, and also after a drive train of 600 milli seconds. The longest coupling interval that resulted in an abrupt change in the QRS morphology was considered equal to the effective refractory period of the His bundle or right ventricular myocardium.                                                  Program His bundle pacing was performed from 50 different sites in 32 patients. In 34 out of 36 cases of nonselective His bundle pacing, the right ventricular myocardial effective refractory period was shorter than the His bundle effective a refractory period. 271 milliseconds versus 353 milliseconds, P less than 0.0001. Program His bundle pacing using a drive train typically resulted in an abrupt change of the QRS morphology. From nonselective His bundle to right ventricular myocardial QRS 34 out of 36 cases, or to selective His bundle QRS in two out of 36 cases. Program His bundle pacing deliver during native conduction resulted in obtaining selective His bundle QRS in 20 out of 34 patients, and right ventricular myocardial QRS in 14 out of 34 of the nonselective His bundle cases.                                                  In right ventricular myocardial only pacing cases, so-called false nonselective His bundle pacing, and equals 14. Such responses were not observed. The QRS morphology remained stable. Therefore His bundle pacing correctly diagnosed, using programs stimulation, all nonselective His bundle cases in all right ventricular myocardial pacing cases.                                                  In our next paper Aditya Saini and associates sought to determine whether the device electric cam can be used to differentiate between selective, nonselective His bundle pacing, and right ventricular septal capture. In 148 consecutive patients, His bundle pacing was performed. The near field ventricular electrogram morphology, the near field ventricular electrogram time to peak and the far field ventricular electrogram QRS duration were recorded while pacing the His bundle was simultaneous 12 lead ECG rhythm strips. The mean baseline QRS duration was 108 milliseconds, with QRS duration greater than 120 milliseconds in 57 or 39% of patients, including 27 with right bundle branch block, 18 with left bundle branch block, and 12 with an IVCD.                                                  Selective His bundle pacing was noted in 54 or 36% of patients. A positive near field ventricular electrogram time to peak, and a near field ventricular electrogram time to peak of greater than 40 milliseconds were highly sensitive, 94% and 93% respectively, and specific 90% and 94% for selective His bundle pacing, irrespective of baseline QRS duration. All three parameters including positive near field ventricular electrogram time to peak, the near field ventricular electrogram time to peak greater than 40 milliseconds, and far field ventricular electrogram QRS duration less than 120 milliseconds had high predictive negative predictive value, 97%, 95%, and 92%. Therefore, a novel device-based algorithm for a selective His bundle pacing was proposed.                                                  Electrogram transitions correlated with ECG transitions during threshold testing, and can accurately predict and differentiate between selective His bundle pacing, nonselective His bundle pacing, and right ventricular septal pacing with a cumulative positive predictive value of 91% and 100% in patients with a baseline QRS duration of less than 120 milliseconds.                                                  In the next paper, Pugazhendhi Vijayaraman and associates examined whether Cardiac Resynchronization Therapy could be optimized by sequential His bundle pacing followed by left ventricular pacing, which the authors called His optimize CRT or hot CRT. Hot CRT was successfully achieved in 25 of 27 patients. The QRS duration and baseline was 183 milliseconds, and significantly narrowed to 162 milliseconds with biventricular pacing, to 151 milli seconds during His bundle pacing, and further to 120 milliseconds during hot CRT pacing, P less than 0.0001. During a mean follow-up of 14 months, left ventricular ejection fraction improved from 24 to 38%, P less than 0.0001, and New York Heart Association Functional Class changed from 3.3 to 2.04. 21 out of the 25 patients, or 84% were clinical responders, while 23 of 25, 92% showed echocardiographic response.                                                  In our next paper, Parikshit Sharma and associates compared permanent His bundle pacing using three-dimensional electro anatomic mapping in low fluoroscopy in 10 patients, and compared the outcomes with conventional fluoroscopy guided His bundle pacing implants in 20 patients. His bundle pacing was successful in nine out of 10 patients using electro anatomic mapping, and 100% successful in the conventional patients. The mean His bundled fluoroscopy time was lower in electro anatomic mapping group, 0.2 minutes compared to eight minutes in the conventional group, P equals 0.002. The His bundle capture threshold was lower in the electro anatomic mapping group, 0.7 at one millisecond compared to the conventional group, 1.15 at one millisecond, P equals 0.04. There were no procedure related complications or lead dislodgements in either group.                                                  In our next paper, Michael Orlov and associates describe a new technique in which pacing leads for permanent His bundle pacing were connected to electro anatomical mapping in 28 patients. The selective and nonselective His bundle capture sites were tagged. The His bundle cloud was 360 millimeters squared, and the lead was successfully deployed in 25 patients in the threshold of the His bundle pacing, and implant was 1.5 volts at 1.5 milli seconds.                                                  In our final paper, Haran Burri and associates provide practical recommendations for programming pacemakers with His bundle pacing in order to deliver optimal therapy and ensure patient's safety. The authors discuss the important role of electrocardiographic analysis of His bundle capture. They also advise that ventricular capture management should be programmed inactive because of the absence of an evoked potential. The authors discuss the option of placing the His bundle electrode in the left and trigger a report of a cardiac resynchronization therapy pacemaker.                                                  The readers will find this overview of programming His bundle pacing very informative. In this issue, we also have a very special year-end review, which highlights many of the top discoveries in our field. You will not want to miss it.                                                  Okay. That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time.                                                  This program is copyright American Heart Association, 2019.

Dr Paul Wong:                   Welcome to the monthly podcast on the beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wong, Editor-in Chief with some of the key highlights from this month's issue.                                                 This month's issue is dedicated to a new exciting topic, His bundle pacing. His bundle pacing is designed to achieve a more physiological human dynamic response than right ventricular pacing alone, which may be needed in patients with AV conduction abnormalities. In our first paper, Marek Jastrzebski and associates examined whether program stimulation may be used to distinguish nonselective His bundle capture from right ventricular myocardial capture. Premature beats were introduced at 10 millisecond steps during intrinsic rhythm, and also after a drive train of 600 milli seconds. The longest coupling interval that resulted in an abrupt change in the QRS morphology was considered equal to the effective refractory period of the His bundle or right ventricular myocardium.                                                 Program His bundle pacing was performed from 50 different sites in 32 patients. In 34 out of 36 cases of nonselective His bundle pacing, the right ventricular myocardial effective refractory period was shorter than the His bundle effective a refractory period. 271 milliseconds versus 353 milliseconds, P less than 0.0001. Program His bundle pacing using a drive train typically resulted in an abrupt change of the QRS morphology. From nonselective His bundle to right ventricular myocardial QRS 34 out of 36 cases, or to selective His bundle QRS in two out of 36 cases. Program His bundle pacing deliver during native conduction resulted in obtaining selective His bundle QRS in 20 out of 34 patients, and right ventricular myocardial QRS in 14 out of 34 of the nonselective His bundle cases.                                                 In right ventricular myocardial only pacing cases, so-called false nonselective His bundle pacing, and equals 14. Such responses were not observed. The QRS morphology remained stable. Therefore His bundle pacing correctly diagnosed, using programs stimulation, all nonselective His bundle cases in all right ventricular myocardial pacing cases.                                                 In our next paper Aditya Saini and associates sought to determine whether the device electric cam can be used to differentiate between selective, nonselective His bundle pacing, and right ventricular septal capture. In 148 consecutive patients, His bundle pacing was performed. The near field ventricular electrogram morphology, the near field ventricular electrogram time to peak and the far field ventricular electrogram QRS duration were recorded while pacing the His bundle was simultaneous 12 lead ECG rhythm strips. The mean baseline QRS duration was 108 milliseconds, with QRS duration greater than 120 milliseconds in 57 or 39% of patients, including 27 with right bundle branch block, 18 with left bundle branch block, and 12 with an IVCD.                                                 Selective His bundle pacing was noted in 54 or 36% of patients. A positive near field ventricular electrogram time to peak, and a near field ventricular electrogram time to peak of greater than 40 milliseconds were highly sensitive, 94% and 93% respectively, and specific 90% and 94% for selective His bundle pacing, irrespective of baseline QRS duration. All three parameters including positive near field ventricular electrogram time to peak, the near field ventricular electrogram time to peak greater than 40 milliseconds, and far field ventricular electrogram QRS duration less than 120 milliseconds had high predictive negative predictive value, 97%, 95%, and 92%. Therefore, a novel device-based algorithm for a selective His bundle pacing was proposed.                                                 Electrogram transitions correlated with ECG transitions during threshold testing, and can accurately predict and differentiate between selective His bundle pacing, nonselective His bundle pacing, and right ventricular septal pacing with a cumulative positive predictive value of 91% and 100% in patients with a baseline QRS duration of less than 120 milliseconds.                                                 In the next paper, Pugazhendhi Vijayaraman and associates examined whether Cardiac Resynchronization Therapy could be optimized by sequential His bundle pacing followed by left ventricular pacing, which the authors called His optimize CRT or hot CRT. Hot CRT was successfully achieved in 25 of 27 patients. The QRS duration and baseline was 183 milliseconds, and significantly narrowed to 162 milliseconds with biventricular pacing, to 151 milli seconds during His bundle pacing, and further to 120 milliseconds during hot CRT pacing, P less than 0.0001. During a mean follow-up of 14 months, left ventricular ejection fraction improved from 24 to 38%, P less than 0.0001, and New York Heart Association Functional Class changed from 3.3 to 2.04. 21 out of the 25 patients, or 84% were clinical responders, while 23 of 25, 92% showed echocardiographic response.                                                 In our next paper, Parikshit Sharma and associates compared permanent His bundle pacing using three-dimensional electro anatomic mapping in low fluoroscopy in 10 patients, and compared the outcomes with conventional fluoroscopy guided His bundle pacing implants in 20 patients. His bundle pacing was successful in nine out of 10 patients using electro anatomic mapping, and 100% successful in the conventional patients. The mean His bundled fluoroscopy time was lower in electro anatomic mapping group, 0.2 minutes compared to eight minutes in the conventional group, P equals 0.002. The His bundle capture threshold was lower in the electro anatomic mapping group, 0.7 at one millisecond compared to the conventional group, 1.15 at one millisecond, P equals 0.04. There were no procedure related complications or lead dislodgements in either group.                                                 In our next paper, Michael Orlov and associates describe a new technique in which pacing leads for permanent His bundle pacing were connected to electro anatomical mapping in 28 patients. The selective and nonselective His bundle capture sites were tagged. The His bundle cloud was 360 millimeters squared, and the lead was successfully deployed in 25 patients in the threshold of the His bundle pacing, and implant was 1.5 volts at 1.5 milli seconds.                                                 In our final paper, Haran Burri and associates provide practical recommendations for programming pacemakers with His bundle pacing in order to deliver optimal therapy and ensure patient's safety. The authors discuss the important role of electrocardiographic analysis of His bundle capture. They also advise that ventricular capture management should be programmed inactive because of the absence of an evoked potential. The authors discuss the option of placing the His bundle electrode in the left and trigger a report of a cardiac resynchronization therapy pacemaker.                                                 The readers will find this overview of programming His bundle pacing very informative. In this issue, we also have a very special year-end review, which highlights many of the top discoveries in our field. You will not want to miss it.                                                 Okay. That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time.                                                 This program is copyright American Heart Association, 2019.

Circulation: Arrhythmia and Electrophysiology February 2019 Issue

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue.                                                  In our first article, Daniel Alyesh, Konstantinos Siontis and associates described myocardial calcifications in patients with ischemic cardiomyopathy undergoing ventricular tachycardia ablation in comparison to a control group of patients without ventricular tachycardia. They found that in 56 consecutive post-infarction patients, myocardial calcifications were identified in 39 or 70% of post-infarction ventricular tachycardia patients compared to 6 or 11% of patients without ventricular tachycardia. A calcification volume of 0.538 centimeters cube distinguished patients with calcification-associated ventricular tachycardia from patients without calcification-associated ventricular tachycardias; area under the curve, 0.87; sensitivity, 0.87; specificity, 0.88. A non-confluent calcification pattern was associated with ventricular tachycardia target sites independent of calcification volume, P equals 0.01. Myocardial calcifications corresponding to areas of electrical non-excitability forming a border for re-entry were found in 33% of all ventricular tachycardias for which target sites were identified, and in 62% of patients with myocardial calcifications.                                                  In our next paper, Mia Fangel and associates examined whether glycemic status evaluated by hemoglobin A1c has an effect on the risk of thromboembolism among patients with atrial fibrillation and Type 2 diabetes. They used a cohort study from 5,386 patients with incident non-valvular atrial fibrillation and Type 2 diabetes in Danish registries. Compared with patients with hemoglobin A1c of less than or equal to 48 millimole per mole, they observed a higher risk of thromboembolism among patients with hemoglobin A1c 49 to 58 millimoles per mole with a hazard ratio of 1.49 and a hemoglobin A1c greater than 58 millimole per mole with a hazard ratio of 1.59 after adjusting for confounding factors. Surprisingly, in patients with diabetes duration of 10 years or more, higher hemoglobin A1c levels were not associated with a higher risk of thromboembolism.                                                  In our next paper, Niek Beurskens and associates compared tricuspid valve dysfunction in leadless pacemaker therapy to dual chamber transvenous pacing systems. They studied 53 patients receiving a leadless pacemaker, including 28 with a Nanostim and 25 with a Micra device. Of these 53 patients, 23 or 43% had tricuspid regurgitation that was graded as being more severe at 12 months. Compared with an apical position, a right ventricular septal position of the leadless pacemaker was associated with increased tricuspid valve incompetence, odds ratio, 5.20; P equals 0.03. An increase in mitral valve regurgitation was observed in 38% of patients. Leadless pacemaker implantation resulted in a reduction of right ventricular function. Leadless pacemaker implantation was further associated with a reduction in left ventricular ejection fraction and elevated LV TI index. The changes in tricuspid regurgitation in leadless pacing group was similar to the changes in dual-chamber transvenous pacemaker group, 43% versus 38% respectively; P equals 0.39.                                                  In our next paper, Jurgen Duchenne and associates examined whether regional left ventricular glucose metabolism correlates with regional work in an animal model with reversible dyssynchrony due to pacing. In 12 sheep, after 8 weeks of right atrial and right ventricular free wall pacing, there is evidence of left ventricular dilatation and thinning of the septum and thickening of the lateral wall. The authors employed motion compensation and anatomical correction in order to provide reliable regional estimates of myocardial glucose metabolism. They found that in homogenous regional distribution of myocardial workload due to left bundle branch block triggers adaptive remodeling of the left ventricle, leading to a more homogenous load distribution per volume unit myocardium. In reverse, cardiac resynchronization therapy leads acutely to an inhomogeneous distribution of workload, which homogenizes over time due to reverse remodeling. The authors concluded that redistribution of regional loading appears as a mode of action of cardiac resynchronization therapy so that myocardial mechanics should be the main treatment target of cardiac resynchronization therapy.                                                  In our next paper, Jihye Jang and associates examined the association between local conduction velocity and late gadolinium enhancement and myocardial thickness in a swine model of healed left ventricular infarction. They studied six swine with healed myocardial infarction and two controls. The authors found a significantly slower conduction was found in late gadolinium enhancement regions, 0.33 versus 0.54 meters per second, P less than 0.001, and regions of wall thinning, 0.38 versus 0.55 meters per second, P also less than 0.001; areas with greater late gadolinium enhancement heterogeneity and wall thickness gradient exhibited slower conduction velocity.                                                  In our next paper, Xi Zhang and Xiaohui Kuang and associates studied whether restricting contact force to less than 20 grams reduces the risk of esophageal injury in patients with atrial fibrillation undergoing circumferential pulmonary vein isolation. In a prospective, single-center, randomized study, 89 consecutive patients, mean age 57.2 years, 57% men, with atrial fibrillation, 68.5% paroxysmal and 31.5% persistent were randomized to restrictive contact force group or non-contact force group. The primary end point was a rate of esophageal injury post ablation. The same power setting, similar ablation time, and average measured catheter tip temperature during posterior wall ablation just opposite to the esophagus were present in both groups, there were no cases of esophageal injury in the restricted contact force group versus 9 or 20% of cases of esophageal injury post ablation in the non-contact force group. There are similar rates of freedom from atrial tachyarrhythmias at a mean of 31.3 months follow-up, 68.2% versus 64.4%.                                                  In our next paper, J. Martijn Bos and associates examined whether sodium channel blockers like mexiletine may have a potential role in LQT1 and LQT2, two forms of potassium channel mediated long QT syndrome. They retrospectively studied 12 patients, 5 females, median age at diagnosis 14.1 years with genetically established long QT2 in 10 or a combination of LQT1/LQT2 in 1 or LQT2/LQT3 in 1, who all received mexiletine. Prior to diagnosis, six patients were symptomatic and prior to initiation of mexiletine, four patients experienced one breakthrough cardiac event on beta blocker therapy. Median age at first mexiletine dose was 24.3 years. After mexiletine, the median QTc decreased by 65 milliseconds from 547 milliseconds pre-mexiletine to 470 milliseconds post-mexiletine, P equals 0.0005 for all patients. In eight patients or 67%, the QTc decreased by 40 milliseconds with a mean decrease in QTc of 91 milliseconds, P less than 0.008. For the 11 patients maintained on mexiletine therapy, there have been no breakthrough cardiac events during follow-up.                                                  In our final paper, Andrea Mazzanti and associates assessed whether low dose quinidine in Brugada Syndrome patients reduces the occurrence of life-threatening arrhythmic events in this population. They compared the clinical course of 53 Brugada Syndrome patients treated with quinidine to that of 441 untreated controls, matched by sex, age, symptoms, and duration of observation. The 53 Brugada Syndrome patients, 89% males, median age 39.8 years, received quinidine at 439 milligrams per day for 5.0 years. Therapy was stopped in three cases or 6% for side effects. Quinidine reduced by 26% the risk of experiencing life-threatening arrhythmic events in cases versus controls; hazard ratio, 0.74; P equals 0.62. In 27 of 123 Brugada Syndrome patients symptomatic for life-threatening arrhythmic events who were treated for 7.0 years, the annual rate of life-threatening arrhythmic events decreased from 14.7% while off-quinidine to 3.9% while on-quinidine, P equals 0.03. The authors noted that recurrent life-threatening arrhythmic events were recorded in 4 or 15% of cardiac arrest survivors while on-quinidine, underscoring the importance of implantable defibrillator therapy.                                                  That's it for this month. We hope that you will find the Journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue.                                                 In our first article, Daniel Alyesh, Konstantinos Siontis and associates described myocardial calcifications in patients with ischemic cardiomyopathy undergoing ventricular tachycardia ablation in comparison to a control group of patients without ventricular tachycardia. They found that in 56 consecutive post-infarction patients, myocardial calcifications were identified in 39 or 70% of post-infarction ventricular tachycardia patients compared to 6 or 11% of patients without ventricular tachycardia. A calcification volume of 0.538 centimeters cube distinguished patients with calcification-associated ventricular tachycardia from patients without calcification-associated ventricular tachycardias; area under the curve, 0.87; sensitivity, 0.87; specificity, 0.88. A non-confluent calcification pattern was associated with ventricular tachycardia target sites independent of calcification volume, P equals 0.01. Myocardial calcifications corresponding to areas of electrical non-excitability forming a border for re-entry were found in 33% of all ventricular tachycardias for which target sites were identified, and in 62% of patients with myocardial calcifications.                                                 In our next paper, Mia Fangel and associates examined whether glycemic status evaluated by hemoglobin A1c has an effect on the risk of thromboembolism among patients with atrial fibrillation and Type 2 diabetes. They used a cohort study from 5,386 patients with incident non-valvular atrial fibrillation and Type 2 diabetes in Danish registries. Compared with patients with hemoglobin A1c of less than or equal to 48 millimole per mole, they observed a higher risk of thromboembolism among patients with hemoglobin A1c 49 to 58 millimoles per mole with a hazard ratio of 1.49 and a hemoglobin A1c greater than 58 millimole per mole with a hazard ratio of 1.59 after adjusting for confounding factors. Surprisingly, in patients with diabetes duration of 10 years or more, higher hemoglobin A1c levels were not associated with a higher risk of thromboembolism.                                                 In our next paper, Niek Beurskens and associates compared tricuspid valve dysfunction in leadless pacemaker therapy to dual chamber transvenous pacing systems. They studied 53 patients receiving a leadless pacemaker, including 28 with a Nanostim and 25 with a Micra device. Of these 53 patients, 23 or 43% had tricuspid regurgitation that was graded as being more severe at 12 months. Compared with an apical position, a right ventricular septal position of the leadless pacemaker was associated with increased tricuspid valve incompetence, odds ratio, 5.20; P equals 0.03. An increase in mitral valve regurgitation was observed in 38% of patients. Leadless pacemaker implantation resulted in a reduction of right ventricular function. Leadless pacemaker implantation was further associated with a reduction in left ventricular ejection fraction and elevated LV TI index. The changes in tricuspid regurgitation in leadless pacing group was similar to the changes in dual-chamber transvenous pacemaker group, 43% versus 38% respectively; P equals 0.39.                                                 In our next paper, Jurgen Duchenne and associates examined whether regional left ventricular glucose metabolism correlates with regional work in an animal model with reversible dyssynchrony due to pacing. In 12 sheep, after 8 weeks of right atrial and right ventricular free wall pacing, there is evidence of left ventricular dilatation and thinning of the septum and thickening of the lateral wall. The authors employed motion compensation and anatomical correction in order to provide reliable regional estimates of myocardial glucose metabolism. They found that in homogenous regional distribution of myocardial workload due to left bundle branch block triggers adaptive remodeling of the left ventricle, leading to a more homogenous load distribution per volume unit myocardium. In reverse, cardiac resynchronization therapy leads acutely to an inhomogeneous distribution of workload, which homogenizes over time due to reverse remodeling. The authors concluded that redistribution of regional loading appears as a mode of action of cardiac resynchronization therapy so that myocardial mechanics should be the main treatment target of cardiac resynchronization therapy.                                                 In our next paper, Jihye Jang and associates examined the association between local conduction velocity and late gadolinium enhancement and myocardial thickness in a swine model of healed left ventricular infarction. They studied six swine with healed myocardial infarction and two controls. The authors found a significantly slower conduction was found in late gadolinium enhancement regions, 0.33 versus 0.54 meters per second, P less than 0.001, and regions of wall thinning, 0.38 versus 0.55 meters per second, P also less than 0.001; areas with greater late gadolinium enhancement heterogeneity and wall thickness gradient exhibited slower conduction velocity.                                                 In our next paper, Xi Zhang and Xiaohui Kuang and associates studied whether restricting contact force to less than 20 grams reduces the risk of esophageal injury in patients with atrial fibrillation undergoing circumferential pulmonary vein isolation. In a prospective, single-center, randomized study, 89 consecutive patients, mean age 57.2 years, 57% men, with atrial fibrillation, 68.5% paroxysmal and 31.5% persistent were randomized to restrictive contact force group or non-contact force group. The primary end point was a rate of esophageal injury post ablation. The same power setting, similar ablation time, and average measured catheter tip temperature during posterior wall ablation just opposite to the esophagus were present in both groups, there were no cases of esophageal injury in the restricted contact force group versus 9 or 20% of cases of esophageal injury post ablation in the non-contact force group. There are similar rates of freedom from atrial tachyarrhythmias at a mean of 31.3 months follow-up, 68.2% versus 64.4%.                                                 In our next paper, J. Martijn Bos and associates examined whether sodium channel blockers like mexiletine may have a potential role in LQT1 and LQT2, two forms of potassium channel mediated long QT syndrome. They retrospectively studied 12 patients, 5 females, median age at diagnosis 14.1 years with genetically established long QT2 in 10 or a combination of LQT1/LQT2 in 1 or LQT2/LQT3 in 1, who all received mexiletine. Prior to diagnosis, six patients were symptomatic and prior to initiation of mexiletine, four patients experienced one breakthrough cardiac event on beta blocker therapy. Median age at first mexiletine dose was 24.3 years. After mexiletine, the median QTc decreased by 65 milliseconds from 547 milliseconds pre-mexiletine to 470 milliseconds post-mexiletine, P equals 0.0005 for all patients. In eight patients or 67%, the QTc decreased by 40 milliseconds with a mean decrease in QTc of 91 milliseconds, P less than 0.008. For the 11 patients maintained on mexiletine therapy, there have been no breakthrough cardiac events during follow-up.                                                 In our final paper, Andrea Mazzanti and associates assessed whether low dose quinidine in Brugada Syndrome patients reduces the occurrence of life-threatening arrhythmic events in this population. They compared the clinical course of 53 Brugada Syndrome patients treated with quinidine to that of 441 untreated controls, matched by sex, age, symptoms, and duration of observation. The 53 Brugada Syndrome patients, 89% males, median age 39.8 years, received quinidine at 439 milligrams per day for 5.0 years. Therapy was stopped in three cases or 6% for side effects. Quinidine reduced by 26% the risk of experiencing life-threatening arrhythmic events in cases versus controls; hazard ratio, 0.74; P equals 0.62. In 27 of 123 Brugada Syndrome patients symptomatic for life-threatening arrhythmic events who were treated for 7.0 years, the annual rate of life-threatening arrhythmic events decreased from 14.7% while off-quinidine to 3.9% while on-quinidine, P equals 0.03. The authors noted that recurrent life-threatening arrhythmic events were recorded in 4 or 15% of cardiac arrest survivors while on-quinidine, underscoring the importance of implantable defibrillator therapy.                                                 That's it for this month. We hope that you will find the Journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.

Circulation: Arrhythmia and Electrophysiology May 2019 Issue

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue.                                                  In our first paper, Mark McCauley, Flavia Vitale and associates report that carbon nanotube fibers may improve impaired myocardial conduction. In three sheep, radiofrequency ablation was used to create epicardial conduction delay. In addition, in a rodent model, carbon nanotube fibers were sewn across the atrial ventricular junction. They demonstrated acute ventricular preexcitation, but in chronic studies at four weeks, atrial pacing was required for resumption of AV conduction. Carbon nanotube fibers are conductive, biocompatible with no gross or histopathological evidence of toxicity.                                                  In our next paper, Koichiro Ejima and associates compared outcomes of circumferential pulmonary vein isolation for atrial fibrillation ablation randomized to contact force monitoring or unipolar signal modification in 136 patients with paroxysmal atrial fibrillation. In the unipolar signal modification-guided group, each radiofrequency application was delivered until the development of completely positive unipolar electrograms. In the contact force monitoring-guided group, a contact force of 20 grams, ranged 10 to 30 grams, and a minimum force time integral of 400 gram seconds were the targets for each radiofrequency application. The freedom from atrial tachyarrhythmia recurrence at 12 months was 85% in the unipolar signal modification-guided group and 70% in the contact force monitoring-guided group, P equals 0.031. The radiofrequency time for pulmonary vein isolation was shorter in the unipolar signal modification-guided group than contact force monitoring-guided group, but was not statistically significant, P equals 0.077. The incidence of time-dependent in ATP-provoked early electrical reconnections between the left atrium and pulmonary veins, procedural time, fluoroscopic time, and average force-time integral did not significantly differ between the two groups.                                                  In our next paper, Vishal Luther and associates tested whether ripple mapping is superior to conventional annotation-based local activation time mapping for atrial tachycardia diagnosis. Patients with atrial tachycardia were randomized, either ripple mapping or local activation time mapping. The primary endpoint was atrial tachycardia termination with delivery of the planned ablation lesion set. The inability to terminate atrial tachycardia with the first lesion set, the use of more than one entrainment maneuver, or the need to cross over to the other mapping arm were defined as failure to achieve the primary endpoint. The primary endpoint occurred in 38 of 42 patients or 90% in the ripple mapping group, and 29 of 41 patients, 71%, in the local activation time mapping group, P equals 0.45. The primary endpoint was achieved without any entrainment in 31 out of 42 patients or 74% with ripple mapping, and 18 out of 41 patients or 44% with local activation time mapping, P equals 0.01. Of those patients who failed to achieve the primary endpoint, atrial tachycardia termination was achieved in 9 out of 12 patients or 75% in the local activation time mapping group following crossover to ripple mapping with entrainment, but zero out of four patients, 0%, in ripple mapping group crossing over to local activation time mapping with entrainment, P equals 0.04.                                                  In our next paper, Franziska Fochler and associates examined whether anatomical targeting of late gadolinium enhancement MRI-detected gaps and superficial atrial scar is feasible and effective to treat recurrent atrial arrhythmias post-atrial fibrillation ablation. The authors studied 102 patients who underwent initial atrial fibrillation ablation and repeat ablation for recurrent atrial arrhythmias within one-year. 46 patients or 45% with atrial fibrillation recurrence were assigned to group one and underwent fibrosis homogenization as the second procedure. 56 patients or 55% with atrial tachycardia recurrence were assigned to group two and underwent late gadolinium enhancement MRI detected scar-based dechanneling. Both groups underwent re-isolation of pulmonary veins, if necessary.                                                  In the first 25 patients from group two, the atrial tachycardia was electroanatomically mapped and a critical isthmus was defined. It was found that those isthmi were located in the regions with non-transmural scarring detected by late gadolinium enhancement MRI. In the last 31 patients from group 2, an empirical late gadolinium enhancement MRI-based dechanneling was performed solely based on late gadolinium enhancement MRI results. During one-year follow-up after the second ablation, 67% of patients group one and 64% of patients group two were free from occurrence. In group two, 64% in the electroanatomic-guided and 65% in the late gadolinium enhancement MRI dechanneling group were free from recurrence. The authors concluded that homogenization of existing scar is appropriate treatment for recurrent atrial fibrillation while dechanneling of existing isthmi seem the appropriate approach for patients recurring with atrial tachycardia.                                                  In our next paper, George Leef, Fatemah Shenasa, Neal Bhatia and associates examined whether wave front field mapping of persistent atrial fibrillation can reveal an underlying network of a small number of spatially anchored rotational and focal sites. They examined unipolar atrial fibrillation electrograms from 64-pole baskets in 54 patients from an international registry in whom persistent atrial fibrillation was terminated by targeted ablation. They identified 4.0, plus or minus 2.1, spatially anchored rotational focal sites in atrial fibrillation that were a single in seven patients type I or paired chiral-antichiral type II rotational drivers that controlled most of the atrial area. Ablation of one or two large drivers terminated all cases of these types of atrial fibrillation. Third, interaction of three to five drivers type III, n equals 42, was present with changing areas of control. Targeted ablation at driver center terminate atrial fibrillation and required more ablation in type III versus I, P equals 0.02 in the left atrium.                                                  In our next paper, Ryan Azarrafiy and associates examined survival after superior vena cava tear using an endovascular balloon. Data were prospectively collected from both a United States Food and Drug Administration-maintained database and physician reports of adverse events as they occurred. Confirmed superior vena cava tears were analyzed for patient demographics, case details, and index hospitalization mortality. Over a period of two years, 116 confirmed superior vena cava events were identified, of which 44% involve proper balloon use and 50% involve no use or improper use. When an endovascular balloon was properly used, 45 of 51 patients, or 88.2%, survived in comparison to 37 out of 65, or 56.9%, when a balloon was not used or improperly used; P equals 0.0002. Furthermore, multivariate regression modeling found that proper balloon deployment was an independent, negative predictor of in-hospital mortality for patients who experienced a superior vena cava laceration, odds ratio of 0.13; P value less than 0.001.                                                  In our next paper, Bharatraj Banavalikar and associates examined 28 patients with focal atrial tachycardia, mean age 34.6 years, females 60.7%, were included in the study. Most common symptoms were palpitations, 85.7%, followed by shortness of breath, 25%. The mean atrial tachycardia rate was 170 beats per minute and mean left ventricular ejection fraction was 54.7%. Overall, 18 or 64.3% patients responded within six hours of the first dose of ivabradine; 13 out of the 18 ivabradine responders subsequently underwent catheter ablation. Focal atrial tachycardia originating in the atrial appendages was a predictor of ivabradine response compared with those arising from other atrial sites, P equals 0.46.                                                  In our next paper, Takumi Yamada and associates studied 26 consecutive patients with idiopathic origins that were identified at the left ventricular summit. The authors studied 26 consecutive patients with idiopathic left ventricular summit ventricular arrhythmias in the basal and apical left ventricular summit in 15 and 11 patients, respectively. Radiofrequency ablation of the apical left ventricular summit ventricular arrhythmias were successful in the great cardiac vein in nine patients and in the apical left ventricular outflow tract in two. Ablation of the basal left ventricular summit was successful in the aortomitral continuity in nine patients, at the junction of the left and right coronary cusp in 4 and the left coronary cusp in two. Three apical left ventricular summit ventricular arrhythmias exhibited an eccentric endocardial pattern that was from basal to apical left ventricular outflow tract. In 11 basal left ventricular summit ventricular arrhythmias, the activation pattern was eccentric because ventricular activation within the great cardiac vein in the apical left ventricular summit was earlier than that in the basal left ventricular outflow tract. In two left ventricular summit ventricular arrhythmias, the activation was eccentric because a relatively early ventricular activation was recorded at multiple sites away from the successful ablation site. The authors concluded that eccentric activation patterns often occurred during idiopathic left ventricular, ventricular arrhythmias, which could mislead catheter ablation of those arrhythmias.                                                  In our next paper, Anand Thiyagarajah and associates performed a systematic review and meta-analysis of studies performing posterior wall isolation for atrial fibrillation. Of 17 studies, 13 employed box isolation, 3 single ring isolation, and 2 debulking ablation, and included 1,643 patients, of which 31% had paroxysmal atrial fibrillation. The acute procedural success for achieving posterior wall isolation was 94%. Single-procedure 12-month freedom from atrial arrhythmias was 65% overall and 61.9% for persistent atrial fibrillation. Randomized control trials comparing posterior wall isolation to pulmonary vein isolation, three studies in 444 patients, yielded conflicting results and could not confirm incremental benefit to posterior wall isolation; 15 major complications, 0.1%, including two atrio-esophageal fistulas, were reported.                                                  In a research letter, Tadashi Hoshiyama and associates examined the effect of contact vector direction on the ability of pulmonary vein isolation. In a review article, Belinda Gray and associates describes sudden cardiac death in the young, ages 35 years or less. A significant proportion of sudden cardiac deaths in this group may be precipitated by underlying inherited cardiac conditions, including both heritable cardiomyopathies and inherited arrhythmic syndromes. Tragically, sudden deaths may be the first manifestation of disease in a family. Both clinical and genetic evaluation of surviving family members becomes important.                                                  That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time.                                                  This program is copyright American Heart Association 2019.

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue.                                                 In our first paper, Mark McCauley, Flavia Vitale and associates report that carbon nanotube fibers may improve impaired myocardial conduction. In three sheep, radiofrequency ablation was used to create epicardial conduction delay. In addition, in a rodent model, carbon nanotube fibers were sewn across the atrial ventricular junction. They demonstrated acute ventricular preexcitation, but in chronic studies at four weeks, atrial pacing was required for resumption of AV conduction. Carbon nanotube fibers are conductive, biocompatible with no gross or histopathological evidence of toxicity.                                                 In our next paper, Koichiro Ejima and associates compared outcomes of circumferential pulmonary vein isolation for atrial fibrillation ablation randomized to contact force monitoring or unipolar signal modification in 136 patients with paroxysmal atrial fibrillation. In the unipolar signal modification-guided group, each radiofrequency application was delivered until the development of completely positive unipolar electrograms. In the contact force monitoring-guided group, a contact force of 20 grams, ranged 10 to 30 grams, and a minimum force time integral of 400 gram seconds were the targets for each radiofrequency application. The freedom from atrial tachyarrhythmia recurrence at 12 months was 85% in the unipolar signal modification-guided group and 70% in the contact force monitoring-guided group, P equals 0.031. The radiofrequency time for pulmonary vein isolation was shorter in the unipolar signal modification-guided group than contact force monitoring-guided group, but was not statistically significant, P equals 0.077. The incidence of time-dependent in ATP-provoked early electrical reconnections between the left atrium and pulmonary veins, procedural time, fluoroscopic time, and average force-time integral did not significantly differ between the two groups.                                                 In our next paper, Vishal Luther and associates tested whether ripple mapping is superior to conventional annotation-based local activation time mapping for atrial tachycardia diagnosis. Patients with atrial tachycardia were randomized, either ripple mapping or local activation time mapping. The primary endpoint was atrial tachycardia termination with delivery of the planned ablation lesion set. The inability to terminate atrial tachycardia with the first lesion set, the use of more than one entrainment maneuver, or the need to cross over to the other mapping arm were defined as failure to achieve the primary endpoint. The primary endpoint occurred in 38 of 42 patients or 90% in the ripple mapping group, and 29 of 41 patients, 71%, in the local activation time mapping group, P equals 0.45. The primary endpoint was achieved without any entrainment in 31 out of 42 patients or 74% with ripple mapping, and 18 out of 41 patients or 44% with local activation time mapping, P equals 0.01. Of those patients who failed to achieve the primary endpoint, atrial tachycardia termination was achieved in 9 out of 12 patients or 75% in the local activation time mapping group following crossover to ripple mapping with entrainment, but zero out of four patients, 0%, in ripple mapping group crossing over to local activation time mapping with entrainment, P equals 0.04.                                                 In our next paper, Franziska Fochler and associates examined whether anatomical targeting of late gadolinium enhancement MRI-detected gaps and superficial atrial scar is feasible and effective to treat recurrent atrial arrhythmias post-atrial fibrillation ablation. The authors studied 102 patients who underwent initial atrial fibrillation ablation and repeat ablation for recurrent atrial arrhythmias within one-year. 46 patients or 45% with atrial fibrillation recurrence were assigned to group one and underwent fibrosis homogenization as the second procedure. 56 patients or 55% with atrial tachycardia recurrence were assigned to group two and underwent late gadolinium enhancement MRI detected scar-based dechanneling. Both groups underwent re-isolation of pulmonary veins, if necessary.                                                 In the first 25 patients from group two, the atrial tachycardia was electroanatomically mapped and a critical isthmus was defined. It was found that those isthmi were located in the regions with non-transmural scarring detected by late gadolinium enhancement MRI. In the last 31 patients from group 2, an empirical late gadolinium enhancement MRI-based dechanneling was performed solely based on late gadolinium enhancement MRI results. During one-year follow-up after the second ablation, 67% of patients group one and 64% of patients group two were free from occurrence. In group two, 64% in the electroanatomic-guided and 65% in the late gadolinium enhancement MRI dechanneling group were free from recurrence. The authors concluded that homogenization of existing scar is appropriate treatment for recurrent atrial fibrillation while dechanneling of existing isthmi seem the appropriate approach for patients recurring with atrial tachycardia.                                                 In our next paper, George Leef, Fatemah Shenasa, Neal Bhatia and associates examined whether wave front field mapping of persistent atrial fibrillation can reveal an underlying network of a small number of spatially anchored rotational and focal sites. They examined unipolar atrial fibrillation electrograms from 64-pole baskets in 54 patients from an international registry in whom persistent atrial fibrillation was terminated by targeted ablation. They identified 4.0, plus or minus 2.1, spatially anchored rotational focal sites in atrial fibrillation that were a single in seven patients type I or paired chiral-antichiral type II rotational drivers that controlled most of the atrial area. Ablation of one or two large drivers terminated all cases of these types of atrial fibrillation. Third, interaction of three to five drivers type III, n equals 42, was present with changing areas of control. Targeted ablation at driver center terminate atrial fibrillation and required more ablation in type III versus I, P equals 0.02 in the left atrium.                                                 In our next paper, Ryan Azarrafiy and associates examined survival after superior vena cava tear using an endovascular balloon. Data were prospectively collected from both a United States Food and Drug Administration-maintained database and physician reports of adverse events as they occurred. Confirmed superior vena cava tears were analyzed for patient demographics, case details, and index hospitalization mortality. Over a period of two years, 116 confirmed superior vena cava events were identified, of which 44% involve proper balloon use and 50% involve no use or improper use. When an endovascular balloon was properly used, 45 of 51 patients, or 88.2%, survived in comparison to 37 out of 65, or 56.9%, when a balloon was not used or improperly used; P equals 0.0002. Furthermore, multivariate regression modeling found that proper balloon deployment was an independent, negative predictor of in-hospital mortality for patients who experienced a superior vena cava laceration, odds ratio of 0.13; P value less than 0.001.                                                 In our next paper, Bharatraj Banavalikar and associates examined 28 patients with focal atrial tachycardia, mean age 34.6 years, females 60.7%, were included in the study. Most common symptoms were palpitations, 85.7%, followed by shortness of breath, 25%. The mean atrial tachycardia rate was 170 beats per minute and mean left ventricular ejection fraction was 54.7%. Overall, 18 or 64.3% patients responded within six hours of the first dose of ivabradine; 13 out of the 18 ivabradine responders subsequently underwent catheter ablation. Focal atrial tachycardia originating in the atrial appendages was a predictor of ivabradine response compared with those arising from other atrial sites, P equals 0.46.                                                 In our next paper, Takumi Yamada and associates studied 26 consecutive patients with idiopathic origins that were identified at the left ventricular summit. The authors studied 26 consecutive patients with idiopathic left ventricular summit ventricular arrhythmias in the basal and apical left ventricular summit in 15 and 11 patients, respectively. Radiofrequency ablation of the apical left ventricular summit ventricular arrhythmias were successful in the great cardiac vein in nine patients and in the apical left ventricular outflow tract in two. Ablation of the basal left ventricular summit was successful in the aortomitral continuity in nine patients, at the junction of the left and right coronary cusp in 4 and the left coronary cusp in two. Three apical left ventricular summit ventricular arrhythmias exhibited an eccentric endocardial pattern that was from basal to apical left ventricular outflow tract. In 11 basal left ventricular summit ventricular arrhythmias, the activation pattern was eccentric because ventricular activation within the great cardiac vein in the apical left ventricular summit was earlier than that in the basal left ventricular outflow tract. In two left ventricular summit ventricular arrhythmias, the activation was eccentric because a relatively early ventricular activation was recorded at multiple sites away from the successful ablation site. The authors concluded that eccentric activation patterns often occurred during idiopathic left ventricular, ventricular arrhythmias, which could mislead catheter ablation of those arrhythmias.                                                 In our next paper, Anand Thiyagarajah and associates performed a systematic review and meta-analysis of studies performing posterior wall isolation for atrial fibrillation. Of 17 studies, 13 employed box isolation, 3 single ring isolation, and 2 debulking ablation, and included 1,643 patients, of which 31% had paroxysmal atrial fibrillation. The acute procedural success for achieving posterior wall isolation was 94%. Single-procedure 12-month freedom from atrial arrhythmias was 65% overall and 61.9% for persistent atrial fibrillation. Randomized control trials comparing posterior wall isolation to pulmonary vein isolation, three studies in 444 patients, yielded conflicting results and could not confirm incremental benefit to posterior wall isolation; 15 major complications, 0.1%, including two atrio-esophageal fistulas, were reported.                                                 In a research letter, Tadashi Hoshiyama and associates examined the effect of contact vector direction on the ability of pulmonary vein isolation. In a review article, Belinda Gray and associates describes sudden cardiac death in the young, ages 35 years or less. A significant proportion of sudden cardiac deaths in this group may be precipitated by underlying inherited cardiac conditions, including both heritable cardiomyopathies and inherited arrhythmic syndromes. Tragically, sudden deaths may be the first manifestation of disease in a family. Both clinical and genetic evaluation of surviving family members becomes important.                                                 That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time.                                                 This program is copyright American Heart Association 2019.

Circulation: Arrhythmia and Electrophysiology August 2019 Issue

Dr. Wang:            Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wong, editor-in-chief, with some of the key highlights from this month's issue.                                  In our first paper, Jeremy Wasserlauf and associates compare the accuracy of an atrial fibrillation sensing smartwatch with simultaneous recordings from an insertable cardiac monitor.                                  The authors use smart rhythm 2.0, a convolutional neuro-network, trained on anonymized data of heart rate, activity level and EKGs from 7500 AliveCor users.                                  The network was validated on data collected in 24 patients with insertable cardiac monitor, and a history of paroxysmal atrial fibrillation who simultaneously wore the atrial fibrillation sensing smart watch with smart rhythm 0.1 software.                                  The primary outcome was sensitivity of the atrial fibrillation sensing smart watch for atrial fibrillation episodes of greater than equal to one hour. Secondary end points include sensitivity of atrial fibrillation sensing smart watch for detection of atrial fibrillation by subject and sensitivity for total duration across all subjects.                                  Subjects with greater than 50% false positive atrial fibrillation episodes on insertable cardiac monitor were excluded.                                  The authors analyzed 31,349 hours meaning 11.3 hours per day of simultaneous atrial fibrillation sensing smart watch and insertable cardiac monitor recordings in 24 patients. Insertable cardiac monitor detected 82 episodes of atrial fibrillation of one hour duration or greater while the atrial fibrillation sensing smartwatch was worn. With a total duration of 1,127 hours.                                  Of these, the smart rhythm 2.0 neural network detected 80 episodes. Episode sensitivity 97.5% with total duration 1,101 hours. Duration sensitivity 97.7%.                                  Three of the 18 subjects with atrial fibrillation of one hour or greater had atrial fibrillation only when the watch was not being worn. Patient sensitivity 83.3% or 100% during the time worn. Positive predictive value for atrial fibrillation episodes was 39.9%.                                  The authors concluded that an atrial fibrillation sensing smartwatch is highly sensitive to detection of atrial fibrillation and assessment of atrial fibrillation duration in an ambulatory population when compared to insertable cardiac monitor.                                  In our next paper, Liliana Tavares and associates examine the autonomic nervous system response to apnea in its mechanistic connection to atrial fibrillation. They study the effects of ablation of cardiac sensory neurons with resiniferatoxin, a neurotoxic transient receptor potential vanilloid one agonist.                                  In a canine model, apnea was induced by stopping ventilation until oxygen saturation decreased in 90%. Nerve recordings from bilateral vagal nerves left stellate ganglion and anterior right ganglion plexi were obtained before and during apnea, before and after resiniferatoxin injection in the anterior white ganglion plexi in seven animals.                                  Each refractory period and atrial fibrillation inducibility upon single extra stimulation was assessed before and during apnea, before and after intrapericardial resiniferatoxin administration in nine animals.                                  The authors found that apnea increased anterior wide ganglion plexi activity followed by cluster crescendo vagal bursts synchronized with heart rate and blood pressure oscillation.                                  Upon further oxygen desaturation, a tonic increase in left stellate ganglion activity in blood pressure oscillations ensued. Apnea induced atrial effective refractory shortening from 110 to 90 milliseconds, P less than 0.001 and atrial fibrillation induction in nine animals vs. zero out of nine at baseline.                                  After resiniferatoxin administration increases in ganglion plexi and left stellate ganglion activity, and blood pressure during apnea were abolished, in addition, the atrial effector refractory period increased to 127 milliseconds, P=0.0001 and atrial fibrillation was not induced.                                  Vagal bursts remain unchanged. Ganglion plexi cells showed cytoplasmic microvacuolation and apoptosis. The authors concluded that apnea increased ganglion plexi activity followed by vagal bursts and tonic left stellate ganglion firing. Resiniferatoxin decreases sympathetic and ganglion plexi nerve activity, abolishes apnea's electrophysiotic response and atrial fibrillation inducibility indicating that sensory neurons play a role in apnea induced atrial fibrillation.                                  In our next paper, Thomas Pambrun and associates examined whether using unipolar signal modification as a local end point would improve the safety and efficacy of high-power ablation during pulmonary vein isolation. They studied four swine and 100 consecutive patients referred for pulmonary vein isolation with the first 50 patients in a control group using 25 to 30 watts and the last 50 patients in a study group with 40 to 50 watts.                                  Atrial radiofrequency applications were stopped two seconds in the study group and swine or five seconds in the control group after unipolar signal modification. Ventricular radiofrequency applications of 500 joules were performed at the swine epicardium.                                  The authors found that swine did not show any extracardiac damage related to atrial lesions. At equal energy of 500 joules, 50 watt lesions were deeper, three vs. 2.6 millimeters, P=0.3 and wider, 6.2 vs. five millimeters, P=0.006 and 25 watt lesions.                                  In a clinical study, there were no complications occurring at either power output. The study group displayed higher first pass pulmonary vein isolation, 92% vs. 73%, P less than 0.001. In addition, the study group had a lower acute pulmonary vein reconnection, 2% vs. 17%, P less than 0.001 as well as reduced procedure time, 73.1 vs. 107.4 minutes and ablation team, 13 vs. 30.3 minutes. Sinus rhythm maintenance at 12 months was similar, 90% and 88%.                                  The authors concluded that high power pulmonary vein isolation guided by unipolar signal modification safely decreases procedural burden while achieving similar 12-month outcomes.                                  In our next paper, Toshiaki Sato and associates attempted to identify predictors of low his-bundle pacing threshold. They studied 51 patients, 53% with atrial ventricular block undergoing his-bundle pacing for bradycardia with an intrinsic QRS duration of less than 120 milliseconds.                                  His-bundle pacing lead positioning was guided by unipolar his-bundle electrograms recorded with an electrophysiology recording system. In total, 153 attempts at anchoring the his-bundle pacing lead were made, of which 45 achieved acceptable his-bundle pacing thresholds, less than or equal to 2.5 volts at one millisecond.                                  The amplitude of negative deflection in unipolar his-bundle electrograms and the selective his-bundle pacing at fixation where independently associated with achieving a acceptable threshold. A negative amplitude of greater than or equal to 0.06 millivolts in the his-bundle electrograms was determined as the optimal value for identifying acceptable threshold. This deep negative his-bundle electrogram was recorded with a his-bundle pacing threshold of 1.4 volts in 34 attempts, significantly lower than the positive his-bundle electrogram without deep negative deflection, 2.8 volts in 31 trials or greater than five volts in 38 trials.                                  The permanent his-bundle pacing lead remained with a deep negative, greater than or equal to 0.06 millivolts or positive his-bundle electrogram in 28 or 14 patients respectively and with a positive or negative his-bundle pacing injury current in 19 and 23 patients respectively.                                  During follow-up, increased his-bundle pacing threshold of greater than one volt was significantly more prevalent in the positive his-bundle electrogram group. The his-bundle pacing threshold of deep negative his-bundle electrogram and his-bundle injury current but not of selective his-bundle pacing group were significantly lower than other sub-groups during follow-up.                                  In the next paper, Claire Martin and associates examined whether altering activation wavefront affects activation timing and local abnormal ventricular activity characterization in patients with ischemic cardiomyopathy. They use the ultra-high density arrhythmia to generate maps for all stable ventricular tachycardias and with pacing from the atrium, right ventricular apex and left ventricular branch of the coronary sinus.                                  56 pace maps and 23 ventricular tachycardia circuits were mapped in 22 patients. In 79% of activation maps, there was one or greater lines of block in the pace conduction wavefront with 93% having fixed block and 32% showing functional partial block. Bipolar scar was larger with atrial than right ventricular, 31.7 centimeters squared vs. 27.6 centimeters squared, P = 0.003 or left ventricular pacing, 31.7 centimeters squared vs. 27.0 centimeters squared, P = 0.009.                                  Local abnormal ventricular activities areas were smaller with atrial than right ventricular pacing, 12.3 centimeters squared vs. 18.4 centimeters squared or left ventricular pacing, 12.3 centimeters squared vs. 17.1 centimeters squared. Local abnormal ventricular activities were larger with wavefront propagation perpendicular vs. parallel to the line of block along isthmus boundaries, 9.3 vs. 13.6 centimeters squared P = 0.01.                                  All patients had successful tachycardia isthmus ablation in 11 months follow-up, two patients had a recurrence.                                  In our next paper, Andrew Tseng and Katie Kunze and associates conducted a systematic review and network meta-analysis on the effect of medication device therapies and reduced ejection fraction on all-cause mortality. Randomized control trials published between January 1980 and July 2017 were identified.                                  The authors found that combination therapy of angiotensin converting enzyme inhibitors or angiotensin receptor blockers with beta blockers alone or in addition to implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillators demonstrated significant reduction in all cause of mortality when compared to placebo.                                  By probability rank, implantable cardio defibrillator plus angiotensin receptor blockers plus beta blockers plus mineralocorticoid receptor blockers, implantable cardioverter defibrillators plus angiotensin receptor blockers plus beta blockers and angiotensin receptor-neprilysin inhibitor plus beta blockers and mineralocorticoid receptor antag as combination therapies have the highest probability of being ranked the best treatment. There was no significant difference in the rate of mortality when comparing angiotensin receptor-neprilysin inhibitors plus beta blockers plus mineralocorticoid receptor antagonist to ICD plus optimal pharmacologic combination therapy.                                  In our next paper, Karl-Heinz Kuck and associates examined repeat ablation in the fire and ice trial, which examined efficacy and safety of pulmonary vein isolation using cryoballoon vs. radio-frequency current ablation in patients with drug refractory symptomatic paroxysmal atrial fibrillation.                                  Patients with re-ablation procedures during fire and ice were retrospectively consented and rolled at 13 trial centers. 89, 36 cryo-balloon and 53 radio-frequency patients were studied. Paroxysmal atrial fibrillation was the predominant recurring arrhythmia, 69% prior to re-ablation. Re-ablations occurred at the median of 173 and 182 days in the cryoballoon and radio frequency cohorts.                                  The number of reconnected pulmonary veins was significantly higher in the radio frequency than the cryo-balloon, 2.1 vs. 1.4 P = 0.01, which was significantly driven by more connected left superior pulmonary veins and markedly more reconnected right superior pulmonary veins.                                  The number of predominantly radio frequency lesions applied during re-ablation was significantly greater in patients originally treated with radio frequency, 3.3 vs. 2.5, P=0.015 with no difference in overall acute success.                                  After re-ablation, no differences in procedure related rehospitalization or antiarrhythmic drug utilization was observed between cohorts.                                  In the next paper, Ayelet Shapira-Daniels and Michael Barkagan and associates examined the ability of reducing baseline impedance to improve ventricular ablation success. In 16 patients with ventricular tachycardia or frequent ventricular premature complexes with failed rate of frequency ablation with irrigated catheters, the impedance was modulated by adding or repositioning return patches.                                  Ablation was repeated at similar location and power settings. The authors studied six patients with idiopathic ventricular premature complexes originated from the left ventricular summit, N=4 or papillary muscles, N=2. Six patients with non-infarct related ventricular tachycardia and four patients with infarc related ventricular tachycardia. Prior unsuccessful radio frequency ablation at critical sites had a number of 10.4 applications, power of 43.3 watts, duration 55.3 seconds and impedance reduction, 14.6 Ohms in low ionic solution was used in 81%.                                  Modulating the return patches resulted in reduced baseline impedance, 111.7 vs. 34.7 ohms, P less than 0.0001. Increased current output 0.6 vs. 0.56 amps, P also less than 0.0001. And impedance dropped 16.8 ohms.                                  Repeat ablation at similar locations had successful effect in 12 out of 16 or 75% patients. During a follow-up duration of 13 months, 10 out of 12 or 83% patients remained free of arrhythmia occurrence. The frequency of steam pops was similar between higher and lower baseline impedance settings.                                  The authors concluded that in patients with deep ventricular substrate, reducing the baseline impedance is a simple, safe and effective technique for increasing the effect of radio frequency ablation.                                  However, the combination with low ionic solutions may increase the risk for steam pops and neurological events.                                  Our last paper is a review by Robert Anderson and associates. The authors summarize all of the published 12 lead ECD algorithms used to localize ventricular arrhythmias from the right ventricular and left ventricular outflow tracks.                                  That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time!                                  This program is copyright American Heart Association 2019.

Dr. Wang:            Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wong, editor-in-chief, with some of the key highlights from this month's issue.                                 In our first paper, Jeremy Wasserlauf and associates compare the accuracy of an atrial fibrillation sensing smartwatch with simultaneous recordings from an insertable cardiac monitor.                                 The authors use smart rhythm 2.0, a convolutional neuro-network, trained on anonymized data of heart rate, activity level and EKGs from 7500 AliveCor users.                                 The network was validated on data collected in 24 patients with insertable cardiac monitor, and a history of paroxysmal atrial fibrillation who simultaneously wore the atrial fibrillation sensing smart watch with smart rhythm 0.1 software.                                 The primary outcome was sensitivity of the atrial fibrillation sensing smart watch for atrial fibrillation episodes of greater than equal to one hour. Secondary end points include sensitivity of atrial fibrillation sensing smart watch for detection of atrial fibrillation by subject and sensitivity for total duration across all subjects.                                 Subjects with greater than 50% false positive atrial fibrillation episodes on insertable cardiac monitor were excluded.                                 The authors analyzed 31,349 hours meaning 11.3 hours per day of simultaneous atrial fibrillation sensing smart watch and insertable cardiac monitor recordings in 24 patients. Insertable cardiac monitor detected 82 episodes of atrial fibrillation of one hour duration or greater while the atrial fibrillation sensing smartwatch was worn. With a total duration of 1,127 hours.                                 Of these, the smart rhythm 2.0 neural network detected 80 episodes. Episode sensitivity 97.5% with total duration 1,101 hours. Duration sensitivity 97.7%.                                 Three of the 18 subjects with atrial fibrillation of one hour or greater had atrial fibrillation only when the watch was not being worn. Patient sensitivity 83.3% or 100% during the time worn. Positive predictive value for atrial fibrillation episodes was 39.9%.                                 The authors concluded that an atrial fibrillation sensing smartwatch is highly sensitive to detection of atrial fibrillation and assessment of atrial fibrillation duration in an ambulatory population when compared to insertable cardiac monitor.                                 In our next paper, Liliana Tavares and associates examine the autonomic nervous system response to apnea in its mechanistic connection to atrial fibrillation. They study the effects of ablation of cardiac sensory neurons with resiniferatoxin, a neurotoxic transient receptor potential vanilloid one agonist.                                 In a canine model, apnea was induced by stopping ventilation until oxygen saturation decreased in 90%. Nerve recordings from bilateral vagal nerves left stellate ganglion and anterior right ganglion plexi were obtained before and during apnea, before and after resiniferatoxin injection in the anterior white ganglion plexi in seven animals.                                 Each refractory period and atrial fibrillation inducibility upon single extra stimulation was assessed before and during apnea, before and after intrapericardial resiniferatoxin administration in nine animals.                                 The authors found that apnea increased anterior wide ganglion plexi activity followed by cluster crescendo vagal bursts synchronized with heart rate and blood pressure oscillation.                                 Upon further oxygen desaturation, a tonic increase in left stellate ganglion activity in blood pressure oscillations ensued. Apnea induced atrial effective refractory shortening from 110 to 90 milliseconds, P less than 0.001 and atrial fibrillation induction in nine animals vs. zero out of nine at baseline.                                 After resiniferatoxin administration increases in ganglion plexi and left stellate ganglion activity, and blood pressure during apnea were abolished, in addition, the atrial effector refractory period increased to 127 milliseconds, P=0.0001 and atrial fibrillation was not induced.                                 Vagal bursts remain unchanged. Ganglion plexi cells showed cytoplasmic microvacuolation and apoptosis. The authors concluded that apnea increased ganglion plexi activity followed by vagal bursts and tonic left stellate ganglion firing. Resiniferatoxin decreases sympathetic and ganglion plexi nerve activity, abolishes apnea's electrophysiotic response and atrial fibrillation inducibility indicating that sensory neurons play a role in apnea induced atrial fibrillation.                                 In our next paper, Thomas Pambrun and associates examined whether using unipolar signal modification as a local end point would improve the safety and efficacy of high-power ablation during pulmonary vein isolation. They studied four swine and 100 consecutive patients referred for pulmonary vein isolation with the first 50 patients in a control group using 25 to 30 watts and the last 50 patients in a study group with 40 to 50 watts.                                 Atrial radiofrequency applications were stopped two seconds in the study group and swine or five seconds in the control group after unipolar signal modification. Ventricular radiofrequency applications of 500 joules were performed at the swine epicardium.                                 The authors found that swine did not show any extracardiac damage related to atrial lesions. At equal energy of 500 joules, 50 watt lesions were deeper, three vs. 2.6 millimeters, P=0.3 and wider, 6.2 vs. five millimeters, P=0.006 and 25 watt lesions.                                 In a clinical study, there were no complications occurring at either power output. The study group displayed higher first pass pulmonary vein isolation, 92% vs. 73%, P less than 0.001. In addition, the study group had a lower acute pulmonary vein reconnection, 2% vs. 17%, P less than 0.001 as well as reduced procedure time, 73.1 vs. 107.4 minutes and ablation team, 13 vs. 30.3 minutes. Sinus rhythm maintenance at 12 months was similar, 90% and 88%.                                 The authors concluded that high power pulmonary vein isolation guided by unipolar signal modification safely decreases procedural burden while achieving similar 12-month outcomes.                                 In our next paper, Toshiaki Sato and associates attempted to identify predictors of low his-bundle pacing threshold. They studied 51 patients, 53% with atrial ventricular block undergoing his-bundle pacing for bradycardia with an intrinsic QRS duration of less than 120 milliseconds.                                 His-bundle pacing lead positioning was guided by unipolar his-bundle electrograms recorded with an electrophysiology recording system. In total, 153 attempts at anchoring the his-bundle pacing lead were made, of which 45 achieved acceptable his-bundle pacing thresholds, less than or equal to 2.5 volts at one millisecond.                                 The amplitude of negative deflection in unipolar his-bundle electrograms and the selective his-bundle pacing at fixation where independently associated with achieving a acceptable threshold. A negative amplitude of greater than or equal to 0.06 millivolts in the his-bundle electrograms was determined as the optimal value for identifying acceptable threshold. This deep negative his-bundle electrogram was recorded with a his-bundle pacing threshold of 1.4 volts in 34 attempts, significantly lower than the positive his-bundle electrogram without deep negative deflection, 2.8 volts in 31 trials or greater than five volts in 38 trials.                                 The permanent his-bundle pacing lead remained with a deep negative, greater than or equal to 0.06 millivolts or positive his-bundle electrogram in 28 or 14 patients respectively and with a positive or negative his-bundle pacing injury current in 19 and 23 patients respectively.                                 During follow-up, increased his-bundle pacing threshold of greater than one volt was significantly more prevalent in the positive his-bundle electrogram group. The his-bundle pacing threshold of deep negative his-bundle electrogram and his-bundle injury current but not of selective his-bundle pacing group were significantly lower than other sub-groups during follow-up.                                 In the next paper, Claire Martin and associates examined whether altering activation wavefront affects activation timing and local abnormal ventricular activity characterization in patients with ischemic cardiomyopathy. They use the ultra-high density arrhythmia to generate maps for all stable ventricular tachycardias and with pacing from the atrium, right ventricular apex and left ventricular branch of the coronary sinus.                                 56 pace maps and 23 ventricular tachycardia circuits were mapped in 22 patients. In 79% of activation maps, there was one or greater lines of block in the pace conduction wavefront with 93% having fixed block and 32% showing functional partial block. Bipolar scar was larger with atrial than right ventricular, 31.7 centimeters squared vs. 27.6 centimeters squared, P = 0.003 or left ventricular pacing, 31.7 centimeters squared vs. 27.0 centimeters squared, P = 0.009.                                 Local abnormal ventricular activities areas were smaller with atrial than right ventricular pacing, 12.3 centimeters squared vs. 18.4 centimeters squared or left ventricular pacing, 12.3 centimeters squared vs. 17.1 centimeters squared. Local abnormal ventricular activities were larger with wavefront propagation perpendicular vs. parallel to the line of block along isthmus boundaries, 9.3 vs. 13.6 centimeters squared P = 0.01.                                 All patients had successful tachycardia isthmus ablation in 11 months follow-up, two patients had a recurrence.                                 In our next paper, Andrew Tseng and Katie Kunze and associates conducted a systematic review and network meta-analysis on the effect of medication device therapies and reduced ejection fraction on all-cause mortality. Randomized control trials published between January 1980 and July 2017 were identified.                                 The authors found that combination therapy of angiotensin converting enzyme inhibitors or angiotensin receptor blockers with beta blockers alone or in addition to implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillators demonstrated significant reduction in all cause of mortality when compared to placebo.                                 By probability rank, implantable cardio defibrillator plus angiotensin receptor blockers plus beta blockers plus mineralocorticoid receptor blockers, implantable cardioverter defibrillators plus angiotensin receptor blockers plus beta blockers and angiotensin receptor-neprilysin inhibitor plus beta blockers and mineralocorticoid receptor antag as combination therapies have the highest probability of being ranked the best treatment. There was no significant difference in the rate of mortality when comparing angiotensin receptor-neprilysin inhibitors plus beta blockers plus mineralocorticoid receptor antagonist to ICD plus optimal pharmacologic combination therapy.                                 In our next paper, Karl-Heinz Kuck and associates examined repeat ablation in the fire and ice trial, which examined efficacy and safety of pulmonary vein isolation using cryoballoon vs. radio-frequency current ablation in patients with drug refractory symptomatic paroxysmal atrial fibrillation.                                 Patients with re-ablation procedures during fire and ice were retrospectively consented and rolled at 13 trial centers. 89, 36 cryo-balloon and 53 radio-frequency patients were studied. Paroxysmal atrial fibrillation was the predominant recurring arrhythmia, 69% prior to re-ablation. Re-ablations occurred at the median of 173 and 182 days in the cryoballoon and radio frequency cohorts.                                 The number of reconnected pulmonary veins was significantly higher in the radio frequency than the cryo-balloon, 2.1 vs. 1.4 P = 0.01, which was significantly driven by more connected left superior pulmonary veins and markedly more reconnected right superior pulmonary veins.                                 The number of predominantly radio frequency lesions applied during re-ablation was significantly greater in patients originally treated with radio frequency, 3.3 vs. 2.5, P=0.015 with no difference in overall acute success.                                 After re-ablation, no differences in procedure related rehospitalization or antiarrhythmic drug utilization was observed between cohorts.                                 In the next paper, Ayelet Shapira-Daniels and Michael Barkagan and associates examined the ability of reducing baseline impedance to improve ventricular ablation success. In 16 patients with ventricular tachycardia or frequent ventricular premature complexes with failed rate of frequency ablation with irrigated catheters, the impedance was modulated by adding or repositioning return patches.                                 Ablation was repeated at similar location and power settings. The authors studied six patients with idiopathic ventricular premature complexes originated from the left ventricular summit, N=4 or papillary muscles, N=2. Six patients with non-infarct related ventricular tachycardia and four patients with infarc related ventricular tachycardia. Prior unsuccessful radio frequency ablation at critical sites had a number of 10.4 applications, power of 43.3 watts, duration 55.3 seconds and impedance reduction, 14.6 Ohms in low ionic solution was used in 81%.                                 Modulating the return patches resulted in reduced baseline impedance, 111.7 vs. 34.7 ohms, P less than 0.0001. Increased current output 0.6 vs. 0.56 amps, P also less than 0.0001. And impedance dropped 16.8 ohms.                                 Repeat ablation at similar locations had successful effect in 12 out of 16 or 75% patients. During a follow-up duration of 13 months, 10 out of 12 or 83% patients remained free of arrhythmia occurrence. The frequency of steam pops was similar between higher and lower baseline impedance settings.                                 The authors concluded that in patients with deep ventricular substrate, reducing the baseline impedance is a simple, safe and effective technique for increasing the effect of radio frequency ablation.                                 However, the combination with low ionic solutions may increase the risk for steam pops and neurological events.                                 Our last paper is a review by Robert Anderson and associates. The authors summarize all of the published 12 lead ECD algorithms used to localize ventricular arrhythmias from the right ventricular and left ventricular outflow tracks.                                 That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time!                                 This program is copyright American Heart Association 2019.

Circulation: Arrhythmia and Electrophysiology June 2019 Issue

Dr Paul Wang:                   Welcome to the monthly podcast "On the Beat" for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, Editor-in Chief, with some of the key highlights from this month's issue.                                                  In our first manuscript, Marie Bayer Elming and associates, examined whether the right ventricular ejection fraction can identify patients with non-ischemic systolic heart failure, more likely to benefit from ICD implantation. The Danish study, to assess the efficacy of ICDs in patients with non-ischemic systolic heart failure, on mortality, the Danish study, randomized patients with non-ischemic systolic heart failure to ICD our control. In 239 patients with interpretable cardiovascular magnetic resonance images, the right ventricular volume and ejection fraction was measured. Right ventricular ejection fraction was an independent predictor of all-cause mortality, with a hazard ration 1.34 per 10% absolute decrease in our right ventricular ejection fraction. P=0.02. There is statistically significant interaction between right ventricular ejection fraction and the effect of ICD implantation. P=0.001. ICD implantation significantly reduced all-cause mortality in patients with right ventricular systolic dysfunction. Hazard ratio 0.41, but not in patients without right ventricular systolic dysfunction.                                                  Thus, in this post-hoc analysis of the Danish trial, ICD therapy was associated with survival benefit in patients with bi-ventricular heart failure.                                                  In our next paper, Dawn Pedrotty and Volodymyr Kuzmenko and associates, have proposed a concept of using a stretchable, flexible, bio patch, with conductive properties, to attempt to restore conduction across regions in which activation is disrupted. They use carbon nanotube patches, composed of nanofibrillated cellulose, in single wall carbon nanotube ink, 3-D printed in conductive patterns onto bacterial nanocellulose.                                                  Electro anatomic mapping was performed on normal epicardium and repeated over surgically disruptive epicardium, and finally with the patch applied passively. The patch resulted in restored conduction based on mapping.                                                  In our next paper, Ayman Hussein and colleagues developed a fully automated platform to collect patient reported outcomes in a prospective cohort of atrial fibrillation ablation. Two thousand one hundred and seventy-five patients were eligible to receive 10,903 patient reported outcome assessment invitations. More follow up assessments were obtained with automated patient reported outcomes in routine follow-up, compared with routine follow up alone, P &gt; 0.001, which allowed for longer duration of follow up, 378 vs 217 days. By automated patient reported outcomes, a large number of disease specific variables were collected and showed improvement in quality of life. Baseline median AF symptom severity score of 12 and ranged between 2 and 3 on subsequent assessments, P &gt; 0.0001. This improvement was also true for each of the atrial fibrillation symptom severity score components. In patient reported outcomes, there was a significant reduction in atrial fibrillation burden, such as frequency and duration episodes and associated healthcare utilization including emergency visits and hospitalizations after the ablation procedures.                                                  In our next paper, Nicolas Johner, Dipen Shah, and associates, examined the role of post pacing intervals shorter than tachycardia cycling during entrainment mapping. The author studied 24 non-cavotricuspid isthmus dependent macro oriented atrial flutters in 19 consecutive patients. High density electro anatomic activation maps were acquired with a 64-electrode basket catheter of 102 entrainment mapping sites. Post pacing interval difference less than 30 was observed at 72 sites on complete maps of 24 atypical atrial flutters compared to sites with the difference in post pacing intervals 0 to 30, with 45 sites difference in the post pacing interval less than 0 at 27 were more commonly located within isthmuses less than 15mm wide and more frequently located in within 5mm of the leading wave front. It also exhibited slower local conduction, lower voltages in more frequently fractioned electrograms. The authors concluded that in atrial flutter, sites with differences with the post pacing interval are markers of limited width critical isthmuses with slower conduction velocity, while sites with difference in post pacing interval 0 to 30ms are often not in close proximity to the reentrance circuit. Virtual electrode simultaneous down and up stream, antidromic capture of a confined isthmus of slow conduction can explain a difference in the post pacing interval less than 0.                                                  In the next paper, José Manuel Alfonso-Almazán, and associates studied the safety and efficacy parameters associated with catheter-based radiofrequency delivery at the root of the aorta and pulmonary artery. The author studied 34 pigs undergoing in vivo catheter based ablation using continuous contact force and lesion index monitoring during 60 second radiofrequency delivery with an open, irrigated tip catheter. Twenty-eight animals were allocated to groups receiving 40 watts, 50 watts, or 60 watts and acute, chronic arterial damage was quantified by multi photon microscopy in ex vivo samples. Adjacent microlesion were quantified in parallel samples. The remaining 8 pigs, these were used to validate safety and efficacy parameters. Acute collagen elastic alterations were significantly associated with radiofrequency power, although chronic assessment revealed vascular wall recovery in patients without [steam pop 00:06:56]. The main parameters associated with steam pops were median peak temperature greater than 42C, and impedance falls greater than 23 ohms. Unlike other parameters, lesion index values of 9.1 units were associated with the presence of adjacent myocardial lesions in both univariate and multivariate analyses. In the validation group, lesion index values using 40 watts over a range of contact forces correlated with the size of radiofrequency lesions. Lesion index values obtained during 40 watts radiofrequency application reliably monitor safe and effective lesion creation at the root of the great arteries.                                                  In our next paper, Eiichiro Oka and associates examine the prevalence and significance of the early repolarization electrocardiographic pattern and its mechanistic insight based on cardiac magnetic resonance findings in patients with acute myocarditis. The author studied 30 patients with the diagnosis of acute myocarditis. Nine had an early repolarization electrocardiographical pattern, which was defined as a terminal QRS notching or slurring with an amplitude of greater than zero-point millivolts in at least two inferior and/or lateral leads. The early repolarization group, while the remaining 21 cases had broad ST elevation or pathological QAs.                                                  The non-early repolarization group. The cardiac prepotency level was significantly higher in the non-early repolarization group than the early repolarization group. The ECD changes returned to baseline, along with a normalization of the cardiac biomarkers. Nine of the 21 non-early repolarization group patients, but none of the 9 early repolarization groups developed fulminant course of lethal ventricular arrhythmias. T2-weighted cardiac magnetic resonance imaging showed high intensity signals over the entire transmittal left vertical in the non-early repolarization group, where as they were localized to the left ventricle epicardium in early repolarization group. The early repolarization pattern in acute myocarditis was transient and reversible, and was not associated with a worse prognosis. Inflammation or swelling localized to the left ventricular epicardium, due to myocarditis, may provide a mechanistic insight into the early repolarization pattern.                                                  In our next paper, Beatrix Scholz and Jan Sebastian Schulte and associates analyzed whether the histone deacetylase class I and II inhibitor valproic acid is able to attenuate atrial remodeling in CREM-IbΔCx (TG) transgenic mice. A mouse model of extensive atrial remodeling with age dependent progression from spontaneous atrial ectopy to paroxysmal and finally long lasting atrial fibrillation. Valproic acid was administered for 7 or 25 weeks to transgenic and control mice. Valproic acid attenuated many components of atrial remodeling that were present in the transgenic mice.                                                  Valproic acid significantly reduced atrial dilation, cardiomyocyte enlargement, atrial fibrosis, and the disorganization of myocytes ultrastructure. It significantly reduced the occurrence of atrial thrombi, reversed action potential alterations, and finally delayed the onset of atrial fibrillation by 4 to 8 weeks. Increased histone H4 acetylation in atria from valproic acid treated transgenic mice verified effective in in vivo histone deacetylase inhibition. Cardiomyocyte specific genetic inactivation of histone deacetylase HDAC 2 in transgenic mice attenuated the ultrastructural disorganization of myocytes compared to valproic acid. The author suggests that valproic acid, clinically available, well tolerated, and prescribed to many patients for years, has a therapeutic potential to delay the development of atrial remodeling in the onset of atrial fibrillation in patients at risk.                                                  In our next paper, Bence Hegyi and associates measure the major inward currents in their calcium channel and beta-adrenergic dependence under physiologic action potential clamp in rabbit ventricular myocytes in chronic pressure volume overload induced heart failure versus age matched controls. They found that CAM kinase II dependent up regulation of late sodium current in heart failure significantly contributes to the action potential prolongation in increased short-term variability of action potential repolarization, which may lead to increased arrhythmia propensity and is further exacerbated by adrenergic stress.                                                  In a research letter, Arnaud Bisson and associates examined mitral regurgitation in 838, or 10%, of 8675 patients with atrial fibrillation. A total 135, or 16%, had severe mitral regurgitation. During mean follow-up with 2.5 years, 688 ischemic stroke or thromboembolic events were recorded. mitral regurgitation was associated with a non-significant higher risk of these embolic events. After adjustment for anticoagulant and antiplatelet use, CHA2DS2-VASc and HAS-BLED scores, patients with mitral regurgitation tended to have a higher all cause or cardiovascular mortality but had similar risks of ischemic stroke or thromboembolic events, when compared to patients with no mitral regurgitation. Severe mitral regurgitation was also associated with similar risk for ischemic stroke and thromboembolic events when compared with other atrial fibrillation patients. However, our findings indicate that in patients with atrial fibrillation, neither mitral regurgitation nor severe mitral regurgitation, appears to independently be associated with a different risk of ischemic stroke or thromboembolic events. The perceived protective effect of mitral regurgitation against the risk of thromboembolic events is not relevant in atrial fibrillation when using a contemporary risk score scheme, the CHA2DS2-VASc score.                                                  In our final research paper, Jack Z. Li and associates noted that in 2017, an aggregate of four manufacturers of devices yielded 89.6% with the DF-4 ICD implants. While DF-4 and DF-1 leads generally have comparable performance, several concerns over reduced versatility of the DF-4 have been raised. First, to downgrade an ICD with a DF-4 lead to a pacemaker, a generator change, a new right ventricular pace sense lead must be implanted. The DF-4 pin is incompatible with the IS-1 port and there is no straightforward way to bridge this gap. In contrast, the DF-1 IS-1 lead requires only capping of the DF-1 pin. Second, if an ICD with DF-4 lead has either a distal coil or a right ventricular pacing malfunction, a new lead must be implanted. Third, if a ICD with DF-4 lead has a high defibrillation threshold, management requires either a new DF-1 IS-1 lead with an adapter for a subcutaneous array, or an adapter that inserts into the DF-4 port and receives both the DF-4 lead and the DF-1 pin of the subcutaneous lead. Physicians should have the foresight to select DF-1 leads at the time of initial implant in selected circumstances, such as high possibility for elevated defibrillation threshold requiring a subcutaneous lead or array.                                                  That's it for this month! We hope that you'll find the journal to be the go-to place for everyone interested in the field. See ya next time.                                                  This program is copyright American Heart Association 2019.

Dr Paul Wang:                   Welcome to the monthly podcast "On the Beat" for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, Editor-in Chief, with some of the key highlights from this month's issue.                                                 In our first manuscript, Marie Bayer Elming and associates, examined whether the right ventricular ejection fraction can identify patients with non-ischemic systolic heart failure, more likely to benefit from ICD implantation. The Danish study, to assess the efficacy of ICDs in patients with non-ischemic systolic heart failure, on mortality, the Danish study, randomized patients with non-ischemic systolic heart failure to ICD our control. In 239 patients with interpretable cardiovascular magnetic resonance images, the right ventricular volume and ejection fraction was measured. Right ventricular ejection fraction was an independent predictor of all-cause mortality, with a hazard ration 1.34 per 10% absolute decrease in our right ventricular ejection fraction. P=0.02. There is statistically significant interaction between right ventricular ejection fraction and the effect of ICD implantation. P=0.001. ICD implantation significantly reduced all-cause mortality in patients with right ventricular systolic dysfunction. Hazard ratio 0.41, but not in patients without right ventricular systolic dysfunction.                                                 Thus, in this post-hoc analysis of the Danish trial, ICD therapy was associated with survival benefit in patients with bi-ventricular heart failure.                                                 In our next paper, Dawn Pedrotty and Volodymyr Kuzmenko and associates, have proposed a concept of using a stretchable, flexible, bio patch, with conductive properties, to attempt to restore conduction across regions in which activation is disrupted. They use carbon nanotube patches, composed of nanofibrillated cellulose, in single wall carbon nanotube ink, 3-D printed in conductive patterns onto bacterial nanocellulose.                                                 Electro anatomic mapping was performed on normal epicardium and repeated over surgically disruptive epicardium, and finally with the patch applied passively. The patch resulted in restored conduction based on mapping.                                                 In our next paper, Ayman Hussein and colleagues developed a fully automated platform to collect patient reported outcomes in a prospective cohort of atrial fibrillation ablation. Two thousand one hundred and seventy-five patients were eligible to receive 10,903 patient reported outcome assessment invitations. More follow up assessments were obtained with automated patient reported outcomes in routine follow-up, compared with routine follow up alone, P &gt; 0.001, which allowed for longer duration of follow up, 378 vs 217 days. By automated patient reported outcomes, a large number of disease specific variables were collected and showed improvement in quality of life. Baseline median AF symptom severity score of 12 and ranged between 2 and 3 on subsequent assessments, P &gt; 0.0001. This improvement was also true for each of the atrial fibrillation symptom severity score components. In patient reported outcomes, there was a significant reduction in atrial fibrillation burden, such as frequency and duration episodes and associated healthcare utilization including emergency visits and hospitalizations after the ablation procedures.                                                 In our next paper, Nicolas Johner, Dipen Shah, and associates, examined the role of post pacing intervals shorter than tachycardia cycling during entrainment mapping. The author studied 24 non-cavotricuspid isthmus dependent macro oriented atrial flutters in 19 consecutive patients. High density electro anatomic activation maps were acquired with a 64-electrode basket catheter of 102 entrainment mapping sites. Post pacing interval difference less than 30 was observed at 72 sites on complete maps of 24 atypical atrial flutters compared to sites with the difference in post pacing intervals 0 to 30, with 45 sites difference in the post pacing interval less than 0 at 27 were more commonly located within isthmuses less than 15mm wide and more frequently located in within 5mm of the leading wave front. It also exhibited slower local conduction, lower voltages in more frequently fractioned electrograms. The authors concluded that in atrial flutter, sites with differences with the post pacing interval are markers of limited width critical isthmuses with slower conduction velocity, while sites with difference in post pacing interval 0 to 30ms are often not in close proximity to the reentrance circuit. Virtual electrode simultaneous down and up stream, antidromic capture of a confined isthmus of slow conduction can explain a difference in the post pacing interval less than 0.                                                 In the next paper, José Manuel Alfonso-Almazán, and associates studied the safety and efficacy parameters associated with catheter-based radiofrequency delivery at the root of the aorta and pulmonary artery. The author studied 34 pigs undergoing in vivo catheter based ablation using continuous contact force and lesion index monitoring during 60 second radiofrequency delivery with an open, irrigated tip catheter. Twenty-eight animals were allocated to groups receiving 40 watts, 50 watts, or 60 watts and acute, chronic arterial damage was quantified by multi photon microscopy in ex vivo samples. Adjacent microlesion were quantified in parallel samples. The remaining 8 pigs, these were used to validate safety and efficacy parameters. Acute collagen elastic alterations were significantly associated with radiofrequency power, although chronic assessment revealed vascular wall recovery in patients without [steam pop 00:06:56]. The main parameters associated with steam pops were median peak temperature greater than 42C, and impedance falls greater than 23 ohms. Unlike other parameters, lesion index values of 9.1 units were associated with the presence of adjacent myocardial lesions in both univariate and multivariate analyses. In the validation group, lesion index values using 40 watts over a range of contact forces correlated with the size of radiofrequency lesions. Lesion index values obtained during 40 watts radiofrequency application reliably monitor safe and effective lesion creation at the root of the great arteries.                                                 In our next paper, Eiichiro Oka and associates examine the prevalence and significance of the early repolarization electrocardiographic pattern and its mechanistic insight based on cardiac magnetic resonance findings in patients with acute myocarditis. The author studied 30 patients with the diagnosis of acute myocarditis. Nine had an early repolarization electrocardiographical pattern, which was defined as a terminal QRS notching or slurring with an amplitude of greater than zero-point millivolts in at least two inferior and/or lateral leads. The early repolarization group, while the remaining 21 cases had broad ST elevation or pathological QAs.                                                 The non-early repolarization group. The cardiac prepotency level was significantly higher in the non-early repolarization group than the early repolarization group. The ECD changes returned to baseline, along with a normalization of the cardiac biomarkers. Nine of the 21 non-early repolarization group patients, but none of the 9 early repolarization groups developed fulminant course of lethal ventricular arrhythmias. T2-weighted cardiac magnetic resonance imaging showed high intensity signals over the entire transmittal left vertical in the non-early repolarization group, where as they were localized to the left ventricle epicardium in early repolarization group. The early repolarization pattern in acute myocarditis was transient and reversible, and was not associated with a worse prognosis. Inflammation or swelling localized to the left ventricular epicardium, due to myocarditis, may provide a mechanistic insight into the early repolarization pattern.                                                 In our next paper, Beatrix Scholz and Jan Sebastian Schulte and associates analyzed whether the histone deacetylase class I and II inhibitor valproic acid is able to attenuate atrial remodeling in CREM-IbΔCx (TG) transgenic mice. A mouse model of extensive atrial remodeling with age dependent progression from spontaneous atrial ectopy to paroxysmal and finally long lasting atrial fibrillation. Valproic acid was administered for 7 or 25 weeks to transgenic and control mice. Valproic acid attenuated many components of atrial remodeling that were present in the transgenic mice.                                                 Valproic acid significantly reduced atrial dilation, cardiomyocyte enlargement, atrial fibrosis, and the disorganization of myocytes ultrastructure. It significantly reduced the occurrence of atrial thrombi, reversed action potential alterations, and finally delayed the onset of atrial fibrillation by 4 to 8 weeks. Increased histone H4 acetylation in atria from valproic acid treated transgenic mice verified effective in in vivo histone deacetylase inhibition. Cardiomyocyte specific genetic inactivation of histone deacetylase HDAC 2 in transgenic mice attenuated the ultrastructural disorganization of myocytes compared to valproic acid. The author suggests that valproic acid, clinically available, well tolerated, and prescribed to many patients for years, has a therapeutic potential to delay the development of atrial remodeling in the onset of atrial fibrillation in patients at risk.                                                 In our next paper, Bence Hegyi and associates measure the major inward currents in their calcium channel and beta-adrenergic dependence under physiologic action potential clamp in rabbit ventricular myocytes in chronic pressure volume overload induced heart failure versus age matched controls. They found that CAM kinase II dependent up regulation of late sodium current in heart failure significantly contributes to the action potential prolongation in increased short-term variability of action potential repolarization, which may lead to increased arrhythmia propensity and is further exacerbated by adrenergic stress.                                                 In a research letter, Arnaud Bisson and associates examined mitral regurgitation in 838, or 10%, of 8675 patients with atrial fibrillation. A total 135, or 16%, had severe mitral regurgitation. During mean follow-up with 2.5 years, 688 ischemic stroke or thromboembolic events were recorded. mitral regurgitation was associated with a non-significant higher risk of these embolic events. After adjustment for anticoagulant and antiplatelet use, CHA2DS2-VASc and HAS-BLED scores, patients with mitral regurgitation tended to have a higher all cause or cardiovascular mortality but had similar risks of ischemic stroke or thromboembolic events, when compared to patients with no mitral regurgitation. Severe mitral regurgitation was also associated with similar risk for ischemic stroke and thromboembolic events when compared with other atrial fibrillation patients. However, our findings indicate that in patients with atrial fibrillation, neither mitral regurgitation nor severe mitral regurgitation, appears to independently be associated with a different risk of ischemic stroke or thromboembolic events. The perceived protective effect of mitral regurgitation against the risk of thromboembolic events is not relevant in atrial fibrillation when using a contemporary risk score scheme, the CHA2DS2-VASc score.                                                 In our final research paper, Jack Z. Li and associates noted that in 2017, an aggregate of four manufacturers of devices yielded 89.6% with the DF-4 ICD implants. While DF-4 and DF-1 leads generally have comparable performance, several concerns over reduced versatility of the DF-4 have been raised. First, to downgrade an ICD with a DF-4 lead to a pacemaker, a generator change, a new right ventricular pace sense lead must be implanted. The DF-4 pin is incompatible with the IS-1 port and there is no straightforward way to bridge this gap. In contrast, the DF-1 IS-1 lead requires only capping of the DF-1 pin. Second, if an ICD with DF-4 lead has either a distal coil or a right ventricular pacing malfunction, a new lead must be implanted. Third, if a ICD with DF-4 lead has a high defibrillation threshold, management requires either a new DF-1 IS-1 lead with an adapter for a subcutaneous array, or an adapter that inserts into the DF-4 port and receives both the DF-4 lead and the DF-1 pin of the subcutaneous lead. Physicians should have the foresight to select DF-1 leads at the time of initial implant in selected circumstances, such as high possibility for elevated defibrillation threshold requiring a subcutaneous lead or array.                                                 That's it for this month! We hope that you'll find the journal to be the go-to place for everyone interested in the field. See ya next time.                                                 This program is copyright American Heart Association 2019.

Circulation: Arrhythmia and Electrophysiology March 2019 Issue

Dr Paul Wang:                   Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor in Chief, with some of the key highlights from this month's issue.                                                  In our first paper Lucas Boersma and associates examined the final two-year outcome data from 47 centers, in 1,020 patients receiving the left atrial appendage occlusion watchman devices. Their study population had a mean age of 73.4 years, with 311 having prior ischemic stroke or TIA, 153 having prior hemorrhagic stroke, and 318 having prior major bleeding. 49% had a CHAS II vast score of 5 or greater, and 40% had a HAS-BLED score of three or greater. Oral anticoagulation was contraindicated in 72%. During follow up, 161 patients, or 16.4% died, 22 strokes were observed or 1.3 per 100 patient years representing an 83% reduction versus historic data. And 47 major non-procedural bleeding events were observed, or 2.7 per 100 patient years representing a 46% reduction versus historic data.                                                  Device thrombus was observed in 34 patients or 4.1%, and was not correlated to the drug regimen during follow up. P=0.28.                                                  In our next paper, Anish Amin and Associates examined whether high voltage impedance and subcutaneous or SICD system implant position are associated with ventricular fibrillation or VF conversion success with a sub-maximal joule shock. In the SICD investigational device exemption study, a successful conversion test required two consecutive VF conversions at 65 joules in either shock vector. Sub-optimal device position was defined as an inferior electrode or pulse generator, or electrode coil depth of greater than three mm anterior to the sternum, based on chest radiograph. Of 314 patients who underwent SICD implantation, 282 patients were included in this analysis. There were 637 inductions to test defibrillation at 65 joules. 62 conversion failures, or 9.7%, occurred in 42 or 14.9% of patients.                                                  Lower body mass index or BMI, and lower shock impedance, were associated with higher conversion success rate. Whereas white race was associated with lower conversion success rate. Sub-optimal position was more common in obese patients. Inferior electrode and greater distance between the lead and sternum were associated with a higher impedance. When appropriate system position was achieved, conversion failure was not associated with high BMI.                                                  In our next paper, Je-Wook Park and associates examined the left atrial pressure after repeat radiofrequency catheter ablation procedures. Among 1,848 patients who underwent atrial fibrillation or AF catheter ablation, the authors measured the left atrial pressure, LAP, immediately following the transseptal puncture in sinus rhythm in 1,687 patients before De novo ablation, median age 59 years, 72.4% male and 72.8% paroxysmal AF, and in 142 with second procedures. In the same 142 patients, the degree of left atrial stiffness, reflected by LAPP, the difference between LAP peak and LAP nater, was significantly higher in the second procedure than in the De novo procedure. P

Dr Paul Wang:                   Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor in Chief, with some of the key highlights from this month's issue.                                                 In our first paper Lucas Boersma and associates examined the final two-year outcome data from 47 centers, in 1,020 patients receiving the left atrial appendage occlusion watchman devices. Their study population had a mean age of 73.4 years, with 311 having prior ischemic stroke or TIA, 153 having prior hemorrhagic stroke, and 318 having prior major bleeding. 49% had a CHAS II vast score of 5 or greater, and 40% had a HAS-BLED score of three or greater. Oral anticoagulation was contraindicated in 72%. During follow up, 161 patients, or 16.4% died, 22 strokes were observed or 1.3 per 100 patient years representing an 83% reduction versus historic data. And 47 major non-procedural bleeding events were observed, or 2.7 per 100 patient years representing a 46% reduction versus historic data.                                                 Device thrombus was observed in 34 patients or 4.1%, and was not correlated to the drug regimen during follow up. P=0.28.                                                 In our next paper, Anish Amin and Associates examined whether high voltage impedance and subcutaneous or SICD system implant position are associated with ventricular fibrillation or VF conversion success with a sub-maximal joule shock. In the SICD investigational device exemption study, a successful conversion test required two consecutive VF conversions at 65 joules in either shock vector. Sub-optimal device position was defined as an inferior electrode or pulse generator, or electrode coil depth of greater than three mm anterior to the sternum, based on chest radiograph. Of 314 patients who underwent SICD implantation, 282 patients were included in this analysis. There were 637 inductions to test defibrillation at 65 joules. 62 conversion failures, or 9.7%, occurred in 42 or 14.9% of patients.                                                 Lower body mass index or BMI, and lower shock impedance, were associated with higher conversion success rate. Whereas white race was associated with lower conversion success rate. Sub-optimal position was more common in obese patients. Inferior electrode and greater distance between the lead and sternum were associated with a higher impedance. When appropriate system position was achieved, conversion failure was not associated with high BMI.                                                 In our next paper, Je-Wook Park and associates examined the left atrial pressure after repeat radiofrequency catheter ablation procedures. Among 1,848 patients who underwent atrial fibrillation or AF catheter ablation, the authors measured the left atrial pressure, LAP, immediately following the transseptal puncture in sinus rhythm in 1,687 patients before De novo ablation, median age 59 years, 72.4% male and 72.8% paroxysmal AF, and in 142 with second procedures. In the same 142 patients, the degree of left atrial stiffness, reflected by LAPP, the difference between LAP peak and LAP nater, was significantly higher in the second procedure than in the De novo procedure. P

Circulation: Arrhythmia and Electrophysiology April 2019 Issue

Paul Wang:         Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue. In our first paper from the Finland Group Registry, Nordenswan and her colleagues have further defined the risk of sudden cardiac death in ventricular arrhythmias in patients with cardiac sarcoidosis. While it has been observed that there's a high risk of lethal arrhythmias in cardiac sarcoidosis patients with high grade AV block, the incidents in these patients with lone AV block, in the absence of known VT or left ventricular dysfunction, has not been described. From the patients with myocardial inflammatory diseases in their registry, the authors identified 143 cardiac sarcoidosis patients with high grade AV block. Of these patients, 90 had lone AV block. For these patients, the five-year composite incidence of sudden cardiac death or VT was 24%, in comparison with 54% in AV block with ventricular tachycardia or severe left ventricular dysfunction, and 24% with AV block in non-severe left ventricular dysfunction.                                  These findings support implementation of an implantable cardioverter defibrillator for cardiac sarcoidosis patients with lone AV block. A recent study by Gold and Colleagues suggests atrial ventricular optimization improves reverse remodeling in patients with significant intraventricular electrical delay. In this sub-study of the Smart AV Trial, 275 subjects were randomized to either electrogram-based AV optimization, smart delay, or nominal AV delay, 120 milliseconds. In this mostly male cohort, with a mean age of 65 years, and a left ventricular ejection fraction of 28% at follow up, at six months the benefit of AV optimization increased as intraventricular electrical delay prolonged, defined as the time between the peaks of the right and left ventricular electrograms. The longest cohort trial of intraventricular conduction delay had 4.26 times greater odds of remodeling response with AV optimization compared with nominal AV delay. This suggests that the left ventricular lead position in AV optimization might have a synergistic effect in reverse remodeling in cardiac resynchronization patients.                                  Concerns have long been raised that anorexia nervosa causes QT interval prolongation predisposing these individuals to life-threatening ventricular arrhythmias and sudden cardiac death. Fredrickson and Associates made progress in challenging this conclusion, demonstrating that despite a slightly increased incidence in borderline mean QTC, greater than 440 milliseconds, in 430 female anorexia nervosa patients, compared to 123 healthy controls from the Danish Civil Register, there was no difference in the risk of prolonged corrected QT interval greater than 460 milliseconds between the two groups.                                  However, during a 10-year follow up, anorexia nervosa patients had a slightly increased risk of ventricular tachycardiac, aborted cardiac arrest, and cardiac arrest compared to healthy controls. Incidence of 0.5% in the anorexia nervosa patients versus 0.07% in healthy controls. In addition, anorexia nervosa patients had a significantly increased risk of all-cause mortality with a hazard ratio of 11.2 over 10 years compared to population-based cohort, suggesting that anorexia nervosa increases the risk of medical complications, including cardiac complications, but these are not directly related to anorexia nervosa's effects on corrected QT interval.                                  In our next paper, Ahmed Karim Talib and Associates reported on the outcomes of endocardial ablation of drug-resistant ventricular fibrillation in Brugada syndrome. Endocardial mapping ablation was performed in 21 patients with one or more episodes of ventricular fibrillation. Endocardial mapping revealed low voltage fractionated endocardial electrograms in 19% of patients. All patients underwent ablation of ventricular fibrillation triggers, followed by endocardial substrate modification. Noninducibility of ventricular fibrillation and normalization of Brugada ECG was documented in 14, in three patients, respectively. During a mean follow up of 54 months, seven patients, or 33%, experienced ventricular fibrillation recurrences, presence of cruris notching in D1 was associated with the presence of low-voltage fractionated endocardial electrograms in ablation failure.                                  In our next paper, Jae Yeong Cho and Associates tried to elucidate the mechanism of sudden cardiac death in patients with heart failure with preserved ejection fraction using an ambulatory recording in a rat model. They showed that rats who had a clinical phenotype of heart failure with preserved ejection fraction had prolonged QT and QTC intervals and reduced heart rate variability compared to the controls. Importantly, the rats with heart failure and preserved ejection fraction had significantly higher rates of spontaneous ventricular arrhythmias, and about a third died suddenly with ventricular arrhythmia being the terminal rhythm.                                  In our next paper, Elad Anter and Colleagues used a novel mapping algorithm which integrated atrial activation mapping, vector analysis, and the physiologic constraints of atrial excitation to determine an atrial arrhythmias mechanism in circuitry. Ander's group initially applied this technique to historical controls and found that atrial tachycardias were diagnosed and their termination site predicted with 92.5% accuracy. When this algorithm was then applied prospectively to mapping of unknown atrial arrhythmias in 20 patients, this technique was able to identify macroreentrant, localized reentrant in focal tachycardias, even when standard mapping techniques had failed. This enhanced mapping capability allowed for significantly shorter ablation time when compared to historical controls, 3.2 +/- 1.7 minutes versus 17.3 +/- 6.6 minutes.                                  In our next paper Richard Walton and Colleagues explored the anatomical and electrical characteristics of the moderator band which provides a substrate for macroreentrant ventricular tachycardia. Ventricular wedge preparations with intact moderator bands were studied from humans in two cases and sheep in 15 cases. The moderator band structure was remarkably organized as two excitable yet uncoupled compartments of myocardium in [inaudible 00:07:45]. In humans, actual potential duration was significantly shorter in the moderator band than the right ventricular myocardium. S1, S2 moderator band pacing induced unidirectional propagation via the moderator band myocardium, permitting sustained macroreentrant ventricular tachycardia.                                  In sheep, the instance of ventricular tachycardia for right ventricular moderator band, or S1 right ventricular, and S2 moderator band pacing was 1.3%, 5.1%, and 10.3%, respectively. Severing the moderator band led to ventricular tachycardiac termination, confirming a primary arrhythmic role. Inducible preparations had shorter actual potential durations in the moderator band than right ventricle, whereas noninducible preparations showed no difference.                                  In our final paper, Witt and Associates studied the outcomes of 1421 patients who underwent ICD generator placement at Mayo Clinic, Minnesota and Beth Israel Deaconess Medical Center. During a mean follow up of 2.7 years appropriate ICD therapy occurred in 30.6% of the patients, predicted by low left ventricular ejection fraction and history of appropriate ICD therapy prior to generator replacement. On the other hand, 23.7% died prior to appropriate ICD therapy, predicted by old age, low left ventricular ejection fraction, diabetes mellitus, chronic lung disease, peripheral vascular disease, low hemoglobin level, and low glomerular filtration rate. The progressive increase in mortality after ICD generator change was observed in those who had aggregation of non-cardiac co-morbidities.                                  That's it for this month. We hope that you'll find the Journal to be the go-to place for everyone interested in the field. See you next time.

Paul Wang:         Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue. In our first paper from the Finland Group Registry, Nordenswan and her colleagues have further defined the risk of sudden cardiac death in ventricular arrhythmias in patients with cardiac sarcoidosis. While it has been observed that there's a high risk of lethal arrhythmias in cardiac sarcoidosis patients with high grade AV block, the incidents in these patients with lone AV block, in the absence of known VT or left ventricular dysfunction, has not been described. From the patients with myocardial inflammatory diseases in their registry, the authors identified 143 cardiac sarcoidosis patients with high grade AV block. Of these patients, 90 had lone AV block. For these patients, the five-year composite incidence of sudden cardiac death or VT was 24%, in comparison with 54% in AV block with ventricular tachycardia or severe left ventricular dysfunction, and 24% with AV block in non-severe left ventricular dysfunction.                                 These findings support implementation of an implantable cardioverter defibrillator for cardiac sarcoidosis patients with lone AV block. A recent study by Gold and Colleagues suggests atrial ventricular optimization improves reverse remodeling in patients with significant intraventricular electrical delay. In this sub-study of the Smart AV Trial, 275 subjects were randomized to either electrogram-based AV optimization, smart delay, or nominal AV delay, 120 milliseconds. In this mostly male cohort, with a mean age of 65 years, and a left ventricular ejection fraction of 28% at follow up, at six months the benefit of AV optimization increased as intraventricular electrical delay prolonged, defined as the time between the peaks of the right and left ventricular electrograms. The longest cohort trial of intraventricular conduction delay had 4.26 times greater odds of remodeling response with AV optimization compared with nominal AV delay. This suggests that the left ventricular lead position in AV optimization might have a synergistic effect in reverse remodeling in cardiac resynchronization patients.                                 Concerns have long been raised that anorexia nervosa causes QT interval prolongation predisposing these individuals to life-threatening ventricular arrhythmias and sudden cardiac death. Fredrickson and Associates made progress in challenging this conclusion, demonstrating that despite a slightly increased incidence in borderline mean QTC, greater than 440 milliseconds, in 430 female anorexia nervosa patients, compared to 123 healthy controls from the Danish Civil Register, there was no difference in the risk of prolonged corrected QT interval greater than 460 milliseconds between the two groups.                                 However, during a 10-year follow up, anorexia nervosa patients had a slightly increased risk of ventricular tachycardiac, aborted cardiac arrest, and cardiac arrest compared to healthy controls. Incidence of 0.5% in the anorexia nervosa patients versus 0.07% in healthy controls. In addition, anorexia nervosa patients had a significantly increased risk of all-cause mortality with a hazard ratio of 11.2 over 10 years compared to population-based cohort, suggesting that anorexia nervosa increases the risk of medical complications, including cardiac complications, but these are not directly related to anorexia nervosa's effects on corrected QT interval.                                 In our next paper, Ahmed Karim Talib and Associates reported on the outcomes of endocardial ablation of drug-resistant ventricular fibrillation in Brugada syndrome. Endocardial mapping ablation was performed in 21 patients with one or more episodes of ventricular fibrillation. Endocardial mapping revealed low voltage fractionated endocardial electrograms in 19% of patients. All patients underwent ablation of ventricular fibrillation triggers, followed by endocardial substrate modification. Noninducibility of ventricular fibrillation and normalization of Brugada ECG was documented in 14, in three patients, respectively. During a mean follow up of 54 months, seven patients, or 33%, experienced ventricular fibrillation recurrences, presence of cruris notching in D1 was associated with the presence of low-voltage fractionated endocardial electrograms in ablation failure.                                 In our next paper, Jae Yeong Cho and Associates tried to elucidate the mechanism of sudden cardiac death in patients with heart failure with preserved ejection fraction using an ambulatory recording in a rat model. They showed that rats who had a clinical phenotype of heart failure with preserved ejection fraction had prolonged QT and QTC intervals and reduced heart rate variability compared to the controls. Importantly, the rats with heart failure and preserved ejection fraction had significantly higher rates of spontaneous ventricular arrhythmias, and about a third died suddenly with ventricular arrhythmia being the terminal rhythm.                                 In our next paper, Elad Anter and Colleagues used a novel mapping algorithm which integrated atrial activation mapping, vector analysis, and the physiologic constraints of atrial excitation to determine an atrial arrhythmias mechanism in circuitry. Ander's group initially applied this technique to historical controls and found that atrial tachycardias were diagnosed and their termination site predicted with 92.5% accuracy. When this algorithm was then applied prospectively to mapping of unknown atrial arrhythmias in 20 patients, this technique was able to identify macroreentrant, localized reentrant in focal tachycardias, even when standard mapping techniques had failed. This enhanced mapping capability allowed for significantly shorter ablation time when compared to historical controls, 3.2 +/- 1.7 minutes versus 17.3 +/- 6.6 minutes.                                 In our next paper Richard Walton and Colleagues explored the anatomical and electrical characteristics of the moderator band which provides a substrate for macroreentrant ventricular tachycardia. Ventricular wedge preparations with intact moderator bands were studied from humans in two cases and sheep in 15 cases. The moderator band structure was remarkably organized as two excitable yet uncoupled compartments of myocardium in [inaudible 00:07:45]. In humans, actual potential duration was significantly shorter in the moderator band than the right ventricular myocardium. S1, S2 moderator band pacing induced unidirectional propagation via the moderator band myocardium, permitting sustained macroreentrant ventricular tachycardia.                                 In sheep, the instance of ventricular tachycardia for right ventricular moderator band, or S1 right ventricular, and S2 moderator band pacing was 1.3%, 5.1%, and 10.3%, respectively. Severing the moderator band led to ventricular tachycardiac termination, confirming a primary arrhythmic role. Inducible preparations had shorter actual potential durations in the moderator band than right ventricle, whereas noninducible preparations showed no difference.                                 In our final paper, Witt and Associates studied the outcomes of 1421 patients who underwent ICD generator placement at Mayo Clinic, Minnesota and Beth Israel Deaconess Medical Center. During a mean follow up of 2.7 years appropriate ICD therapy occurred in 30.6% of the patients, predicted by low left ventricular ejection fraction and history of appropriate ICD therapy prior to generator replacement. On the other hand, 23.7% died prior to appropriate ICD therapy, predicted by old age, low left ventricular ejection fraction, diabetes mellitus, chronic lung disease, peripheral vascular disease, low hemoglobin level, and low glomerular filtration rate. The progressive increase in mortality after ICD generator change was observed in those who had aggregation of non-cardiac co-morbidities.                                 That's it for this month. We hope that you'll find the Journal to be the go-to place for everyone interested in the field. See you next time.

Circulation: Arrhythmia and Electrophysiology August 2018 Issue

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, editor in chief, with some of the key highlights for this month's issue.                                                  In our first paper, Pasquale Vergara and Associates develop a predictive risk score to assess the outcome of ventricular tachycardia ablation creating what they call the IVT score. The authors examined 16 demographics, clinical, and procedural related variables in 1,251 patients. They used a technique called survival tree analysis, which uses a recursive partitioning algorithm to find relationships among variables.                                                  They then compared the survival time and time to VT recurrence in groups derived from survival tree analysis using a log rank test. A random forest analysis was then run to extract a variable importance index and internally validate the survival tree models. They found that the left ventricular ejection fraction, ICD, or CRT device, previous ablation were the best predictors of ventricular tachycardia recurrence. While left ventricular ejection fraction, previous ablation, electrical storm was identified as best predictors of mortality.                                                  They identified a high-risk group in which 65% of patients survived and 52.1% were free from VT occurrence. A medium risk group in which 84% survived and 72% were free of VT, and a low risk group in which 97% of patients survived and 88% were free of VT recurrence.                                                  In our next paper, Alwin Zweerink and Associates examined the relationship between cure restoration and left ventricular dimension as predictors of outcomes after cardiac re-synchronization therapy. The present study evaluates the effect of normalization of the cure restoration to left ventricular dimension on the prediction of survival after CRT implantation. They study 250 heart failure patients with left ventricular ejection fraction less than or equal to 35% in cure restoration greater than or equal to 120 milliseconds, and they normalize the cure restoration based on the left ventricular dimension. The left ventricular and diastolic volumes obtained using cardiac magnetic resonance imaging.                                                  Before CRT implantation were used for cure restoration normalization. During a follow up period of 3.9 years, 79 patients or 32% reached the primary end point, which combined death, left ventricular assist device, or heart transplantation. Using univariable cox regression they found that although the unadjusted cure restoration was unrelated to CRT outcome, P=0.116, the normalized cure restoration was a strong predictor of survival. Hazard ratio 0.81 per 0.1 milliseconds per milliliter, P=0.008.                                                  Women demonstrated higher normalized cure restorations than men, 0.2 milliseconds per milliliter, versus 0.55 millisecond per milliliter, P=0.003, and showed better survival after CRT. Hazard ratio 0.52 with P=0.018.                                                  In our next study, Markus Linhart and Associates examined the impact of catheter ablation gaps on outcomes after first pulmonary vein isolation. Using delayed gadolinium enhancement cardiac magnetic resonance imaging three months after radio frequency ablation, they found that in 94 patients, 62% with paroxysmal atrial fibrillation, that there was a mean number of 5.4 gaps per patients. Atrial fibrillation recurrence within the first year of ablation was observed in 21 patients with paroxysmal AF, 36%, and 19 patients with persistent atrial fibrillation, 53%.                                                  In the unit variate analysis, CHA2DS2 -VASc score, afib type and relative gap length were predictors of recurrence. In multi-variant analysis, only relative gap length was significantly associated with recurrence. Hazard ratio 1.16 per each 10% of the gap.                                                  In our next paper, Antonius van Stipdonk, Iris ter Horst, Marielle Kloosterman, Alexander Maass, Kevin Vernooy and Associates examined the value of cueres area compared to that of cure restoration and morphology as predictors of clinical echocardiographical outcomes following cardiac resynchronization therapy. The authors found that in 1,492 cardiac resynchronization therapy patients during a mean follow up of 3.4 years, 32% of patients reached the combined prior endpoint of all-cause mortality, cardiac transplantation, and left ventricular assist device implantation.                                                  The authors found that cure restoration identified patients that did not experience the primary endpoint better than QRS morphology in cure restoration area under the curve 0.61 versus 0.55 and 0.51, P value less than 0.001. They also found that QRS area identifies patients with echocardiograph remodeling in response to CRT better than the QRS morphology and duration, area under the curve 0.69 versus 0.58 and 0.58, P &lt; 0.001. In addition, QRS area was the only independent electrocardiographic determine associated with the primary endpoint. Hazard ratio 0.50 QRS area retained its significant associative outcomes in both patients with and without left bundle branch block in cure restoration greater than 150 milliseconds.                                                  Our next paper is a research letter in which Brian Hansen, Ning Li and Associates report the first in-vivo use in a canine model of near infrared optical mapping. In-vivo optical action potential showed a sharp upstroke that corresponded with atrial activation at a neighboring electrode. Imaging during in-vivo atrial fibrillation episodes showed re-entrant activation around the sinoatrial region minimizing the effect of motion artifact in validation in structurally remodeled hearts would be the next steps for this promising technology.                                                  Also, in a research letter, James Hummel and Associates studied whether infrared thermography over a six-centimeter segment can be effectively used to guide atrial fibrillation ablation. Thermography continuously sampled 7,680 points over a full 360 degree and refreshed every second. Ablation was guided by 3D mapping and performed using a 3.5-millimeter irrigated tip. Power was reduced to 25-watts on the left atrial posterior wall and could be further reduced to 20-watts in areas where there was excessive esophageal temperature rise. Esophageal temperature cutoff for radio frequency power delivery was initially 46 degrees and progressively raised to 50 degrees throughout the study at the discretion of the operators.                                                  All patients underwent upper endoscopy on post-ablation day one to three by a gastroenterologist blinded to temperature data. Thirty-four patients were studied, 94% of patients had luminal esophageal temperatures above 40 degrees during ablation of the posterior wall. Thermal events with Tmex greater than 40 degrees occurred commonly averaging 6.5 seconds during a procedure. On average, 231 seconds of ablation were performed with Tmex greater than 40 degrees centigrade. However, the excursions above threshold cutoff Tmex greater than 50 degrees centigrade lasted only 1.5 seconds per patient. In total, 38% of patients, 13 out of 34 had at least one energy delivery discontinued for exceeding threshold. This occurred eight out of 17 times or 47% when the cutoff was 46 degrees centigrade and five out of 15, or 33% at 50 degrees centigrade.                                                  On endoscopy one patient, 3% had thermal injury related to malpositioning of the infrared thermal probe below the region of ablation. Another patient had three lesions spanning 16 centimeters likely related to mechanical trauma with probe placement. The authors concluded that esophageal injury does not seem to occur with esophageal temperatures less than 50 degrees centigrade using thermography.                                                  In a review paper in this issue, Bruce Lerman and Associates discussed adenosine as a potent but underutilized tool that is useful in clarifying in clinical diagnoses of arrhythmias. Adenosine mediates its electrophysiological effect through binding to the cell surface adenosine receptor A1R, a G-protein receptor. In the sinoatrial node, activation of IKADO by adenosine results in negative chronotrophy, a manifestation of its modern effects on membrane hyperpolarization and a decrease in the rate of phase four depolarization. Adenosine also mediates its cellular effects in atrial and AV nodal cells predominantly through activation of IKADO. In atrial myocytes, this results in a shortening of action potential duration in decrease in refractoriness. By shortening the atrial refractory period without changing atrial conduction velocity, the wavelength of activation is shortened. A mechanism through which adenosine can facilitate induction of atrial fibrillation. Adenosine also exerts an antiadrenergic effect in atrial tissue, reducing cyclic AMP stimulated levels of L-type calcium current.                                                  Adenosine has a negative dromotropic effect on the AV node. The most potent effects of adenosine are expressed in N-cells. In these cells, as well as AN-cells, adenosine decreases excitability by reducing the plateau amplitude in abbreviating action potential duration. In addition, it reduces the rate of rise of the upstroke of N-cells. NH-cells are insensitive to adenosine. Adenosine terminates permanent form of junctional recipriatachycardia in the retrograde accessory pathway limb. The mechanism in which adenosine causes block in the retrograde decremental accessory pathway is thought to be by hyper-polarizing the pathways membrane potential. Adenosine has been helpful in illuminating differences in etiology of decremental conduction in three predominant antigrid decremental accessory pathways. Atrial ventricular pathways, atrial physicular pathways, and nodoventricular pathways.                                                  Adenosine can elicit dormant conduction defined as a restoration of excitability by adenosine in tissue rendered inexcitable by partial cellular damage secondary to ablation. There are three discrete clinical scenarios in which adenosine reveals dormant conduction - after pulmonary vein isolation, after achieving bi-directional cavo-tricuspid isthmus block, and following successful ablation of antegrade and retrograde accessory potential. Adenosine, through activation of IKADO hyperpolarizing these cells so that the sodium channels are reactivated, restoring excitability. Adenosine, though its inhibition of cyclic ANP mediated increases in the slow inward calcium current and its downstream inhibitory effects on SR-calcium release, INCX and ITI, terminates focal arrhythmias caused by triggered activity. The response to adenosine may indicate triggered activity where termination occurs versus insensitivity of localized re-entry to adenosine.                                                  That's it for this month, we hope that you will find The Journal to be the go-to place for everyone interested in the field. See you next time.

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, editor in chief, with some of the key highlights for this month's issue.                                                 In our first paper, Pasquale Vergara and Associates develop a predictive risk score to assess the outcome of ventricular tachycardia ablation creating what they call the IVT score. The authors examined 16 demographics, clinical, and procedural related variables in 1,251 patients. They used a technique called survival tree analysis, which uses a recursive partitioning algorithm to find relationships among variables.                                                 They then compared the survival time and time to VT recurrence in groups derived from survival tree analysis using a log rank test. A random forest analysis was then run to extract a variable importance index and internally validate the survival tree models. They found that the left ventricular ejection fraction, ICD, or CRT device, previous ablation were the best predictors of ventricular tachycardia recurrence. While left ventricular ejection fraction, previous ablation, electrical storm was identified as best predictors of mortality.                                                 They identified a high-risk group in which 65% of patients survived and 52.1% were free from VT occurrence. A medium risk group in which 84% survived and 72% were free of VT, and a low risk group in which 97% of patients survived and 88% were free of VT recurrence.                                                 In our next paper, Alwin Zweerink and Associates examined the relationship between cure restoration and left ventricular dimension as predictors of outcomes after cardiac re-synchronization therapy. The present study evaluates the effect of normalization of the cure restoration to left ventricular dimension on the prediction of survival after CRT implantation. They study 250 heart failure patients with left ventricular ejection fraction less than or equal to 35% in cure restoration greater than or equal to 120 milliseconds, and they normalize the cure restoration based on the left ventricular dimension. The left ventricular and diastolic volumes obtained using cardiac magnetic resonance imaging.                                                 Before CRT implantation were used for cure restoration normalization. During a follow up period of 3.9 years, 79 patients or 32% reached the primary end point, which combined death, left ventricular assist device, or heart transplantation. Using univariable cox regression they found that although the unadjusted cure restoration was unrelated to CRT outcome, P=0.116, the normalized cure restoration was a strong predictor of survival. Hazard ratio 0.81 per 0.1 milliseconds per milliliter, P=0.008.                                                 Women demonstrated higher normalized cure restorations than men, 0.2 milliseconds per milliliter, versus 0.55 millisecond per milliliter, P=0.003, and showed better survival after CRT. Hazard ratio 0.52 with P=0.018.                                                 In our next study, Markus Linhart and Associates examined the impact of catheter ablation gaps on outcomes after first pulmonary vein isolation. Using delayed gadolinium enhancement cardiac magnetic resonance imaging three months after radio frequency ablation, they found that in 94 patients, 62% with paroxysmal atrial fibrillation, that there was a mean number of 5.4 gaps per patients. Atrial fibrillation recurrence within the first year of ablation was observed in 21 patients with paroxysmal AF, 36%, and 19 patients with persistent atrial fibrillation, 53%.                                                 In the unit variate analysis, CHA2DS2 -VASc score, afib type and relative gap length were predictors of recurrence. In multi-variant analysis, only relative gap length was significantly associated with recurrence. Hazard ratio 1.16 per each 10% of the gap.                                                 In our next paper, Antonius van Stipdonk, Iris ter Horst, Marielle Kloosterman, Alexander Maass, Kevin Vernooy and Associates examined the value of cueres area compared to that of cure restoration and morphology as predictors of clinical echocardiographical outcomes following cardiac resynchronization therapy. The authors found that in 1,492 cardiac resynchronization therapy patients during a mean follow up of 3.4 years, 32% of patients reached the combined prior endpoint of all-cause mortality, cardiac transplantation, and left ventricular assist device implantation.                                                 The authors found that cure restoration identified patients that did not experience the primary endpoint better than QRS morphology in cure restoration area under the curve 0.61 versus 0.55 and 0.51, P value less than 0.001. They also found that QRS area identifies patients with echocardiograph remodeling in response to CRT better than the QRS morphology and duration, area under the curve 0.69 versus 0.58 and 0.58, P &lt; 0.001. In addition, QRS area was the only independent electrocardiographic determine associated with the primary endpoint. Hazard ratio 0.50 QRS area retained its significant associative outcomes in both patients with and without left bundle branch block in cure restoration greater than 150 milliseconds.                                                 Our next paper is a research letter in which Brian Hansen, Ning Li and Associates report the first in-vivo use in a canine model of near infrared optical mapping. In-vivo optical action potential showed a sharp upstroke that corresponded with atrial activation at a neighboring electrode. Imaging during in-vivo atrial fibrillation episodes showed re-entrant activation around the sinoatrial region minimizing the effect of motion artifact in validation in structurally remodeled hearts would be the next steps for this promising technology.                                                 Also, in a research letter, James Hummel and Associates studied whether infrared thermography over a six-centimeter segment can be effectively used to guide atrial fibrillation ablation. Thermography continuously sampled 7,680 points over a full 360 degree and refreshed every second. Ablation was guided by 3D mapping and performed using a 3.5-millimeter irrigated tip. Power was reduced to 25-watts on the left atrial posterior wall and could be further reduced to 20-watts in areas where there was excessive esophageal temperature rise. Esophageal temperature cutoff for radio frequency power delivery was initially 46 degrees and progressively raised to 50 degrees throughout the study at the discretion of the operators.                                                 All patients underwent upper endoscopy on post-ablation day one to three by a gastroenterologist blinded to temperature data. Thirty-four patients were studied, 94% of patients had luminal esophageal temperatures above 40 degrees during ablation of the posterior wall. Thermal events with Tmex greater than 40 degrees occurred commonly averaging 6.5 seconds during a procedure. On average, 231 seconds of ablation were performed with Tmex greater than 40 degrees centigrade. However, the excursions above threshold cutoff Tmex greater than 50 degrees centigrade lasted only 1.5 seconds per patient. In total, 38% of patients, 13 out of 34 had at least one energy delivery discontinued for exceeding threshold. This occurred eight out of 17 times or 47% when the cutoff was 46 degrees centigrade and five out of 15, or 33% at 50 degrees centigrade.                                                 On endoscopy one patient, 3% had thermal injury related to malpositioning of the infrared thermal probe below the region of ablation. Another patient had three lesions spanning 16 centimeters likely related to mechanical trauma with probe placement. The authors concluded that esophageal injury does not seem to occur with esophageal temperatures less than 50 degrees centigrade using thermography.                                                 In a review paper in this issue, Bruce Lerman and Associates discussed adenosine as a potent but underutilized tool that is useful in clarifying in clinical diagnoses of arrhythmias. Adenosine mediates its electrophysiological effect through binding to the cell surface adenosine receptor A1R, a G-protein receptor. In the sinoatrial node, activation of IKADO by adenosine results in negative chronotrophy, a manifestation of its modern effects on membrane hyperpolarization and a decrease in the rate of phase four depolarization. Adenosine also mediates its cellular effects in atrial and AV nodal cells predominantly through activation of IKADO. In atrial myocytes, this results in a shortening of action potential duration in decrease in refractoriness. By shortening the atrial refractory period without changing atrial conduction velocity, the wavelength of activation is shortened. A mechanism through which adenosine can facilitate induction of atrial fibrillation. Adenosine also exerts an antiadrenergic effect in atrial tissue, reducing cyclic AMP stimulated levels of L-type calcium current.                                                 Adenosine has a negative dromotropic effect on the AV node. The most potent effects of adenosine are expressed in N-cells. In these cells, as well as AN-cells, adenosine decreases excitability by reducing the plateau amplitude in abbreviating action potential duration. In addition, it reduces the rate of rise of the upstroke of N-cells. NH-cells are insensitive to adenosine. Adenosine terminates permanent form of junctional recipriatachycardia in the retrograde accessory pathway limb. The mechanism in which adenosine causes block in the retrograde decremental accessory pathway is thought to be by hyper-polarizing the pathways membrane potential. Adenosine has been helpful in illuminating differences in etiology of decremental conduction in three predominant antigrid decremental accessory pathways. Atrial ventricular pathways, atrial physicular pathways, and nodoventricular pathways.                                                 Adenosine can elicit dormant conduction defined as a restoration of excitability by adenosine in tissue rendered inexcitable by partial cellular damage secondary to ablation. There are three discrete clinical scenarios in which adenosine reveals dormant conduction - after pulmonary vein isolation, after achieving bi-directional cavo-tricuspid isthmus block, and following successful ablation of antegrade and retrograde accessory potential. Adenosine, through activation of IKADO hyperpolarizing these cells so that the sodium channels are reactivated, restoring excitability. Adenosine, though its inhibition of cyclic ANP mediated increases in the slow inward calcium current and its downstream inhibitory effects on SR-calcium release, INCX and ITI, terminates focal arrhythmias caused by triggered activity. The response to adenosine may indicate triggered activity where termination occurs versus insensitivity of localized re-entry to adenosine.                                                 That's it for this month, we hope that you will find The Journal to be the go-to place for everyone interested in the field. See you next time.

Circulation: Arrhythmia and Electrophysiology December 2018 Issue

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue. Dr Paul Wang:                   In our first paper, Farhad Pashakhanloo and associates examine the three-dimensional structure of the healed infarct and the ventricular tachycardia reentrant pathways in high-resolution models of infarcted porcine hearts. The authors used ex vivo late gadolinium enhancement in diffusion tensor MRI data of eight chronically infarcted porcine hearts at sub-millimeter resolution in a novel scar map thickness metric to reveal the heterogeneous organization of infarct. The authors use simulation to model ventricular tachycardia pathways. They found that a surviving sub-endocardial tissue later of varying thickness less than or equal to 2.2 millimeters surrounding the scar participated in the majority of ventricular tachycardias. The authors concluded that these analyses provided a better understanding of infarc-related ventricular tachycardia. Dr Paul Wang:                   In our next paper, Thomas Hadberg Lynge and associates studied the incidence of sudden cardiac death in a population of congenital heart disease in Denmark. Among 24.4 million person years over a nine-year period, there were 11,451 deaths that were examined. Of 809 cases of sudden cardiac death, 90, or 11% of the cases, were from congenital heart disease. Of these cases, 53, or 59% had the diagnosis of congenital heart disease prior to death. The incidence of sudden cardiac death was 9.6 times higher among patients with congenital heart disease compared to patients without congenital heart disease, p

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue. Dr Paul Wang:                   In our first paper, Farhad Pashakhanloo and associates examine the three-dimensional structure of the healed infarct and the ventricular tachycardia reentrant pathways in high-resolution models of infarcted porcine hearts. The authors used ex vivo late gadolinium enhancement in diffusion tensor MRI data of eight chronically infarcted porcine hearts at sub-millimeter resolution in a novel scar map thickness metric to reveal the heterogeneous organization of infarct. The authors use simulation to model ventricular tachycardia pathways. They found that a surviving sub-endocardial tissue later of varying thickness less than or equal to 2.2 millimeters surrounding the scar participated in the majority of ventricular tachycardias. The authors concluded that these analyses provided a better understanding of infarc-related ventricular tachycardia. Dr Paul Wang:                   In our next paper, Thomas Hadberg Lynge and associates studied the incidence of sudden cardiac death in a population of congenital heart disease in Denmark. Among 24.4 million person years over a nine-year period, there were 11,451 deaths that were examined. Of 809 cases of sudden cardiac death, 90, or 11% of the cases, were from congenital heart disease. Of these cases, 53, or 59% had the diagnosis of congenital heart disease prior to death. The incidence of sudden cardiac death was 9.6 times higher among patients with congenital heart disease compared to patients without congenital heart disease, p

Circulation: Arrhythmia and Electrophysiology On the Beat June 2018

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. In our first paper this month, Shaan Khurshid and associates determine the frequency of rhythm abnormalities in 502,627 adults in the UK Biobank, a national prospective cohort. They found that 2.35% had a baseline rhythm abnormality. The prevalence increased with age, with 4.84% of individuals aged 65 to 73 years having rhythm abnormalities. During over three million person- years of follow up, nearly 16,000 new rhythm abnormalities were detected. Atrial fibrillation was the most frequent with three per thousand person-years. Bradyarrhythmia with almost one per thousand person-years. Conduction system disease is about one per one thousand years. Supraventricular and ventricular arrhythmias, each about one half per one thousand person-years. Older age was associated with a hazard ratio of 2.35 for each 10 year increase. Male sex, hypertension, chronic kidney disease and heart failure were all associated with new rhythm abnormalities. In our next paper, Fabien Squara and associates evaluated a method of determining the septal or free wall positioning of pacemaker or ICD leads during fluoroscopy. They compared in 50 patients a classical approach using posterior anterior, right anterior oblique 30 degrees, and left anterior oblique 40 degrees fluoroscopic imaging’s to 50 patients undergoing an individualized left anterior oblique or LAO approach. This individualized LAO approach view provided a true view of the interventricular septum. This angle was defined by the degree of LAO that allowed the perfect superimposition of the RV apex, using the tip of the right ventricular lead, temporarily placed at the apex, and one of the superior vena cava, inferior vena cava access using a guide wire. Transthoracic echo was used to confirm position of the right ventricular lead. Septal, or free wall, right ventricular lead positioning was correctly identified in 96% of patients in the individualized group, versus 76% in the classical group. P equals 0.004. For septal lead positioning fluoroscopy had 100% sensitivity, and an 89.5 specificity in an individualized group, versus 91.4% sensitivity, and a 40% specificity in the classical group. In our next paper, Elsayed Soliman and associates examined the lifetime risk of atrial fibrillation based on race and socioeconomic status. In the atherosclerosis risk in communities, ARIC, cohort, of 15,343 participants without atrial fibrillation, patients were recruited in 1987 to 1989, when they were 45 to 64 years of age, and followed through 2014. The authors identify 2,760 atrial fibrillation cases during a mean follow up of 21 years. The authors found that the lifetime risk of atrial fibrillation in the ARIC cohort was approximately one in three among whites, and one in five among African Americans. And, the socioeconomic status was inversely associated with cumulative incidents of atrial fibrillation before the last decades of life. In our next paper, Jonathan Steinberg and associates sought to determine the impact of atrial fibrillation episode duration threshold on atrial fibrillation incidents and burden in pacemaker patients in a prospective registry. In 615 pacemaker patients was device detected atrial fibrillation over a mean follow up of 3.7 years, 599 had one or more atrial fibrillation episodes of 30 seconds duration, with a mean number of 22 episodes. At 12 months, freedom from atrial fibrillation ranged from 25.5% to 73.1%, based on a duration threshold from 30 seconds up to 24 hours. Of patients with a first episode of 30 seconds to two minutes, 35.8% were free from subsequent episodes greater than two minutes at 180 days. The mean atrial fibrillation burden of 0.2% for patients with first episodes between 30 seconds and 3.8 hours, was significantly less than the 9.5% burden for those with greater than 3.8 hours. The authors concluded that small differences in atrial fibrillation episode duration definition can significantly affect the perceived incidents of atrial fibrillation impact reported outcomes, including atrial fibrillation success. An initial atrial fibrillation episode of 30 seconds does not predict clinically meaningful atrial fibrillation burden. In the next paper, Hongwu Chen and Linsheng Shi and associates examined the distinct electrophysiologic features of bundle branch reentrant ventricular tachycardia in patients without structural heart disease. They described nine patients, mean age 29.6 years, with normal left ventricular function and bundle branch reentrant ventricular tachycardia, with a right bundle branch block pattern in one patient, and left bundle branch block patterns in nine patients. In all left bundle branch block pattern ventricular tachycardia, the mean ventricular tachycardia cycling was 329.3 milliseconds, and the median HV interval during tachycardia was longer than that of baseline, 78 versus 71 milliseconds. The H to right bundle interval during ventricular tachycardia was slightly shorter, however, the right bundle to ventricular interval was markedly longer than that during sinus rhythm, 50 versus 30 milliseconds. In six patients with three dimensional mapping of the left ventricle, a slow anterograde, or retrograde conduction over the left His-Purkinje system with normal myocardial voltage was identified. In addition, Purkinje related ventricular tachycardias were also induced in five patients. Ablation was applied to the distal left bundle branch block in patients with baseline left bundle branch block, and in one narrow QRS patient with sustained Purkinje related ventricular tachycardia, while right bundle branch was targeted in other patients. During a mean follow up at 31.4 months, frequent premature ventricular contractions occurred in one patient, and new ventricular tachycardia developed in the other patient. In the next paper, Michel Haissaguerre and associates examined detailed mapping in 24 patients who survived idiopathic ventricular fibrillation. They used multi-electrode body surface recordings to identify the drivers maintaining ventricular fibrillation, and analyze electrograms in the driver regions, using endocardial and epicardial catheter mapping during sinus rhythm. Ventricular fibrillation occurred spontaneous in three patients, and was induced in 16, while VF was non-inducible in five. Ventricular fibrillation mapping demonstrated reentrant and focal activities, 87% and 13% respectively. The activities were dominant in one ventricle in nine patients, while they were biventricular in the others. During sinus rhythm, areas of abnormal electrograms were identified in 15 out of 24 patients, or 62.5%, revealing localized structural alterations, in the right ventricle in 11, the left ventricle in one, in both in three. They covered a limited surface, 13 centimeters squared, representing 5% of the total surface, and recorded predominantly on the epicardium. 76% of these areas were co-located with ventricular fibrillation drivers. In nine patients without structural alterations, the authors observed a high incidence of Purkinje triggers, seven out of nine, versus four out of 15. Catheter ablation resulted in arrhythmia-free outcomes in 15 out of 18 patients at a 17 month follow up. In our next paper, David Spar and associates describe the effectiveness, safety, and compliance of the wearable cardioverter defibrillator in the identification and treatment of life-threatening ventricular arrhythmias in all US pediatric patients who wore a wearable defibrillator from 2009 to 2016, ages less than 18 years. The 455 patients had a median age of 15 years, median duration of wearable cardioverter defibrillator use of 33 days, and median patient wear time of 20.6 hours per day. The study population was divided into two groups, 63 patients with an ICD problem, or 392 patients without an ICD problem. The wear time was greater than 20 hours in both groups. There were seven deaths, or 1.5%. All patients were not wearing the wearable cardioverter defibrillator at the time of death. Eight patients, 1.8%, received at least one wearable cardioverter defibrillator shock treatment. Of the six patients who had appropriate therapy, there were seven episodes of either polymorphic ventricular tachycardia, or ventricular fibrillation, with a total of 13 treatments delivered. All episodes were successfully converted, and the patient survived. In our next paper, Marc Lemoine and associates used human-induced pluripotential stem cell-derived cardiomyocytes to examine differences in repolarization reserve. The authors compared the contribution of IKs and IKr on action potential durations in human left ventricular tissue, and the human induced pluripotential stem cell derived cardiomyocytes, or IPS-derived engineered heart tissue. They found that the IPS-derived heart tissue showed spontaneous diastolic depolarization in action potential duration, which were sensitive to low concentrations of Ivabradine. IKr block by E-4031 prolonged action potential duration 90 with similar EC50 in both the IPS-derived heart tissue and the human left ventricular tissue. But a larger effect size in the IPS-derived heart tissue, 281 milliseconds versus 110 milliseconds, in the human left ventricular tissue. While IKr block alone evoked early after depolarizations, it triggered activity in 50% of the IPS-derived heart tissue. Slow pacing reduced extracellular potassium blocking of IKr, IKs and IK1 were necessary to induce early after depolarizations in human left ventricular tissue. In accordance with their clinical safety, Moxifloxacin and Verapamil did not induce EADs in IPS-derived heart tissue. In both IPS-derived heart tissue and human left ventricular tissue, IKs block by HMR 1556 prolonged action potential duration 90 slightly in the combined presence of E-4031 and isoprenaline. In our next paper, Elizabeth Saarel and associates sought to obtain contemporary digital ECG measurements in healthy children from North America to evaluate the effects of sex and race, and to compare the results to commonly published data sets, using 2400 digital ECGs, collected for children less than 18 years of age with normal electrocardiograms at 19 centers in the pediatric heart network. The authors found that the QTc in lead II was greater for females compared to males for age groups three years or older, for whites compared to African Americans, for ages 12 years or older. The R wave amplitude in V6 was greater for males compared to females for age groups 12 years and greater; for African Americans compared to white or other race categories for age groups three years or greater; and greater compared to commonly used public data set groups for ages 12 years and greater. In our next paper, Pyotr Platonov and associates examined T-wave morphology as a possible predictor of cardiac events in patients with type 2 long QT syndrome mutation carriers with normal QTc intervals. The authors compared 154 LQT2 mutation carriers with QTc less than 360 milliseconds in men, and less than 470 milliseconds in women, with 1007 unaffected family members. Flat, notched, or negative T-waves in leads II or V5 on baseline ECG were considered abnormal. Using Cox regression analysis, the associations between T-wave morphology, the presence in mutations in the poor region of KCNH2, and the risk of cardiac events defined that syncope aborted cardiac arrest, defibrillator therapy, or sudden cardiac arrests were assessed. The authors found that LQT2 female carriers with abnormal T-wave morphology had a threefold increased risk of cardiac events compared to LQT2 female carriers with normal T-waves, while this association was not seen in males. LQT2 males with poor location of mutations had a six-fold increased risk of cardiac events than non-poor location males, while no such association was found in females. In our last paper, Yaniv Bar-Cohen and associates describe a percutaneous pacemaker entirely implanted in the pericardium, using a sheath for sub-xiphoid access to the pericardial space, and a miniaturized camera with fiber optic illumination, the micro-pacemakers were successfully implanted in six pigs. All animals were studied during follow up, survived without symptoms. That's it for this month. We hope that you'll find the Journal to be the go-to place for everyone interested in the field. See you next time!

Dr Paul Wang:                   Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. In our first paper this month, Shaan Khurshid and associates determine the frequency of rhythm abnormalities in 502,627 adults in the UK Biobank, a national prospective cohort. They found that 2.35% had a baseline rhythm abnormality. The prevalence increased with age, with 4.84% of individuals aged 65 to 73 years having rhythm abnormalities. During over three million person- years of follow up, nearly 16,000 new rhythm abnormalities were detected. Atrial fibrillation was the most frequent with three per thousand person-years. Bradyarrhythmia with almost one per thousand person-years. Conduction system disease is about one per one thousand years. Supraventricular and ventricular arrhythmias, each about one half per one thousand person-years. Older age was associated with a hazard ratio of 2.35 for each 10 year increase. Male sex, hypertension, chronic kidney disease and heart failure were all associated with new rhythm abnormalities. In our next paper, Fabien Squara and associates evaluated a method of determining the septal or free wall positioning of pacemaker or ICD leads during fluoroscopy. They compared in 50 patients a classical approach using posterior anterior, right anterior oblique 30 degrees, and left anterior oblique 40 degrees fluoroscopic imaging’s to 50 patients undergoing an individualized left anterior oblique or LAO approach. This individualized LAO approach view provided a true view of the interventricular septum. This angle was defined by the degree of LAO that allowed the perfect superimposition of the RV apex, using the tip of the right ventricular lead, temporarily placed at the apex, and one of the superior vena cava, inferior vena cava access using a guide wire. Transthoracic echo was used to confirm position of the right ventricular lead. Septal, or free wall, right ventricular lead positioning was correctly identified in 96% of patients in the individualized group, versus 76% in the classical group. P equals 0.004. For septal lead positioning fluoroscopy had 100% sensitivity, and an 89.5 specificity in an individualized group, versus 91.4% sensitivity, and a 40% specificity in the classical group. In our next paper, Elsayed Soliman and associates examined the lifetime risk of atrial fibrillation based on race and socioeconomic status. In the atherosclerosis risk in communities, ARIC, cohort, of 15,343 participants without atrial fibrillation, patients were recruited in 1987 to 1989, when they were 45 to 64 years of age, and followed through 2014. The authors identify 2,760 atrial fibrillation cases during a mean follow up of 21 years. The authors found that the lifetime risk of atrial fibrillation in the ARIC cohort was approximately one in three among whites, and one in five among African Americans. And, the socioeconomic status was inversely associated with cumulative incidents of atrial fibrillation before the last decades of life. In our next paper, Jonathan Steinberg and associates sought to determine the impact of atrial fibrillation episode duration threshold on atrial fibrillation incidents and burden in pacemaker patients in a prospective registry. In 615 pacemaker patients was device detected atrial fibrillation over a mean follow up of 3.7 years, 599 had one or more atrial fibrillation episodes of 30 seconds duration, with a mean number of 22 episodes. At 12 months, freedom from atrial fibrillation ranged from 25.5% to 73.1%, based on a duration threshold from 30 seconds up to 24 hours. Of patients with a first episode of 30 seconds to two minutes, 35.8% were free from subsequent episodes greater than two minutes at 180 days. The mean atrial fibrillation burden of 0.2% for patients with first episodes between 30 seconds and 3.8 hours, was significantly less than the 9.5% burden for those with greater than 3.8 hours. The authors concluded that small differences in atrial fibrillation episode duration definition can significantly affect the perceived incidents of atrial fibrillation impact reported outcomes, including atrial fibrillation success. An initial atrial fibrillation episode of 30 seconds does not predict clinically meaningful atrial fibrillation burden. In the next paper, Hongwu Chen and Linsheng Shi and associates examined the distinct electrophysiologic features of bundle branch reentrant ventricular tachycardia in patients without structural heart disease. They described nine patients, mean age 29.6 years, with normal left ventricular function and bundle branch reentrant ventricular tachycardia, with a right bundle branch block pattern in one patient, and left bundle branch block patterns in nine patients. In all left bundle branch block pattern ventricular tachycardia, the mean ventricular tachycardia cycling was 329.3 milliseconds, and the median HV interval during tachycardia was longer than that of baseline, 78 versus 71 milliseconds. The H to right bundle interval during ventricular tachycardia was slightly shorter, however, the right bundle to ventricular interval was markedly longer than that during sinus rhythm, 50 versus 30 milliseconds. In six patients with three dimensional mapping of the left ventricle, a slow anterograde, or retrograde conduction over the left His-Purkinje system with normal myocardial voltage was identified. In addition, Purkinje related ventricular tachycardias were also induced in five patients. Ablation was applied to the distal left bundle branch block in patients with baseline left bundle branch block, and in one narrow QRS patient with sustained Purkinje related ventricular tachycardia, while right bundle branch was targeted in other patients. During a mean follow up at 31.4 months, frequent premature ventricular contractions occurred in one patient, and new ventricular tachycardia developed in the other patient. In the next paper, Michel Haissaguerre and associates examined detailed mapping in 24 patients who survived idiopathic ventricular fibrillation. They used multi-electrode body surface recordings to identify the drivers maintaining ventricular fibrillation, and analyze electrograms in the driver regions, using endocardial and epicardial catheter mapping during sinus rhythm. Ventricular fibrillation occurred spontaneous in three patients, and was induced in 16, while VF was non-inducible in five. Ventricular fibrillation mapping demonstrated reentrant and focal activities, 87% and 13% respectively. The activities were dominant in one ventricle in nine patients, while they were biventricular in the others. During sinus rhythm, areas of abnormal electrograms were identified in 15 out of 24 patients, or 62.5%, revealing localized structural alterations, in the right ventricle in 11, the left ventricle in one, in both in three. They covered a limited surface, 13 centimeters squared, representing 5% of the total surface, and recorded predominantly on the epicardium. 76% of these areas were co-located with ventricular fibrillation drivers. In nine patients without structural alterations, the authors observed a high incidence of Purkinje triggers, seven out of nine, versus four out of 15. Catheter ablation resulted in arrhythmia-free outcomes in 15 out of 18 patients at a 17 month follow up. In our next paper, David Spar and associates describe the effectiveness, safety, and compliance of the wearable cardioverter defibrillator in the identification and treatment of life-threatening ventricular arrhythmias in all US pediatric patients who wore a wearable defibrillator from 2009 to 2016, ages less than 18 years. The 455 patients had a median age of 15 years, median duration of wearable cardioverter defibrillator use of 33 days, and median patient wear time of 20.6 hours per day. The study population was divided into two groups, 63 patients with an ICD problem, or 392 patients without an ICD problem. The wear time was greater than 20 hours in both groups. There were seven deaths, or 1.5%. All patients were not wearing the wearable cardioverter defibrillator at the time of death. Eight patients, 1.8%, received at least one wearable cardioverter defibrillator shock treatment. Of the six patients who had appropriate therapy, there were seven episodes of either polymorphic ventricular tachycardia, or ventricular fibrillation, with a total of 13 treatments delivered. All episodes were successfully converted, and the patient survived. In our next paper, Marc Lemoine and associates used human-induced pluripotential stem cell-derived cardiomyocytes to examine differences in repolarization reserve. The authors compared the contribution of IKs and IKr on action potential durations in human left ventricular tissue, and the human induced pluripotential stem cell derived cardiomyocytes, or IPS-derived engineered heart tissue. They found that the IPS-derived heart tissue showed spontaneous diastolic depolarization in action potential duration, which were sensitive to low concentrations of Ivabradine. IKr block by E-4031 prolonged action potential duration 90 with similar EC50 in both the IPS-derived heart tissue and the human left ventricular tissue. But a larger effect size in the IPS-derived heart tissue, 281 milliseconds versus 110 milliseconds, in the human left ventricular tissue. While IKr block alone evoked early after depolarizations, it triggered activity in 50% of the IPS-derived heart tissue. Slow pacing reduced extracellular potassium blocking of IKr, IKs and IK1 were necessary to induce early after depolarizations in human left ventricular tissue. In accordance with their clinical safety, Moxifloxacin and Verapamil did not induce EADs in IPS-derived heart tissue. In both IPS-derived heart tissue and human left ventricular tissue, IKs block by HMR 1556 prolonged action potential duration 90 slightly in the combined presence of E-4031 and isoprenaline. In our next paper, Elizabeth Saarel and associates sought to obtain contemporary digital ECG measurements in healthy children from North America to evaluate the effects of sex and race, and to compare the results to commonly published data sets, using 2400 digital ECGs, collected for children less than 18 years of age with normal electrocardiograms at 19 centers in the pediatric heart network. The authors found that the QTc in lead II was greater for females compared to males for age groups three years or older, for whites compared to African Americans, for ages 12 years or older. The R wave amplitude in V6 was greater for males compared to females for age groups 12 years and greater; for African Americans compared to white or other race categories for age groups three years or greater; and greater compared to commonly used public data set groups for ages 12 years and greater. In our next paper, Pyotr Platonov and associates examined T-wave morphology as a possible predictor of cardiac events in patients with type 2 long QT syndrome mutation carriers with normal QTc intervals. The authors compared 154 LQT2 mutation carriers with QTc less than 360 milliseconds in men, and less than 470 milliseconds in women, with 1007 unaffected family members. Flat, notched, or negative T-waves in leads II or V5 on baseline ECG were considered abnormal. Using Cox regression analysis, the associations between T-wave morphology, the presence in mutations in the poor region of KCNH2, and the risk of cardiac events defined that syncope aborted cardiac arrest, defibrillator therapy, or sudden cardiac arrests were assessed. The authors found that LQT2 female carriers with abnormal T-wave morphology had a threefold increased risk of cardiac events compared to LQT2 female carriers with normal T-waves, while this association was not seen in males. LQT2 males with poor location of mutations had a six-fold increased risk of cardiac events than non-poor location males, while no such association was found in females. In our last paper, Yaniv Bar-Cohen and associates describe a percutaneous pacemaker entirely implanted in the pericardium, using a sheath for sub-xiphoid access to the pericardial space, and a miniaturized camera with fiber optic illumination, the micro-pacemakers were successfully implanted in six pigs. All animals were studied during follow up, survived without symptoms. That's it for this month. We hope that you'll find the Journal to be the go-to place for everyone interested in the field. See you next time!

Circulation: Arrhythmia and Electrophysiology on the Beat July 2018

Paul J. Wang: Welcome to the monthly podcast On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor in chief with some of the key highlights from this month's issue. In our first paper in the real time mapping of AF drivers RADAR study, Subbarao Choudry and associates examined in a single arm first in human investigator-initiated FDA IDE study, a novel system for real time, high resolution identification of atrial fibrillation, AF drivers, in persistent or long-standing persistent AF. They enrolled 64 subjects at four centers, 73% male age, 64.7 years, BMI 31.7. LA size 54. Longstanding AF, 83% longstanding persistent, 17%. prior AF ablation, 41%. After 12.6 months of follow-up, 68% remained AF free off all antiarrhythmics. 74% remained AF free and 66% remained AF, AT and A-flutter free on or off antiarrhythmic drugs. AF terminated with atrial fibrillation ablation in 35 patients, 55% overall. And in 23 out of 38, 61% of de novo ablation patients. For patients with AF termination during atrial ablation, 82% remained AF free and 74% AF, AT or A-flutter free during follow-up on or off antiarrhythmic drugs. Patients undergoing first time AFib ablation had higher rates of freedom from AF than the redo group. In our next paper, David Briceño and associates examined 19 consecutive patients presenting with left bundle branch block ventricular tachycardia in the setting of arrhythmogenic right ventricular cardiomyopathy, ARVC, with procedures separated by at least nine months and a mean of 50 months. The authors found there was no significant progression of voltage bipolar 38 centimeters squared versus 53 centimeters squared, p=0.09 or unipolar 116 centimeters squared versus 159 centimeters squared, p=0.36 for the entire group. There was a significant increase in right ventricular RV volumes, percentage increase 28%. 206 milliliters versus 263 milliliters, P less than 0.001 for the entire study population. Larger scars at baseline but not changes over time were associated with a significant increase in RV volume, p=0.006 for bipolar and p=0.03 for unipolar. Most patients with progressive RV dilatation, 57%, had moderate in two patients or severe in six patients, tricuspid regurgitation recorded either at initial or repeat ablation procedure. The authors found that in patients with ARVC presenting with recurrent ventricular tachycardia, more than 10% increase in right ventricular endocardial surface area of bipolar voltages consistent with scar is uncommon during intermediate follow-up. Most recurrent ventricular tachycardias are localized to regions of prior defined scar. In our next paper, Susan Heckbert and associates examined detection of atrial fibrillation in 1,556 individuals participating in an ancillary study involving ambulatory ECG monitoring part of the cross-sectional analysis in the multiethnic study of atherosclerosis, MESA, a community based cohort study that enrolled 6,814 Americans free of clinically recognized cardiovascular disease in 2000 to 2002. Among 1,556 participants, 41% were white, 25% African American, 21% Hispanic, 14% Chinese, 51% were women mean age 74 years. The prevalence of clinically detected atrial fibrillation after 14.4 years follow-up was 11.3% in whites, 6.6% in African Americans, 7.8% in Hispanics and 9.9% in Chinese and was significantly lower in African Americans than in whites in both unadjusted and risk factor adjusted analyses, p less than 0.001. By contrast, in the same individuals, the proportion of monitor detected atrial fibrillation using a 14-day ambulatory ECG monitor was similar in the four race or ethnic groups. 7.1%, 6.4%, 6.9% and 5.2% compared with white, all p greater than 0.5. The authors concluded that the prevalence of clinically detected atrial fibrillation was substantially lower in African Americans than white participants with or without adjustments for atrial fibrillation risk factors. However, unbiased atrial fibrillation detection by ambulatory monitoring the same individuals reveal little difference in the proportion with atrial fibrillation by race, ethnicity, supporting the hypothesis of differential detection by race, ethnicity in the clinical recognition of atrial fibrillation. In our next paper, Maria Teresa Barrio-Lopez and associates examined the presence of epicardial connections between pulmonary veins and other anatomical structures. The authors considered an epicardial connection was present if one, the first pass around the pulmonary vein antrum did not produce pulmonary vein isolation. And two, subsequent atrial activation during pulmonary vein pacing showed that the earliest site was located away from the ablation line and later activation sites were obscured near the ablation line. Out of the 534 patients included, 72 or 13.5%, were found to have 81 epicardial connections. There was a significant association between the presence of epicardial connections in structural heart disease, 15.3% in patients without epicardial connections versus 36.5% in patients with epicardial connections, p less than 0.001. In patent foramen ovale, 4.6% versus 13.5%, p=0.002. The presence of a left common trunk was significantly associated with the absence of epicardial connection. 29.6% in patients without epicardial connections versus 16.2% in patients with epicardial connections, p=0.014. Patients with epicardial connections had a lower acute success of pulmonary vein isolation compared to patients with epicardial connection, 99.1% versus 86.1%, p less than 0.001. After adjusting for age, sex, type of atrial fibrillation, left atrial area, hypertension, structural heart disease, presence of left common trunk, patent foramen ovale and time for atrial fibrillation and diagnosis to the ablation, the authors found a significantly higher risk of atrial tachyarrhythmia recurrences in patients with epicardial connections compared to patients without epicardial connections, hazard ratio 1.7, p=0.04. In our next paper, Benzy Padanilam and associates examined the role of premature His complexes to differentiate AV nodal reentry tachycardia from atrioventricular reentry tachycardia high output pacing at the distal His location delivered premature His complexes. Atrioventricular reentrant tachycardia was predicted when late premature His complexes perturbed tachycardia or when early premature His complexes led to atrial advancement by amount equal or greater than the degree of premature His complex prematurity. Among the 73 SVTs, the test accurately predicted atrioventricular reentry tachycardia, n=29 in AV nodal reentry tachycardia, n=44 in all cases. Late premature His complexes advanced the circuit in all 29 atrioventricular reentry tachycardias in none of the AV nodal reentry tachycardias, sensitivity and specificity 100%. With earlier premature His complexes, the degree of atrial advancement was equal or greater than the premature His complex prematurity in 26 out of 29 atrioventricular reentrant tachycardia and none of the AV nodal reentrant tachycardias, 90% sensitivity and a 100% specificity. The mean prematurity of the premature His complex required to perturb AV nodal reentry tachycardia was 48 milliseconds, range 28 to 70 milliseconds. And the advancement less than the prematurity of the premature His complex, mean 32 milliseconds range, 18 to 54 milliseconds. In our next paper, Masateru Takigawa and associates examined the recurrence rate and mechanisms of atrial fibrillation ablation related atrial tachycardia recurrence among 147 patients with atrial tachycardias treated with arrhythmia system. 46.3% had recurrence at a mean of 4.2 months and 44 patients received a redo procedure. Atrial tachycardia circuits in the first procedure were compared to those in the redo procedure. Although mappable atrial tachycardias were not observed in seven patients, 68 atrial tachycardias were observed in 37 patients during the first procedure, perimitral flutter in 26 patients, roof-dependent macroreentrant atrial tachycardia in 18, peritricuspid flutter in 10, non-macro atrial tachycardia in 14 and focal atrial tachycardia in three. During the redo atrial tachycardia procedure, 54 atrial tachycardias were observed in 41 patients, perimitral flutter in 24, roof-dependent macroreentrant atrial tachycardia in 14, peritricuspid flutter in one, non-macroreentrant tachycardia in 14, and focal atrial tachycardia in one. Recurrence of perimitral flutter and roof-dependent macroreentrant atrial tachycardia were observed in 57.7% and 44.4% respectively, while peritricuspid flutter did not recur. Either the same focal atrial tachycardia nor the same non-macroreentrant tachycardia were observed except in one case with septal scar related to biatrial tachycardia. Epicardial structure related to atrial tachycardia were involved in 18 out of 24 or 75% in perimitral flutter, in 28.6% in roof-dependent macroreentry atrial tachycardia, in 28.6% in non-macroreentry tachycardia. Out of the 21 patients with a circuit including epicardial structures, six patients treated with ethanol infusion in the vein of Marshall did not show any atrial tachycardia recurrence although 53.3% treated with radiofrequency showed atrial tachycardia recurrence, p=0.04. In our next paper, Yaya Yu, Xuecheng Wang and associates compared the incidence and characteristics of ablation related asymptomatic cerebral emboli between high resolution diffusion weighted DWI and conventional DWI image. They examined 55 consecutive atrial fibrillation ablation patients undergoing high resolution DWI one day prior to ablation and repeated high resolution DWI and conventional DWI within 48 hours of post ablation. The authors found that high resolution DWI revealed a higher incidence of acute asymptomatic cerebral emboli compared to conventional DWI, 67.3% versus 41.8%, p less than 0.001. And significantly more asymptomatic cerebral emboli, 106 versus 45 lesions, p=0.001. For asymptomatic cerebral emboli, seen on both scans, the size measured by high resolution DWI was larger, 5.42 versus 4.21 millimeters, p less than 0.001. No patients had any impaired neurocognitive performance during follow-up. Impaired left ventricular ejection fraction, p=0.012 and low interoperative activated clotting time ACT p=0.009, level was associated with occurrence of asymptomatic cerebral emboli in a multivariate analysis. In our next paper, Ahmed AlTurki and Mariam Marafi and associates performed a systematic review and meta-analysis to assess the risk of stroke, myocardial infarction and death following postoperative atrial fibrillation after non-cardiac surgery. The authors included 28 studies, enrolling 2,612,816 patients in their final analyses. At one month, in ten studies, postoperative atrial fibrillation with associated with approximately three-fold increased risk of stroke, odds ratio 2.82, p less than 0.001. Postoperative atrial fibrillation was associated with ≈4-fold increase in the long-term risk of stroke, odds ratio 4.12, p ≤ to 0.001. In eight studies with 12 months or greater follow-up, there was a significant increase in the risk of stroke and myocardial infarction associated with postoperative atrial fibrillation, odds ratio 3.44, p value, p less than 0.001. And odds ratio for myocardial infarction 4.02, p less than 0.001. Postoperative atrial fibrillation was associated with a threefold increase in all of cause mortality 30 days, 15.0% versus 5.4%, odds ratio 3.36. In a research letter, Zhiyong Qian, Xiaofeng Hou, Yao Wang and associates validated physiological left bundle branch block pacing using high density ventricular mapping in a swine model. In another research letter by Shinsuke Miyazaki and associates, the authors examined whether the durability of pulmonary vein isolation can be predicted by the time to isolation in second generation cryoballoon ablation. That's it for this month. We hope that you will find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.

Paul J. Wang: Welcome to the monthly podcast On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor in chief with some of the key highlights from this month's issue. In our first paper in the real time mapping of AF drivers RADAR study, Subbarao Choudry and associates examined in a single arm first in human investigator-initiated FDA IDE study, a novel system for real time, high resolution identification of atrial fibrillation, AF drivers, in persistent or long-standing persistent AF. They enrolled 64 subjects at four centers, 73% male age, 64.7 years, BMI 31.7. LA size 54. Longstanding AF, 83% longstanding persistent, 17%. prior AF ablation, 41%. After 12.6 months of follow-up, 68% remained AF free off all antiarrhythmics. 74% remained AF free and 66% remained AF, AT and A-flutter free on or off antiarrhythmic drugs. AF terminated with atrial fibrillation ablation in 35 patients, 55% overall. And in 23 out of 38, 61% of de novo ablation patients. For patients with AF termination during atrial ablation, 82% remained AF free and 74% AF, AT or A-flutter free during follow-up on or off antiarrhythmic drugs. Patients undergoing first time AFib ablation had higher rates of freedom from AF than the redo group. In our next paper, David Briceño and associates examined 19 consecutive patients presenting with left bundle branch block ventricular tachycardia in the setting of arrhythmogenic right ventricular cardiomyopathy, ARVC, with procedures separated by at least nine months and a mean of 50 months. The authors found there was no significant progression of voltage bipolar 38 centimeters squared versus 53 centimeters squared, p=0.09 or unipolar 116 centimeters squared versus 159 centimeters squared, p=0.36 for the entire group. There was a significant increase in right ventricular RV volumes, percentage increase 28%. 206 milliliters versus 263 milliliters, P less than 0.001 for the entire study population. Larger scars at baseline but not changes over time were associated with a significant increase in RV volume, p=0.006 for bipolar and p=0.03 for unipolar. Most patients with progressive RV dilatation, 57%, had moderate in two patients or severe in six patients, tricuspid regurgitation recorded either at initial or repeat ablation procedure. The authors found that in patients with ARVC presenting with recurrent ventricular tachycardia, more than 10% increase in right ventricular endocardial surface area of bipolar voltages consistent with scar is uncommon during intermediate follow-up. Most recurrent ventricular tachycardias are localized to regions of prior defined scar. In our next paper, Susan Heckbert and associates examined detection of atrial fibrillation in 1,556 individuals participating in an ancillary study involving ambulatory ECG monitoring part of the cross-sectional analysis in the multiethnic study of atherosclerosis, MESA, a community based cohort study that enrolled 6,814 Americans free of clinically recognized cardiovascular disease in 2000 to 2002. Among 1,556 participants, 41% were white, 25% African American, 21% Hispanic, 14% Chinese, 51% were women mean age 74 years. The prevalence of clinically detected atrial fibrillation after 14.4 years follow-up was 11.3% in whites, 6.6% in African Americans, 7.8% in Hispanics and 9.9% in Chinese and was significantly lower in African Americans than in whites in both unadjusted and risk factor adjusted analyses, p less than 0.001. By contrast, in the same individuals, the proportion of monitor detected atrial fibrillation using a 14-day ambulatory ECG monitor was similar in the four race or ethnic groups. 7.1%, 6.4%, 6.9% and 5.2% compared with white, all p greater than 0.5. The authors concluded that the prevalence of clinically detected atrial fibrillation was substantially lower in African Americans than white participants with or without adjustments for atrial fibrillation risk factors. However, unbiased atrial fibrillation detection by ambulatory monitoring the same individuals reveal little difference in the proportion with atrial fibrillation by race, ethnicity, supporting the hypothesis of differential detection by race, ethnicity in the clinical recognition of atrial fibrillation. In our next paper, Maria Teresa Barrio-Lopez and associates examined the presence of epicardial connections between pulmonary veins and other anatomical structures. The authors considered an epicardial connection was present if one, the first pass around the pulmonary vein antrum did not produce pulmonary vein isolation. And two, subsequent atrial activation during pulmonary vein pacing showed that the earliest site was located away from the ablation line and later activation sites were obscured near the ablation line. Out of the 534 patients included, 72 or 13.5%, were found to have 81 epicardial connections. There was a significant association between the presence of epicardial connections in structural heart disease, 15.3% in patients without epicardial connections versus 36.5% in patients with epicardial connections, p less than 0.001. In patent foramen ovale, 4.6% versus 13.5%, p=0.002. The presence of a left common trunk was significantly associated with the absence of epicardial connection. 29.6% in patients without epicardial connections versus 16.2% in patients with epicardial connections, p=0.014. Patients with epicardial connections had a lower acute success of pulmonary vein isolation compared to patients with epicardial connection, 99.1% versus 86.1%, p less than 0.001. After adjusting for age, sex, type of atrial fibrillation, left atrial area, hypertension, structural heart disease, presence of left common trunk, patent foramen ovale and time for atrial fibrillation and diagnosis to the ablation, the authors found a significantly higher risk of atrial tachyarrhythmia recurrences in patients with epicardial connections compared to patients without epicardial connections, hazard ratio 1.7, p=0.04. In our next paper, Benzy Padanilam and associates examined the role of premature His complexes to differentiate AV nodal reentry tachycardia from atrioventricular reentry tachycardia high output pacing at the distal His location delivered premature His complexes. Atrioventricular reentrant tachycardia was predicted when late premature His complexes perturbed tachycardia or when early premature His complexes led to atrial advancement by amount equal or greater than the degree of premature His complex prematurity. Among the 73 SVTs, the test accurately predicted atrioventricular reentry tachycardia, n=29 in AV nodal reentry tachycardia, n=44 in all cases. Late premature His complexes advanced the circuit in all 29 atrioventricular reentry tachycardias in none of the AV nodal reentry tachycardias, sensitivity and specificity 100%. With earlier premature His complexes, the degree of atrial advancement was equal or greater than the premature His complex prematurity in 26 out of 29 atrioventricular reentrant tachycardia and none of the AV nodal reentrant tachycardias, 90% sensitivity and a 100% specificity. The mean prematurity of the premature His complex required to perturb AV nodal reentry tachycardia was 48 milliseconds, range 28 to 70 milliseconds. And the advancement less than the prematurity of the premature His complex, mean 32 milliseconds range, 18 to 54 milliseconds. In our next paper, Masateru Takigawa and associates examined the recurrence rate and mechanisms of atrial fibrillation ablation related atrial tachycardia recurrence among 147 patients with atrial tachycardias treated with arrhythmia system. 46.3% had recurrence at a mean of 4.2 months and 44 patients received a redo procedure. Atrial tachycardia circuits in the first procedure were compared to those in the redo procedure. Although mappable atrial tachycardias were not observed in seven patients, 68 atrial tachycardias were observed in 37 patients during the first procedure, perimitral flutter in 26 patients, roof-dependent macroreentrant atrial tachycardia in 18, peritricuspid flutter in 10, non-macro atrial tachycardia in 14 and focal atrial tachycardia in three. During the redo atrial tachycardia procedure, 54 atrial tachycardias were observed in 41 patients, perimitral flutter in 24, roof-dependent macroreentrant atrial tachycardia in 14, peritricuspid flutter in one, non-macroreentrant tachycardia in 14, and focal atrial tachycardia in one. Recurrence of perimitral flutter and roof-dependent macroreentrant atrial tachycardia were observed in 57.7% and 44.4% respectively, while peritricuspid flutter did not recur. Either the same focal atrial tachycardia nor the same non-macroreentrant tachycardia were observed except in one case with septal scar related to biatrial tachycardia. Epicardial structure related to atrial tachycardia were involved in 18 out of 24 or 75% in perimitral flutter, in 28.6% in roof-dependent macroreentry atrial tachycardia, in 28.6% in non-macroreentry tachycardia. Out of the 21 patients with a circuit including epicardial structures, six patients treated with ethanol infusion in the vein of Marshall did not show any atrial tachycardia recurrence although 53.3% treated with radiofrequency showed atrial tachycardia recurrence, p=0.04. In our next paper, Yaya Yu, Xuecheng Wang and associates compared the incidence and characteristics of ablation related asymptomatic cerebral emboli between high resolution diffusion weighted DWI and conventional DWI image. They examined 55 consecutive atrial fibrillation ablation patients undergoing high resolution DWI one day prior to ablation and repeated high resolution DWI and conventional DWI within 48 hours of post ablation. The authors found that high resolution DWI revealed a higher incidence of acute asymptomatic cerebral emboli compared to conventional DWI, 67.3% versus 41.8%, p less than 0.001. And significantly more asymptomatic cerebral emboli, 106 versus 45 lesions, p=0.001. For asymptomatic cerebral emboli, seen on both scans, the size measured by high resolution DWI was larger, 5.42 versus 4.21 millimeters, p less than 0.001. No patients had any impaired neurocognitive performance during follow-up. Impaired left ventricular ejection fraction, p=0.012 and low interoperative activated clotting time ACT p=0.009, level was associated with occurrence of asymptomatic cerebral emboli in a multivariate analysis. In our next paper, Ahmed AlTurki and Mariam Marafi and associates performed a systematic review and meta-analysis to assess the risk of stroke, myocardial infarction and death following postoperative atrial fibrillation after non-cardiac surgery. The authors included 28 studies, enrolling 2,612,816 patients in their final analyses. At one month, in ten studies, postoperative atrial fibrillation with associated with approximately three-fold increased risk of stroke, odds ratio 2.82, p less than 0.001. Postoperative atrial fibrillation was associated with ≈4-fold increase in the long-term risk of stroke, odds ratio 4.12, p ≤ to 0.001. In eight studies with 12 months or greater follow-up, there was a significant increase in the risk of stroke and myocardial infarction associated with postoperative atrial fibrillation, odds ratio 3.44, p value, p less than 0.001. And odds ratio for myocardial infarction 4.02, p less than 0.001. Postoperative atrial fibrillation was associated with a threefold increase in all of cause mortality 30 days, 15.0% versus 5.4%, odds ratio 3.36. In a research letter, Zhiyong Qian, Xiaofeng Hou, Yao Wang and associates validated physiological left bundle branch block pacing using high density ventricular mapping in a swine model. In another research letter by Shinsuke Miyazaki and associates, the authors examined whether the durability of pulmonary vein isolation can be predicted by the time to isolation in second generation cryoballoon ablation. That's it for this month. We hope that you will find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.

Circulation: Arrhythmia and Electrophysiology January 2020 Issue

Paul Wang:         Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief, with some of the key highlights from this month's issue.                                  In our first study, Filip Plesinger and associates examined whether a computerized analysis of the body surface 12-lead ECG can be used to measure the ventricular electrical activation delay as a predictor of heart failure or death following resynchronization therapy in a MADIT-CRT trial.                                  The authors found that left bundle branch block patients with baseline ventricular electrical activation delay less than 31.2 milliseconds had a 35% risk of MADIT-CRT endpoints, while patients with ventricular electrical activation delay greater than or equal to 31.2 milliseconds had a 14% risk, P value of less than 0.001.                                  The hazard ratio for predicting primary endpoints in patients with low ventricular electrical activation delay was 2.34 with a P value of less than 0.01. However, ventricular electrical activation delay was not predicted in patients with right bundle branch block or IVCD.                                  In our next study, Karl-Heinz Kuck and associates examined the predictors of long-term clinical outcomes after catheter ablation of atrial fibrillation in 750 patients in the FIRE AND ICE Trial. Using propensity score stratification methods to count for differences in baseline characteristics between sexes, the authors found that female sex with a hazard ratio of 1.37, P equals 0.01, and prior direct current cardioversion with a hazard ratio of 1.40, P equals 0.013 were independently associated with atrial fibrillation recurrence.                                  Female sex with hazard ratio of 1.36, P value of 0.035 and hypertension with a hazard ratio of 1.48, P value of 0.013 independently predicted cardiovascular rehospitalization. A longer history of atrial fibrillation with a hazard ratio of 1.03, P value of 0.039 increased the rate of repeat ablation.                                  After propensity score adjustment, women continued to have higher rates of primary efficacy failure with adjusted hazard ratio of 1.51, P less than 0.05 and cardiovascular rehospitalization with a hazard ratio of 1.40, P less than 0.05.                                  In the next study, Laura Bear and associates examined the reliability of inverse electrocardiographic mapping of cardiac electrical activity from recorded body surface potentials. In five anesthetized closed-chest pigs, torso and ventricular epicardial potentials were recorded simultaneously during sinus rhythm, epicardial, and endocardial ventricular pacing. Two approaches, coupled finite/boundary element methods and a meshless approach based on the method of fundamental solutions, were compared.                                  The authors found that inverse mapping underestimated epicardial potentials more than twofold, P less than 0.0001. Mean correlation coefficients for reconstructed epicardial potential distributions ranged from 0.60 to 0.64 across all methods. Epicardial electrograms were recovered with reasonable fidelity at approximately 50% of the sites, but variation was substantial.                                  General activation spread was reproduced with a mean correlation coefficient of 0.72 to 0.78 for activation time maps with spatio-temporal smoothing. Epicardial foci were identified with a mean location error approximately 16 millimeters. Inverse mapping with method of fundamental solutions was better than coupled finite/boundary element methods.                                  The authors concluded that spatio-temporal variability of recovered electrograms may limit the resolution, with implications for accuracy of arrhythmia localization.                                  In the next study, Pejman Raeisi-Giglou and colleagues examined the incidence of pulmonary vein stenosis in 10,368 patients undergoing atrial fibrillation ablation from 2000 to 2015. Computed tomography scans were performed three to six months after the procedures. Severe pulmonary vein stenosis was observed in 52 patients, or 0.5%. The left superior pulmonary vein represented 51% of all severely stenosed veins.                                  Percutaneous interventions were performed in 43 patients, and complications occurred in five, including three pulmonary vein ruptures, one stroke and one phrenic injury. Over a median follow-up of 25 months, 41, or 79%, of patients remained arrhythmia-free.                                   In our next paper, Koichi Nagashima and associates compared hot balloon ablation and cryoballoon ablation in a 165 consecutive patients who underwent initial atrial fibrillation catheter ablation. Of the 165 patients, 74 propensity score-matched patients equally divided between hot balloon ablation and cryoballoon ablation were studied.                                  Patients' characteristics included age, sex, body mass index, atrial fibrillation subtype, CHA2DS2-VASc score, and left atrial dimension were similar between the two groups. 52% of the hot balloon ablation patients required touch-up with radiofrequency ablation for residual/dormant pulmonary vein conduction versus 24% of the cryoballoon ablation patients with a P value of 0.02.                                  The anterior aspect of the left superior pulmonary vein was the site in 41% of the touch-ups after hot balloon versus the inferior aspect of the inferior pulmonary veins in 22% of the touch-ups after cryoballoon ablation. Hot balloon lesions were smaller with an area of 23.8 centimeters squared compared to cryoballoon ablation lesions having an area of 33.5 centimeters squared with a P value of 0.0007. Within 12 months, both methods had an AF recurrence of 16%.                                  In our next paper, Mildred Opondo and associates randomized 61 patients, mean age 52 years, to either 10 months of high intensity exercise or yoga. The authors found that left atrial volume, Vo2 max, and left ventricular end-diastolic volume increased in the exercise group with no change in the control with a P value of less than 0.0001.                                  The authors did not find significant changes in atrial electrical activity and hypothesized that a longer duration training may be required to induce electrical changes.                                  In our next paper, because there's evidence that the distal part of the ligament of Marshall might be a sympathetic conduit between the left stellate ganglion and the ventricles, Shan Liu and associates randomly divided 29 dogs into a sham ablation group, a ligament of Marshall ablation group, and a left stellate ganglion ablation group. Ablation was performed before occlusion of the left anterior coronary artery.                                  Ligament of Marshall ablation attenuated blood pressure elevation induced by left stellate ganglion stimulation. Both ligament of Marshall ablation and left stellate ganglion ablation similarly prolonged ventricular refractory period and reduced the incidence of ventricular arrhythmias compared with sham ablation.                                  In our next study, Smith and Tester and associates examined the heterologous functional validation studies of putative long-QT syndrome subtype 2, LQT2, associated variants. Genetic testing of 292 sudden infant death syndrome cases identified nine KCNH2 variants, while some of the channels associated the variants can lead to accelerated deactivation and activation gating. Other current levels were similar to wild-type.                                  The authors examined the electronic health records of patients who were genotype positive for these particular sudden infant death syndrome–linked KCNH2 variants and found all of them had a median heart rate–corrected QT intervals less than 480 milliseconds and none had been diagnosed with long-QT syndrome or suffered cardiac arrest.                                  Simulating the impact of dysfunctional gating variants using computational models of the human ventricular action potential predicted that they have little impact on action potential duration. The authors concluded that these rare Kv11.1 missense variants are not long-QT2 causative variants and, therefore, do not represent the pathogenic substrate for sudden infant death syndrome in the variant-positive infants.                                  In our next study, Tina Baykaner and associates performed a systematic literature review and meta-analysis to determine outcomes from ablation of atrial fibrillation drivers in addition to pulmonary vein isolation or as a stand-alone procedure. The authors found 17 studies with a cohort size of 3,294 patients.                                  Atrial fibrillation driver ablation, when added to a pulmonary vein ablation or a stand-alone procedure compared the controls, produced an odds ratio of 3.1 with a P value of 0.02 for freedom from atrial fibrillation and an odds ratio of 1.8 with a P value of less 0.01 for freedom of all arrhythmias in four controlled studies.                                  Adding atrial fibrillation driver ablation to pulmonary vein ablation resulted in a freedom from atrial fibrillation of 72.5%, P value of less than 0.01 and a freedom from all arrhythmias of 57.8% with a P value less than 0.01. Atrial fibrillation termination was 40.5% and predicted favorable outcome from ablation with a P value of less than 0.05. Large multicenter randomized trials are needed to precisely define the benefits of adding driver ablation to a pulmonary vein isolation.                                  In our next study, Hidekazu Kondo and associates found that the adverse atrial remodeling, including atrial inflammation, lipidosis and fibrosis, were induced in both wild-type and Interleukin-10 knockout mice by high fat diet, but the effects were exaggerated in the Interleukin-10 knockout mice. Vulnerability to atrial fibrillation was also significantly enhanced by the high fat diet.                                  The total amount of epicardial and pericardial adipose tissue volume was increased with high fat diet. Proinflammatory and profibrotic cytokines of epicardial and pericardial adipose tissue were also upregulated. In contrast, the protein level of adiponectin was downregulated by the high fat diet. Systemic Interleukin-10 administration markedly ameliorated the high fat diet induced obesity-caused left atrial remodeling and vulnerability to atrial fibrillation.                                  The authors concluded that Interleukin-10 treatment may limit the progression of atrial fibrillation occurring in the setting of a high fat diet.                                  In our next paper, Garcia and Campbell and associates demonstrated the ability to deliver amiodarone epicardially over a sustained period of time. The authors demonstrated in a pig model of atrial fibrillation that an amiodarone containing polyethylene glycol-based hydrogel placed directly on the atrial myocardium in a minimally invasive catheter procedure significantly reduced the duration of sustained atrial fibrillation at 21 and 28 days. The authors found that inducibility of atrial fibrillation was also reduced.                                  In our final paper, Htet Khine and associates examined the effect of spaceflight on the changes in atrial structure, supraventricular beats, and atrial electrophysiology, and to determine whether spaceflight could increase the risk of atrial fibrillation.                                  The authors found that, in 13 that in astronauts, the left atrial volume transiently increased after six months in space without changing atrial function. Right atrial size remained unchanged, while one astronaut had a very large increase in supraventricular ectopic beats, none developed atrial fibrillation. The P-wave amplitude duration did not change over time, but RMS 20 decreased on all fight days except landing day.                                  That's it for this month. Thanks for listening to On the Beat. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next month.

Paul Wang:         Welcome to the monthly podcast, On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief, with some of the key highlights from this month's issue.                                 In our first study, Filip Plesinger and associates examined whether a computerized analysis of the body surface 12-lead ECG can be used to measure the ventricular electrical activation delay as a predictor of heart failure or death following resynchronization therapy in a MADIT-CRT trial.                                 The authors found that left bundle branch block patients with baseline ventricular electrical activation delay less than 31.2 milliseconds had a 35% risk of MADIT-CRT endpoints, while patients with ventricular electrical activation delay greater than or equal to 31.2 milliseconds had a 14% risk, P value of less than 0.001.                                 The hazard ratio for predicting primary endpoints in patients with low ventricular electrical activation delay was 2.34 with a P value of less than 0.01. However, ventricular electrical activation delay was not predicted in patients with right bundle branch block or IVCD.                                 In our next study, Karl-Heinz Kuck and associates examined the predictors of long-term clinical outcomes after catheter ablation of atrial fibrillation in 750 patients in the FIRE AND ICE Trial. Using propensity score stratification methods to count for differences in baseline characteristics between sexes, the authors found that female sex with a hazard ratio of 1.37, P equals 0.01, and prior direct current cardioversion with a hazard ratio of 1.40, P equals 0.013 were independently associated with atrial fibrillation recurrence.                                 Female sex with hazard ratio of 1.36, P value of 0.035 and hypertension with a hazard ratio of 1.48, P value of 0.013 independently predicted cardiovascular rehospitalization. A longer history of atrial fibrillation with a hazard ratio of 1.03, P value of 0.039 increased the rate of repeat ablation.                                 After propensity score adjustment, women continued to have higher rates of primary efficacy failure with adjusted hazard ratio of 1.51, P less than 0.05 and cardiovascular rehospitalization with a hazard ratio of 1.40, P less than 0.05.                                 In the next study, Laura Bear and associates examined the reliability of inverse electrocardiographic mapping of cardiac electrical activity from recorded body surface potentials. In five anesthetized closed-chest pigs, torso and ventricular epicardial potentials were recorded simultaneously during sinus rhythm, epicardial, and endocardial ventricular pacing. Two approaches, coupled finite/boundary element methods and a meshless approach based on the method of fundamental solutions, were compared.                                 The authors found that inverse mapping underestimated epicardial potentials more than twofold, P less than 0.0001. Mean correlation coefficients for reconstructed epicardial potential distributions ranged from 0.60 to 0.64 across all methods. Epicardial electrograms were recovered with reasonable fidelity at approximately 50% of the sites, but variation was substantial.                                 General activation spread was reproduced with a mean correlation coefficient of 0.72 to 0.78 for activation time maps with spatio-temporal smoothing. Epicardial foci were identified with a mean location error approximately 16 millimeters. Inverse mapping with method of fundamental solutions was better than coupled finite/boundary element methods.                                 The authors concluded that spatio-temporal variability of recovered electrograms may limit the resolution, with implications for accuracy of arrhythmia localization.                                 In the next study, Pejman Raeisi-Giglou and colleagues examined the incidence of pulmonary vein stenosis in 10,368 patients undergoing atrial fibrillation ablation from 2000 to 2015. Computed tomography scans were performed three to six months after the procedures. Severe pulmonary vein stenosis was observed in 52 patients, or 0.5%. The left superior pulmonary vein represented 51% of all severely stenosed veins.                                 Percutaneous interventions were performed in 43 patients, and complications occurred in five, including three pulmonary vein ruptures, one stroke and one phrenic injury. Over a median follow-up of 25 months, 41, or 79%, of patients remained arrhythmia-free.                                  In our next paper, Koichi Nagashima and associates compared hot balloon ablation and cryoballoon ablation in a 165 consecutive patients who underwent initial atrial fibrillation catheter ablation. Of the 165 patients, 74 propensity score-matched patients equally divided between hot balloon ablation and cryoballoon ablation were studied.                                 Patients' characteristics included age, sex, body mass index, atrial fibrillation subtype, CHA2DS2-VASc score, and left atrial dimension were similar between the two groups. 52% of the hot balloon ablation patients required touch-up with radiofrequency ablation for residual/dormant pulmonary vein conduction versus 24% of the cryoballoon ablation patients with a P value of 0.02.                                 The anterior aspect of the left superior pulmonary vein was the site in 41% of the touch-ups after hot balloon versus the inferior aspect of the inferior pulmonary veins in 22% of the touch-ups after cryoballoon ablation. Hot balloon lesions were smaller with an area of 23.8 centimeters squared compared to cryoballoon ablation lesions having an area of 33.5 centimeters squared with a P value of 0.0007. Within 12 months, both methods had an AF recurrence of 16%.                                 In our next paper, Mildred Opondo and associates randomized 61 patients, mean age 52 years, to either 10 months of high intensity exercise or yoga. The authors found that left atrial volume, Vo2 max, and left ventricular end-diastolic volume increased in the exercise group with no change in the control with a P value of less than 0.0001.                                 The authors did not find significant changes in atrial electrical activity and hypothesized that a longer duration training may be required to induce electrical changes.                                 In our next paper, because there's evidence that the distal part of the ligament of Marshall might be a sympathetic conduit between the left stellate ganglion and the ventricles, Shan Liu and associates randomly divided 29 dogs into a sham ablation group, a ligament of Marshall ablation group, and a left stellate ganglion ablation group. Ablation was performed before occlusion of the left anterior coronary artery.                                 Ligament of Marshall ablation attenuated blood pressure elevation induced by left stellate ganglion stimulation. Both ligament of Marshall ablation and left stellate ganglion ablation similarly prolonged ventricular refractory period and reduced the incidence of ventricular arrhythmias compared with sham ablation.                                 In our next study, Smith and Tester and associates examined the heterologous functional validation studies of putative long-QT syndrome subtype 2, LQT2, associated variants. Genetic testing of 292 sudden infant death syndrome cases identified nine KCNH2 variants, while some of the channels associated the variants can lead to accelerated deactivation and activation gating. Other current levels were similar to wild-type.                                 The authors examined the electronic health records of patients who were genotype positive for these particular sudden infant death syndrome–linked KCNH2 variants and found all of them had a median heart rate–corrected QT intervals less than 480 milliseconds and none had been diagnosed with long-QT syndrome or suffered cardiac arrest.                                 Simulating the impact of dysfunctional gating variants using computational models of the human ventricular action potential predicted that they have little impact on action potential duration. The authors concluded that these rare Kv11.1 missense variants are not long-QT2 causative variants and, therefore, do not represent the pathogenic substrate for sudden infant death syndrome in the variant-positive infants.                                 In our next study, Tina Baykaner and associates performed a systematic literature review and meta-analysis to determine outcomes from ablation of atrial fibrillation drivers in addition to pulmonary vein isolation or as a stand-alone procedure. The authors found 17 studies with a cohort size of 3,294 patients.                                 Atrial fibrillation driver ablation, when added to a pulmonary vein ablation or a stand-alone procedure compared the controls, produced an odds ratio of 3.1 with a P value of 0.02 for freedom from atrial fibrillation and an odds ratio of 1.8 with a P value of less 0.01 for freedom of all arrhythmias in four controlled studies.                                 Adding atrial fibrillation driver ablation to pulmonary vein ablation resulted in a freedom from atrial fibrillation of 72.5%, P value of less than 0.01 and a freedom from all arrhythmias of 57.8% with a P value less than 0.01. Atrial fibrillation termination was 40.5% and predicted favorable outcome from ablation with a P value of less than 0.05. Large multicenter randomized trials are needed to precisely define the benefits of adding driver ablation to a pulmonary vein isolation.                                 In our next study, Hidekazu Kondo and associates found that the adverse atrial remodeling, including atrial inflammation, lipidosis and fibrosis, were induced in both wild-type and Interleukin-10 knockout mice by high fat diet, but the effects were exaggerated in the Interleukin-10 knockout mice. Vulnerability to atrial fibrillation was also significantly enhanced by the high fat diet.                                 The total amount of epicardial and pericardial adipose tissue volume was increased with high fat diet. Proinflammatory and profibrotic cytokines of epicardial and pericardial adipose tissue were also upregulated. In contrast, the protein level of adiponectin was downregulated by the high fat diet. Systemic Interleukin-10 administration markedly ameliorated the high fat diet induced obesity-caused left atrial remodeling and vulnerability to atrial fibrillation.                                 The authors concluded that Interleukin-10 treatment may limit the progression of atrial fibrillation occurring in the setting of a high fat diet.                                 In our next paper, Garcia and Campbell and associates demonstrated the ability to deliver amiodarone epicardially over a sustained period of time. The authors demonstrated in a pig model of atrial fibrillation that an amiodarone containing polyethylene glycol-based hydrogel placed directly on the atrial myocardium in a minimally invasive catheter procedure significantly reduced the duration of sustained atrial fibrillation at 21 and 28 days. The authors found that inducibility of atrial fibrillation was also reduced.                                 In our final paper, Htet Khine and associates examined the effect of spaceflight on the changes in atrial structure, supraventricular beats, and atrial electrophysiology, and to determine whether spaceflight could increase the risk of atrial fibrillation.                                 The authors found that, in 13 that in astronauts, the left atrial volume transiently increased after six months in space without changing atrial function. Right atrial size remained unchanged, while one astronaut had a very large increase in supraventricular ectopic beats, none developed atrial fibrillation. The P-wave amplitude duration did not change over time, but RMS 20 decreased on all fight days except landing day.                                 That's it for this month. Thanks for listening to On the Beat. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next month.

Circulation: Arrhythmia and Electrophysiology On the Beat May 2018

Dr Paul Wang:   Welcome to the monthly podcast, On The Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue.                                  In our first paper, Ruairidh Martin and associates used ultra-high-density mapping to access the ventricular tachycardia circuit dependent upon re-entry, with scar regions in 36 tachycardias in 31 patients. The author has found that 11 of the ventricular tachycardia circuits and isthmuses were single-loop, and 25 were double-loop. Three had two entrances, five had two exits, and fifteen had dead-end activation. Isthmuses were defined by barriers which included anatomical obstacles, lines of block, and slow conduction in 27 out of 36 isthmuses. The barrier to conduction in isthmus appeared to be partially functional in 75% of circuits. Isthmus voltage is often higher in ventricular tachycardia than in sinus or paced rhythms. The authors found that conduction velocity in the VT isthmus slowed at the isthmus entrances and exits when compared with mid-isthmus. The mean conduction velocity was 0.08 meters per second in entrance zones, 0.29 meters per second in isthmus regions, p &lt; 0.0001, and 0.11 meters per second in exit regions. P = 0.002.                                  In our next paper Daniel Duprez and associates found that plasma collagen biomarkers, particularly at elevated levels, were associated with excess risk of atrial fibrillation. In a stratified sample of the Multi-Ethnic Study of Atherosclerosis (MESA), initially age 45 to 84 years, the authors examined in 3,071 participants plasma Procollagen Type III N-Terminal Propeptide, also known as P3NP, which reflects collagen synthesis in degradation in Collagen Type I Carboxy-Terminal Telopeptide, also known as ICTP, which reflects collagen degradation at baseline. The authors aimed to determine if the levels of these biomarkers were associated with incident atrial fibrillation in participants initially free of overt cardiovascular disease. Incident atrial fibrillation in ten-year follow-up was based on a hospital ICD code for atrial fibrillation or atrial flutter, in or outpatient Medicare claims, or ECG ten years after baseline. The authors found that baseline levels of these markers were positively related, both p &lt; 0.0001 to incident atrial fibrillation in a model adjusting for age, race, ethnicity, and sex. These findings were attenuated but remain statistically significant after further adjustment for systolic blood pressure, height, body mass index, smoking, and renal function.                                  In our next paper, Ahmet Adiyaman and associates conducted a randomized controlled trial comparing the safety and efficacy of minimally invasive thoracoscopic pulmonary vein isolation with left atrial appendage ligation versus percutaneous catheter ablation pulmonary vein isolation. In 52 patients with symptomatic paroxysmal or early persistent atrial fibrillation, paroxysmal atrial fibrillation was present in 74% of patients. The authors found that percutaneous pulmonary vein isolation with a 56% single procedure arrhythmia-free survival at two years was not inferior to minimally invasive thoracoscopic pulmonary vein isolation with left atrial appendage ligation, which had a 29% arrhythmia freedom, p = 0.059. Procedure-related major adverse events occurred in 21% of patients undergoing minimally invasive thoracoscopic pulmonary vein isolation, compared to none undergoing percutaneous catheter ablation with p = 0.029.                                  In the next paper, Richard Ang and associates examined whether the glucagon-like peptide-1 receptor agonist exendin 4 has an effect on ventricular action potential duration in susceptibility to ventricular arrhythmia in the rat heart in vivo and ex vivo. Ventricular monophasic action potentials recorded in anesthetized rats in vivo in isolated profused rat hearts in sinus rhythm and/or ventricular pacing. In vivo systemic administration of exendin 4 increased heart rate and this effect was abolished by beta adrenoceptor blockade. Despite causing sympathetic activation, exendin 4 increased axon potential duration at 90% repolarization, APD90, during ventricular pacing by 7% and reversed the effect of beta adrenoceptor agonist Dobutamine on APD90. In isolated profused hearts, 3 nanomolar exendin 4 increased APD90 by 14% with no effect on heart rate. Exendin 4 also reduced ventricular arrhythmia inducibility in conditions of beta adrenoceptor stimulation with Isoproterenol. Exendin 4 effects on action potential duration in ventricular arrhythmia susceptibility were prevented in conditions of muscarinic receptor blockade or inhibition of nitric oxide synthase. The authors concluded that glucagon-like peptide-1 receptor activation effectively reverses the effects of beta adrenoceptor stimulation on cardiac ventricular excitability and reduces ventricular arrhythmic potential. The effect of glucagon-like peptide-1 receptor activation on the ventricular myocardium is indirect, mediated by acetylcholine and nitric oxide, and, therefore, might be explained by stimulation of cardiac parasympathetic neurons.                                  In our next paper, Michael Barkagan and associates examined the role of modulating baseline impedance on ablation lesion dimension. Radiofrequency ablation was performed using an irrigated catheter at a fixed power setting of 30 watts 20 seconds and a multi-step impedance load from 100 to 210Ω ex vivo in 20 swine hearts and in vivo in the right atrium and in thigh preparations. Ablation was performed using similar power settings at three baseline impedances: low, 90 to 130Ω; intermediate, 131 to 180Ω; and high, 181 to 224Ω. The relationship between baseline impedance, current, and lesion dimensions were examined. Baseline impedance had a strong negative correlation with current squared for all of these experimental models with R either -0.93 or -0.94. Lesion dimensions at similar power setting were directly related to current squared with R = 0.853 for width and R = 0.814 for depth. In thigh muscle lesion depth was greatest at low impedance, 8.2 millimeters, compared to 6.5 millimeters and intermediate impedance and 4.2 millimeters at high impedance, p &lt; 0.0001. In right atrial lines, low baseline impedance resulted in wider lines, 7.2 millimeters, relative to intermediate 5.8 millimeters and high impedance, 4.7 millimeters, p &lt; 0.0001.                                  In the next study, Virginie Dubes and David Benoist and associates examined the origin of ventricular arrhythmias in animal model of repair of tetralogy of Fallot. They studied six piglets undergoing tetralogy of Fallot repair-like surgery compared to five sham-operated piglets. Twenty-three weeks post-surgery, the authors found that right ventricular dysfunction was present, while left ventricular function was preserved in tetralogy of Fallot pigs. Optical mapping showed longer action potential duration on the tetralogy of Fallot left ventricular epicardial and endocardium. Epicardial conduction velocity was significantly reduced in the longitudinal direction but not the transverse direction in tetralogy of Fallot ventricles compared to sham. Elevated collagen content was found in left ventricular basal and apical sections from the tetralogy of Fallot pigs. The tetralogy of Fallot left ventricles had a lower threshold for arrhythmia induction using incremental pacing protocols.                                  In our next study, Meera Varshneya and associates sought to understand the individual roles of slow and rapid delayed rectifier potassium currents, IKS and IKR, and quantify how effectively each stabilize the actions potential, protecting cells against arrhythmias across multiple species. The authors compared ten mathematical models describing ventricular myocytes from human, rabbit, canine, and guinea pig. They examined variability within heterogeneous cell population, tested the susceptibility of cells to a pro-rhythmic behavior, and studied how IKS and IKR responded to changes in the action potential. They found, one, models of higher baseline IKS exhibited less cell-to-cell variability in action potential duration; two, models with higher baseline IKS were less susceptible to early afterdepolarizations induced by depolarizing perturbations; three, as action potential durations lengthened, IKS increases more profoundly than IKR, thereby providing negative feedback that resists excessive action potential duration prolongation; and four, the increase in IKS that occurs during β-Adrenergic stimulation is critical for protecting cardiac myocytes from early afterdepolarizations under these conditions. The authors concluded that slow, delayed rectifier current is uniformly protected across a variety of cell types, suggesting that IKS enhancement could be potentially anti-arrhythmic.                                  In our final paper, Piotr Podziemski and Stef Zeemering and associates performed a direct one-to-one comparison between phase and activation time mapping in high-density epicardial direct contact mapping files of human atrial fibrillation. The authors examined 38 unipolar electrum files of ten seconds duration recorded in 20 patients with atrial fibrillation using a 16 x 16 electrode array placed on the epicardial surface of the left atrial posterior wall or right atrial free wall. Using sinusoidal recomposition and Hilbert Transform, 138 phase singularities were detected, with 104 out of 138 phase singularities detected within on electro distance, 1.5 millimeters, from a line of conduction block between non-rotating wave fronts determined by activation mapping. Only 18 rotating wave fronts were detected out of 8,219 detected waves based on wave mapping. Fourteen out of these 18 cases were detected as phase singularities in phase mapping. Phase analysis of filter electrograms produced by simulated wave fronts separated by conduction block also identified phase singularities on the line of conduction block. The authors found that phase singularities identified by phase analysis of filter epicardial electrograms colocalized with conduction block lines identified by activation mapping. The authors concluded that detection of phase singularity using phase analysis has a low specificity for identifying rotating wave fronts using activation mapping of human atrial fibrillation.                  That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time.

Dr Paul Wang:   Welcome to the monthly podcast, On The Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor-in-chief, with some of the key highlights from this month's issue.                                 In our first paper, Ruairidh Martin and associates used ultra-high-density mapping to access the ventricular tachycardia circuit dependent upon re-entry, with scar regions in 36 tachycardias in 31 patients. The author has found that 11 of the ventricular tachycardia circuits and isthmuses were single-loop, and 25 were double-loop. Three had two entrances, five had two exits, and fifteen had dead-end activation. Isthmuses were defined by barriers which included anatomical obstacles, lines of block, and slow conduction in 27 out of 36 isthmuses. The barrier to conduction in isthmus appeared to be partially functional in 75% of circuits. Isthmus voltage is often higher in ventricular tachycardia than in sinus or paced rhythms. The authors found that conduction velocity in the VT isthmus slowed at the isthmus entrances and exits when compared with mid-isthmus. The mean conduction velocity was 0.08 meters per second in entrance zones, 0.29 meters per second in isthmus regions, p &lt; 0.0001, and 0.11 meters per second in exit regions. P = 0.002.                                 In our next paper Daniel Duprez and associates found that plasma collagen biomarkers, particularly at elevated levels, were associated with excess risk of atrial fibrillation. In a stratified sample of the Multi-Ethnic Study of Atherosclerosis (MESA), initially age 45 to 84 years, the authors examined in 3,071 participants plasma Procollagen Type III N-Terminal Propeptide, also known as P3NP, which reflects collagen synthesis in degradation in Collagen Type I Carboxy-Terminal Telopeptide, also known as ICTP, which reflects collagen degradation at baseline. The authors aimed to determine if the levels of these biomarkers were associated with incident atrial fibrillation in participants initially free of overt cardiovascular disease. Incident atrial fibrillation in ten-year follow-up was based on a hospital ICD code for atrial fibrillation or atrial flutter, in or outpatient Medicare claims, or ECG ten years after baseline. The authors found that baseline levels of these markers were positively related, both p &lt; 0.0001 to incident atrial fibrillation in a model adjusting for age, race, ethnicity, and sex. These findings were attenuated but remain statistically significant after further adjustment for systolic blood pressure, height, body mass index, smoking, and renal function.                                 In our next paper, Ahmet Adiyaman and associates conducted a randomized controlled trial comparing the safety and efficacy of minimally invasive thoracoscopic pulmonary vein isolation with left atrial appendage ligation versus percutaneous catheter ablation pulmonary vein isolation. In 52 patients with symptomatic paroxysmal or early persistent atrial fibrillation, paroxysmal atrial fibrillation was present in 74% of patients. The authors found that percutaneous pulmonary vein isolation with a 56% single procedure arrhythmia-free survival at two years was not inferior to minimally invasive thoracoscopic pulmonary vein isolation with left atrial appendage ligation, which had a 29% arrhythmia freedom, p = 0.059. Procedure-related major adverse events occurred in 21% of patients undergoing minimally invasive thoracoscopic pulmonary vein isolation, compared to none undergoing percutaneous catheter ablation with p = 0.029.                                 In the next paper, Richard Ang and associates examined whether the glucagon-like peptide-1 receptor agonist exendin 4 has an effect on ventricular action potential duration in susceptibility to ventricular arrhythmia in the rat heart in vivo and ex vivo. Ventricular monophasic action potentials recorded in anesthetized rats in vivo in isolated profused rat hearts in sinus rhythm and/or ventricular pacing. In vivo systemic administration of exendin 4 increased heart rate and this effect was abolished by beta adrenoceptor blockade. Despite causing sympathetic activation, exendin 4 increased axon potential duration at 90% repolarization, APD90, during ventricular pacing by 7% and reversed the effect of beta adrenoceptor agonist Dobutamine on APD90. In isolated profused hearts, 3 nanomolar exendin 4 increased APD90 by 14% with no effect on heart rate. Exendin 4 also reduced ventricular arrhythmia inducibility in conditions of beta adrenoceptor stimulation with Isoproterenol. Exendin 4 effects on action potential duration in ventricular arrhythmia susceptibility were prevented in conditions of muscarinic receptor blockade or inhibition of nitric oxide synthase. The authors concluded that glucagon-like peptide-1 receptor activation effectively reverses the effects of beta adrenoceptor stimulation on cardiac ventricular excitability and reduces ventricular arrhythmic potential. The effect of glucagon-like peptide-1 receptor activation on the ventricular myocardium is indirect, mediated by acetylcholine and nitric oxide, and, therefore, might be explained by stimulation of cardiac parasympathetic neurons.                                 In our next paper, Michael Barkagan and associates examined the role of modulating baseline impedance on ablation lesion dimension. Radiofrequency ablation was performed using an irrigated catheter at a fixed power setting of 30 watts 20 seconds and a multi-step impedance load from 100 to 210Ω ex vivo in 20 swine hearts and in vivo in the right atrium and in thigh preparations. Ablation was performed using similar power settings at three baseline impedances: low, 90 to 130Ω; intermediate, 131 to 180Ω; and high, 181 to 224Ω. The relationship between baseline impedance, current, and lesion dimensions were examined. Baseline impedance had a strong negative correlation with current squared for all of these experimental models with R either -0.93 or -0.94. Lesion dimensions at similar power setting were directly related to current squared with R = 0.853 for width and R = 0.814 for depth. In thigh muscle lesion depth was greatest at low impedance, 8.2 millimeters, compared to 6.5 millimeters and intermediate impedance and 4.2 millimeters at high impedance, p &lt; 0.0001. In right atrial lines, low baseline impedance resulted in wider lines, 7.2 millimeters, relative to intermediate 5.8 millimeters and high impedance, 4.7 millimeters, p &lt; 0.0001.                                 In the next study, Virginie Dubes and David Benoist and associates examined the origin of ventricular arrhythmias in animal model of repair of tetralogy of Fallot. They studied six piglets undergoing tetralogy of Fallot repair-like surgery compared to five sham-operated piglets. Twenty-three weeks post-surgery, the authors found that right ventricular dysfunction was present, while left ventricular function was preserved in tetralogy of Fallot pigs. Optical mapping showed longer action potential duration on the tetralogy of Fallot left ventricular epicardial and endocardium. Epicardial conduction velocity was significantly reduced in the longitudinal direction but not the transverse direction in tetralogy of Fallot ventricles compared to sham. Elevated collagen content was found in left ventricular basal and apical sections from the tetralogy of Fallot pigs. The tetralogy of Fallot left ventricles had a lower threshold for arrhythmia induction using incremental pacing protocols.                                 In our next study, Meera Varshneya and associates sought to understand the individual roles of slow and rapid delayed rectifier potassium currents, IKS and IKR, and quantify how effectively each stabilize the actions potential, protecting cells against arrhythmias across multiple species. The authors compared ten mathematical models describing ventricular myocytes from human, rabbit, canine, and guinea pig. They examined variability within heterogeneous cell population, tested the susceptibility of cells to a pro-rhythmic behavior, and studied how IKS and IKR responded to changes in the action potential. They found, one, models of higher baseline IKS exhibited less cell-to-cell variability in action potential duration; two, models with higher baseline IKS were less susceptible to early afterdepolarizations induced by depolarizing perturbations; three, as action potential durations lengthened, IKS increases more profoundly than IKR, thereby providing negative feedback that resists excessive action potential duration prolongation; and four, the increase in IKS that occurs during β-Adrenergic stimulation is critical for protecting cardiac myocytes from early afterdepolarizations under these conditions. The authors concluded that slow, delayed rectifier current is uniformly protected across a variety of cell types, suggesting that IKS enhancement could be potentially anti-arrhythmic.                                 In our final paper, Piotr Podziemski and Stef Zeemering and associates performed a direct one-to-one comparison between phase and activation time mapping in high-density epicardial direct contact mapping files of human atrial fibrillation. The authors examined 38 unipolar electrum files of ten seconds duration recorded in 20 patients with atrial fibrillation using a 16 x 16 electrode array placed on the epicardial surface of the left atrial posterior wall or right atrial free wall. Using sinusoidal recomposition and Hilbert Transform, 138 phase singularities were detected, with 104 out of 138 phase singularities detected within on electro distance, 1.5 millimeters, from a line of conduction block between non-rotating wave fronts determined by activation mapping. Only 18 rotating wave fronts were detected out of 8,219 detected waves based on wave mapping. Fourteen out of these 18 cases were detected as phase singularities in phase mapping. Phase analysis of filter electrograms produced by simulated wave fronts separated by conduction block also identified phase singularities on the line of conduction block. The authors found that phase singularities identified by phase analysis of filter epicardial electrograms colocalized with conduction block lines identified by activation mapping. The authors concluded that detection of phase singularity using phase analysis has a low specificity for identifying rotating wave fronts using activation mapping of human atrial fibrillation.                 That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time.

Circulation: Arrhythmia and Electrophysiology October 2018 Issue

Dr Paul Wang:                   Welcome to the monthly podcast On The Beat, where Circulation: Arrhythmia and Electrophysiology. I'm Doctor Paul Wang, editor in chief, with some of the key highlights from this month's issue.                                                  In our first paper, Parikshit Sharma and associates reported on the use of permanent his bundle pacing to improve hemodynamics in 39 patients with right bundle branch block. His bundle pacing was successfully performed in 37, or 95 percent of the patients, and resulted in narrowing of the QRS complex from 158 milliseconds to 127 milliseconds. P = 0.0001. An increase in left ventricular ejection fraction from 31 percent to 39 percent. P = 0.004, an improvement in the New York Heart Association functional class from 2.8 to 2.0 P = 0.0001. This work suggests that his bundle pacing maybe helpful in right bundle branch block patients with left ventricular dysfunction.                                                  In our next paper, Philippe Debruyne and associates added to our understanding of using catheter ablation to modulate the autonomic nervous system in patients with neurally mediated syncope, signs of no dysfunction and functional AV block. Prior reports of autonomic modulation using catheter ablation have required extensive ablation in both atria. In this article, the authors report a significant 95% reduction in syncope at six months as a result of targeted ablation in the right atrium alone, focusing on partial ablation of the interior right ganglionated plexus. Ablation is quite limited, taking a mean of seven minutes and creating a mean surface area of 11 millimeters squared. This technique has promise as a possible treatment for avoiding a need of pacemaker implantation in some patients.                                                  In our next paper, Shankar Baskar and associates examined the characteristics and outcomes of pediatric patients receiving implantable cardioverter defibrillators and compared them to their adult counterparts. They examined ICD recipients in the NCDRICD registry from 2010 to 2016. There were 562,209 total ICD implants, including 3461 pediatric patients. Of the pediatric patients, 60 percent of implants were for primary prevention with non-ischemic cardiomyopathy being present in 60 percent of the patients, the most common underlying disease. Over time, there is an increasing trend of both primary and secondary prevention ICD implantations, P less than 0.05. Compared to adults, pediatric patients were likely to have structural heart disease, hypertrophic cardiomyopathy, ion channelopathy, and to receive a single chamber device. All P less than 0.001. There is no difference in in-hospital complications between the adult and the pediatric cohorts, 2.4 percent versus 2.6 percent. However, among pediatric patients, lower weight, Ebstein's anomaly, worse New York Heart Association class dual chamber and resynchronization defibrillator were associated with greater risk of complications. Although, re-intervention for generator replacement or upgrade was more common in adults, the time to re-intervention was shorter in the pediatric cohort.                                                  In our next paper, Ahmed Hussein and associates examine the effect of using ablation index guiding ablation in 40 patients with persistent HO fibrillation on the rate of pulmonary vein reconnection. Pulmonary vein reconnection was seen as a mandatory repeat electro-physiologic study in 22 percent of patients, effecting seven percent of pulmonary veins. Ablation on the intravenous cryna was required in 44 percent of patients to achieve durable pulmonary vein isolation. Atrial tachyarrhythmia occurrence was documented in eight to 20 percent of patients, only one of whom had pulmonary vein reconnection at repeat study. At 12 months, 30 out of 40, or 95 percent of patients, were in sinus rhythm, with four or 10 percent of patients having starting antiarrhythmic drugs. Higher body mass index and excessive alcohol consumption were the only significant factors associated with atrial tachyarrhythmia occurrence.                                                  In our next paper, Atsushi Hirayama and associates examined whether acute exasperation of chronic obstructive pulmonary disease increases the risk of repeated atrial fibrillation related health care utilization. They examine 944 patients who are hospitalized for acute exasperation of chronic obstructive pulmonary disease and had emergency department visit or hospitalization for atrial fibrillation during a 450 day period. Compared to the reference period, the rate of atrial fibrillation related emergency department visits or hospitalizations significantly increased in the first 90 days after acute exasperation of chronic obstructive pulmonary disease. 7.3 versus 14.1 per one hundred person months, resulting in a risk ratio of 1.93.                                                  In our next paper, Namsik Yoon and associates examined the mechanisms underlying the electrocardiographic and arrhythmic manifestation of experimental models of early repolarization syndrome and the ameliorative effects of radio-frequency ablation. The authors recorded axis potentials, bi-polar electrograms, and transmural pseudo electrocardiograms for coronary perfused canine left ventricular wedge preparations in 11 animals.                                                  The ITO agonist, NS5806, the calcium channel blocker Verapamil and acetylcholine were used to pharmacologically mimic the effects of genetic defects associated with early repolarization syndrome. The provocative agents induce prominent j waves in the ECG secondary to the accentuation of the action potential notch in the epicardium but not the endocardium. Bipolar recordings displayed low voltage fractionated potential in the epicardium due to temporal and spatial variability and appearance of the action potential dome conceal the phase two reentry develop when the axon potential dome was lost at some epicardial sites but not others. Appearing in the bipolar electrogram, is discrete high frequency spikes. Successful propagation of the concealed phase two reentered beat precipitated ventricular tachycardia or ventricular fibrillation. Radiofrequency ablation of epicardium destroyed the cell displaying abnormal repolarization and thus suppressed the j waves and the development of ventricular tachycardia and ventricular fibrillation in six out of six preparations.                                                  Stavros Stavrakis and associates described ten patients out of 843 patients, or 1.2 percent with AV nodal reentry tachycardia who required ablation of the basal inferolateral left atria, during stable antegrade slow, retrograde fast, AV nodal reentry tachycardia, a single late atrial extra stimulus was delivered at the inferolateral left atria, near the mitral annulus. All patients had failed ablation in the inferior triangle of Koch, and or roof of the coronary sinus. In all ten patients, a late atrial extra stimulus advanced the his bundle potential by at least ten milliseconds and reset the tachycardia. Ablation at that site, eliminates slow pathway conduction and terminated the tachycardia. Ablation was successful at the site of the latest atrial extra stimulus delivered 49 milliseconds after the onset of this his bundle potential. In their series, no recurrent tachycardia was noted at one year follow up.                                                  In our final paper, Justine Bhar-Amato and Malcolm Finlay and associates examine the hypothesis that increased cholinergic tone exerts its pro-rhythmic effects in Brugada Syndrome through increasing dispersion of transmural repolarization in patients with spontaneous and drug induced Brugada Syndrome. Using a recording array in the right ventricular outflow tract and a micro-catheter in the great cardiac vein to record intracardial and epicardial signals, the authors constructed S1S2 restitution curves from the right ventricular apex at baseline and after edrophonium challenge.                                                  The authors studied eight Brugada Syndrome patients and compared them to eight control patients with super ventricular tachycardia. Electrophysiological studies in controls demonstrated shorter endocardial than epicardial right ventricular activation times, mean difference 26 milliseconds. In contrast, Brugada Syndrome patients showed longer endocardial than epicardial activation times, mean difference -15 milliseconds. Brugada Syndrome patients significantly larger transmural gradient in their activation recovery intervals, mean intervals 20.5 versus 3.5 milliseconds, with longer endocardial than epicardial activation recovery intervals. Edrophonium challenge increased the gradients in both controls to a mean of 16 milliseconds. In Brugada Syndrome, to 29.7 milliseconds. However, these changes were attributed to epicardial activation recovery, interval prolongation in control patients. In endocardial activation recovery interval prolongation in Brugada Syndrome patients. Dynamic changes in repolarization gradients were also observed across the right ventricular wall in Brugada Syndrome patients.                                                  That's it for this month. We hope that you'll find the journal to be the go to place for everyone interest in the field. See you next time.

Dr Paul Wang:                   Welcome to the monthly podcast On The Beat, where Circulation: Arrhythmia and Electrophysiology. I'm Doctor Paul Wang, editor in chief, with some of the key highlights from this month's issue.                                                 In our first paper, Parikshit Sharma and associates reported on the use of permanent his bundle pacing to improve hemodynamics in 39 patients with right bundle branch block. His bundle pacing was successfully performed in 37, or 95 percent of the patients, and resulted in narrowing of the QRS complex from 158 milliseconds to 127 milliseconds. P = 0.0001. An increase in left ventricular ejection fraction from 31 percent to 39 percent. P = 0.004, an improvement in the New York Heart Association functional class from 2.8 to 2.0 P = 0.0001. This work suggests that his bundle pacing maybe helpful in right bundle branch block patients with left ventricular dysfunction.                                                 In our next paper, Philippe Debruyne and associates added to our understanding of using catheter ablation to modulate the autonomic nervous system in patients with neurally mediated syncope, signs of no dysfunction and functional AV block. Prior reports of autonomic modulation using catheter ablation have required extensive ablation in both atria. In this article, the authors report a significant 95% reduction in syncope at six months as a result of targeted ablation in the right atrium alone, focusing on partial ablation of the interior right ganglionated plexus. Ablation is quite limited, taking a mean of seven minutes and creating a mean surface area of 11 millimeters squared. This technique has promise as a possible treatment for avoiding a need of pacemaker implantation in some patients.                                                 In our next paper, Shankar Baskar and associates examined the characteristics and outcomes of pediatric patients receiving implantable cardioverter defibrillators and compared them to their adult counterparts. They examined ICD recipients in the NCDRICD registry from 2010 to 2016. There were 562,209 total ICD implants, including 3461 pediatric patients. Of the pediatric patients, 60 percent of implants were for primary prevention with non-ischemic cardiomyopathy being present in 60 percent of the patients, the most common underlying disease. Over time, there is an increasing trend of both primary and secondary prevention ICD implantations, P less than 0.05. Compared to adults, pediatric patients were likely to have structural heart disease, hypertrophic cardiomyopathy, ion channelopathy, and to receive a single chamber device. All P less than 0.001. There is no difference in in-hospital complications between the adult and the pediatric cohorts, 2.4 percent versus 2.6 percent. However, among pediatric patients, lower weight, Ebstein's anomaly, worse New York Heart Association class dual chamber and resynchronization defibrillator were associated with greater risk of complications. Although, re-intervention for generator replacement or upgrade was more common in adults, the time to re-intervention was shorter in the pediatric cohort.                                                 In our next paper, Ahmed Hussein and associates examine the effect of using ablation index guiding ablation in 40 patients with persistent HO fibrillation on the rate of pulmonary vein reconnection. Pulmonary vein reconnection was seen as a mandatory repeat electro-physiologic study in 22 percent of patients, effecting seven percent of pulmonary veins. Ablation on the intravenous cryna was required in 44 percent of patients to achieve durable pulmonary vein isolation. Atrial tachyarrhythmia occurrence was documented in eight to 20 percent of patients, only one of whom had pulmonary vein reconnection at repeat study. At 12 months, 30 out of 40, or 95 percent of patients, were in sinus rhythm, with four or 10 percent of patients having starting antiarrhythmic drugs. Higher body mass index and excessive alcohol consumption were the only significant factors associated with atrial tachyarrhythmia occurrence.                                                 In our next paper, Atsushi Hirayama and associates examined whether acute exasperation of chronic obstructive pulmonary disease increases the risk of repeated atrial fibrillation related health care utilization. They examine 944 patients who are hospitalized for acute exasperation of chronic obstructive pulmonary disease and had emergency department visit or hospitalization for atrial fibrillation during a 450 day period. Compared to the reference period, the rate of atrial fibrillation related emergency department visits or hospitalizations significantly increased in the first 90 days after acute exasperation of chronic obstructive pulmonary disease. 7.3 versus 14.1 per one hundred person months, resulting in a risk ratio of 1.93.                                                 In our next paper, Namsik Yoon and associates examined the mechanisms underlying the electrocardiographic and arrhythmic manifestation of experimental models of early repolarization syndrome and the ameliorative effects of radio-frequency ablation. The authors recorded axis potentials, bi-polar electrograms, and transmural pseudo electrocardiograms for coronary perfused canine left ventricular wedge preparations in 11 animals.                                                 The ITO agonist, NS5806, the calcium channel blocker Verapamil and acetylcholine were used to pharmacologically mimic the effects of genetic defects associated with early repolarization syndrome. The provocative agents induce prominent j waves in the ECG secondary to the accentuation of the action potential notch in the epicardium but not the endocardium. Bipolar recordings displayed low voltage fractionated potential in the epicardium due to temporal and spatial variability and appearance of the action potential dome conceal the phase two reentry develop when the axon potential dome was lost at some epicardial sites but not others. Appearing in the bipolar electrogram, is discrete high frequency spikes. Successful propagation of the concealed phase two reentered beat precipitated ventricular tachycardia or ventricular fibrillation. Radiofrequency ablation of epicardium destroyed the cell displaying abnormal repolarization and thus suppressed the j waves and the development of ventricular tachycardia and ventricular fibrillation in six out of six preparations.                                                 Stavros Stavrakis and associates described ten patients out of 843 patients, or 1.2 percent with AV nodal reentry tachycardia who required ablation of the basal inferolateral left atria, during stable antegrade slow, retrograde fast, AV nodal reentry tachycardia, a single late atrial extra stimulus was delivered at the inferolateral left atria, near the mitral annulus. All patients had failed ablation in the inferior triangle of Koch, and or roof of the coronary sinus. In all ten patients, a late atrial extra stimulus advanced the his bundle potential by at least ten milliseconds and reset the tachycardia. Ablation at that site, eliminates slow pathway conduction and terminated the tachycardia. Ablation was successful at the site of the latest atrial extra stimulus delivered 49 milliseconds after the onset of this his bundle potential. In their series, no recurrent tachycardia was noted at one year follow up.                                                 In our final paper, Justine Bhar-Amato and Malcolm Finlay and associates examine the hypothesis that increased cholinergic tone exerts its pro-rhythmic effects in Brugada Syndrome through increasing dispersion of transmural repolarization in patients with spontaneous and drug induced Brugada Syndrome. Using a recording array in the right ventricular outflow tract and a micro-catheter in the great cardiac vein to record intracardial and epicardial signals, the authors constructed S1S2 restitution curves from the right ventricular apex at baseline and after edrophonium challenge.                                                 The authors studied eight Brugada Syndrome patients and compared them to eight control patients with super ventricular tachycardia. Electrophysiological studies in controls demonstrated shorter endocardial than epicardial right ventricular activation times, mean difference 26 milliseconds. In contrast, Brugada Syndrome patients showed longer endocardial than epicardial activation times, mean difference -15 milliseconds. Brugada Syndrome patients significantly larger transmural gradient in their activation recovery intervals, mean intervals 20.5 versus 3.5 milliseconds, with longer endocardial than epicardial activation recovery intervals. Edrophonium challenge increased the gradients in both controls to a mean of 16 milliseconds. In Brugada Syndrome, to 29.7 milliseconds. However, these changes were attributed to epicardial activation recovery, interval prolongation in control patients. In endocardial activation recovery interval prolongation in Brugada Syndrome patients. Dynamic changes in repolarization gradients were also observed across the right ventricular wall in Brugada Syndrome patients.                                                 That's it for this month. We hope that you'll find the journal to be the go to place for everyone interest in the field. See you next time.

Circulation: Arrhythmia and Electrophysiology September 2018 Issue

Paul J. Wang: Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief with some of the key highlights from this month's issue. In our first paper, Jacob Koruth and Associates examine the ability to produce ablation lesions using pulse field ablation, which is tissue specific and non-thermal in swine compared to radio frequency ablation. All 46 targeted veins were successfully isolated on the first attempt in all cohorts. Pulmonary vein isolation durability was assessed in 28 veins, including the SVC. Durability was higher in the pulsed field ablation bipolar group, 18 out of 20 in the bipolar group, 10 out of 18 in the monopolar group, and 3 out of 6 in the radio frequency group. P = 0.002. Transmit morality rates were similar across groups with evidence of nerve damage only with radiofrequency. In our next paper, Vivek Reddy and Associates is part of the multicentered first-in-human study, RADIANCE, examine the ability of a novel compliant radio frequency balloon catheter with 10 irrigated flexible electrodes to simultaneously and independently deliver energy. At four sites, 39 patients with paroxysmal atrial fibrillation underwent pulmonary vein isolation using energy delivery simultaneously from all electrodes up to 30 seconds posteriorly, and 60 seconds anteriorly. 152 of 152 targeted pulmonary veins were isolated. 79.6% with a single application. Electrical reconnection occurred in only 7 out of 150 pulmonary veins or 4.7% upon adenosine isoproterenol challenge. Esophageal temperature was monitored in all patients. The esophagus was also mechanically deviated in ten patients. At three months, imaging revealed no pulmonary vein stenosis and early atrial recurrence occurred in only 10 out of 39 or 25.6% of patients. In our next paper Takeshi Kitamura and Associates examine the effect of substrate based ventricular tachycardia ablation targeting local abnormal ventricular activity on recurrent ventricular fibrillation events in patients with structural heart disease. In a retrospective two center study of a total of 686 patients with incident ventricular tachycardia ablation procedure targeting local abnormal ventricular activity, 21 patients, age 57 years left ventricular ejection fraction 30%, had both ventricular tachycardia and ventricular fibrillation. A total of 80 ventricular fibrillation events were recorded in the ICD logs, the six months preceding ablation. Complete and partial local abnormal ventricular activity elimination was achieved in 11 or 52%, in 10 or 58% of patients respectively. Catheter ablation was associated with a highly significant reduction in ventricular fibrillation recurrences. P less than 0.0001 which were limited to three or 14 patients at six months. The total number of ventricular events therefore, decreased from 80 to three with a median of 1.0 to 0.0 in the six months prior to and following ablation respectively. The reduction in ventricular fibrillation events was significantly greater in patients with catheter ablation compared to 21 match controls during a 6- month period preceding and following a baseline assessment. The authors concluded that substrate guided ventricular tachycardia ablation, targeting local abnormal ventricular activity, may be associated with a significant reduction in recurrent ventricular fibrillation, suggesting that ventricular tachycardia and ventricular fibrillation share overlapping arrhythmogenic substrate in patients with structural heart disease. In our next paper, Feng Hu and Associates examine the effect of right anterior ganglion aided plexi ablation on vagal response during circumferential pulmonary vein isolation. 80 patients with paroxysmal atrial fibrillation who underwent first time ablation were prospectively enrolled and randomly assigned to two groups. Group A (n = 40) circumferential pulmonary vein isolation starting with the right pulmonary veins at the right anterior ganglion plexi site. In group B (n = 40) circumferential pulmonary vein isolation starting with the left pulmonary veins first, and the last ablation site being the right anterior ganglionic plexi site. During circumferential pulmonary vein isolation, the positive vagal response was observed in only one patient in group A, in 25 patients in group B. P less than 0.001. A total of 21 patients with positive vagal response in group B needed temporary ventricular pacing during the procedure, while the only patient with positive vagal response in group A did not need temporary ventricular pacing, P less than 0.001. Compared with baseline basic cycle length, sinus node recovery time, and AV node Wenckebach pacing cycle length were decreased significantly after pulmonary vein isolation procedure in both groups, all P less than 0.05 and without differences between the two groups. In our next paper, Karl-Heinz Kuck and Associates reported the results of the randomized atrial fibrillation management and congestive heart failure with ablation, AMICA trial. Patients with persistent or long standing persistent atrial fibrillation and left ventricular ejection fraction ≤ 35%, were randomly allocated to catheter ablation of atrial fibrillation or best medical therapy. The primary study endpoint was the absolute increase in left ventricular ejection fraction from baseline at one year. Pulmonary vein isolation was the primary ablation approach. Best medical therapy comprised rate or rhythm control. All patients were discharged after index hospitalization with a cardioverter defibrillator or resynchronization therapy defibrillator implanted. This study was terminated early for futility of 140 patients, 65 years, 90% men available for endpoint analysis, 68 and 72 patients were assigned to ablation in best medical therapy respectively. At one year, left ventricular ejection fraction had increased in ablation patients by 8.8% and in medical therapy by 7.3%, P = 0.36. Sinus rhythm was recorded on 12-lead electrocardiograms at 1 year. In 61 of 83 ablation patients, or 73.5%, and 42 out of 82 best medical therapy patients or 50%. Device-recorded atrial fibrillation at one year, was 0% or maximally 50% of the time in 28 of 39 ablation patients, so 72% in 16 out of 36 best medical therapy patients or 44%. There were no differences in secondary endpoint outcomes of six-minute walk tests, quality of life or NT pro BNP between the ablation and best medical therapy patients. In our next paper, Dhanunjaya Lakkireddy and Associates examined the association between unrecognized inflammation and premature ventricular contraction. In a single-center prospective study, 107 patients with 5,000 or more PVCs per 24 hours, which were symptomatic, and no known ischemic heart disease, underwent combination of laboratory testing including FDG or 18F-fluorodeoxyglucose pet scan, cardiac magnetic resonance imaging, and biopsy. The mean age cohort was 57 years, 41% were males, a left ventricular ejection fraction was 47%. Positive pet scan was seen in 51%, and 51% had preserved left ventricular function. Based on clinical profile, FDG pet imaging, cardiac magnetic resonance imaging, and histological data, 58% received immunosuppressive therapy alone and 25% received immunosuppressive therapy and catheter ablation. Optimal response was seen in 67% over a mean follow-up of six months in patients with left ventricular systolic dysfunction, 37% showed a mean improvement in left ventricular ejection fraction of 13%. In our next paper, Clare Atzema and Associates examined the association of rapid (3 days), early (7 days), and basic (30 days), outpatient physician follow-up with short and long-term outcomes in atrial fibrillation patients discharged from an emergency department. In 163 emergency departments in Ontario, Canada with a diagnosis of atrial fibrillation, they use landmark analysis with propensity score matching. In the 10,657 patients with rapid follow-up care who are propensity score matched to a patient with follow-up between 4 and 7 days, the hazard of a return emergency visit was reduced by 11%. In the 17,234 patients with early follow-up who are matched to a patient with care between 8 and 30 days, the 1-year mortality was 11% lower, and 1-year hospitalization was 6% lower. Relative to no 30-day care, basic follow-up care was associated with an increased hazard ratio of 90-day hospitalization, but no longer was associated with mortality. The authors concluded that compared to follow-up care between 8 and 30 days, follow-up care within a week after discharge from an emergency department with atrial fibrillation, was associated with a reduction in death, in hospitalization at 1 year, in association not present with 30-day follow-up. In our next paper, James Freeman and Associates evaluate outcomes including death, myocardial infarction, stroke or systemic embolism, intracranial bleeding, major bleeding hospitalization in patients undergoing atrial fibrillation ablation compared with a propensity score match cohort of patients treated with anti-arrhythmic medications only in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) I and II registries. Among 21,595 patients, 6% underwent de novo atrial fibrillation ablation. The propensity score matched cohort included 1087 patients who underwent atrial fibrillation matched one-to-one with 1087 patients treated with an antiarrhythmic medication only. There were no significant differences in the risk of all-cause and cardiovascular death in most other major cardiovascular and neurologic events. Atrial fibrillation catheter ablation was associated with an increased risk of all cause hospitalization hazard ratio 1.24 particularly in the 3 months after the procedure. Among those who underwent atrial relation ablation with CHA2DS2 VAS score, 2 for men and 3 for women, 23% had oral anticoagulation discontinued after ablation. Among those with discontinue oral anticoagulation, the median time to discontinuation was 6.2 months. Thus, the authors found no difference in adjusted rates of cardiovascular and all-cause death, between patients treated with atrial fibrillation catheter ablation and antiarrhythmic medications only. In our next paper, Michael Liu and Associates examined R-from-T as a common mechanism of arrhythmia initiation in long QT syndrome. In their study, spontaneous initiation of polymorphic ventricular tachycardia was elicited by gradually ramping up ICa,L to simulate the early phase of sympathetic surge or changing the heart rate, reproducing the different genotype-dependent clinical electrocardiographic features in LQTS type 2 and 3, T-wave alternans was observed followed by premature ventricular complexes. Compensatory pauses occurred resulting in short-long sequences, as ICa,L increased further polymorphic ventricular tachycardia episodes occurred, always proceeded by short-long-short sequences. However, in LQTS type 1 once a PVC occurred, it almost immediately led to an episode of polymorphic ventricular tachycardia. Arrhythmias in LQT2 and 3 were bradycardia dependent, whereas LQT1 was not. In all 3 genotypes, PVCs always originated spontaneously from the steep repolarization gradient region and manifested on ECG as R-on-T. the authors called this mechanism R-on-T to distinguish it from the classic explanation of R-on-T arrhythmogenesis when an exogenous PVC coincidentally encounters a repolarization region. In R-from-T, the PVC and the T wave are causally related, where the steep repolarization gradients combine with enhanced ICa,L leading to the PVCs emerging from the T wave. Since enhanced ICa,L  was required for R-from-T to occur, suppressing window ICa,L  effectively prevented arrhythmias in all 3 genotypes. In our next paper, Dhani Dharmaprani and Associates hypothesized phase singularity formation and destruction in fibrillation could be modeled as a self-regenerating Poisson renewal processes, producing exponential distributions of inter event times governed by constant rate parameters defined by prevailing properties of each system. The authors studied 5 systems, human persistent atrial fibrillation in 20 cases, tachypaced atrial fibrillation in sheep in 5 cases, rat atrial fibrillation in 4 cases, and rat ventricular fibrillation in 11 cases, as well as computer simulated fibrillation. Phase singularity time to event data were fitted by exponential probability distribution functions computed using maximum entropy theory, and rates of phase singularity formation and destruction were determined. A systematic review is conducted to cross validate with sources from the literature. In all systems phase singularity lifetime and inter formation times were consistent with underlying Poisson renewal processes. The authors conclude that Poisson renewal theory provides an evolutionarily preserved universal framework to quantify formation and destruction of rotational events in cardiac fibrillation. In our issue, there was a very interesting special report on hypothermia outcomes after transvenous lead extraction complications requiring cardiothoracic surgery by Peter Hu and Associates. In addition, there is a very interesting review of atrial fibrillation mediated cardiomyopathy by Kevin Heist and Associates. That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.

Paul J. Wang: Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, Editor-in-Chief with some of the key highlights from this month's issue. In our first paper, Jacob Koruth and Associates examine the ability to produce ablation lesions using pulse field ablation, which is tissue specific and non-thermal in swine compared to radio frequency ablation. All 46 targeted veins were successfully isolated on the first attempt in all cohorts. Pulmonary vein isolation durability was assessed in 28 veins, including the SVC. Durability was higher in the pulsed field ablation bipolar group, 18 out of 20 in the bipolar group, 10 out of 18 in the monopolar group, and 3 out of 6 in the radio frequency group. P = 0.002. Transmit morality rates were similar across groups with evidence of nerve damage only with radiofrequency. In our next paper, Vivek Reddy and Associates is part of the multicentered first-in-human study, RADIANCE, examine the ability of a novel compliant radio frequency balloon catheter with 10 irrigated flexible electrodes to simultaneously and independently deliver energy. At four sites, 39 patients with paroxysmal atrial fibrillation underwent pulmonary vein isolation using energy delivery simultaneously from all electrodes up to 30 seconds posteriorly, and 60 seconds anteriorly. 152 of 152 targeted pulmonary veins were isolated. 79.6% with a single application. Electrical reconnection occurred in only 7 out of 150 pulmonary veins or 4.7% upon adenosine isoproterenol challenge. Esophageal temperature was monitored in all patients. The esophagus was also mechanically deviated in ten patients. At three months, imaging revealed no pulmonary vein stenosis and early atrial recurrence occurred in only 10 out of 39 or 25.6% of patients. In our next paper Takeshi Kitamura and Associates examine the effect of substrate based ventricular tachycardia ablation targeting local abnormal ventricular activity on recurrent ventricular fibrillation events in patients with structural heart disease. In a retrospective two center study of a total of 686 patients with incident ventricular tachycardia ablation procedure targeting local abnormal ventricular activity, 21 patients, age 57 years left ventricular ejection fraction 30%, had both ventricular tachycardia and ventricular fibrillation. A total of 80 ventricular fibrillation events were recorded in the ICD logs, the six months preceding ablation. Complete and partial local abnormal ventricular activity elimination was achieved in 11 or 52%, in 10 or 58% of patients respectively. Catheter ablation was associated with a highly significant reduction in ventricular fibrillation recurrences. P less than 0.0001 which were limited to three or 14 patients at six months. The total number of ventricular events therefore, decreased from 80 to three with a median of 1.0 to 0.0 in the six months prior to and following ablation respectively. The reduction in ventricular fibrillation events was significantly greater in patients with catheter ablation compared to 21 match controls during a 6- month period preceding and following a baseline assessment. The authors concluded that substrate guided ventricular tachycardia ablation, targeting local abnormal ventricular activity, may be associated with a significant reduction in recurrent ventricular fibrillation, suggesting that ventricular tachycardia and ventricular fibrillation share overlapping arrhythmogenic substrate in patients with structural heart disease. In our next paper, Feng Hu and Associates examine the effect of right anterior ganglion aided plexi ablation on vagal response during circumferential pulmonary vein isolation. 80 patients with paroxysmal atrial fibrillation who underwent first time ablation were prospectively enrolled and randomly assigned to two groups. Group A (n = 40) circumferential pulmonary vein isolation starting with the right pulmonary veins at the right anterior ganglion plexi site. In group B (n = 40) circumferential pulmonary vein isolation starting with the left pulmonary veins first, and the last ablation site being the right anterior ganglionic plexi site. During circumferential pulmonary vein isolation, the positive vagal response was observed in only one patient in group A, in 25 patients in group B. P less than 0.001. A total of 21 patients with positive vagal response in group B needed temporary ventricular pacing during the procedure, while the only patient with positive vagal response in group A did not need temporary ventricular pacing, P less than 0.001. Compared with baseline basic cycle length, sinus node recovery time, and AV node Wenckebach pacing cycle length were decreased significantly after pulmonary vein isolation procedure in both groups, all P less than 0.05 and without differences between the two groups. In our next paper, Karl-Heinz Kuck and Associates reported the results of the randomized atrial fibrillation management and congestive heart failure with ablation, AMICA trial. Patients with persistent or long standing persistent atrial fibrillation and left ventricular ejection fraction ≤ 35%, were randomly allocated to catheter ablation of atrial fibrillation or best medical therapy. The primary study endpoint was the absolute increase in left ventricular ejection fraction from baseline at one year. Pulmonary vein isolation was the primary ablation approach. Best medical therapy comprised rate or rhythm control. All patients were discharged after index hospitalization with a cardioverter defibrillator or resynchronization therapy defibrillator implanted. This study was terminated early for futility of 140 patients, 65 years, 90% men available for endpoint analysis, 68 and 72 patients were assigned to ablation in best medical therapy respectively. At one year, left ventricular ejection fraction had increased in ablation patients by 8.8% and in medical therapy by 7.3%, P = 0.36. Sinus rhythm was recorded on 12-lead electrocardiograms at 1 year. In 61 of 83 ablation patients, or 73.5%, and 42 out of 82 best medical therapy patients or 50%. Device-recorded atrial fibrillation at one year, was 0% or maximally 50% of the time in 28 of 39 ablation patients, so 72% in 16 out of 36 best medical therapy patients or 44%. There were no differences in secondary endpoint outcomes of six-minute walk tests, quality of life or NT pro BNP between the ablation and best medical therapy patients. In our next paper, Dhanunjaya Lakkireddy and Associates examined the association between unrecognized inflammation and premature ventricular contraction. In a single-center prospective study, 107 patients with 5,000 or more PVCs per 24 hours, which were symptomatic, and no known ischemic heart disease, underwent combination of laboratory testing including FDG or 18F-fluorodeoxyglucose pet scan, cardiac magnetic resonance imaging, and biopsy. The mean age cohort was 57 years, 41% were males, a left ventricular ejection fraction was 47%. Positive pet scan was seen in 51%, and 51% had preserved left ventricular function. Based on clinical profile, FDG pet imaging, cardiac magnetic resonance imaging, and histological data, 58% received immunosuppressive therapy alone and 25% received immunosuppressive therapy and catheter ablation. Optimal response was seen in 67% over a mean follow-up of six months in patients with left ventricular systolic dysfunction, 37% showed a mean improvement in left ventricular ejection fraction of 13%. In our next paper, Clare Atzema and Associates examined the association of rapid (3 days), early (7 days), and basic (30 days), outpatient physician follow-up with short and long-term outcomes in atrial fibrillation patients discharged from an emergency department. In 163 emergency departments in Ontario, Canada with a diagnosis of atrial fibrillation, they use landmark analysis with propensity score matching. In the 10,657 patients with rapid follow-up care who are propensity score matched to a patient with follow-up between 4 and 7 days, the hazard of a return emergency visit was reduced by 11%. In the 17,234 patients with early follow-up who are matched to a patient with care between 8 and 30 days, the 1-year mortality was 11% lower, and 1-year hospitalization was 6% lower. Relative to no 30-day care, basic follow-up care was associated with an increased hazard ratio of 90-day hospitalization, but no longer was associated with mortality. The authors concluded that compared to follow-up care between 8 and 30 days, follow-up care within a week after discharge from an emergency department with atrial fibrillation, was associated with a reduction in death, in hospitalization at 1 year, in association not present with 30-day follow-up. In our next paper, James Freeman and Associates evaluate outcomes including death, myocardial infarction, stroke or systemic embolism, intracranial bleeding, major bleeding hospitalization in patients undergoing atrial fibrillation ablation compared with a propensity score match cohort of patients treated with anti-arrhythmic medications only in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) I and II registries. Among 21,595 patients, 6% underwent de novo atrial fibrillation ablation. The propensity score matched cohort included 1087 patients who underwent atrial fibrillation matched one-to-one with 1087 patients treated with an antiarrhythmic medication only. There were no significant differences in the risk of all-cause and cardiovascular death in most other major cardiovascular and neurologic events. Atrial fibrillation catheter ablation was associated with an increased risk of all cause hospitalization hazard ratio 1.24 particularly in the 3 months after the procedure. Among those who underwent atrial relation ablation with CHA2DS2 VAS score, 2 for men and 3 for women, 23% had oral anticoagulation discontinued after ablation. Among those with discontinue oral anticoagulation, the median time to discontinuation was 6.2 months. Thus, the authors found no difference in adjusted rates of cardiovascular and all-cause death, between patients treated with atrial fibrillation catheter ablation and antiarrhythmic medications only. In our next paper, Michael Liu and Associates examined R-from-T as a common mechanism of arrhythmia initiation in long QT syndrome. In their study, spontaneous initiation of polymorphic ventricular tachycardia was elicited by gradually ramping up ICa,L to simulate the early phase of sympathetic surge or changing the heart rate, reproducing the different genotype-dependent clinical electrocardiographic features in LQTS type 2 and 3, T-wave alternans was observed followed by premature ventricular complexes. Compensatory pauses occurred resulting in short-long sequences, as ICa,L increased further polymorphic ventricular tachycardia episodes occurred, always proceeded by short-long-short sequences. However, in LQTS type 1 once a PVC occurred, it almost immediately led to an episode of polymorphic ventricular tachycardia. Arrhythmias in LQT2 and 3 were bradycardia dependent, whereas LQT1 was not. In all 3 genotypes, PVCs always originated spontaneously from the steep repolarization gradient region and manifested on ECG as R-on-T. the authors called this mechanism R-on-T to distinguish it from the classic explanation of R-on-T arrhythmogenesis when an exogenous PVC coincidentally encounters a repolarization region. In R-from-T, the PVC and the T wave are causally related, where the steep repolarization gradients combine with enhanced ICa,L leading to the PVCs emerging from the T wave. Since enhanced ICa,L  was required for R-from-T to occur, suppressing window ICa,L  effectively prevented arrhythmias in all 3 genotypes. In our next paper, Dhani Dharmaprani and Associates hypothesized phase singularity formation and destruction in fibrillation could be modeled as a self-regenerating Poisson renewal processes, producing exponential distributions of inter event times governed by constant rate parameters defined by prevailing properties of each system. The authors studied 5 systems, human persistent atrial fibrillation in 20 cases, tachypaced atrial fibrillation in sheep in 5 cases, rat atrial fibrillation in 4 cases, and rat ventricular fibrillation in 11 cases, as well as computer simulated fibrillation. Phase singularity time to event data were fitted by exponential probability distribution functions computed using maximum entropy theory, and rates of phase singularity formation and destruction were determined. A systematic review is conducted to cross validate with sources from the literature. In all systems phase singularity lifetime and inter formation times were consistent with underlying Poisson renewal processes. The authors conclude that Poisson renewal theory provides an evolutionarily preserved universal framework to quantify formation and destruction of rotational events in cardiac fibrillation. In our issue, there was a very interesting special report on hypothermia outcomes after transvenous lead extraction complications requiring cardiothoracic surgery by Peter Hu and Associates. In addition, there is a very interesting review of atrial fibrillation mediated cardiomyopathy by Kevin Heist and Associates. That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2019.

Circulation: Arrhythmia and Electrophysiology December 2019 Issue

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