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

Paul J. Wang:

Welcome to the monthly podcast, On the Beat for Circulation, Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, editor-in-chief with some of the key highlights from this month's issue.

In our first paper, Bruce Wilkoff and associates evaluated antibacterial envelope cost effectiveness compared to standard of care infection prevention strategies in the US healthcare system. Decision tree model was used to compare costs and outcomes of the antimicrobial envelope used adjunctive to standard of care infection prevention versus standard of care alone over a lifelong time horizon. The analysis was performed from an integrated payer provider network perspective. Infection rates, antimicrobial envelope effectiveness, infection treatment costs and patterns, infection related mortality and utility estimates were obtained from the WRAP-IT study. Life expectancy and long-term costs associated with device replacement, follow-up, and healthcare utilization were sourced from the literature. Costs and quality life adjusted years were discounted at 3%. An upper willingness-to-pay threshold of $100,000 per quality adjusted life year was used to determine cost-effectiveness in alignment with the American College of Cardiology and American Heart Association practice guidelines and as supported by the World Health Organization and contemporary literature. The base case incremental cost-effectiveness ratio (ICER) of the antibacterial envelope compared with standard-of-care was $112,603 per quality-adjusted life year. The ICER remained lower than the threshold in 74% of iterations in the probabilistic sensitivity analysis and was most sensitive to the following model inputs: infection-related mortality, life expectancy, and infection cost. The authors concluded that the absorbable antibacterial envelope was associated with a cost-effectiveness ratio below contemporary benchmarks in the WRAP-IT patient population, suggesting that the envelope provides value for the US healthcare system by reducing the incidence of CIED infection.

In our next paper, Peter Loh and associates in this study aim to investigate the feasibility and safety of single pulse irreversible electroporation (IRE) pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). Ten patients with symptomatic paroxysmal or persistent AF underwent single pulse IRE pulmonary vein isolation under general anesthesia. Three-dimensional reconstruction and electroanatomical voltage mapping of the left atrium and pulmonary veins were performed using a conventional circular mapping catheter. Pulmonary vein isolation was performed by delivering nonarcing, nonbarotraumatic 6 ms, 200 Joule direct current IRE applications via a custom nondeflectable 14-polar circular IRE ablation catheter with a variable hoop diameter (16–27 millimeters). A deflectable sheath was used to maneuver the ablation catheter. A minimum of 2 IRE applications with slightly different catheter positions were delivered per vein to achieve circular tissue contact, even if pulmonary vein potentials were abolished after the first application. Bidirectional pulmonary vein isolation was confirmed with the circular mapping catheter and a post ablation voltage map. After a 30-minute waiting period, adenosine testing was used to reveal dormant pulmonary vein conduction. All 40 pulmonary veins could be successfully isolated with a mean of 2.4 IRE applications per pulmonary vein. Mean delivery peak voltage and peak current were 2154 volts and 33.9 amperes. No pulmonary vein reconnections occurred during the waiting period and adenosine testing. No periprocedural complications were observed. The authors concluded that in 10 patients in this first in-human study, acute bidirectional electrical pulmonary vein isolation could be achieved safely using single pulse IRE ablation.

In our next paper, Christian Sohns and associates studied the relationship between left ventricular ejection fraction (LVEF) New York Heart Association (NYHA) class on presentation and the end points of mortality and heart failure (HF) admissions in the CASTLE-AF study population. Furthermore, predictors for LVEF improvement were examined. The CASTLE-AF patients with coexisting heart failure and AF (n=363) were randomized in a multicenter prospective controlled fashion to ablation (n=179) versus pharmacological therapy (n=184). Left ventricular function in NYHA class were assessed at baseline after randomization and at each follow-up visit. In the ablation arm, a significantly higher number of patients experienced an improvement in their LVEF to greater than 35% at the end of the study (odds ratio, 2.17; P

Paul J. Wang:

Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-chief, with some of the key highlights from this month's issue.

In our first paper, Zak Loring and associates examined 3,139 patients undergoing atrial fibrillation (AF) ablation, between 2016 and 2018 in the Get With The Guidelines-Atrial Fibrillation Registry from 24 US centers. Patients undergoing AF ablation were predominantly male (63.9%) and Caucasian (93.2%) with a median age of 65. Hypertension was the most common comorbidity (67.6%), and persistent atrial fibrillation patients had more comorbidities than paroxysmal AF patients. Drug refractory, paroxysmal AF was most common ablation indication (class I, 53.6%) followed by drug refractory, persistent AF (class I, 41.8%). Radio-frequency, RF ablation, with contact force sensing was the most common ablation modality (70.5%) and 23.7% of patients underwent cryoballoon ablation. Pulmonary vein isolation was performed in 94.6% of de novo ablations. The most common adjunctive lesion included left atrial roof or posterior/inferior lines and cavotricuspid isthmus ablation. Complications were uncommon (5.1%) and were life-threatening in 0.7% of cases.

In our next paper, Brian Howard and associates hypothesize that pulse field ablation (PFA) would reduce pulmonary vein stenosis risk and collateral injury compared to irrigated radiofrequency ablation (IRF). IRF and PFA deliveries were randomized in eight dogs with two superior pulmonary veins (PVs), ablated with using one technology and two inferior PVs ablated with the other technology. IRF energy (25-30 watts) or PFA with delivered (16 pulse trains) at each PV in a proximal and in a distal site. Contrast computed tomography (CT scans) were collected at 0, 2, 4 and 8, and 12 week, including termination time points to monitor PV cross-sectional area at each PV ablation site. Maximum average change in normalized cross-sectional area at 4 weeks was 46.1%±45.1% post IRF compared to -5.5±20.5% for PFA (P≤ to 0.001). Necropsy showed expansive PFA lesions without stenosis in the proximal PV sites compared to more confined and often incomplete lesions after IRF. At the distal PV sites only IRF ablations were grossly identified based on focal fibrosis. Mild pulmonary chronic parenchymal hemorrhage was noted in three left superior pulmonary vein lobes after IRF. Damage to vagus nerves, as well as evidence of esophagus dilation, occurred at sites associated with IRF. In contrast, no lung, vagal nerve, or esophageal injury was observed at PFA sites.

In our next paper, Mohamed Diab and associates aimed to assess the safety of ablation for atrial fibrillation (AF) with trans-esophageal (TEE) screening on intracardiac echocardiography (ICE) imaging of the appendage in direct oral anticoagulant (DOAC) compliant patients. They studied 900 patients with a medium CHA2DS2-VASc score of two. Interquartile range one to three. All consecutive patients presenting with AF or atrial flutter on DOAC were included. All were on DOACs (333 Rivaroxaban, 285 Dabigatran, 281 Apixaban and one Edoxaban). Thromboembolic complications occurred in four patients (0.3%), two ischemic strokes, one transient ischemic attack without residual deficit and one splenic infarct, all with no further complications. Bleeding complications incurred in 5 patients (0.4%), including 2 pericardial effusions (1 intraoperative, 1 after 30 days, both drained), and 3 groin hematomas (1 due to needing heparin for venous thrombosis, none requiring intervention). No patients required emergent surgeries.

In our next paper, Alexios Hadjis and associates aim to explore the role of complete diastolic pathway activation mapping on ventricular tachycardia (VT) recurrence. They studied 85 consecutive patients who underwent VT ablation using and guided by high-density mapping. During activation mapping, the presence of electrical activity in all segments of diastole defined the evidence of having had recorded the whole diastolic interval. Patients were categorized as having recorded the full diastolic pathway, partial diastolic pathway or no diastolic pathway map performed. Recurrences of VT were defined as appropriate IC therapies or on the basis of EC documented arrhythmia. Complete recording of the diastolic pathway was achieved in 36 of 85 (42.4%). Partial recording of the diastolic pathway of clinical VT was achieved in 24 of 85 (28.2%). No recording of the diastolic pathway of clinical VT was feasible in 25 of 85 patients (29.4%). At a mean of 12.8 months, freedom from VT recurrences was 67% in the overall cohort. At a mean of 12.8 months, freedom from VT recurrence was 88% in patients who had full diastolic activity recorded, 50% of partial diastolic activity recorded and 55% in those who underwent substrate modification (P=0.02). The authors concluded that mapping of the entire diastolic pathway was associated with a higher freedom from VT occurrence compared to partial diastolic pathway recording and substrate modification. The use of multielectrode mapping catheters in recording diastolic activity may help predict those VTs employing intramural circuits and further optimize ablation strategies.

In our next paper, Hui-Nam Pak and associates investigated whether electrical posterior box isolation (POBI) may improve rhythm outcome of catheter ablation in patients in whom persistent atrial fibrillation changes to paroxysmal atrial fibrillation after antiarrythmic drug medication and cardioversion. They prospectively randomized 114 patients, 75% male, 59.8 years old to circumferential pulmonary vein ablation (CPVI) alone (n=57) and an additional POBI group (n=57). Primary endpoint was AF recurrence after a single procedure, and secondary endpoints were recurrence pattern, cardioversion rate and response to antiarrhythmic drugs (AAD). After a mean follow-up of 23.8 months, the clinical recurrence rate did not significantly differ between the CPVI alone and additional POBI group (31.6% versus 28.1%; P=0.682). The recurrence rate as atrial tachycardias, 5.3% versus 12.3% (P=0.14) and cardioversion rates, 5.3% versus 10.5% (P=0.25) were not significantly different between the CPVI and POBI group. At the final follow-up, sinus rhythm was maintained without antiarryhthmic drug in 52.6% of CPVI group and 59.6% of the POBI group (P=0.45). No significant difference was found in major complications between the two groups, 5.3% versus 1.8% (P=0.618). But the total ablation time was significantly longer in the POBI group (4187 seconds versus 5337 seconds; P

Paul J. Wang:

Welcome to the monthly podcast, On the BEAT, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor in Chief, with some of the key highlights from this month's issue.

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

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 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 (endo 22%, epi 19.2%, P = 0.169, mean duration 590 ms) and non-sustained focal waves (endo 1.2% and epi 1.6%, P = 0.669) were also observed. Apparent transmural migration of rotational activations (n=6) from the epi- to the endocardium was seen in 2 patients. EGM fractionation was significantly higher in the epicardium than endocardium (61.2% versus 51.6%, P < 0.0001). The authors concluded that simultaneous endo-epi phase mapping of prolonged human persistent AF recordings showed significant EED marked temporal heterogeneity, discordant and transitioning wavefronts patterns and complex fractionations. No sustained focal activity was observed. Such complex 3-dimensional interactions provide insights into why endocardial mapping alone may not fully characterize the AF mechanism and why endocardial ablation may not be sufficient.

In our next paper, Andrew Beaser and associates hypothesize that intravascular ultrasound [IVUS] could accurately visualize and quantify intravascular lead adherence and degree of intravascular lead adherence correlates with transvenous lead extraction difficulty. Serial imaging of leads occurred prior to transvenous lead extraction using IVUS. Intravascular lead adherence areas were classified as high or low grade. Degree of extraction difficulty was assessed using 2 metrics and correlated with intravascular lead adherence grade. Lead extraction difficulty was calculated for each patient and compared to IVUS findings. 158 vascular segments in 60 patients were analyzed: 141 (89%) low grade versus 17 (11%) high grade. Median extraction time (low = 0 versus high grade 97 seconds, P < 0.001) and median laser pulsations delivered (low = zero versus high grade 5,852, P < 0.001) were significantly higher in the high-grade segments. Most patients with low lead extraction difficulty score had low intravascular lead adherence grades. 86% of patients with high lead extraction difficulty score had low IVUS grade, and the degree of transvenous lead extraction difficulty was similar to patients with low IVUS grades and lead extraction difficulty scores.

In our next paper, András Bratincsák, and associates sought to create the foundation of normative ECG standards in the young using Z-scores. 102 ECG variables were collected from a retrospective cohort of 27,085 study subjects with no known heart conditions, age zero to 39 years. The cohort was divided into 16 age groups by gender. Median interquartile range and range were calculated for each variable adjusted to body surface area. Normative standards were developed for all 102 ECG variables, including heart rate; P, R, and T axis; R-T axis deviation; PR interval, QS duration, QT, and QTc interval; P, Q, R, S, and T amplitudes in 12 leads; as well as QRS and T wave integrals. Incremental Z-score values between negative 2.5 and 2.5 were calculated to establish the upper and lower limits of normal. Historical ECG interpretive concepts were reassessed and new concepts observed. The author summarized that electronically acquired ECG values based on the largest pediatric and young adult cohort ever compiled provide the first detailed, standardized, quantitative foundation of traditional and novel ECG variables.

In our next paper, Jungmin Hwang and associates hypothesize that suppressing the late sodium current may counterbalance the reduced repolarization reserve in long QT syndrome [LQTS] and prevent early depolarization [EAD] and polymorphic ventricular tachycardia [PVT]. They tested the effects of selective late sodium channel blocker GS967 on polymorphic ventricular tachycardia [PVT] induction in a transgenic rabbit model of type two using intact heart optical mapping, cellular electrophysiology, and confocal calcium imaging and computer modeling. They found that GS967 reduced ventricular fibrillation [VF] induction under a rapid pacing protocol (7 out of 14 hearts in control versus 1 out of 14 at 100 nanomolar) without altering action potential duration [APD] or restitution and dispersion. GS967 suppressed PVT incidents by reducing calcium mediated EADs and focal activity during isoproterenol perfusion (at 30 nanomolar, 7 out of 12 and a 100 nanomolar, 8 out of 12 without EADs and PVTs). Confocal calcium imaging of LQT myocytes revealed GS967 shortened calcium transient duration by accelerating sodium calcium exchanger mediated calcium efflux from cytosol, thereby reducing EADs. Computer modeling revealed the inward late sodium current potentiates EADs in the LQT setting through providing additional depolarizing currents through action potential plateau phase, and increasing intracellular sodium that decreases the depolarizing sodium calcium exchanger, thereby suppressing the action potential plateau and delaying the activation of slowly activating delayed rectifier current, IKS. Suggesting important roles in the late sodium current in regulating intracellular sodium. Thus, the authors concluded that selective late sodium channel blockade by GS967 prevents EADs and abolishes PVT in LQT rabbits by counterbalancing the reduced repolarization reserve and normalizing intracellular sodium.

In our next paper, Pietro Lazzerini, Mohamed Boutjdir and associates, hypothesize that systemic inflammation per se can significantly prolong QTc during infection via cytokine-mediated changes in potassium channel expression. They found in patients with acute infections, regardless of concomitant QT-prolonging anti-microbial therapy, QTc was significantly prolonged but rapidly normalized in parallel to C-reactive protein [CRP] and cytokine level reduction. Consistently, in Torsades de Pointes cohort, concomitant acute infections were prevalent 30% despite only a minority (25%) of these cases were treated with QT-prolonging anti-microbials. KCN J2, potassium channel expression in peripheral blood mononuclear cells was strongly correlated to that in ventricles, inversely associated to CRP and interleukin one changes in acute infection patients. The authors concluded that acute infection, systemic inflammation rapidly induces cytokine-mediated ventricular electrical remodeling and significant QTc prolongation, regardless of concomitant antimicrobial therapy.

In a research letter, Christophe Beyls and associates examined the risk of bradycardia and critically ill COVID-19 patients treated with Lopinavir [LPV], a protease inhibitor of HIV-1, and Ritonavir [RTV], another protease inhibitor that strongly inhibits hepatic cytochrome P 450 [CYP3A4] activity in order to increase the Lopinavir plasma concentration. During the first month of the outbreak, patients admitted to the ICU with positive PCR for COVID-19 received LPV (200 mg)/RVT (50 mg) twice daily for 10 days. Bradycardia was defined as heart rate below 60 for a period of more than 24 hours. All patients were monitored 24 hours a day for all hemodynamic parameters, including heart rate with a five-lead ECG. Monitors were linked to a computerized system allowing to extract hemodynamic data. LPV/RTV plasma concentration was monitored using analytic method, combining high propensity performance, liquid chromatography and tandem mass spectrometry at 72 hours and every 72 hours. They prospectively included 41 COVID-19 patients who received LPV/RTV treatment. Nine or 22% patients experienced bradycardia. No patients had a pre-existing nodal pathology on the ECG on admission. Among the 9 patients with bradycardia, 8 or 88% were sinus bradycardia and one (12%) third-degree AV block. Causality may be considered as bradycardia occurred at least 48 hours after LPV/RTV initiation, bradycardia resolved after discontinuation or dose reduction and no alternative cause was found. Patients who presented with bradycardia were older, had a higher RTV plasma concentration and a lower lymphocyte count. In our study, no correlation was found between RTV plasma concentration, LPV plasma concentration, and mean heart rate at day three. No patient had bradycardia in the first 48 hours after LPV/RTV administration. For patients with LPV RTV plasma level overdose, the dose of LPV RTV was divided by two until the next dose. For the patient with third degree AV block LPV/RTV was stopped. None of the patients had any known cytochrome CYP3A4-inhibiting drugs. The authors concluded that the results suggest that RTV plasma overdose in elderly critical ill patients may increase the risk of bradycardia.

In a research letter, Emily Zeitler and associates surveyed cardiac implantable device [CID] patients. A total of 109 patients were approached to participate, nine declined. Most respondents were white (79%), male (60%) with a mean age of 73 years. The median number of correct responses to the 11 factual questions was six. Respondents held some common misconceptions. For example, 25% of respondents believe that FDA determines the cost of the device. Trust in the FDA was high; 67% of respondents agreed "I trust the FDA". Respondents mostly agreed "the FDA would not approve my device unless it was a hundred percent safe". Only 6% of respondents agreed, "we would be better off if there was no FDA," and a similarly small fraction disagreed with "when it comes to medical devices, the U.S. does the best job in the world at keeping people safe". Most respondents, 69% demonstrated fear of device recalls by agreeing with "if there was a recall of all are part of my device, I think I would be worried or scared." On average, respondents were comfortable sacrificing some privacy for device surveillance, 75% agreed with "once the device has been approved, the FDA should continue to monitor for signs that there are problems with the device even if it means that private health information about me is collected". Respondents seemed to believe that the FDA was risk averse; 56% believed that the FDA does not approve devices unless they're a hundred percent safe. This is in contrast to trends shifting the demonstration of safety to post-approval settings and expanding acceptable forms of data for regulatory approval.

In a research letter, Laura Rottner, Christoph Sinning and associates examined novel high resolution imaging system based on a wide band dielectric technology, and reports the first clinical experience of feasibility and reliability of cryoballoon [CB] occlusion tool as compared to fluoroscopic and 3D transesophogeal [TEE] assessment during pulmonary vein isolation [PVI]. In consecutive patients with symptomatic atrial fibrillation [AF], cryoballoon-based ablation was performed with a novel 3D wide-band dielectric imaging system. Pulmonary vein [PV] occlusion was assessed with fluoroscopy in 3D-TEE and concomitantly correlated with the novel CB occlusion tool. The endpoint was defined as persistent PV isolation verified by spiral mapping catheter recordings 30 minutes after the last CB application. A total of 36 (90%) of PVs in 10 patients with paroxysmal (40%) and persistent (60%) were analyzed. In all patients, a normal PV anatomy with four separate PVs was documented. Visualization via 3D-TEE was feasible in 80% septal PVs and 100% of lateral PVs. In 67% of PVs, total PV occlusion was confirmed by all 3 imaging modalities. In 17% of PVs, incomplete PV occlusion was initially demonstrated by TEE and 3D dielectric imaging, whereas fluoroscopy suggested complete occlusion in initial analysis. After repositioning of the CB at 3 PVs, complete PV occlusion was verified by all three modalities. In 3 out of 36 (8%), no occlusion was initially seen by any imaging modality, for which the CB was repositioned resulting in total PV occlusion as confirmed by all three modalities. Two out of 36 PVs (6%) were confirmed to be occluded via fluoroscopy in 3D-TEE, but not by the CB occlusion tool. There was only one out of 36 PVs (3%), which were confirmed to be included by the CB tool and 3D-TEE, but not by fluoroscopy. A negative and positive predictive value of 1.0 and 0.6 was seen when comparing PV occlusion by the novel occlusion tool compared to PV collusion, verified by fluoroscopy and 3D-TEE.

In a special report, Jun Hirokami, and associates aim to clarify the spatial correlations between fractionated potential detected by Lumipoint with non-PV trigger. They enrolled 30 symptomatic atrial fibrillation [AF] patients who underwent non pulmonary vein [PV] foci ablation. 4 patients underwent the first procedure, 17 underwent second procedure and eight underwent third procedure, and one underwent a fourth procedure. They highlighted the fractionated signal area in atrial muscle [FAAM] during sinus rhythm and atrial pacing, thereby producing a digital FAAM map. They retrospectively applied Lumipoint to 30 patients in order to clarify the relationship between FAAM and non-pulmonary vein [PV] foci. Non-PV foci were successfully identified in all patients. They identified four patients with multiple non-PV foci. Of these four patients, one had non-PV foci at the superior vena cava and left arterial anterior wall. One had non-PV foci at the SVC and LA bottom wall. And two had non-PV foci at the SVC and interatrial septum. They only analyze 30 non-PV foci unrelated to SVC because the SVC isolation was routinely performed for non-PVC foci at the SVC. In order to analyze the correlation between FAAM and location of non-PV triggers, they determined the cutoff points of peaks slider, which non-PV triggers were completely located within the FAAM in. The accuracy of predicting location of the non-PV triggers was summarized using area under the receiver operating curve, a UROC curve. The optimal cutoff point of peak sliders to predict the location of non-PV was determined by the Youden Index. The Youden Index established the optimal cutoff point of the maximum peaks slider was 7; sensitivity was 0.906 and specificity 0.770. The peaks slider 7 was the most accurate predictor fractionated signals location area to the location of non-PV triggers. (area under the curve 0.902). The mean area of peaks slider 7 was six centimeters squared or 4.3% of the atrium. The authors concluded that the proof-of-concept observational study demonstrated that novel visualization tool of FAAM map successfully identified non-PV triggers that did not induce atrial fibrillation and/or non-PV foci, which potentially serve as substrates for AF maintenance.

In a special report, Leslie Saxon and associates update their prior publication providing further detail on mitigation adoption rates for the entirety of the U.S. patient population with implanted cardiac rhythm management devices falling under FDA cyber security advisories from any device manufacturer. They also provided limited data on known cybersecurity mitigation adoption outside the U.S. They report a unique complication resulting for introducing firmware to already implanted devices. Discuss how evolving FDA policies towards firmware mitigation adoption may increasingly determine how and when updates occur. They found that patients under 50 years of age and those over 80 years were less likely to receive the software upgrades, and male versus females had greater rates of upgrades. The upgrade rates varied according to U.S. Region and date of implant. Resynchronization devices were less likely to receive the upgrade, as were pacemaker dependent patient. Those ICD patients initially falling under the battery advisers were upgraded more frequently. The number of advisory patients followed in clinic was a significant predictor for firmware upgrade adoption, particularly for pacemakers that were often upgraded in smaller size clinics. Overall, only 24% of devices for all groups, and 22% of devices not impacted by the battery advisory were upgraded. For Abbott devices, the home communicator cyber security vulnerabilities were mitigated with an automatic software patch that was updated using the Merlin network, and adoption rates were nearly a hundred percent. For the entire patient cohort with impacted pacemaker and ICDs, U.S. and global adoption rates remain low at 24 to 35% with a low rate of complications. Most reported complications for pacemakers and ICD were symptoms (transient palpitations, dizziness, or syncope) that resulted from the temporary change in mode to VVI or transient loss of programmer telemetry while performing the upgrade (pacemaker 0.05%; ICD 0.01%). Globally, a total of 9 pacemakers and 8 ICDs required replacement, as a result of performing the firmware upgrade due to irreversible reversion to a backup pacing mode and loss of defibrillation therapy (ICDs). Analysis of the returned ICD pulse generaotrs found at 7 cases, the cause related to a capacitor bond failure that was exposed only when extended telemetry as required by the upgrade. The failure mechanism was an isolated component failure in the remaining ICD. The programmer based test has recently been FDA approved and can be performed prior to firmware upgrade to identify ICD patients at risk for capacitor bond failure. A total of 256 ICDs were susceptible to loss of RF telemetry after receiving a firmware update, and this has since been mitigated with a software patch. For Medtronic programmers, the initial mitigation responses of cybersecurity advisory was to take the programmers off the network. The network connection was enhanced with one or more security protections provided to the programmers using a flash drive, so the programmers can now be secured from potential cyber intrusion when connected to the network. Medtronic ICDs are currently being upgraded. The upgrade is being provided to impacted patients automatically when the device is interrogated with the programmer during follow-up. Metronic is introducing upgrades in phased approach with all expected to be completed by the beginning of 2021. There are 9% or 55,000 ICDs under this advisory that cannot receive the update due to design or safety constraints. Since the 2017 Abbott advisories identify cybersecurity vulnerabilities in pacemakers and ICDs with the potential for exploits have been increased, including 2 additional FDA advisories issued for another manufacturer. Medtronic's connected communication product and implantable defibrillators in the past 12 months. The authors comment that a recent report and a smaller number of Abbott impacted pacemaker and ICD patients from Canada reported marked differences in mitigation adoption rates between pacemakers and ICDs. This was due to an increase incremental clinical familiarity and comfort with performing the updates as experience and education surrounding these issues evolve. The authors indicate that automating cybersecurity updates without process in place for determining safety, for alerting patients or clinicians that have been delivered, may also be associated with yet unknown risks. Newer generation devices and communication protocols may render cyber security, advisories less frequent as cybersecurity integration is considered an essential aspect of device design.

In a review article, Albert Feeny and associates discuss the use of artificial intelligence [AI] and machine learning [ML] in medicine, which are currently areas of intense exploration showing potential to automate human tasks or even perform tasks beyond human capabilities. The first objective of this review is to provide the novice reader with a literacy of AI/ML methods, and to provide a foundation of how one may conduct an ML study. The review provides a technical overview of some of the most commonly used terms, challenges in AI/ML studies with reference to recent studies in cardiac electrophysiology to illustrate key points. The second objective of this review is to use examples from the recent literature to discuss how AI and ML are changing clinical practice and research in cardiac electrophysiology with emphasis on disease detection and diagnosis, prediction, and patient outcomes and novel characterization of disease. The final objective is to highlight important considerations and challenges for appropriate variation, adoption, and deployment of AI technologies and practice.

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. Thank you.

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 during the action potential and is absent during diastole. The goal of this study was to determine if triggered calcium waves affect cellular electrophysiological properties. The authors use simultaneous recordings of intracellular calcium, and action potentials for the measurement of maximum diastolic potential and action potential duration during triggered calcium waves in isolated dog atrial myocytes. Computer simulations then explored electrophysiological behavior arising from triggered calcium waves at the tissue scale. At 3.3 to five Hertz, triggered calcium waves occurred during the action potential and outlasted several action potential cycles. Maximum diastolic potential was reduced and actual potential duration was significant prolonged during trigger calcium waves. All electrophysiological responses that triggered calcium waves were abolished by using SCA 0400 and ORM 10103, indicating that sodium calcium exchange current caused depolarization. The time constant recovery from inactivation of calcium current was 40 to 70 ms in atrial myocytes, depending on the holding potential. This current could be responsible for action potential (AP) activation during repolarization induced by triggered waves. Modeling studies demonstrate the characteristic properties of triggered calcium waves are potentially arrhythmogenic by promoting both conduction block and reentry arising from the repolarization induced by triggered calcium waves. The authors concluded that triggered calcium waves activate inward sodium calcium exchange and dramatically reduce atrial maximum diastolic potential and prolonged action potential duration establishing the substrate for reentry that could contribute to initiation and maintenance of atrial arrhythmias.

In our next paper Faisal Merchant and Omid Sayadi and associates evaluate the ability of a real-time, closed loop system to record and analyze repolarization alternans from multiple intracardiac leads and deliver dynamically R-wave triggered pacing stimuli during the absolute refractory period. They examined the ability of this system to control repolarization alternans and reduce arrhythmia susceptibility, in vivo. R-wave trigger pacing can induce repolarization alternans, the magnitude of which can be modulated by varying the amplitude, pulse width, or size of the pacing vector. Using a swine model (n = 9), the authors demonstrated that to induce 1 microvolt change in the alternans voltage on the body surface, coronary sinus or left ventricle, requires a delivery charge of 0.04, 0.05 and 0.06 microcoulombs, respectively, while to induce one unit change of the case score requires a delivery charge of 0.93, 0.32 and 0.33 microcoulombs, respectively. For all body surface and intracardiac leads a Delta alternans voltage and Delta K score between baseline and R-wave triggered pace peaks increases consistently with an increase in the pacing pulse amplitude, pulse width and vector spacing. Additionally, the author showed that the proposed method can be used to suppress spontaneously occurring alternans (n = 7), in the presence of myocardial ischemia. Suppression of repolarization alternans by pacing during the absolute refractory period results in a significant reduction in arrhythmia susceptibility, evidenced by lower S rank score during program ventricular stimulation compared to baseline prior to ischemia.

In a perspective outlining the cardiovascular effects of chloroquine and hydroxychloroquine, Ohad Oren and associates describe their belief that the use of chloroquine and hydroxychloroquine in COVID-19 should be limited to randomized, controlled trials. For critically ill patients, unable to enroll in a trial, selective in-hospital use could be considered with careful clinical monitoring in keeping with the FDA's emergency use authorization. The authors suggested that studies evaluating chloroquine and hydroxychloroquine should systematically collect baseline demographic data, results from electrocardiographic and echocardiographic monitoring prior to and during treatment and rates of adverse cardiovascular events in both the near and long-term.

In a research letter, Federico Migliore and Alessandro Zorzi and associates found a 28% decrease in the number of urgent pacemaker implantations during the six weeks after the first COVID-19 case, from 122 to 88 (P = 0.02), compared to the six weeks before the first COVID-19 case. The proportion of female patients requiring urgent pacemaker implantation after the COVID-19 outbreak decreased from six out of 122 (49%) to 30 out of 88 (34%) (P = 0.03).

In a special report Stephanie Kochav and associates described 4 cases of cardiac arrhythmias in COVID-19, including AV block, atrial fibrillation, polymorphic ventricular tachycardia, and pulseless electrical activity arrest.

In a year in review, Suraj Kapa and associates discuss a number of the many advances in our understanding of arrhythmia mechanisms, diagnosis, and new therapies in the past year. Data suggests that secretoneurin may be a marker for patients at risk of ventricular arrhythmias, while natriuretic peptide receptor C may have a role in atrial fibrosis. In atrial specific 2-pore potassium channel TASK-1 may be a therapeutic target for atrial fibrillation. Sensory neurons may play a key role in sleep apnea related to atrial fibrillation. Bariatric surgery is associated with improved atrial fibrillation outcome. Artificial intelligence applied to electrocardiography has yielded estimates of age, gender, and overall health. We've seen new tools for collection of patient centered outcomes following catheter ablation. There's been significant advances in the ability to identify ventricular tachycardia termination sites through high density mapping of deceleration zones. We've learned that right ventricular dysfunction may be a predictor of survival benefit after ICD implantation in non ischemic cardiomyopathy patients. We've seen further insights in the role of his bundle pacing on improving outcomes. As our understanding of cardiac laminopathies advance, we have new tools to predict arrhythmic event rates in gene carriers. And finally, we've seen numerous advances in the treatment of arrhythmias in patients with congenital heart disease.

That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time. This program is copyright American Heart Association 2020.

Paul J. Wang:

Welcome to the monthly podcast, On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue. In our first paper, 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 fat while acutely sparing nearby coronary arteries. Epicardial ablations via subxiphoid access in pigs were performed at 90 to 100 Watts at four minutes at sites near coronary arteries and produced mean lesion depth of 10 millimeters, width 18 millimeters, and length 29 millimeters through median epicardial fat thickness of 1.2 millimeters. Endocardial ablations at 180 Watts achieved depths of 10.7 millimeters, width of 16.6 millimeters, and length of 20 millimeters. Acute coronary occlusion or spasm was not observed at median separation distance of 2.7 millimeters.

In our next paper, Jad Ballout and associates examined 21 consecutive patients with cardiogenic shock and refractory ventricular arrhythmias undergoing bailout ablation due to inability to wean off of mechanical support. Mean age was 61 years, 86% were males, median left ventricular injection fraction 20%, 81% ischemic cardiomyopathy. The type of mechanical support in place prior to the procedure was intra-aortic balloon pump in 14 patients, Impella in 2, ECMO in 2, ECMO and intra-aortic balloon pump in 2, and ECMO and Impella in 1. In the cardio voltage maps with myocardial scar in 90% (19 patients), the clinical ventricular tachycardias VTs were inducible in 13% (62 patients), whereas 6 patients had PVC induced ventricular fibrillation, VT (29%), and VT could not be induced in 2 patients (9%). Activation mapping was possible in all 13 patients with inducible clinical VTs, substrate modification was performed in 15 patients with scar in 79%. After ablation and scar modification, the arrhythmia was noninducible in 19 patients (91%). Seventeen (81%) were eventually weaned off mechanical support successfully with the majority of patients being discharged home and surviving beyond one year. However, 6 (29%) died during the index admission with persistent cardiogenic shock.

In a research letter, Parveen Garg and associates examined the multi-ethnic study of atherosclerosis [MESA] incident atrial fibrillation a population with 50% African-American or Hispanic. After adjusting for age, race, ethnicity, sex education, income, clinic site, height, body, mass index, cigarette, smoking, diabetes, systolic and diastolic blood pressure, and hypertensive medications, physical activity, alcohol consumption, lipid parameter to lipid lowering therapy, the baseline lipoprotein A level greater or equal to 30 milligram per deciliter was inversely associated with developing atrial fibrillation compared those with lower levels (hazard ratio 0.84). However, the mechanism of this paradoxical association is unclear.

In another research letter, Yoshihide Takahashi and associates reported that 49 patients undergoing ablation of persistent atrial fibrillation had at least one focal site and rotational activation in 57%. Of these, 19 patients underwent a repeat ablation for recurrent atrial fibrillation. AF was mapped in 17 patients and 131 focal activation sites were ablated. There were 105 displayed focal activation sites during the de novo ablation and 89 focal activation sites during the repeat ablation. During the de novo ablation, rotation activation was observed in 19 sites. Of the 19 sites, 12 (63%) displayed rotational activity, also with the repeat ablation. The author suggested focal or rotational activation sites can be classified into two types, ones critical for AF recurrence and the ones that are bystander.

That's it for this month. We hope that you'll find the journal to be the go-to place for everyone interested in the field. See you next time.

This program is copyright American Heart Association, 2020.

Correction: In the study by Pierre Qian and associates, the epicardial ablations via subxiphoid access were performed in sheep, not pigs, as previously stated.

Paul J. Wang:

Welcome to the monthly podcast On the Beat, for Circulation: Arrhythmia and Electrophysiology. I'm Dr. Paul Wang, Editor-in-Chief, with some of the key highlights from this month's issue.

In our first paper, David Okada and associates assess the ability of a novel machine learning approach for quantifying 3D spatial complexity of gray scale patterns on late gadolinium-enhanced cardiac magnetic resonance images to predict ventricular arrhythmias in patients with ischemic cardiomyopathy.

They examined 122 consecutive ischemic cardiomyopathy patients with left ventricular ejection fraction of 35%, without prior history of reentrant ventricular arrhythmias. These patients underwent late gadolinium-enhanced cardiac magnetic resonance imaging. From raw gray scale data, the authors generated graphs encoding the 3D geometry of the left ventricle. They then assess the global regularity of signal intensity patterns using Fourier-like analysis and generated a substrate spatial complexity profile for each patient. A machine learning statistical algorithm was employed to discern which substrate spatial complexity profiles correlated with ventricular arrhythmic events. That is appropriate ICD firings and arrhythmic sudden cardiac death.

At five years of follow-up from the statistical machine learning results, a complexity score ranging from zero to one was calculated for each patient that was tested using multivariate Cox regression models. At five years of follow-up, 40 patients had ventricular arrhythmia events. The machine learning algorithm classified with overall 81% accuracy and correctly classified 86% of those without ventricular arrhythmia. Overall negative predictive value was 91%. Average complexity score was significantly higher in patients with ventricular arrhythmia events versus those without P

Paul J. Wang:

Welcome to the monthly podcast On the Beat for circulation, arrhythmia, and electrophysiology. I'm Dr. Paul Wang, Editor In Chief, with some of the key highlights from this month's issue.

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 and adapted to low spatial resolution sequentially acquired data. Ventricular fibrillation, or VF, optical mapping was performed and Langendorff-perfused Sprague Dawley rat hearts, N = 18. And novel algorithms were developed using Granger causality analysis to quantify causal dependence of neighboring signals and plot Granger causality analysis vectors, quantify global organization using causality pairing index, a measure of neighboring causal signal pairs, and localize rotational drivers by quantifying the circular interdependence of neighboring signals with the circular interdependence value.

Granger causality analysis based mapping tools were optimized for low spatial resolution by down sampled optical mapping data validated against high resolution phase mapping analysis and further tested in previous VF optical mapping recordings of coronary perfused donor heart LV wedge preparations, N = 12, and adaptive for sequentially acquired intracardiac electric Grande during human persistent atrial relation mapping, N=16. The authors found that global VF organization quantified by causality pairing index showed a negative correlation at progressively lower resolutions in organized VF with high causality pairing index values. Ranger causality analysis vector mapping characterize dominant propagating patterns and localized stable rotational drivers with the circular interdependence value showing a significant difference in driver versus non driver regions, P = 0.0002. These findings were further confirmed in human VF in persistent atrial fibrillation, a positive correlation was found between causality peri-index and presence of stable rotational drivers. 50% of patients had rotational drivers with a low incidence of 0.9 rotational drivers per patient.

In a special report, Piotr Futyma and associates report on the use of bipolar radiofrequency ablation of ventricular arrhythmias originating in the vicinity of the His bundle. Bryce Alexander and associates report in a research letter the patient acceptance of cybersecurity upgrade in ICDs.

That's it for this month. We hope that you'll find the journal to be the go to place for everyone interested in the field. See you next time.

This program is copyright American Heart Association 2020.

Paul J. Wang: Welcome to the monthly podcast On the Beat for Circulation: Arrhythmia and Electrophysiology. I'm Dr Paul Wang, editor in chief, with some of the key highlights from this month's issue.

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.