Circulation: Arrhythmia and Electrophysiology On the Beat

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<0.001). Acute complication rates were similar between groups, LAAEI 1.3% and non-LAAEI 0.73% (p=0.36). At five year follow-up, 382 (70%) patients in the LAAEI group remained on oral anticoagulation versus 217 (39.7%) in the non-LAAEI group. No thromboembolic events occurred in either group on oral anticoagulation. In patients who were off oral anticoagulation, a five year follow-up, thromboembolic events occurred in 15 of 164 (9.1%) in the LAAEI group and 4 out of 329 (1.2%) in the non-LAAEI group (p<0.001). The authors concluded that at five year follow-up, LAAEI was associated with significantly higher freedom from all atrial arrhythmia recurrence in patients with persistent and long-standing persistent AF without increasing acute procedural complication rate. In patients off oral anticoagulation, there appears to be a higher risk of thromboembolic events in the LAAEI group.   In the next paper, Niraj Varma and Associates postulated that left ventricular (LV) epicardial pacing results in slowly propagating pace wave fronts effect that may limit cardiac resynchronization therapy (CRT) efficacy in patients with left ventricular (LV) enlargement using conventional biventricular or bi-V pacing and single LV pacing, but may be mitigated by LV pacing by two widely spaced sites using MultiPoint pacing (MPP) with anatomic separation (AS) of 30 millimeters or more. They tested this hypothesis in the multi-centered MPT IDE trial. Following implant, quadripolar biventricular pacing was activated in all patients (n=506). From 3 to 9 months post implant among patients with available baseline LV and diastolic volumes LVEDV measures and 188 received bi-V pacing and 43 receiving MPP-AS. Patients were dichotomized by median baselines LVEDV indexed to height. Outcomes were measured by the clinical composite score (CCS) as the primary endpoint, quality of life, left ventricular remodeling, EF greater than 5% and systolic volume decreased 10% in heart failure event or cardiovascular death. LVEDVI median was 1.4 millimeters per centimeter. Baseline characteristics differed in patients with LVEDVI greater than median versus LVEDVI less than or equal to median. Among patients with LVEDVI greater than median, bi-V was less efficacious compared to patients with LVEDVIs less than or equal to median. Clinical composite scores 65% versus 79%. In contrast, MPP-AS programming generated greater composite score response (92% versus 65%, P=0.03) and improved quality of life (31 versus -15.7, P=0.38) versus bi-V pacing with LVEDV greater than median. Reverse remodeling trended better with MPP-AS programming. When LVEDVI was greater than median, heart failure event rate increased following the three months randomization point in bi-V but no heart failure event occurred in patients with MPP-AS programming between three and six months in LVEDVI greater than median. All measured outcomes did not differ in patients receiving MPP-AS and bi-V pacing with LVEDVI less than or equal to median. The authors concluded that conventional biventricular pacing even with a quadripolar lead has reduced efficacy in patients with left ventricular enlargement however in patients with larger hearts and programmed to MPP-AS the greatest response rate was observed.   In our next paper, Chih-Min Liu, Shih-Lin Chang, Hung-Hsun Chen and Associates, applied deep learning to pre-ablation pulmonary vein computed tomography (PVCT) geometric slices to create a predictive model for non-pulmonary vein (NPV) triggers in patients with paroxysmal atrial fibrillation (PAF). They retrospectively analyzed 521 PAF patients who underwent catheter ablation of PAF. Among them, PVCT geometric slices from 358 nonrecurrent AF patients one to three millimeters

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<0.001). Compared with the pharmacological therapy arm, both ablation patient groups were severe, less than 20% or moderate/severe, greater than 20% and less than 35% baseline LVEF had a significantly lower number of composite end points (hazard ratio 0.60; P=0.006), all-cause mortality (hazard radio 0.54; P=0.019), and cardiovascular hospitalizations (hazard ratio 0.66; P=0.017). In the ablation group, NYHA I/II patients at the time of treatment had the strongest improvement in clinical outcomes (primary end point: hazard ratio 0.43; P<0.001; mortality: hazard ratio 0.30; P=0.001). The authors concluded that compared with pharmacological treatment, AF ablation was associated with a significant improvement in LVEF, independent from the severity of left ventricular dysfunction, indicating that AF ablation should be performed at early stages of a patient’s heart failure symptoms. In the next paper, Milena Leo and associates conducted a randomized study to compare risk of esophageal heating and acute procedure success of different LSI-guided ablation protocols combining higher or lower radiofrequency power or different target LSI values. Eighty consecutive patients were prospectively enrolled and randomized to one of 4 combinations of radiofrequency (RF) power and target LSI for ablation of the left atrial posterior wall (that is 20 watts LSI 4, 20 watts LSI 5, 40 watts LSI 4, and 40 watts LSI 5). The primary end point of the study was the occurrence and number of esophageal temperature alerts (ETAs) per patient during ablation. Acute indicators of procedure success were considered as secondary end points. Long-term follow-up data was also collected for all patients. Esophageal temperature alerts (ETAs) occurred in a similar proportion of patients in all groups. Significantly, shorter RF durations was required to achieve the target LSI in the 40 watt groups. Less than 50% of the RF lesions reached the target LSI of 5 when using 20 watts despite a longer RF duration. A lower rate of first-pass pulmonary vein isolation and a higher rate of acute pulmonary vein reconnection were recorded in the group 20 watts LSI 5. A lower AF recurrence rate was observed in the 40 watt groups compared with the 20 watts groups at 29 months follow-up. The authors concluded that when guided by LSI, posterior wall ablation with 40 watts is associated with a similar rate of ETAs and a lower AF recurrence rate at follow-up if compared with 20 watts. These data will provide a basis to plan future randomized trials. In the next paper, Shohreh Honarbakhsh and associates in this study aimed to determine whether STAR mapping using sequential recordings from conventional pulmonary vein mapping catheters could achieve similar results. Patients with persistent AF less than 2 years were included. Following pulmonary vein isolation (PVI), AF drivers were identified on sequential STAR maps created with PentaRay, IntellaMap Orion, or Advisor HD Grid catheters. Patients had a minimum of 10 multipolar recordings of 30 seconds each. These were processed in real-time and AF drivers were targeted with ablation. An ablation response was determined as AF termination or cycle length slowing greater than or equal to 30 milliseconds. Thirty patients were included, 62.4 years old, AF duration 14.1 months, of which 3 had AF terminated on pulmonary vein isolation, leaving 27 patients that underwent STAR-guided AF driver ablation. Eighty-three potential AF drivers were identified 3.1 per patient of which 70 were targeted with ablation (2.6 per patient). An ablation response was seen at 54 AFDs, 77.1% of AF drivers with 21 AF termination and 33 cycle length slowing and occurred in all 27 patients. No complications occurred. At 17.3 months, 22 out of 27 or 81.5% of patients undergoing STAR-guided ablation were free from atrial fibrillation, atrial tachycardia off antiarrhythmic drugs. The authors concluded that STAR-guided AF driver ablation through sequential mapping with a multipolar catheter effectively achieved an ablation response in all patients. AF termination in a majority of patients, with a high freedom from atrial fibrillation atrial tachycardia off antiarrhythmic drugs at long-term follow-up. In our next paper, Takashi Kaneshiro and associates sought to evaluate the characteristics of esophageal injuries in atrial fibrillation (AF) ablation using high power short duration setting. After exclusion of 5 patients with their esophagus at the right portion of left atrium and 21 patients with additional ablations such as box isolation and/or low voltage area in left atrium posterior wall, 271 consecutive patients, 62 years, 56 women, who underwent pulmonary vein isolation (PVI) by radiofrequency catheter ablation were analyzed. In the 101 patients, high power short duration setting at 45 to 50 watts with an Ablation Index module was used. In the remaining 170 patients, before introduction of the high power short duration setting, a conventional power setting of 20 to 30 watts with contact force monitoring was used, that is the conventional group. They performed esophagogastroduodenoscopy after pulmonary vein isolation in all patients and investigated the incidence and characteristics of esophageal thermal injury. Although the incidence of esophageal thermal injury was signi

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<0.001). In our next paper, Dan Musat and associates assess the incidents and predictors of very late occurrence (VLR) when atrial fibrillation occurs 12 months or more after ablation in patients who underwent cryoballoon pulmonary vein isolation alone (PVI), had an ILR and were confirmed AF free (atrial fibrillation free) for at least one year. They included 188 patients, mean 66 years, 62% male and 54% paroxysmal atrial fibrillation with CHA2DS2-VASc 2.6. After one year post PVI, 49% of patients remained AF free. During subsequent follow-up, 32% had very late recurrence of atrial fibrillation. The only independent risk factor for very late recurrence was an elevated CHA2DS2-VASc score (hazard ratio 1.317; P=0.06). Patients with CHA2DS2-VASc score greater than four represented a quarter of the population and were at highest risk. In our next paper, Daniele Pastori, Danilo Menichelli, Gregory Yip and associates in the ATHERO-AF Study Group investigate the association between family history of atrial fibrillation (AF) in cardiovascular events (CVEs), major adverse events (MACE), and cardiovascular mortality. They conducted a multicenter prospective observational cohort study, including 1,722 nonvalvular AF patients from February 2008 to August 2019 in Italy. Family history of AF was defined as the presence of AF in a first-degree relative: mother, father, sibling, or children. Primary outcome was a composite of CVEs, including fatal/non-fatal ischemic stroke and myocardial infarction and cardiovascular death. Second, they analyze the association with MACE. Mean age 74.6 years, 44% women. Family history of AF was detected in 368 or 21.4% of patients, and 3.5% had two or more relatives affected by AF. Age of AF onset progressively decreased from patients without family history of AF compared to those with single and multiple first-degree affected relatives (P<0.001). During a mean follow-up of 23.7 months or 4,606 patient years, 145 CVEs, that's 3.15% per year, 98 MACE (2.13% per year) and 57 cardiovascular deaths (0.9% per year) occurred. After adjustment for cardiovascular risk factors, family history of AF was associated with a higher risk of CVEs (hazard ratio. 1.524: P=0.039), MACE (hazard ratio 1.917; P=0.006) and cardiovascular mortality (hazard ratio 2.008; P=0.036). Subgroup analysis showed that this association was modified by age, sex, and prior ischemic heart disease. The authors concluded that in a cohort of elderly patients with high atherosclerotic burden, family history of AF was evident in more than 20% of patients and was associated with an increased risk of CVEs and mortality. In our next paper, Louise Reilly and associates created the first patient-inspired KCNJ2 transgenic mouse and studied the effects of this mutation on cardiac function, IK1 and calcium handling to determine the underlying cellular arrhythmic pathogenesis. A cardiac specific KCNJ2-R67Q mouse was generated and bred for heterozygosity. That's R67Q+/-. Echocardiography was performed at rest and under anesthesia. In vivo electrocardiogram, ECG recording, and whole heart optical mapping of intact hearts was performed before and after adrenergic stimulation in wild-type littermates and R67Q+/- mice. In IK1 measurements and action potential AP characterization, intracellular calcium imaging from isolated ventricular myoc

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 < 0.001) and experienced greater mean LVEF improvement (11.1% versus 4.8%, P < 0.001), even among left bundle branch block patients with QRS duration, 150 milliseconds or greater (hazard ratio 0.45, P < 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<0.001), at 12 hours (1.0 versus 6.0, P<0.001), and up to 48 hours post-procedure. Incidence of acute severe pericarditis delayed pericardial effusion and gastrointestinal adverse effects were similar in both groups. Median length of stay was significantly lower in the lyposomal bupivacaine pain group (2.0 versus 3.0, P<0.001). Subgroup analysis demonstrated similar favorable outcomes in both Lariat and epicardial VT ablation groups. In our next paper, Sergio Callegari, Emilio Macchi, and Associates characterize the fibrosis (amount, architecture, cellular components, and ultrastructure) in left atrial biopsies from 121 patients with persistent/long-lasting atrial fibrillation [AF] (group 1; 59 males; 60 years of age; 91 mitral disease-related AF, 30 nonmitral disease-related AF) and 39 patients in sinus rhythm with mitral valve regurgitation (group 2; 32 males; 59 years of age). 10 autopsy hearts served as controls. Qualitatively, the fibrosis exhibited the same characteristics in all cases and displayed particular architectural scenarios (which the authors arbitrarily divided into four stages) ranging from isolated foci to confluent sclerotic areas. The percentage of fibrosis was larger and in a more advanced stage in group 1 versus group 2 and within group 1, in patients with rheumatic disease versus non-rheumatic cases. In AF patients with mitral disease and no rheumatic disease, the percentage of fibrosis and the fibrosis stages correlated with both left atrial volume index and AF duration. The fibrotic areas mainly consisted of type I collagen with only a minor cellular component (especially fibroblasts/myofibroblasts; average value range 69–150 cells/mm2, depending on the areas in AF biopsies). A few fibrocytes, circulating and bone marrow-derived mesenchymal cells, were also detectable. The fibrosis-entrapped cardiomyocytes showed sarcolemmal damage and connexin 43 redistribution/internalization. In our next paper, Shijie Zhou and Associates tested an automated localization system to identify the site of origin of left ventricular [LV] activation in real time using 12-lead ECG. The automated site of origin, solo system, consists of three steps: (1) localization of ventricular segment based on population templates, (2) population-based localization within a segment, and, (3) patient-specific site localization. Localization error was assessed by the distance between the known reference site and the estimated site. In 19 patients undergoing 21 catheter ablation procedures of scar related VT, solo accuracy was estimated using 552 LV left endocardial pacing sites pooled together and 25 VT-exit sites identified by contact mapping. For the 25 VT-exit sites, localization error of the population-based localization steps was within 10 mm. Patient-specific site localization achieved accuracy of within 3.5 mm after including up to 11 pacing (training) sites. Using 3 remotes (67.8 mm from the reference VT-exit site), and then 5 close pacing sites, resulted in localization error of 7.2 mm for the 25 identified VT-exit sites. In 2 emulated clinical procedure with 2 induced VT's, the solo system achieved accuracy within 4 mm. In our next paper, Ryan Koene and associates examined outcomes of use of dofetilide in atrial fibrillation [AF] patients with left ventricular ejection fraction [LVEF]≤35% without prior implantable cardioverter defibrillator [ICD] cardiac resynchronization therapy [CRT], or AF ablation. An analysis of 168 consecutive patients from 2007 to 2016 was performed. Incidences of adverse events, drug discontinuation, ICD, or CRT implementation, LVEF improvement (>35%) and recovery (50% or greater), AF recurrence, and AF ablation were determined. Multi-variate regression analysis to identify predictors of LVEF improvement/recovery was performed. The mean age was 64 years. Dofetilide was discontinued prior to hospital discharge in 46 (27%) because of QT prolongation (14%), torsades de pointe or polymorphic ventricular tachycardia/ventricular fibrillation (6% [sustained 3%, nonsustained 3%]), in effectiveness (5%), and other causes (3%). At one year 43% remained on dofetilide. Freedom from AF was 42% at 1 year and 40% underwent future AF ablation. LVEF recovered to 50% or greater in 45% and an improved to greater than 35% in 73%. Predictors of LVEF improvement included presence of AF during echoca

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, Demilade Adedinsewo and associates assess the accuracy of an artificial intelligence-enabled electrocardiogram [AI-ECG] to identify patients presenting with dyspnea who have left ventricular LV systolic function (defined as LV ejection fraction ≤35%) in the emergency department [ED]. Patients were included if they had at least one standard 12-lead electrocardiogram [ECG] acquired on the date of the ED visit and an echocardiogram performed within 30 days of presentation. Patients with prior LV systolic dysfunction were excluded. A total of 1,606 patients were included. Meantime from ECG echocardiogram was one day. The AI-ECG algorithm identified LV systolic dysfunction with an area under the curve [AUC] of 0.89 and accuracy of 85.9%. Sensitivity was 74%, specificity 87%, negative predictive value 97%, and positive predictive value 40%. To identify an ejection fraction less than 50%, the AUC was 0.85, sensitivity 86%, sensitivity 63%, and specificity 91%. NT-proBNP alone with a cutoff greater than 800 identified LV systolic function with an AUC of 0.80 by comparison. In our next paper, Mahmood Alhusseini and associates hypothesize that convolutional neural networks [CNN] may enable objective analysis of intracardiac activation in atrial fibrillation [AF]. They perform panoramic recording of bi-atrial electrical signals in AF and use the Hilbert-transform to produce 175,000 image grids in 35 patients labeled for a rotational activation by experts who showed consistency, but with variability (kappa [κ]=0.79). In each patient, ablation terminated atrial fibrillation. A CNN was developed and trained on 100,000 AF image grids validated on 25,000 grids, and then tested on a separate 50,000 grids. They found in a separate test cohort of 50,000 grids, CNN reproducibly classified AF image grids into those with or without rotational sites with 95.0% accuracy. This accuracy exceeded that of support vector machines, traditional linear discriminant, and k-nearest neighbor statistical analyses. To probe the CNN, they applied gradient weighted class activation mapping, which revealed that the decision logic closely mimicked rules used by experts (C statistic 0.96). The authors concluded that convolutional neural networks improve the classification of intercardiac AF maps compared to other analyses and agreed with expert evaluation. In our next paper, Kenji Okubo and associates examined whether late potential LP, abolition and ventricular tachycardia [VT] non-inclusive ability predicted long-term outcomes in patients with non-ischemic cardiomyopathy [NICM] undergoing VT ablation. The total 403 patients with NICM (523 procedures) who underwent VT ablation from 2010 to 2016 were included. The underlying structural disease consists of dilated cardiomyopathy (DCM, 49%), arrhythmogenic right ventricular cardiomyopathy (ARVD 17%), postmyocarditis (14%), valvular heart disease (8%), congenital heart disease (2%), hypertrophic cardiomyopathy (2%), and others (5%). Epicardial access was performed in 57% of patients. At baseline, the LPs were present in 60% of patients, and a VT was either inducible or sustained/incessant in 85% of the cases. At the end of the procedure LP abolition was achieved in 79% of cases in VT noninducability in 80%. After a multivariate analysis, the combination of LP abolition and VT noninducibility was independently associated with free survival from VT (hazard ratio, 0.45, p = 0.0002) and cardiac death (hazard ratio 0.38, P = 0.005). The benefit of LP abolition of preventing the VT recurrence in ARVD and postmyocarditis appeared superior to that observed for DCM. In our next paper, Domenico Corradi, Jeffrey Saffitz and associates hypothesize that structural molecular changes in atrial myocardium that correlate with myocardial injury and precede and predict postoperative atrial fibrillation [POAF] may identify new molecular pathways and targets for prevention of this common morbid complication. Right atrial appendage [RAA] samples were prospectively collected during cardiac surgery from 239 patients enrolled in the OPERA trial. 35.2% of patients experienced POAF compared to the non-POAF group. They were significantly older and more likely to have chronic obstructive pulmonary disease or heart failure. They had a higher Euro score and more often underwent valve surgery. No differences in atrial size were observed between POAF and non-POAF patients. The extent of atrial interstitial fibrosis, cardiomyocyte myocytolysis, cardiomyocyte diameter, glycogen storage, or connection 43 distribution at the time of surgery, was not significantly associated with the incidents of POAF. None of these histopathological abnormalities were correlated with level of NT pro-BNP, hs-cTnT, CRP, or oxidative stress biomarkers. The authors concluded that in sinus rhythm patients undergoing cardiac surgery, histopathological changes in RAA do not predict POAF. They did not also correlate with biomarkers of cardiac function, inflammation, and oxidative stress. In our next paper, Mark McCauley, Liang Hong, Arvind Sridhar, and associates hypothesize that obesity decreases sodium channel NAF 1.5 expression via enhanced oxidative stress, thus reducing the sodium current and enhancing susceptibility to atrial fibrillation [AF]. They studied a diet induced obese [DIO] mouse model. Pacing induced AF in 100% of DIO mice versus 25% in controls (P<0.01) with increased AF burden. Cardiac sodium channel expression, sodium current and atrial action potential duration [APD] were reduced and potassium channel expression (Kv1.5) and current IKUR and F2-isoprostanes, NOX2, and protein kinase C expression in atrial fibrosis were significantly increased in DIO mice compared to controls. In mitochondrial antioxidant reduced AF burden, restored sodium current potassium, current IKUR, APD and reversed atrial fibrosis in DIO mice compared to controls. In our next, paper Hirosuke Yamaji and associates conducted a randomized control trial to examine the impact of electrophysiological evaluation of the left atrium on atrial fibrillation [AF] outcome. They examined consecutive persistent and patients with, in 33, and without, 111 patients left atrial [LA] low voltage areas [LA-LVA]. Patients without LA-LVA were randomly assigned to EP test-guided (n=57) and control (n=54). In the EP test-guided group, an adjunctive posterior wall isolation [PWI] was performed in those with positive results (PWI subgroup; n=24) but not those with negative results (n=33). The criteria for positive EP tests were an effective refractory period ≤180 ms, ERP > 20 ms shorter than the other sites, and/or induction of AF/atrial tachycardia during measurements. LVA ablation was performed in the LA-LVA patients during the follow-up period of a mean of 62 weeks, the EP test-guided group had a significantly lower recurrence rate (19%,11/57 versus 41%, 22/54, P=0.012) and a higher Kaplan-Meier AF/AT-free survival curve compared with controls (P=0.01). No significant differences in the recurrence, and AF/AT-free survival curves between PWI (positive EP test) and non-PWI (negative EP test) subgroups were observed. Therefore, PWI for positive EP tests reduced the AF/AT recurrence in the EP test-guided group. A stepwise Cox proportional hazard analysis identified EP test-guided ablation as a factor, reducing recurrence rates. The recurrence rates in LA-LVA ablation group and EP test-guided group were similar. In our next study, Jinxuan Lin and associates assess whether simultaneous pacing of the left and right bundle branch areas may achieve more synchronous ventricular activation than just bundle pacing alone. In symptomatic bradycardia patients, the distal electrode of the bipolar pacing lead was placed at the left bundle branch area via a transventricular-septal approach. This was used to pace the left bundle branch area, while the ring electrode was used to pace the right bundle branch area. Bilateral bundle branch area pacing [BBBP] was achieved by stimulating the cathode and anode in various configurations. BBBP was successfully performed in 22 out of 36 patients. Compared with LBBP, BBBP resulted in greater shortening of QRS duration (109.3 vs 118.4 ms, P < 0.001). LBBP resulted in paced RBBB configuration with a DRVAT of 115 ms and interventricular conduction delay of 34.0 ms. BBBP fully resolved the RBBB morphology in 18 patients. In the remaining 4 patients, RBBP pacing partially corrected the right bundle branch block. In our next paper, Ramanathan Parameswaran, Jonathan Kalman, Geoffrey Lee and associates recorded 2-minute long segments of simultaneous inter-operative mapping of endo- and epicardial lateral right atrial [RA] wall in patients with persistent atrial fibrillation [AF] using 2 high-density grid catheters (16 electrodes, 3 mm spacing). Filtered unipolar and bipolar electrograms [EGMS] of continuous 2-minute AF recordings and electrodes locations were exported for phase analysis. They defined endocardial-epicardial dissociation [EED] as phase differences of ≥20 ms between paired endo- and epi electrodes. Wavefronts [WF] were classified as single rotations, that is single wavefront, focal waves, or disorganized activity as per standard criteria. Endo-Epi wave fronts were simultaneously compared on dynamic phase maps. Complex fractionated electrograms were defined as bipolar electrograms with directional changes occupying at least 70% of the sample area. 14 patients with persistent AF underwent cardiac surgery are included. EED was seen in 50.3% of phase maps with significant temporal heterogeneity. Disorganized activity (endo 41.3%, epi 46.8%, P = 0.0194) and single wave (endo 31.3 versus epi 28.1, P = 0.129) were the dominant patterns. Transient rotations (

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 < 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 < 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 dur

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 < 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 < 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 < 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] < 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 < 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 < 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 fa

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<0.0001, and was independently associated with ventricular arrhythmia events in a multivariate model hazard ratio, 1.5 P=0.002.   In our next paper, Henry Chubb and associates examine the outcomes of cardiac resynchronization therapy studies in pediatric and or congenital heart disease patients using a propensity score match analysis. They examined 63 matched CRT control pairs. Heart transplant or death occurred in 12 subjects or 19% or 37 controls or 59% with a median follow-up of 2.7 years. Cardiac resynchronization therapy was associated with markedly reduced risk of heart transplant or death. Hazard ratio is 0.24 P<0.001. There were no CRT procedural mortality, and there was one systemic infection at 54 months post-implant.   In our next paper Pachon-M and associates examined whether AF nest ablation eliminates the atropine response and decreases RR variability suggesting that they're related to vagal innervation. The authors perform prospective control longitudinal randomized study enrolling 62 patients in two groups, AF nest group that is 32 patients with functional or reflex Bradyarrhythmias or vagal AF treated with AF Nest ablation and a control group, 30 patients with anomalous bundles, ventricular prematures, atrial flutter, AV nodal reentry and atrial tachycardias who were treated with a conventional ablation approach.   In the AF nest group, ablation was delivered at the AF nest detected by fragmentation or fractionation of the endocardial electrograms and by 3D anatomical location of the ganglionated plexus. Vagal response was evaluated before, during and post ablation by five seconds non-contact vagal stimulation at the jugular foramen through the internal jugular veins, analyzing 15 seconds mean heart rate, longest RR pauses and AV block. A pre-ablation non-contact vagal stimulation due sinus pauses, asystole, and transient AV block in both groups showing a strong vagal response.   Post-ablation non-contact vagal stimulation in the AF nest showed complete abolishment of the cardiac vagal response in all cases, P<0.0001, demonstrating robust vagal denervation. However, in the control group, vagal response remained practically unchanged post-ablation showing that non AF nest ablation promotes no significant denervation.   In our next paper, Domingo Uceda and Xiang-Yang Zhu and associates examined whether progressive increases in pericardial fat volume and inflammation, prospectively dampens the heart rate variability in hypercholesterolemic pigs. The author studied wild type or PCSK9 gain-of-function Ossabaw mini-pigs in-vivo before and after three and six months of a normal diet. Four in the wild type group and six in the PKSK9 group. Or high-fat diet, wild type three, in PCSK9, six.   At diet completion, they found that the hypercholesterolemic PCSK9 had significantly depressed heart rate variability, and both high fat diet groups had higher sympathovagal balance compared to the normal diet. P<0.05 versus baseline. Pericardial fat volumes, LDL concentrations correlated inversely with heart rate variability and directly with sympathovagal balance. While a sympathovagal balance correlated directly with plasma norepinephrine. Pericardial fat TNF alpha expression was upregulated in the PKSK9 animals, co-localized with nerve fibers and correlated inversely with root mean square of deviation and pNN50. These findings are consistent with an association between pericardial fat accumulation and alterations in heart rate variability and the autonomic nervous system.   In our next paper, Konstantinos Aronis and Rheeda Ali and associates examined myocardial conduction velocity and myocardial fibrosis density on late gadolinium enhanced cardiac magnetic resonance imaging in patients with ischemic cardiomyopathy. The author studied six patients with ischemic cardiomyopathy undergoing VT ablation, and five with structurally normal left ventricle serving as controls. All patients underwent late gadolinium enhanced cardiac magnetic resonance, and electroatomic mapping in sinus rhythm. Median conduction velocity in ischemic cardiomyopathy patients and controls was 0.41 meters per second and 0.65 meters per second respectively. In ischemic cardiomyopathy patients conduction velocity in areas with no visible fibrosis was 0.81 meters per second. For each 25% increase in normalized late gadolinium-enhanced intensity conduction velocity decreased by 1.34 fold. Dense scar areas have an average of 1.97 to 2.66 fold slower conduction velocity compared to areas without dense scar. Ablation lesions that terminate at VT were localized in areas of slow conduction on conduction velocity maps. The authors found that conduction velocity is inversely associated with late gadolinium enhanced cardiac magnetic resonance fibrosis density in patients with ischemic cardiomyopathy.   In our next paper, Bence Hegyi and associates examined whether the IKR current or the sodium L-type current play counterbalancing roles in the ventricular action potential. The authors found that a comparable amount of net charge carried by these two currents during the physiological action potential, suggesting that the outward potassium current via IKR and the inward sodium current via the sodium L-type current are in balance during physiological repolarization. These two current integrals in control myocytes were highly correlated, but this close correlation was lost in heart failure myocytes. Pretreatment with E-4031 to block IKR mimicking long QT syndrome 2, or ATX II to impair a sodium channel inactivation mimicking long QT3 prolong the action potential duration. However, using GS-967 to inhibit sodium L-type current sufficiently restored action potential control to control in both cases.   Furthermore, the sodium L-type inhibition significantly reduced the beat to beat and short-term variabilities of action potential duration. Sodium L-type current inhibition also restored action potential duration in repolarization stability in heart failure. Conversely, pretreatment with GS-967 shortened action potential duration mimicking short QT syndrome and E-4031 reverted APD shortening. Furthermore, the amplitude of action potential alternans occurring at high pacing frequency was decreased by sodium L-type inhibition, increased by IKR inhibition and restored by a combination of sodium L-type and IKR inhibitions. The author suggests that targeting these two ionic currents to normalize or balance may have significant therapeutic potential in heart diseases with repolarization abnormalities.   In our next paper, Derek Chew and associates examine the impact of the duration between first diagnosis of atrial fibrillation and ablation or diagnosis to ablation time on AF recurrence following catheter ablation by conducting a systematic review and meta analysis of observational studies. They found six studies that met inclusion criteria with a total of 4,950 participants undergoing atrial fibrillation ablation for symptomatic AF. A shorter diagnosis to ablation time of one year or less was associated with a lower relative risk of AF recurrence compared to diagnose to the ablation time greater than one year. Relative risk 0.73 P<0.001.   The authors concluded that the duration between time to first day of AF and AF ablation is associated with an increased likelihood of atrial fibrillation ablation procedural success.   In a research letter by Kapuaola Gellert and associates, 48 hour continuous ECG was found to have an association between sleep apnea and atrial fibrillation in the community-based population study, the ARIC study.   In a special report, Francesco Notaristefano reported that the risk of device pocket hematoma 10 days after CIED surgery showed an independent association with the type of interventional procedure such as device implementation, odds ratio 3.5, implantable cardioverter defibrillator 4.4, cardiac resynchronization therapy, odds ratio 11.7, and antithrombotic treatment, but not with novel oral anticoagulants.   In an interesting review article Nicholas Tan and associates describe the current and future perspectives of left bundle br

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 < 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 < 0.001, Stroke, hazard ratio 1.57 P < 0.001 and mortality, hazard ratio 2.96 P < 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 < 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 < 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 < 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 a

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 < 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 < 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 < 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 < 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 < 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 > 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 > 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 < 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 < 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 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 c

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

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 (<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 i

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, in a single‐center observational cohort study, Owen Donnellan and Associates compared arrhythmia recurrence rates in morbidly obese patients who underwent prior bariatric surgery, with those of non-obese patients following atrial fibrillation ablation. In addition to morbidly obese patients who did not undergo bariatric surgery, they matched 51 morbidly obese patients' body mass index, 40 kilograms per meter squared, who had undergone prior bariatric surgery in a two to one manner with 102 non-obese patients, and 102 morbidly obese patients without bariatric surgery on the basis of age, gender, and timing of atrial fibrillation ablation. From the time of bariatric surgery to ablation, bariatric surgery was associated with a significant reduction in BMI. 47.6 to 36.7 and reduction in systolic blood pressure, 145 to 118, P < 0.001.                                                 During a mean follow up of 29 months following ablation, recurrent arrhythmia occurred in 10 out of 51 or 20 patients in a bariatric surgery group, compared to 25 out of 102 patients, 24.5% in a non-obese group, and 56 out of 102 or 55% in the non-bariatric surgery morbidly obese group. No procedural complications were observed in the bariatric surgery group. In our next paper, Martin Andreas and Associates examined whether noninvasive, low-level, transcutaneous electrical stimulation of the greater auricular nerve reduced the risk of postoperative atrial fibrillation, in a pilot of patients undergoing cardiac surgery. After cardiac surgery, electrodes were applied in the triangular fossa of the ear. Stimulation, amplitude 1-million-amp frequency, one Hertz for 40 minutes, followed by a 20-minute break, was performed for up to two weeks after cardiac surgery. Patients were randomized into sham, N equals 20 or treatment group, N equals 20, for low- level, transcutaneous electrical stimulation. Patients receiving low-level, transcutaneous stimulation had a significant reduced incidence of postoperative atrial fibrillation. Four out of 20, compared to controls 11 out of 20. P equals 0.02.                                                 The median duration of postoperative atrial fibrillation was comparable between the treatment group and control group. No effect on low-level stimulation on CRP or IL-6 levels was detectable. In our next paper, Kazuki Iso and Associates examine whether the vagal response phenomenon is common to patients without atrial fibrillation. Continuous, high- frequent stimulation of the left atrial ganglion and plexus was performed in 42 patients, undergoing ablation for atrial fibrillation. In 21 patients undergoing ablation for left-sided accessory pathway, the high frequency stimulation, 20 Hertz at 25 milliamps of 10 millisecond pulse duration, was applied for five seconds at three sites within the presumed anatomical area of each of the five major left atrial ganglion plexus, for a total of 15 sites per patient. The authors define vagal response to high frequency stimulation, as prolongation of the R interval by > 50% in comparison to the mean pre-high-frequency stimulation RR interval, average over 10 beats.                                                 In active ganglion plexus areas, is areas in which vagal response was elicited. Overall, more active ganglion plexi or GP areas were found in the atrial fibrillation group patients, than in the non-atrial fibrillation group patients. And in all five major GPS, the maximum R interval during high-frequency stimulation was significantly prolonged in atrial fibrillation patients. After multivariate adjustment, association was established between the total number of vagal response sites and the presence of atrial fibrillation. The authors concluded that the significant increase in vagal responses elicited in patients with atrial fibrillation, compared to responses in non-atrial fibrillation patients, suggests that the vagal responses is to hypercan stimulations, reflect an abnormally increased ganglion plexi activity, specific to atrial fibrillation substrates.                                                 In our next paper, Vidal Essebag and Associates combine the data from the Bruise Control One and Two studies to evaluate the effect of concomitant antiplatelet therapy on clinically significant hematomas, and to understand the relative risk of clinically significant hematomas in patients treated with DOAC versus continued Warfarin. The Bruise Control study demonstrated that perioperative Warfarin continuation, reduced clinically- significant hematomas by 80%, compared to Heparin bridging. 3.5% versus 16%. Bruise Control Two observed a similarly low risk of clinically-significant hematomas when comparing continued versus interrupted direct oral anticoagulant. 2.1% in both groups. A total of 1,343 patients were included in Bruise Control One and Bruise Control Two, the primary outcome for both trials with clinically-significant hematomas. There are 408 patients identified as having continued either a single or dual antiplatelet agent at the time of device surgery. Anti-platelet use versus non-use was associated with clinically-significant hematomas in 9.8% versus 4.3%. P less than 0.001 and remained a strong independent predictor with multi-variate adjustment. Odds ratio 1.965, however, multivariate analysis adjusting for anti-platelet use, there was no significant difference in clinically-significant hematomas observed between direct oral anticoagulant use, compared with continued Warfarin.                                                 In our next paper, Markus Rottmann and associates examine the relationship between activation slowing during sinus rhythm, and vulnerability for reentry, and correlated the areas with components of the circuit. In a porcine model of healed infarction, of 15 swine, nine had inducible ventricular tachycardia, 5.2 per animal. While in six swine, VT could not be induced despite stimulation from four RV and LV sites at two drive trains in six extra stimuli down to refract refractoriness. Infarcts with ventricular tachycardia had a greater magnitude of activation slowing, during sinus rhythm, a minimal endocardial activation velocity cutoff, less than 0.1 meters per second. Differentiated inducible from non-inducible infarctions. P equals 0.15. Regions of maximal endocardial slowing during the sinus rhythm corresponded to the VT isthmus. Area under the curve equals 0.84 while bystander sites exhibited near normal activation during sinus rhythm. VT circuits were complex, with 41.7 exhibiting discontinuous propagation with intramural bridges of slow conduction in delayed quasi -simultaneous endocardial activation. Regions forming the VT isthmus borders had facts or activation during sinus rhythm, while regions forming the inner isthmus were activated faster during ventricular tachycardia.                                                 In our next paper, Mary Rooney and Associates sought to define the prevalence of subclinical atrial fibrillation in a community-based elderly population, and to characterize subclinical atrial fibrillation and the incremental diagnostic yield of four versus two weeks of continuous ECG monitoring. They conducted a cross-sectional analysis within the community- based, multi-centered observational atherosclerosis risk in communities. Erik Study, using visit five, 2016 to 2017 data. The 2,616 Erik Study participants who wore a lead-less ambulatory ECG monitor for up to two weeks were age 79 years, 42% men and 26% black. In its subset, 386 participants without clinically-recognized atrial fibrillation wore the monitor twice, each time for two weeks. They characterize the prevalence of subclinical atrial fibrillation, atrial fibrillation detected without clinically recognized atrial relation. Over two weeks of monitoring and the diagnostic yield of four versus two weeks, the authors found that the prevalence of subclinical atrial relation was 2.5%. the prevalence of subclinical each relation was 3.3% among white men, 2.5% among white women, 2.1% among black men and 1.6% among black women.                                                 Subclinical A Fib was mostly intermittent, 75%. Among those with intermittent subclinical atrial fibrillation, 91% had an AF burden of less than or equal to 10%, during the monitoring period. In a subset of 386 patients without clinical atrial fibrillation, 78% more subclinical atrial fibrillation was detected by four weeks versus two weeks of ECG monitoring. In this study, the prevalence of subclinical A Fib was lower than previously reported. And monitoring beyond two weeks provided substantial incremental diagnostic yield.                                                 In our next study, Rafael Ramirez and Yoshio Takemoto and Associates investigated arrhythmic mechanisms of Ranolazine in sheet models, in paroxysmal and persistent atrial fibrillation. Paroxysmal atrial fibrillation was maintained during acute stretch and persistent atrial relation was induced by long-term atrial tachypacing. Isolated Langendorff-perfused sheet parts were optically mapped. In paroxysmal atrial fibrillation, Ranolazine 10 micromolar reduced dominance frequency from 8.3 to 6.2 Hertz. P less than 0.01, before converting to sinus rhythm, decreased singularity point density for 0.07 to 0.039 and left atrial epicardium and prolonged atrial fibrillation cycling. Road or duration tip trajectory in variants of Afib cycle lengths were unaltered. In persistent atrial fibrillation, Ranolazine reduced dominance frequency, prolonged atrial fibrillation cycle length, increased the variance of atrial fibrillation cycling

Dr 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, Ying Tian and associates examine the effects and long-term outcomes of percutaneous stellate ganglion blockade in the setting of drug refractory electrical storm due to ventricular arrhythmia. They studied 30 consecutive patients over nearly a five-year period. They used bupivacaine alone, or in combination with lidocaine injected into the neck with good local anesthetic spread in the vicinity of the left stellate ganglion in 15 patients, or both stellate ganglion in 15 patients.                                 The mean left ventricular ejection fraction was 34%. At 24 hours, 60% of patients were free of ventricular arrhythmia. Patients whose ventricular arrhythmia was controlled had a lower hospital mortality rate than patients whose ventricular arrhythmia continued. 5.6 versus 50%, P equals 0.009. Implantable cardioverter-defibrillator interrogation showed a significant 92% reduction in ventricular arrhythmia episodes from 26 to 2 in the 72 hours after stellate ganglion blockade, P less than 0.001.                                 Patients who died during the same hospitalization, N equals 7, were more likely to have ischemic cardiomyopathy, 100% versus 43.5%. And recurrent ventricular arrhythmias within 24 hours, 85.7% versus 26.1%. There were no procedure related complications.                                 In our next paper, Zachi Attia and associates hypothesized that a convolutional neural network could be trained through a process called 'deep learning' to predict a person's age and gender using only 12-lead electrocardiogram signals. They trained convolutional neural network using 10 second samples of 12-lead ECG signals from 499,727 patients to predict gender and age. The networks were tested on a separate cohort of 275,056 patients. For gender classification, the model obtained 90.4% classification accuracy with an area under the curve of 0.97. In the independent test data, age was estimated as a continuous variable with an average error of 6.9 years, R squared equals 0.7.                                 Among 100 hundred patients with multiple ECGs over the course of at least two decades of life, most patients, 51%, had an average error between real age and convolutional neural network predicted age of less than seven years. Major factors seen amongst patients with convolutional neural network predicted age that exceeded chronologic age by greater than seven years included low ejection fraction, hypertension, and coronary disease, P less than 0.1. In the 27% of patients whose correlation was greater than 0.8, between convolutional neural network predicted and chronological age, no incident events occurred over follow up 30 years.                                 The authors concluded that applying artificial intelligence to the ECG allows prediction of patient, gender, and estimation of age. The ability of artificial intelligent algorithm to determine physiological age with further validation may serve as a measure of overall health.                                 In our next paper, Zain Ul Abideen Asad and associates performed a meta-analysis of randomized control trials in order to compare the efficacy and safety of catheter ablation with medical therapy for atrial fibrillation with the primary outcome being all-cause mortality. They examined 18 randomized controlled trials comprising 4,464 patients. Catheter ablation resulted in significant reduction in all-cause mortality, relative risk of 0.69 that was driven by patients with atrial fibrillation and heart failure in reduced ejection fraction, relative risk 0.52.                                 Catheter ablation resulted in significantly fewer cardiovascular hospitalizations, hazard ratio of 0.56, and fewer recurrences of atrial arrhythmia, relative risk 0.42. Subgroup analysis suggested that younger patients, age less than 65 years, and men derived more benefit from catheter ablation compared to medical therapy.                                 In our next paper, Felipe Kazmirczak, Ko-Hsuan Amy Chen, and associates examined patients with cardiac sarcoidosis meeting guideline criteria for implantable defibrillator implantation in a large retrospective cohort study of patients with biopsy proven sarcoidosis and known or suspected cardiac sarcoidosis undergoing cardiovascular magnetic resonance imaging. The authors found that in 290 patients, the class one and class 2A recommendation identified all patients who experienced a composite endpoint of significant ventricular arrhythmia or sudden cardiac death over a mean follow-up of three years.                                 Patients meeting class one recommendations had a significantly higher incidence of composite endpoint than those meeting class 2A recommendations. Left ventricular ejection fraction greater than 35% with greater than 5.7% late gadolinium enhancement and cardiovascular negative residence imaging was as sensitive as or significantly more specific than left trigger ejection frack greater than 35% with any late gadolinium enhancement. Patients meeting two class 2A recommendations left ventricular ejection fraction greater than 35% would need for a pacemaker, and left ventricle rejection at greater than 35% with late gadolinium enhancement. Greater than 5.7% had high annualized event rates. Excluding two class 2A recommendations, left ventricular ejection fraction greater than 35% with syncope, and left ventricular ejection fraction greater than 35% with inducible ventricular [inaudible] resulted in improved discrimination for the composite endpoint.                                 In our next paper, Kenji Okubo, Antonio Frontera, and associates examined the ability of a new grid mapping catheter for performing substrate and ventricular tachycardia activation mapping during ventricular tachycardia ablation procedures, identifying the low voltage areas and visualizing diastolic pathways. The authors studied 41 consecutive patients undergoing ventricular tachycardia ablation procedure. The grid mapping catheter was used to create three different maps with three bipolar configurations along the spine, across the spine, high density wave solution.                                 The median low voltage area drawn by the high-density wave configuration was 28.9 centimeters squared, but it was 13% and 15% smaller with a low voltage area identified by along and across. The late potential areas identified by the three configurations did not differ. Ventricular tachycardia activation mapping visualizes the full diastolic pathway in 22 out of 40, or 55%. The authors found that identifying the full diastolic pathway led to a higher ongoing VT termination rate during the ablation than in the case of partial recordings, 88% versus 45%, P equals 0.03. In addition, when the full diastolic pathway's identified, the targeted VTS were always non-inducible.                                 In our next paper, Masateru Takigawa, and associates examined whether the spacing orientation, the bipoles of high-density mapping catheters impacts the accuracy of scar detection. The authors analyze the electrograms using high-density HD grid catheter and determine the optimal cutoff for scar detection in six infarcted sheep. For using bipolar voltages to detect MRI defined scar, the area under the receiver operating curve dependent on the spacing and orientation of the bipoles and range from 0.89 to 0.923. The area under the receiver operating curve was significantly larger, P less than 0.01, when only the best points on each site were selected for analysis compared to when all points were used.                                 In our next paper, Darren Tsang and associates examine the impact of prior sternotomy on transvenous lead extraction outcomes. Of 1,480 patients, 455 had prior sternotomy. When compared to patient with no prior sternotomy, those with prior tsunami were more likely to be older, male, and present with more comorbidities and leads targeted for extraction. No statistical difference was identified in major and minor complication rates, clinical success rates, or in hospital mortality.                                 In patients with prior sternotomy, there were no instances of pericardial effusion following extraction. Patients with sternotomies prior to lead extraction experienced vascular cardiac perforation, presented clinically with hemothoraces rather than pericardial effusions.                                 In our next paper, Babak Nazer and associates highlight the electrophysiologic properties in sites of ablation for manifest nodofascicular and nodoventricular accessory pathways that connect the atrial ventricular node and the Purkinje system or ventricular myocardium respectively. Concealed nodoventricular and nodofascicular pathways participate as the retrograde limb of supraventricular tachycardia. Manifest nodofascicular and nodoventricular accessory pathways comprise the antegrade limb of wide complex supraventricular tachycardia but are quite rare.                                 The authors report on eight patients who underwent electrophysiologic studies for wide complex tachycardia three, narrow complex tachycardia one, and for pre-excitation in four patients. The authors found nodofascicular and nodoventricular accessory pathways were an integral part of the supraventricular tachycardia in three patients. In these three cases, cases one and two revealed wide complex tachycardia due to manifest supraventricular tachycardia. Case three with a bi-directional nodofascicular and nodoventricular accessory pathway that conducted retrograde during supraventricular tachycardia, and antegrade causing pre-excitati

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 cathet

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 quar

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

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 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<0.001. The degree of LAPP increase, delta LAPP, was significantly higher in patients who underwent additional extra pulmonary vein left atrial ablation than in those who underwent circumferential PV isolation alone. P=0.01. Extra pulmonary vein left atrial ablation was independently associated with delta LAPP. P=0.045.                                                 An increase LAPP during repeat procedures was independently associated with a reduced diastolic function. P=0.041. However, the EQ5D symptom score did not change after de novo ablation.                                                 In our next paper, Adam Graham and associates examined a median of 711 electrocardiographic imaging, or ECGI, in cardiopirin points per patient to compare simultaneous epicardial mapping using CARTO and ECGI after geometrical co registration in 8 patients. They found that the correlation coefficient measuring the similarity of activation times we equal to 0.66, and the correlation coefficient for repolarization times was 0.55. The minimum distance between epicardial pacing sites, and the region of earliest activation in ECGI was 13.2 mm. Range 0 to 28.3 mm, from 25 pacing sites with stimulation to cuirass interval less than 40 milliseconds.                                                 In our next paper, Michael Barkagan and associates examined high-current, short-duration radiofrequency energy delivery using and expandable spheroid-shaped lattice electrode with effective service tenfold larger than standard irrigated electrodes. It incorporated nine surface temperature sensors, with ablation performed in temperature control mode. In phase one of the study, the authors found that six thigh muscle preparation experiments, ablation with the lattice catheter resulted in wider lesions at both low and high energy settings, 8.7 vs 12.2 mm. P<0.0001, and 19.4 vs 12.3 mm using standard irrigated catheter. P<0.0001.                                                 In phase two of the study, in Eighth Swan, the authors found that right atrial lines created in the posterior lateral walls using low and high-energy settings with the lattice catheter were wider, posterior 14.7 versus 9.2 mm, P<0.001, and lateral, 15.8 versus 5.7 mm, P<0.001.Lattice catheter ablation had 85% shorter ablation time, 12.4 second per centimeter line, versus 79.8 seconds per centimeter line.                                                 On phase three of the study, the authors found at 30 days, 100% of the ablation lines created with lattice catheter remained contiguous, compared to only 14.3% of lines created with a standard irrigated catheter. The authors reported that there were no steam pops or collateral tissue damage.                                                 In our next paper, Anett Ottesen and associated hypothesized that because circulating [inaudible] neuron concentrations are increased in patients with myocardial dysfunction, and predict poor outcome. And because secretive neuron inhibits calcium calmodulin dependent protein kinase ii delta activity, the up regulation of secretive neuron in patients protects against cardiomyocytes mechanisms arrhythmia.                                                 The authors found this secreting neuron levels were elevated in 8 patients with catecholaminergic polymorphic ventricular tachycardia, or in 155 patients after cardiac arrest. AAV9 induced over expression of secretive neuron, attenuated arrhythmic induction during stress testing with isoproterenol. Mechanistic studies map secreta neuron binding to the sub straight binding sight in catalyst region of calcium calmodulin dependent protein kinase ii delta.                                                 Secreta neuron attenuate in isoproterenol induced autophosphorylation of 3NE287 calcium calmodulin dependent protein kinase ii delta, in laying [inaudible] hearts, in inhibited calcium calmodulin dependent kinase ii dependent [inaudible] receptor phosphorylation. Secretor neuron treatment decreased calcium spark frequency in dimensions in cardiomyocytes during isoproterenol challenge, and reduced the instance of calcium wave delayed depolarizations in spontaneous action potentials.                                                 Secreta neuron treatment also lowered the incidence of early after depolarizations during isoproterenol paralleling a reduced magnitude of L type calcium current. Thus, the authors demonstrated that secreta neuron production is upregulated in conditions with cardiomyocytes calcium dysregulation and may provide compensatory protection against cardiomyocytes mechanisms of arrhythmia.                                                 In our final paper, Ne Gang and Shu Wang and associates examined whether Sorting Nexin-17, SNX17, regulates the trafficking process of protein voltage gated channel subfamily A member 5, which has been proposed as a target of interventions for atrial fibrillation. The authors curated a Sorting Nexin-17 knockout rat line. Sorting Nexin-17 hetero zygotes rat survived, and the level of Sorting Nexin-17 protein in the atrium was decreased by 50%.                                                 Sorting Nexin-17 deficiency increased the membrane expression of KV1.5 in atrial specific ultra-rapid delayed rectifier outward potassium current IKUR density, resulting in shorted actual potential duration, and eventually contribute to atrial fibrillation susceptibility.                                                 Sorting Nexin-17 facilitated the endocytic sorting of KV1.5 from the plasma membrane to early endosomes following the 4.1 ezrin radixin moesin called Firm domain. The authors concluded that Sorting Nexin-17 mediates susceptibility to atrial fibrillation through this mechanism, and thus may be a potent target for the development of new drugs for atrial fibrillation.                                                 That's it for this month, we hope that you'll 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.