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

In the next paper, Niraj Varma and Associates postulated that left ventricular (LV) epicardial pacing results in slowly propagating pace wave fronts effect that may limit cardiac resynchronization therapy (CRT) efficacy in patients with left ventricular (LV) enlargement using conventional biventricular or bi-V pacing and single LV pacing, but may be mitigated by LV pacing by two widely spaced sites using MultiPoint pacing (MPP) with anatomic separation (AS) of 30 millimeters or more. They tested this hypothesis in the multi-centered MPT IDE trial. Following implant, quadripolar biventricular pacing was activated in all patients (n=506). From 3 to 9 months post implant among patients with available baseline LV and diastolic volumes LVEDV measures and 188 received bi-V pacing and 43 receiving MPP-AS. Patients were dichotomized by median baselines LVEDV indexed to height. Outcomes were measured by the clinical composite score (CCS) as the primary endpoint, quality of life, left ventricular remodeling, EF greater than 5% and systolic volume decreased 10% in heart failure event or cardiovascular death. LVEDVI median was 1.4 millimeters per centimeter. Baseline characteristics differed in patients with LVEDVI greater than median versus LVEDVI less than or equal to median. Among patients with LVEDVI greater than median, bi-V was less efficacious compared to patients with LVEDVIs less than or equal to median. Clinical composite scores 65% versus 79%. In contrast, MPP-AS programming generated greater composite score response (92% versus 65%, P=0.03) and improved quality of life (31 versus -15.7, P=0.38) versus bi-V pacing with LVEDV greater than median. Reverse remodeling trended better with MPP-AS programming. When LVEDVI was greater than median, heart failure event rate increased following the three months randomization point in bi-V but no heart failure event occurred in patients with MPP-AS programming between three and six months in LVEDVI greater than median. All measured outcomes did not differ in patients receiving MPP-AS and bi-V pacing with LVEDVI less than or equal to median. The authors concluded that conventional biventricular pacing even with a quadripolar lead has reduced efficacy in patients with left ventricular enlargement however in patients with larger hearts and programmed to MPP-AS the greatest response rate was observed.

In our next paper, Chih-Min Liu, Shih-Lin Chang, Hung-Hsun Chen and Associates, applied deep learning to pre-ablation pulmonary vein computed tomography (PVCT) geometric slices to create a predictive model for non-pulmonary vein (NPV) triggers in patients with paroxysmal atrial fibrillation (PAF). They retrospectively analyzed 521 PAF patients who underwent catheter ablation of PAF. Among them, PVCT geometric slices from 358 nonrecurrent AF patients one to three millimeters interspace per slice, 20 to 200 slices per each patient, ranging from the upper border of the left atrium to the bottom of the heart, for a total of 23,683 images of slices were used in the deep learning process, the ResNet34 of the neural network, to create the predictive model of the NPV trigger. There were 298 (83.2%) of patients with only pulmonary vein (PV) triggers and 60 (16.8%) with non-PV triggers plus or minus PV triggers. The patients were randomly assigned to either training, validation, or test groups, and their data was allocated according to those datasets. The image datasets were split into training (N=17,340), validation 3491, and testing 2852 groups, which had completely independent set of patients. The accuracy of prediction in each PVCT image for non-pulmonary vein trigger was 82.4%. The sensitivity and specificity were 64.3% and 88.4%, respectively. For each patient, the accuracy of prediction for a non-pulmonary vein trigger was 88.6%. The sensitivity and specificity were 75.0% and 95.7%, respectively. The area under the curve (AUC) for each image was 0.82 and 0.88, respectively. The authors concluded that the deep learning model using pre-ablation PVCT can be applied to predict trigger origins in PAF patients receiving catheter ablation. The applications model may identify patients at a high risk for non-pulmonary vein trigger before ablation.

In our next paper, Brian Zenger and Associates aim to understand the relationship between physician social media influence and their scholarly and clinical activity. Authors identified attending US electrophysiologists on Twitter. They compared physician Twitter activity to A) scholarly publication record H-index and B) clinical volume according to CMS. The ratio observed versus expected Twitter followers, observed to expected ratio was calculated based on each scholarly K-index and clinical activity. Authors identified 284 physicians with mean Twitter age of 5.0 years and median 568 followers. They had a median of 34.5 peer-reviewed papers, 401 citations, and H-index 9. The median K-index was 0.4. The median EP procedures was 77 and E and M visits 264. The top 1% electrophysiologists for followers accounted for 20% of all followers, 70% of status updates, and a mean H-index of six versus 15 for others (P=0.3) and accounted for 1% of procedural and E and M volumes. They had a mean K-index of 21 versus 0.77 for others (P

In our next paper, Soroosh Kiani and Associates identified four explanted hearts in the context of transplant who received stereotactic body radiation therapy (SBRT) as part of an 11 patient compassionate use series at their institution. Clinical ventricular tachycardias (VTs) and CT defined target volume of SBRT were correlated to the anatomic specimen. Gross pathological, histological, and ultrastructural examination of tissue in the target area of SBRT were performed. All patients had nonischemic cardiomyopathy, and 3 had left ventricular assist devices. In all cases, patients had recurrent sustained ventricular tachycardia (VT) and had multiple failed antiarrhythmics and radiofrequency ablation. Four patients underwent five SBRT therapy sessions with 25 gray single-fraction dose delivered to the area of culprit scar. The time from SBRT to explant was 12 to 250 days. Histopathological features following radiation were comparable in all patients and were characterized by area of subendocardial necrosis surrounded by a rim of fibrosis. In one patient, the surrounding myocardium showed cytoplasmic vacuolization in myocytes and in another patchy interstitial fibrosis. Vascular changes consisted of myointimal thickening with prominence of endothelial cells. Electron microscopy (EM) of myocardium showed irregular, convoluted intercalated disc regions, loss of contractile elements with disrupted and haphazardly arranged myofibrils, and edematous mitochondria with loss of cisternae. The authors reported the first series of findings in human tissue in four patients after SBRT. Histopathological features were consistent across all four patients and were indicative of cell injury, death, and to a lesser extent fibrosis. EM demonstrated features consistent with acute injury. These specimens may provide radiobiological evidence of acute cellular injury during SBRT for VT, which may have an antiarrhythmic effect prior to the onset of fibrosis.

In our next paper, Job Verdonschot, Stephane Heymans, Mark Hazebroek and Associates in their study aimed to depict the underlying cardiac pathophysiologic process of nonresponse to cardiac resynchronization therapy (CRT) in dilated cardiomyopathy (DCM) using endomyocardial biopsies (EMB). Within the Maastricht and Innsbruck registries of DCM patients, 99 patients underwent EMB before CRT implantation, with histological quantification of fibrosis and inflammation, where inflammation was defined as greater than 14 infiltrating cells per millimeter squared. Echocardiographic left ventricular end-systolic volume (LVESV) reduction of 15% or greater after six months was defined as response to CRT. RNA was isolated from cardiac biopsies of a representative subset of responders and nonresponders; 67 patients responded (68%), whereas in 32 (32%) did not respond to CRT. Cardiac inflammation prior to implantation was negatively associated with response to CRT (25% of responders and 47% of nonresponders, odds ratio 0.3, P=0.01). EMB fibrosis did not relate to CRT response. Cardiac inflammation improved the robustness of prediction beyond well-known clinical predictors of CRT response (likelihood ratio test, P

In our next paper, Mohit Turagam, Daniel Musikantow, and Associates extracted data from a registry regarding consecutive patients with confirmed COVID-19 who are receiving continuous telemetric ECG monitoring and had a definitive disposition of hospital discharge or death. Between patients who died versus discharged, they compared a primary composite endpoint of cardiac arrest from ventricular tachycardia, ventricular fibrillation or bradyarrhythmias such as atrioventricular block. Among 800 COVID-19 patients at Mount Sinai Hospital with definitive dispositions, 140 patients had telemetric monitoring and either died (52) or were discharged (88); the median age was 61 years, 73% men, and ethnicity was Caucasian at 34%. Comorbidities included hypertension in 61%, coronary artery disease in 25%, ventricular arrhythmia history in 1.4%, and no significant comorbidities in 16%. Compared to discharged patients, those who had died had elevated peak troponin levels 0.27 versus 0.02 nanograms per milliliter and more primary endpoint events (17% versus 4%, P=0.01), a difference driven by tachyarrhythmias. Fatal tachyarrhythmias invariably occurred in the presence of severe metabolic imbalance, whereas atrioventricular block was largely an independent primary event. The authors concluded that hospitalized COVID-19 patients who die experience malignant cardiac arrhythmias more often than those who survive to discharge. However, these events represent a minority of cardiovascular deaths, and ventricular tachyarrhythmias are mainly associated with severe metabolic derangement.

In our next paper, Sarah Ghonim and Associates examine whether adults with repaired tetratology of Fallot (RTOF) die prematurely for ventricular tachycardia (VT) and sudden cardiac death inducible VT predicts mortality. Ventricular scar, the key substrate for VT, can be noninvasively defined with late gadolinium enhancement, cardiac magnetic resonance (CMR) but whether this relates to inducible VT is unknown. 69 consecutive RTOF patients (43 male, mean 40 years) clinically scheduled for invasive programmed VT-stimulation were prospectively recruited for prior 3D late gadolinium enhancement LGE CMR. Ventricular LGE was segmented and merged with reconstructed cardiac chambers and LGE volume was measured. VT was induced in 22 of 31 patients. Univariable predictors of inducible VT include increased RV LGE (OR 1.15), increased nonapical ventricular LV LGE (OR 1.09), older age (OR 1.6), QRS duration≥180 milliseconds (OR 3.5), history of nonsustained VT (OR 3.5), and previous clinical sustained VT (OR 12.8). Only prior sustained VT (OR 8.02) remained independent in bivariable analyses after controlling for RV LGE volume (OR 1.14) and RV LGE volume of 25 centimeter cubed had 72% sensitivity and 81% specificity for predicting inducible VT (AUC 0.81). At the extreme cutoffs for ruling-out and ruling-in inducible VT, RV LGE>10 cubic centimeters was 100% sensitive and 36 centimeters cubed was 100% specific for predicting inducible VT. Authors conclude that 3D LGE CMR defined scar burden is independently associated with inducible VT and may help refine patient selection with programmed VT-stimulation when applied to at least intermediate clinical risk cohort.

In our next paper, Moussa Saleh, the Northwell COVID-19 Research Consortium and Associates performed a comprehensive search of the electronic medical records using a proprietary python script to identify any mention of QT prolongation, ventricular tachyarrhythmias and cardiac arrest. COVID-19 positive patients that received hydroxychloroquine±azithromycin across 13 hospitals between March 1st and April 15th were included in this study. The primary outcome of torsade de pointes was observed in one (0.015%) out of 6476 hospitalized COVID-19 patients receiving hydroxychloroquine±azithromycin. 67 (1.03%) had hydroxychloroquine±azithromycin held or discontinued due to average QT prolongation of 60 milliseconds from a baseline QTc of 473.7 milliseconds to a peak QTc of 532.6 milliseconds. Of these patients, hydroxychloroquine±azithromycin were discontinued in 58 patients (86.6%) while one or more doses of therapy were held in the remaining nine (13.4%). A simplified approach to monitoring for QT prolongation arrhythmia was implemented on April 5th. There were no deaths related to the medications with the simplified monitoring approach and hydroxychloroquine exposure was reduced. The author concluded that the risk of torsade de pointes is low in hospitalized COVID-19 patients receiving hydroxychloroquine±azithromycin therapy.

In our next paper, Yoshiaki Kaneko and Associates studied 22 consecutive patients with superior fast-slow AV nodal reentrant tachycardia (AVNRT) among which 3 patients had an apparent, but not typical slow-fast AVNRT characterized by a long AH interval and tachycardia (long AH). The diagnosis of superior AV nodal reentrant tachycardia was based on the standard criteria in two patients and the occurrence of Wenckebach AV block during tachycardia, which was attributed to a block at the lower common pathway below the circuit of the AVNRT, detected owing to the lower common pathway potentials in one patient. As with typical slow-fast AVNRT, tachy-long-AH was induced after a jump in the AH interval. In contrast, typical slow-fast AVNRT fluctuation in the ventriculoatrial interval was observed during the tachy-long-AH. Ventricular overdrive pacing was unable to entrain or terminate the tachy-long-AH. Moreover, the tachy-long-AH reciprocally transited to/from superior fast-slow AVNRT spontaneously or was triggered by ventricular contractions while the atrial cycle length and EAA remained unchanged. Both tachycardias were cured by ablation at a single site in the right-side para-Hisian region of two patients and the noncoronary aortic cusp of one patient. Collectively, the essential circuit of both tachycardias was identical, and the tachy-long-AH was diagnosed as another phenotype of superior fast-slow AVNRT accompanied by sustained antegrade conduction via another bystander slow pathway breaking through the His-bundle owing to the repetitive antegrade block at the lower and common pathway, thus presenting as a long AH interval during the ongoing superior fast-slow AVNRT. The authors concluded that an unknown superior fast-slow AVNRT phenotype exists that apparently mimics the typical slow-fast AVNRT and is also an unknown subtype of apparent slow-fast AVNRT.

In our next paper, Tinuola Ajayi, Christy Remein and Associates designed and implemented a virtual atrial fibrillation (AF) Strategically Focused Research Network (SFRN) Cross-Center Fellowship program to enhance the competencies of early-stage AF basic, clinical, and population health researchers through experiential education and mentorship. The pedagogical model involves significant cross-center collaboration to produce a curriculum focused on enhancing AF scientific competencies, fostering career and professional development, and cultivating grant writing skills. Outcomes for success involved clear expectations for fellows to produce manuscripts, presentations, and for those at the appropriate career stage, grant applications. Authors evaluated the effectiveness of the fellowship model versus mixed methods formative and summative surveys. In the two years of the fellowship, fellows generally achieved productivity metrics sought by our pedagogical model, with outcomes for the 12 fellows including 50 AF-related manuscripts, 7 publications, 28 presentations, and 3 grant awards applications. Participant evaluations reported that the fellowship effectively met educational objectives. All fellows reported medium to high satisfaction with the overall fellowship, webinar content and facilitation, staff communication and support, and program organization. The authors concluded that the fellowship model represents an innovative educational strategy by providing a virtual AF training and mentoring curriculum for early career basic, clinical, and population health scientists working across multiple institutions, which is particularly valuable in the pandemic era.

In our next paper, Audrey Dionne and Associates hypothesize that atrioventricular reentrant tachycardia is common in children. Catheter ablation is increasingly used as first-line therapy with a high acute success, but recurrence during follow-up remains a concern. The aim of this study was to identify risk factors for recurrence after accessory pathway (AP) ablation. Cox proportional hazard models were used to examine the association between patient and procedural characteristics and recurrence during follow-up. In 558 accessory pathway ablation procedures, 542 (97%) were acutely successful. During a follow-up of 0.4 years, there were 42 (8%) patients with documented recurrence. On univariate analysis, early recurrence was associated with younger age, congenital heart disease, multiple accessory pathways, accessory pathway location, right sided and posteroseptal versus left sided, cryoablation versus radiofrequency (RF), empiric ablation, the lack of full power RF lesions

In a research letter, Kevin Makati and Associates developed a hybrid epicardial endocardial procedure to address suboptimal treatment outcomes for persistent atrial fibrillation (AF) and longstanding persistent atrial fibrillation. The hybrid convergent procedure combines minimally invasive epicardial radiofrequency (RF) ablation of the left atrial posterior wall and pulmonary vein (PV) antrum with endocardial PV isolation (PVI) and has shown favorable results in achieving sinus rhythm with and without antiarrhythmic drugs including in longstanding persistent atrial fibrillation and with longer follow-up. This investigation used a retrospective analysis of 226 consecutive patients enrolled in the registry TRAC-AFib which collects data and surgical and hybrid ablation procedures. The patients underwent convergent procedures with endocardial cryothermy PVI between November 2011 and May 2018. A total of 201 patients had available follow-up after blanking period for primary effectiveness. 75% of all patients were free of ATAF or atrial tachycardia on previously ineffective antiarrhythmic drugs and 70% were free of AF, atrial flutter, atrial tachycardia off amiodarone. At last follow-up, 77% of patients were off antiarrhythmic drugs and 69% of these patients were free of atrial fibrillation, atrial flutter, or atrial tachycardia. Thus freedom from atrial fibrillation, atrial flutter or atrial tachycardia off antiarrhythmic drugs was 53%. 85% of persistent atrial fibrillation and 70% of longstanding persistent atrial fibrillation were free of atrial fibrillation, atrial flutter, atrial tachycardia with a mean 14.7 and 16.8 months follow-up. 84% of persistent AFib and 64% of longstanding atrial fibrillation patients were free of atrial fibrillation, atrial flutter, atrial tachycardia off amiodarone. This is the largest study using endocardial cryothermy in convergent procedures providing insight in the safety and effectiveness of this alternative energy source after epicardial RF ablation. Results indicate that the cryoconvergent procedure provides a promising solution for persistent atrial fibrillation and longstanding persistent atrial fibrillation evidenced by relatively low atrial fibrillation recurrence rates and marked AF burden reduction after treatment even in longstanding persistent atrial fibrillation.

In this research letter by Sergio Conti and Associates, they sought to determine the impact of various monitoring strategies and procedural success. In STAR AF II, patients with persistent AF were randomized one to four to four fashion to pulmonary vein isolation PVI alone, PVI plus complex fractionated atrial electrograms or PVI plus linear ablation. Patients were followed for 18 months with a visit ECG and 24-hour Holter at 3, 6, 9, 12, and 18 months. In addition, transtelephonic monitoring transmission was performed weekly for 18 months and whenever symptoms were reported. After initial three month blanking, recurrences were defined as any arrhythmia greater than 30 seconds. The pool procedural success rate was reported assuming five different monitoring scenarios, Holter recordings at six and 12 months (group A); Holter at three, six and 12 months (group B); Holter at three, six, nine, and 12 months (group C); Holter at three, six, nine, 12 and 18 months (group D); Holter at three, six, nine, 12, 18 months plus all transtelephonic transmissions (group E). Comparisons of procedural success obtained by each of the following scenarios was performed using Cochran's Q test. 549 patients completed the ablation and 18 month followup. Compliance with the visits with 90%, for followup Holter monitor 85%, for weekly transtelephonic monitoring 75%. The pool of success for all three aims in the study was 44% including all of the Holter recordings and transtelephonic transmissions group E. The pool of success rate for the other monitoring scenarios were as follows: Group A 73.5%, group B 64.6%, group C 62.2%, and group D 58.2%. Cochran's Q test showed a significant difference between the four screening strategies (P

In a research letter, Alessandro Vicentini and Associates in their study aim to investigate the relationship between baseline QTc and mortality. Authors performed retrospective analysis of ECGs of 318 patients admitted to the Policlinico San Mateo Hospital in Pavia, Italy between February 22, 2020 and April 24, 2020. Patients were defined as infected by a positive nasopharyngeal swab for COVID-19 or by clinically diagnosed infection. QT interval was mainly measured from 12-lead ECG using Bazzett's formula. The authors found that the QTc interval in COVID-19 patients is higher than expected in a normal population. They hypothesized that one of the mechanisms explaining this phenomenon is inflammatory cytokines activation which can suppress ITR in heterologous cells and myocytes resulting in prolonged repolarization. Moreover COVID-19 patients were more susceptible to pulmonary thromboembolism which is known to be linked to QT prolongation. Furthermore, prolonged QTc was found to be a strong predictor in hospital mortality with the highest risk in patients with prolonged baseline QTc and further prolongation with a value of greater than or equal to 500 milliseconds observed during hospitalization.

In a research letter, Saverio Iacopino and Associates investigated the arrhythmic complications of patients hospitalized with COVID-19 pneumonia in the intensive care unit or general medicine department at their institution between April 1 and 26, 2020. The authors collected baseline characteristics, laboratory findings, and therapy. All patients were on continuous telemetry during hospitalization. New diagnosis of atrial fibrillation (AF) lasting more than 30 seconds, atrial tachycardia (AT) lasting more than 30 seconds, sustained greater than 30 or nonsustained greater than three beats of ventricular tachycardia (VT) and symptomatic bradycardia requiring permanent cardiac pacemaker that occurred during hospitalization were verified. A daily electrocardiogram (ECG) was also analyzed to measure corrected QT interval and evaluated potential prolongation QT greater than 500 milliseconds. Continuous variables were reported as mean standard deviation. The authors found that patients with arrhythmias had higher inflammatory markers such as peak white blood counts, C-reactive protein and creatinine phosphokinase (CPK) suggesting a more extended inflammatory stress that probably also effected the cardiovascular system. In hospital mortality was also higher in these patients, 50% versus 11%. With a limited number of patients, the authors findings should be considered as preliminary observations that need to be confirmed in larger controlled studies.

In a research letter, Akira Matsumori and Associates found that circulating immunoglobulin free light chains (FLCs) were increased in mice with heart failure due to myocarditis. The authors tested their hypothesis that their differences in concentration of FLCs among patients with lone AFib who are in AFib when they took the samples, heart failure with sinus rhythm in age matched healthy volunteers. FLC kappa and lambda were assayed. Patients with amyloidosis, renal insufficiency and autoimmune disorders were excluded. FLCs have benefits because they are very stable and do not change after long-term storage and up to three freeze-thaw cycles. Separately, after amassing the lone AF (N=28), in heart failure (N=16), with sinus rhythm groups (N=110), group by propensity score using age and sex, all statistics were performed. The median concentrations of circulating FLC lambda and kappa in patients with lone AF and atrial fibrillation in sinus rhythm were significantly different from the healthy volunteer group (P

In a special report, Timothy Markman and Associates aim to investigate the patient and procedural characteristics associated with worsening tricuspid regurgitation after right ventricular (RV) lead placement as well as a time course of these changes. The authors used a prolapse technique, a straight stylet was withdrawn several centimeters from the lead tip to create atraumatic portion that was advanced across the floor of the right atrium creating a loop which crossed the tricuspid valve. They also used a direct method, a curved stylet used to advanced the lead across the tricuspid valve. The authors identified 1599 patients who underwent first time placement of the right ventricular (RV) lead. Of these 583 met study inclusion criteria, including 105 implanted with cardiac resynchronization (CRT) devices. Baseline echocardiograms were performed 47 days prior to implantation and followup echocardiograms 249 days following implantation. By two months, the tricuspid regurgitation (TR) severity increased by mean grade of 0.8 while tricuspid severity remained unchanged over the remainder of the first year in non-CRT patients. Among CRT patients, tricuspid regurgitation progressively decreased to levels lower than pre-device implantation. In univariable ordinal logistic regression, worsening TR severity was positively associated with the prolapse technique (OR 1.49), and inversely associated with CRT implantation (OR 0.59). There was no association between ventricular pacing percentage among non-CRT patients. In multivariable ordinal logistic regression increased TR severity was positively associated with baseline pulmonary artery systolic pressure (OR 1.03) and inversely associated with CRT implantation (OR 0.43). The authors found that TR rapidly increased with a mean 0.8 grade within the first two months. TR steadily improved over the following year in CRT patients.

In a review article, Khaldoun Tarakji and Associates discuss that the field of cardiac electrophysiology has been on the cutting edge of advanced digital technology for many years. More recently, medical device development through traditional clinical trials has been supplemented by direct to consumer products with advancement of the wearables and healthcare apps. The rapid growth of innovation along with mega data generated has created challenges and opportunities. This review summarizes a regulatory landscape applications to clinical practice, opportunities for virtual clinical trials, the use of artificial intelligence to streamline, interpret data, and integration into the electronic medical records and medical practice. Preparation of the new generation of physicians, guidance and promotion by professional societies and the advancement of research in the interpretation and application of big data and the impact of digital technology and healthcare outcomes will help to advance the adoption and future of digital healthcare.

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 and 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 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

In the next paper, Milena Leo and associates conducted a randomized study to compare risk of esophageal heating and acute procedure success of different LSI-guided ablation protocols combining higher or lower radiofrequency power or different target LSI values. Eighty consecutive patients were prospectively enrolled and randomized to one of 4 combinations of radiofrequency (RF) power and target LSI for ablation of the left atrial posterior wall (that is 20 watts LSI 4, 20 watts LSI 5, 40 watts LSI 4, and 40 watts LSI 5). The primary end point of the study was the occurrence and number of esophageal temperature alerts (ETAs) per patient during ablation. Acute indicators of procedure success were considered as secondary end points. Long-term follow-up data was also collected for all patients. Esophageal temperature alerts (ETAs) occurred in a similar proportion of patients in all groups. Significantly, shorter RF durations was required to achieve the target LSI in the 40 watt groups. Less than 50% of the RF lesions reached the target LSI of 5 when using 20 watts despite a longer RF duration. A lower rate of first-pass pulmonary vein isolation and a higher rate of acute pulmonary vein reconnection were recorded in the group 20 watts LSI 5. A lower AF recurrence rate was observed in the 40 watt groups compared with the 20 watts groups at 29 months follow-up. The authors concluded that when guided by LSI, posterior wall ablation with 40 watts is associated with a similar rate of ETAs and a lower AF recurrence rate at follow-up if compared with 20 watts. These data will provide a basis to plan future randomized trials.

In the next paper, Shohreh Honarbakhsh and associates in this study aimed to determine whether STAR mapping using sequential recordings from conventional pulmonary vein mapping catheters could achieve similar results. Patients with persistent AF less than 2 years were included. Following pulmonary vein isolation (PVI), AF drivers were identified on sequential STAR maps created with PentaRay, IntellaMap Orion, or Advisor HD Grid catheters. Patients had a minimum of 10 multipolar recordings of 30 seconds each. These were processed in real-time and AF drivers were targeted with ablation. An ablation response was determined as AF termination or cycle length slowing greater than or equal to 30 milliseconds. Thirty patients were included, 62.4 years old, AF duration 14.1 months, of which 3 had AF terminated on pulmonary vein isolation, leaving 27 patients that underwent STAR-guided AF driver ablation. Eighty-three potential AF drivers were identified 3.1 per patient of which 70 were targeted with ablation (2.6 per patient). An ablation response was seen at 54 AFDs, 77.1% of AF drivers with 21 AF termination and 33 cycle length slowing and occurred in all 27 patients. No complications occurred. At 17.3 months, 22 out of 27 or 81.5% of patients undergoing STAR-guided ablation were free from atrial fibrillation, atrial tachycardia off antiarrhythmic drugs. The authors concluded that STAR-guided AF driver ablation through sequential mapping with a multipolar catheter effectively achieved an ablation response in all patients. AF termination in a majority of patients, with a high freedom from atrial fibrillation atrial tachycardia off antiarrhythmic drugs at long-term follow-up.

In our next paper, Takashi Kaneshiro and associates sought to evaluate the characteristics of esophageal injuries in atrial fibrillation (AF) ablation using high power short duration setting. After exclusion of 5 patients with their esophagus at the right portion of left atrium and 21 patients with additional ablations such as box isolation and/or low voltage area in left atrium posterior wall, 271 consecutive patients, 62 years, 56 women, who underwent pulmonary vein isolation (PVI) by radiofrequency catheter ablation were analyzed. In the 101 patients, high power short duration setting at 45 to 50 watts with an Ablation Index module was used. In the remaining 170 patients, before introduction of the high power short duration setting, a conventional power setting of 20 to 30 watts with contact force monitoring was used, that is the conventional group. They performed esophagogastroduodenoscopy after pulmonary vein isolation in all patients and investigated the incidence and characteristics of esophageal thermal injury. Although the incidence of esophageal thermal injury was significantly higher in the high power short duration group compared with the conventional group (37% versus 22%, P=0.011), the prevalence of esophageal lesions did not differ between the groups (7% versus 8%). Multivariate logistic regression analysis revealed that the use of the high power short duration setting (odds ratio 6.09, P

In our next paper, Prasongchai Sattayaprasert, Sunil Vasireddi and associates hypothesize that in disease the inflammatory secretome of cardiac human mesenchymal stem cells remodels and can regulate arrhythmia substrates. Human cardiac mesenchymal stem cells were isolated from patients with or without heart failure from tissue attached to extracted device leads and from samples taken from explanted donor hearts. Failing human cardiac mesenchymal stem cells or nonfailing human cardiac mesenchymal stem cells were cocultured with normal human myocytes derived from induced pluripotent stem cells. Using fluorescent indicators, action potential duration (APD), calcium alternans, and spontaneous calcium release, incidence was determined. Failing and nonfailing human cardiac mesenchymal stem cells from both sources exhibited similar trilineage differentiation potential and cell surface marker expression as bone marrow human cardiac mesenchymal stem cells. Compared to nonfailing human cardiac mesenchymal stem cells, failing human cardiac mesenchymal stem cells prolonged action potential duration by 24% (P

In the next paper, Atsushi Suzuki and associates conducted this study to use scanned proton beams for ablation of cardiac tissue, investigate electrophysiological outcomes, and characterize the process of lesion formation in a porcine model using particle therapy. Twenty-five animals received scanned proton beam irradiation. ECG-gated computed tomography (CT) scans were acquired at end-expiration breath hold. Structures, the atrioventricular junction (AV junction), or left ventricular myocardium (LV), and organs at risk were contoured. Doses of 30, 40, and 55 gray were delivered during expiration to the AV junction (n=5) and left ventricular myocardium (n=20) of intact animals. In this study, procedural success was tracked by pacemaker interrogation in the AV junction group, time-course magnetic resonance imaging (MR) in the left ventricular group, and correlation of lesion outcomes displayed in gross and microscopic pathology. Protein extraction (active caspase-3) was performed to investigate tissue apoptosis. Doses of 40 and 55 gray caused slowing and interruption of cardiac impulse propagation at the AV junction. In 40 left ventricular irradiated targets, all lesions were identified on magnetic resonance imaging after 12 weeks, being consistent with outcomes from gross pathology. In the majority of cases, lesion size plateaued between 12 and 16 weeks. Active caspase-3 was seen in lesions 12 and 16 weeks after irradiation but not after 20 weeks. . The authors concluded that scanned proton beams can be used as a tool for catheter-free ablation, and time-course of tissue apoptosis was consistent with lesion maturation.

In the next paper, Philippe Maury and associates sought to study surface ECG waveforms and effect of ablation in long-lasting ventricular fibrillation (VF) in patients with left ventricular assist devices. Continuous 12-lead ECG of 5 episodes of long-lasting VF occurring in 3 patients with left ventricular assist devices were analyzed. Spectral analysis (dominant frequency or DF) and quantification of waveform amplitude regularity (URI), and complexity (NDI) were performed over a median of 24 minutes of VF. Radiofrequency (RF) ablation was performed during VF in 2 patients. There was a significant increase in dominant frequency between VF onset and termination but none of the other parameters significantly changed. Some VF parameters varied from patient to patient and from lead to lead. DF decreased after RF ablation in both cases and VF terminated spontaneously shortly after ablation in one case. The previously incessant VFs in these 2 patients did not recur afterward. The authors concluded that VF rate increases over time with left ventricular assist devices and is lowered by ablation. Long-lasting VF may be modified or even terminated by ablation.

In the next paper, Taisuke Ishikawa and associates aim to determine the prevalence of nonsyndromic forms of emerinopathy, which may underlie genetically undefined isolated cardiac conduction disturbance, and the etiology of thromboembolic complications associated with Emery-Dreifuss muscular dystrophy (EMD) mutation. Targeted exon sequencing was performed in 87 probands with familial sick sinus syndrome (n=36) and a progressive cardiac conduction defect (n=51). The authors identified 3 X-linked recessive EMD mutations (start-loss, splicing, missense) in families with cardiac conduction disease. All 3 probands shared a common clinical phenotype of progressive atrial arrhythmias that ultimately resulted in atrial standstill associated with left ventricular noncompaction, but they lacked early contractures and progressive muscle wasting and weakness characteristic of Emery-Dreifuss muscular dystrophy. Because the association of left ventricular noncompaction and Emery-Dreifuss muscular dystrophy has never been reported, they further genetically screened 102 left ventricular noncompaction patients and found a frameshift EMD mutation in a boy with progressive atrial standstill and left ventricular noncompaction without complications of muscular dystrophy. All six male EMD mutation carriers of 4 families underwent pacemaker or defibrillator implantation, whereas two female carriers were asymptomatic. Notably, a strong family history of stroke was observed in these patients was probably due to the increased risk of thromboembolism attributed to both atrial standstill and left ventricular noncompaction. The authors concluded that cardiac emerinopathy is a novel nonsyndromic X-linked progressive atrial standstill associated with left ventricular noncompaction and increased risk of thromboembolism.

In our next paper, Min Gu, Hongxia Niu, Yiran Hu and associates in their study aim to compare his bundle pacing (HBP) implantation with a novel imaging technique versus the standard implantation technique. This study included 50 patients with standard pacing indications randomized to HBP with visualization of the tricuspid valve annulus (n=25, the visualization group) or with the standard method (n=25, the control group). In the visualization group, the tricuspid valve annulus (TVA) was imaged by contrast injection in the right ventricle using fluoroscopy. The site of HBP was identified in relationship to the tricuspid septal leaflet and interventricular septum. Permanent his bundle pacing was successful in 92% in the visualization group and 88% in the control group. The fluoroscopic time in his bundle lead placement was significantly shorter in the visualization group (7.1 minutes) compared to control group (10.1 minutes, P=0.03). Total procedural and fluoroscopic times were also significantly shorter in the visualization group (91 minutes and 9.6 minutes) than the control group (104 minutes and 12.7 minutes, P=0.01 and P=0.04, respectively). There was no significant difference in capture threshold between the groups. In the visualization group, there was a quantitative association between the his bundle pacing site and the tricuspid valve annulus. The authors concluded that visualization technique shortens the procedural and fluoroscopic times for his bundle implantation. Moreover, anatomic localization of his bundle pacing sites is strongly associated with physiological characteristics of pacing, which can help optimize lead placement.

In our next paper, Ethan Rowin and associates study cohort comprises 207 consecutive hypertrophic cardiomyopathy (HCM) patients with primary prevention implantable cardioverter defribillators (ICDs) implanted prior to 2008 and followed for 10 years or more (mean 12 years; range to 31). Patients were 38 years at implant and 45 or 21% experienced appropriate interventions terminating ventricular tachycardia (VT) or ventricular fibrillation (VF). The majority of ICD discharges occurred 5 years or more after implant (29 patients or 64%), including 10 or more years in 16 patients (36%). Initial device therapy increased in frequency from 2.3% of patients at less than 1 year to 8.5% of patients at 10 years or more post implant (P=0.005). Inappropriate ICD shocks in 39 patients occurred most commonly less than 5 years after implant (54%) and decreased in frequency with increasing time from implant from 9.7% of patients at less than 5 years to 3.8% at 10 years or more, P=0.02). Other major device complications including infection and/or lead fractures and dislodgement occurred in 27 patients (12%) but did not increase in frequency over follow-up (P=0.47). There were no arrhythmic sudden death events among the 217 ICD patients. The authors concluded that HCM primary prevention ICD therapy increased progressively over time after implant including substantial proportion with prolonged periods of device dormancy including two thirds of patients five years or more and 10 years or more in one-third. Frequency of inappropriate shocks decreased over follow-up, likely reflecting changes in device programming, while occurrence of device complications, such as lead fractures or infection, did not increase over follow-up.

In the next paper, Alexander Zolotarev, Dmitry Dylov, Vadim Fedorov and associates hypothesize that application of machine learning (ML) to electrogram frequency spectra may accurately automate driver detection by multielectrode mapping (MEM) and add some objectivity to the interpretation of MEM findings. Temporally and spatially stable single atrial fibrillation (AF) drivers were mapped simultaneously in explanted human atria (n=11) by subsurface near-infrared optical mapping 0.2 mm2 resolution and 64-electrode multielectrode (higher density [HD] or lower density [LD] with 3 mm2 and 9 mm2 resolution, respectively). Unipolar MEM and near infrared optical mapping recordings (NIOM) were processed by Fourier transform analysis into 28,407 total Fourier spectra. Thirty-five features of ML were extracted from each Fourier spectrum. Targeted driver ablation and NIOM activation maps efficiently defined the center and periphery of AF driver preferential tracks and provided validated classifications for driver versus nondriver electrodes in MEM arrays. Compared with analysis of single electrogram frequency features, averaging the features from each surrounding 8 electrodes neighborhood, significantly improved classification of AF driver electrograms. The classification metrics increased when less strict annotation, including driver periphery electrodes, were added to driver center annotation. Notably, f1-score for the binary classification of HD catheter data set was significantly higher than that of the LD catheter (0.81 versus 0.66, p

In our next paper, Deborah Friedman and associates provide data regarding any potential fetal/neonatal cardiotoxicity, leveraged an opportunity that is unique in which neonatal electrocardiograms (ECGs) and hydroxychloroquine (HCQ) blood levels were available in a recently completed study evaluating the efficacy of HCQ 400 mg daily to prevent the recurrence of congenital heart block associated with anti-SSA/Ro antibodies. Forty-five ECGs were available for QTc measurements, and levels of HCQ were assessed during each trimester of pregnancy and in the cord blood, providing unambiguous assurance of drug exposure. Overall, there was no correlation between cord blood levels of HCQ and the neonatal QTc (R=0.02, P=0.86) or the mean of HCQ values obtained through each individual pregnancy and the QTc (R=0.04, P=0.80). In total 5 (11%) neonates had prolongation of the QTc>2 standard deviations above historical healthy controls (2 markedly and 3 marginally) but ECGs were otherwise normal. The authors concluded that in aggregate, these data provide reassurance that the maternal use of HCQ is associated with a low incidence of infant QTc prolongation. However, if included in clinical COVID-19 studies, early postnatal ECGs should be considered.

In a research letter, James Hummel and associates sought to examine the time course of QTc prolongation in their database of COVID-19 patients treated with hydroxychloroquine. This study demonstrates that QTc prolongation in hospitalized patients with COVID-19 infection is common and can occur very late, well after the initiation of therapy. Vigilance to minimize multiple concurrent drugs and careful monitoring of renal function and cardiac rhythm are required for hospitalized COVID-19 patients. This, however, should not be extrapolated to non-COVID-19 patients with no comorbidities and who are not using concurrent QT-prolonging medications.

In a research letter, Melissa Moey, Prasanna Sengodan and associates aim to characterize the electrocardiographic characteristics and incidents of patients admitted with SARS-CoV-2. Their study had several limitations. It was a single study observational retrostudy of a small population of patients with SARS-CoV-2 without a comparison group. Data are limited to index hospital admission followup data to see whether EKG electrocardiogram intervals revert to baseline following recovery from infection are lacking. Approximately 70% of patients in their study received hydroxychloroquine (HCQ) and/or azithromycin. However, the latest data have shown ineffectiveness and possible harm with these drugs in treatment of SAR-CoV-2. QRS widening has been previously documented in critically ill intensive care unit ICU patients. Hence, this finding may not be specific to SARS-CoV-2. Additional prospective studies with a larger population and longer follow up period are recommended to validate and further elucidate their findings.

In a research letter, Hikmet Yorgun and associates aim to report their experience in patients with mechanical aortic mitral prosthesis who underwent endocardial ventricular tachycardia (VT) ablation as an index or redo procedure. The author's findings expand the literature regarding the safety and efficacy of transapical approach with limited left ventricular (LV) access, and emphasize the importance of close collaboration between cardiac electrophysiologist and surgeons during the procedure. Limitations include small sample size and short follow-up duration, as well as lack of pre-procedural magnetic resonance imaging, mainly due to the presence of implantable cardioverter defibrillator.

In a research letter, Bradley Peltzer and associates sought to define the incidence and risk factors for arrhythmias among patients hospitalized with COVID-19 and to evaluate associated arrhythmias with outcomes, including mortality. The authors studied all patients with COVID-19, who were admitted consecutively to New York Presbyterian Weill Cornell medicine and New York-Presbyterian Lower Manhattan hospital between March 3rd and April 6th, 2020. The primary outcome of the study was a 30 day all cause mortality. Arrhythmias were identified by review electrocardiograms and telemetry data obtained during hospitalization. There were several limitations to this study. This was a retrospective study with data obtained via chart abstraction, which may be subject to error or misinterpretation. Variation telemetry monitoring systems across hospital units may have led to possible underdetection of arrhythmias in some cases. Because this study focuses on hospital outcomes. Out of hospital deaths following discharge of COVID-19 were not examined. In this analysis of rhythmic complications of over a thousand consecutive patients hospitalized with COVID-19, atrial fibrillation flutter was seen in over 15% and more than 60% of these occurring in patients without any prior history of atrial fibrillation while ventricular tachycardia ventricular fibrillation occurred in less than 3% of patients. Age, male, sex and hypoxia and presentation were independently associated with the occurrence of arrhythmia. The presence of arrhythmia is tracked with markers of disease severity and elevated markers of myocardial injury, inflammation, and fibrinolysis. While there are likely myriad factors that lead to COVID-19 associated arrhythmias, their findings suggests that arrhythmias may predominantly be a marker of COVID-19 severity. Further studies to elucidate the mechanism COVID-19 associated arrhythmias and assess whether treatments targeting SARS-CoV-2 infection and its associated inflammatory response can reduce arrhythmia occurrence or warrant.

In a perspective, Bryce Alexander and Adrian Baranchuk discuss that in the current area of medicine, many patients with terminal illnesses have preexisting cardiac disease that required implantable cardioverter (ICD) placement. The world is currently in the midst of an unprecedented COVID-19 pandemic. While data are still being collected and analyzed, there appears to be significantly increased mortality in older and more comorbid patients with current process of deactivation, the requirement for the physical presence of the electrophysiology (EP) team with the patient may disrupt the dying process and may serve as a vector for transmission of infection back into the community or hospital. Most modern ICDs currently have the ability of unidirectional communication through remote monitoring network. These allow for followup of patients through interrogation device independent of a physical program. Currently there is no capacity for bi-directional remote communication of a program or implanted device. The potential perceived barrier to implementation to strategies, concerns related to cybersecurity of implantable electronic devices (CIECD). While cyber security threats from any network connected medical device cannot be eliminated, the benefits of the features provided may outweigh the possible dangers. In the case of remote deactivation of ICDs, there are several important benefits. For patients, benefits will include preservation of the dying process without outside interruption, as well as possible faster deactivation of the ICD eliminating unwanted shocks. For healthcare providers, this approach could eliminate barriers to ICDs deactivated early in terminal patients and help to develop a structured approach to routine deactivation. On a system level, this approach may reduce costs and allow for less utilization of hospital or clinic space. Given the benefits of remote monitoring and the increased demand to transform practice into tele-health, the authors propose a stepwise approach to remote programming capability, starting with remote deactivation. If able to be accomplished, the inactivation of ICD's at Distance for Dignity of Dying project, the 4D project, will allow for a less interrupted dying process in the palliative patient. And it reduced the risk of infection transmission in the setting of ongoing or future pandemic. If this approach were to prove feasible, it could potentially open the door for future applications of remote reprogramming, including, but not limited to: 1) allowing increased input in the case of loss of capture, 2) adjusting sensitivity, 3) reprogramming to the MRI magnetic resonance imaging mode, 4) asynchronous pacing, tachy detection off prior to electric cardiac response, and 5) lower rate cutoff for slow ventricular tachycardia.

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, 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

In our next paper, Dan Musat and associates assess the incidents and predictors of very late occurrence (VLR) when atrial fibrillation occurs 12 months or more after ablation in patients who underwent cryoballoon pulmonary vein isolation alone (PVI), had an ILR and were confirmed AF free (atrial fibrillation free) for at least one year. They included 188 patients, mean 66 years, 62% male and 54% paroxysmal atrial fibrillation with CHA2DS2-VASc 2.6. After one year post PVI, 49% of patients remained AF free. During subsequent follow-up, 32% had very late recurrence of atrial fibrillation. The only independent risk factor for very late recurrence was an elevated CHA2DS2-VASc score (hazard ratio 1.317; P=0.06). Patients with CHA2DS2-VASc score greater than four represented a quarter of the population and were at highest risk.

In our next paper, Daniele Pastori, Danilo Menichelli, Gregory Yip and associates in the ATHERO-AF Study Group investigate the association between family history of atrial fibrillation (AF) in cardiovascular events (CVEs), major adverse events (MACE), and cardiovascular mortality. They conducted a multicenter prospective observational cohort study, including 1,722 nonvalvular AF patients from February 2008 to August 2019 in Italy. Family history of AF was defined as the presence of AF in a first-degree relative: mother, father, sibling, or children. Primary outcome was a composite of CVEs, including fatal/non-fatal ischemic stroke and myocardial infarction and cardiovascular death. Second, they analyze the association with MACE. Mean age 74.6 years, 44% women. Family history of AF was detected in 368 or 21.4% of patients, and 3.5% had two or more relatives affected by AF. Age of AF onset progressively decreased from patients without family history of AF compared to those with single and multiple first-degree affected relatives (P

In our next paper, Louise Reilly and associates created the first patient-inspired KCNJ2 transgenic mouse and studied the effects of this mutation on cardiac function, IK1 and calcium handling to determine the underlying cellular arrhythmic pathogenesis. A cardiac specific KCNJ2-R67Q mouse was generated and bred for heterozygosity. That's R67Q+/-. Echocardiography was performed at rest and under anesthesia. In vivo electrocardiogram, ECG recording, and whole heart optical mapping of intact hearts was performed before and after adrenergic stimulation in wild-type littermates and R67Q+/- mice. In IK1 measurements and action potential AP characterization, intracellular calcium imaging from isolated ventricular myocytes at baseline and after adrenergic stimulations were performed in wild-type and R67Q+/- mice. R67Q+/- mice (n=17) showed normal cardiac function structure baseline electrical activity compared to wild-type (n=10). Following epinephrine and caffeine, only the R67Q+/- mice had bidirectional ventricular tachycardia, frequent ventricular ectopy and/or bigeminy and optical mapping demonstrated high prevalence of spontaneous and sustained ventricular arrhythmia. Both R67Q+/- (n=8) and wild-type myocytes (n=9) demonstrated typical n-shaped IK1 IV relationship. However, following isoproterenol, max outward IK1 increased by about 20% in wild-type, but decreased by 24% in R67Q+/- (P

In our next paper, Michael Liu and associates use computational modeling to simulate 1D, 2D and 3D tissue under a variety of conditions to test the ability of genetically engineered non-arrhythmogenic stabilizer cells to suppress triggered activity due to delayed or early afterdepolarization. Due to source-sink relationships in cardiac tissue, a minority (20 to 50%) of randomly distributed stabilizer cells engineered to be non-arrhythmogenic can suppress the ability of arrhythmogenic cells to generate delayed or early afterdepolarization related arrhythmias. Stabilizer cell gene therapy strategy can be designed to correct a specific arrhythmogenic mutation such as in CPVT mice studies, or more generally to suppress delayed or early afterdepolarization from any cause by overexpressing the inward rectifier potassium, Kir2.1 in stabilizer cells. The authors propose this as a promising antiarrhythmic strategy.

In our next paper Wei Hu, Dongchen Zhou, and associates used high resolution mapping to study the determinants of flutter wave morphology on surface ECG in patients with peri-mitral atrial flutters (PMAFLs) that develops post atrial fibrillation (AF) ablation or post-cardiac surgery. The mean tachycardia cycle length (TCL) was 264 milliseconds with right atrial RA activation time, 155 milliseconds, 60.8% of the tachycardia cycle length, and the flutter wave duration, 107 milliseconds or 41.6% of the tachycardia cycle length. The overlap between the RA activation time and the flutter wave duration was 102 milliseconds, which takes 68.5% of the RA activation time and 95.7% of the flutter wave duration respectively. The authors found that the ECG flutter wave morphology of PMAFLs is mainly dependent on RA activation pattern. Quantitative analysis also showed that during the flutter wave duration, more percentage of the endocardial area was activated in the RA than in the LA (70.0% versus 45.2%: P

In our next paper, Peter van Dam, Emanuela Locati and associates sought to localize electric activity in Brugada syndrome using novel CINeECG method, which creates an inverse electrocardiogram (IECG) from standard 12-lead electrocardiogram (ECG). They studied 15 spontaneous Brugada syndrome patients and 18 ajmaline-induced Brugada syndrome patients at baseline and after ajmaline in whom epicardial potential duration maps (PDM) were available. 17 type-3 Brugada syndrome patients not showing type-1 Brugada syndrome after ajmaline, that is ajmaline-negative, in 47 normal subjects. In 18 right bundle branch block (RBBB) patients in spontaneous or ajmaline-induced Brugada syndrome patients CineECG localized the terminal forces in the RVOT congruent with arrhythmogenic substrate location detected by epicardial potential duration maps (PDM). The RVOT location was never observed in normal right bundle branch block or ajmaline-negative patients. In most ajmaline-induced Brugada syndrome patients (78%), the RVOT location with already evident at baseline. The CineECG classified all normal subjects and ajmaline-negative patients at baseline as normal or undetermined and all right bundle branch block patients as RBBB while all spontaneous ajmaline-induced Brugada syndrome patients as Brugada. Compared to a standard 12-lead ECG, CineECG at baseline had 100% positive predictive value and an 81% negative predictive value in predicting ajmaline test results.

In our next paper Zhen Wang and associates examined the circadian cardiac electrophysiology properties in relationship to age. The authors examined adult male mice hearts, 12 to 18 weeks, that were isolated during light, ZT4 and ZT9 and dark, ZT14 and ZT21 from adult male mice and aged (18 - 20 months) male hearts. They were isolated at ZT4 and ZT14. All hearts were Langendorff-perfused for optical mapping with voltage and calcium channel sensitive dyes (n=4-7 per group). Cardiac gene and protein expression was assessed using real time PCR (four to six per group) and Western blot, three to four per group. Adult hearts showed circadian differences in actual potential duration (APD) and calcium transient duration with the shortest values at ZT14. The pacing frequency at which calcium T alternans emerge was faster, and average calcium T alternans magnitude was significantly reduced at ZT14 compared to other time points. There was a trend for decreased spontaneous PVCs, premature ventricular contractions, and pacing-induced ventricular arrhythmias at ZT14, and the hearts at ZT14 had diminished responses to isoproterenol compared to ZT4 (ZT4: 49.5% versus ZT14: 22.7% decrease in action potential duration, P

In our next paper, Christopher Cheung and associates reported on the patients who underwent repeat ablation procedures for symptomatic atrial tachyarrhythmia with the objective of evaluating pulmonary vein (PV) reconnections in this CIRCA-DOSE study. This study was a multi-center randomized trial that demonstrated that pulmonary vein isolation (PVI) performed by second generation or contact force (CF-RF) resulted in comparable freedom from atrial tachyarrhythmia as measured by continuous cardiac monitoring using an implantable loop. Among the 346 patients randomized in the CIRCA-DOSE trial, 52 patients, or 15%, underwent a repeat ablation procedure. There were no significant differences in baseline characteristics between patients undergoing repeat ablation and the remaining cohort, apart from higher baseline atrial fibrillation (AF) burden, percent time in AF, and those who underwent a repeat procedure (10.1% versus 1.6%; P=0.002). At the repeat procedure, PV reconnection was noted in 4,752 or 90.4% of patients with no significant difference between the two groups (14 out of 16 or 97.5% after CF-RF and 17 out of 18 or 94.4% after CRYO 4, and 16 out of 18 or 88.9% after CRYO 2, P=0.64). The median number of reconnected PVs per patient was two after CF-RF and two after CRYO 2 and one after CRYO 4 (P=0.46). A total of 89 out of 201 PVs, that's 44.3%, were reconnected. This included 23 out of 52 or 44.2% right superior, 27 out of 52 (51.9%) right inferior, 17 out of 42 (40.5%) left superior and 15 out of 42 (35.7%) left inferior. One out of three or 33% right middle and six out of 10 or 60% of left common. There was no difference in the pattern of reconnection between the CF-RF and cryoballoon groups.

In our next paper, a research letter, Joshua Payne and associates examine how well low energy shock impedance is correlated with high energy shock impedance with subcutaneous implantable cardioverter defibrillator, S-ICD implantation. Consecutive patients received pair 10 and 65 joule shocks were studied. The 65 joule shock was delivered either during induced VF or synchronously during sinus rhythm. All 10 joule shocks were delivered synchronously in sinus rhythm. There were 28 patients in this study, including 24 who underwent new device implantation. Defibrillation threshold testing was performed in 21 or 75% of patients. All but one, 96%, were successfully defibrillated at 65 joules. There was a significantly higher impedance for 10 joule shocks compared to 65 joule shocks, 73.1 ohms versus 70.3 ohms respectively (P=0.023) with a mean difference of 2.8 ohms. The impedances for the two shock energies were highly correlated (R-squared=0.97; P

In our next research letter, Paolo Compagnucci and associates conducted a single center retrospective observational study by enrolling patients in electrophysiologic (EP) procedures at a tertiary level referral center in Italy during the COVID-19 pandemic. They examined all consecutive patients who underwent EP procedures since March 9, 2020 when the novel health care measures were taken in the cardiology department due to the COVID-19 outbreak until April 26, 2020. These patients were compared to those undergoing EP procedures in the preceding six months. During the COVID emergency, only non deferrable procedures were performed giving priority to electrical storm, refractory device infections requiring lead or device extraction, pacemaker or defibrillator implantations and generator changes. During the COVID-19 emergency 79 EP procedures were performed. The most common interventions included generator changes, pacemaker implantation to (2 with leadless devices), defibrillator implantations, catheter ablations and device extractions. In the six months before the lockdown 592 EP procedures were performed, most commonly pacemaker implementations (three with leadless devices), generator change and catheter ablations for atrial fibrillation. Their findings suggest three key messages. One, overall there's a drastic reduction in the numbers of EP procedures due to postponement of non-urgent interventions. Two, EP laboratory model and extensively adopting personal protective equipment (PPE) and other preventative measures proved safe for healthcare professionals. And three, weekly rates of electrical storm catheter ablation significantly increased.

In our next research letter, Seigo Yamashita and associates examine the risk of coronary sinus ablation during mitral isthmus ablation. Out of 712 patients who underwent mitral isthmus (MI) linear ablation in their institution, epicardial ablation within the coronary sinus (CS) was performed in 446 or 62.6% because of incomplete block by endocardial ablation only. 126 of 446 (28.3%) patients had redo procedures due to AF/AT recurrence, and they were retrospectively included in this study. Age 55 years, persistent AFib in 117. The coronary sinus post procedure (CS post) diameter was 5.6 millimeters with a mean reduction in 11.1% compared to coronary sinus pre diameter (CS pre) 6.0 millimeters. Among 126 patients, 15 or 12% demonstrated coronary sinus (CS) stenosis located at three to four or four o'clock in the LAO view in 33%, 20% and 40% of patients respectively with a mean reduction of 61.0%, but all were asymptomatic. These three cases demonstrated severe stenosis with a 5 Fr CS mapping catheter impossible to cross. The severe stenosis was located at the level of three o'clock on the LAO in all. On multi-variable analysis adjusted for age, atrial fibrillation type, minimum CS diameter, and TactiCath use, narrower coronary sinus diameter was the only independent predictor of coronary sinus stenosis (odds ratio 0.07 or P

In our next research letter, Min-Young Kim, Belinda Sandler and associates compare the anatomical distribution of ectopic-triggering ganglionated plexus (GP) to that of atrial ventricular dissociating GP in patients with atrial fibrillation. The highest probability of ectopic-triggering ganglionated plexus greater than 30% were in the roof mid anterior wall around all pulmonary vein ostia except for the right inferior pulmonary vein in the posterior wall, suggesting that they inadvertently ablated during conventional pulmonary vein isolation procedures for atrial fibrillation, possibly explaining why some patients remain symptom-free with reconnected pulmonary veins. On the other hand, the majority of atrial ventricular dissociating GP lie outside the pulmonary vein isolation target regions.

In our next special report, Arwa Younis, May Goldenberg and associates aim to evaluate the yield of MADIT-CRT response score to predict the long-term risks of clinical events and life-threatening ventricular arrhythmias by QRS morphology. Among patients with left bundle branch block, the rate of life-threatening ventricular tachyarrhythmias or death at three years was lowest (8%) among CRTD patients with a high response score and highest among ICD patients with a low response score (22%). Log rank P-value for the difference during follow-up, P

In our next special report, Alexandra Benz and associates prospectively collected data from asymptomatic atrial fibrillation, stroke evaluation, and pacemaker patients in the Atrial Fibrillation Reduction Atrial Pacing Trial, or ASSERT Trial found that implementation of inactive fixation atrial lead was not associated with a higher incidence of atrial fibrillation compared to implantation of a passive fixation atrial lead both early post implantation and over long-term followup.

In our next special report, Siddharth Trivadi and associates conducted a longitudinal follow-up study of speckle tracking strain echocardiography and assessment of myocardium mechanics in patients with idiopathic ventricular arrhythmia. They were able to demonstrate subtle abnormalities in myocardial mechanics and dispersion that persist for prolonged periods of time, despite successful abolishment of the inciting arrhythmia or the absence of overt cardiomyopathy or established arrhythmia-related cardiomyopathy. The study suggests that patients with idiopathic ventricular arrhythmias are not truly idiopathic and that subtle subclinical myocardial changes exist.

In a perspective piece, Pietro Enea Lazzerini and associates provide recommendations about electrocardiographic QTC monitoring along with this decisional guide for optimizing risk-benefit ratio when exploratory drugs are administered. The document also highlights that severely ill COVID-19 patients are frequently burdened by comorbidities, especially electrolyte imbalances, concomitant QT prolonging drugs in the high grade systemic inflammatory state, further increasing torsades de pointes susceptibility. They comment that specifically dampening inflammation-driven arrhythmic risk via IL-6 blockade could reduce the need for withholding or withdrawing potentially useful COVID-19 repurposed pharmacotherapies.

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.

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

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

In our next paper, Sergio Callegari, Emilio Macchi, and Associates characterize the fibrosis (amount, architecture, cellular components, and ultrastructure) in left atrial biopsies from 121 patients with persistent/long-lasting atrial fibrillation [AF] (group 1; 59 males; 60 years of age; 91 mitral disease-related AF, 30 nonmitral disease-related AF) and 39 patients in sinus rhythm with mitral valve regurgitation (group 2; 32 males; 59 years of age). 10 autopsy hearts served as controls. Qualitatively, the fibrosis exhibited the same characteristics in all cases and displayed particular architectural scenarios (which the authors arbitrarily divided into four stages) ranging from isolated foci to confluent sclerotic areas. The percentage of fibrosis was larger and in a more advanced stage in group 1 versus group 2 and within group 1, in patients with rheumatic disease versus non-rheumatic cases. In AF patients with mitral disease and no rheumatic disease, the percentage of fibrosis and the fibrosis stages correlated with both left atrial volume index and AF duration. The fibrotic areas mainly consisted of type I collagen with only a minor cellular component (especially fibroblasts/myofibroblasts; average value range 69–150 cells/mm2, depending on the areas in AF biopsies). A few fibrocytes, circulating and bone marrow-derived mesenchymal cells, were also detectable. The fibrosis-entrapped cardiomyocytes showed sarcolemmal damage and connexin 43 redistribution/internalization.

In our next paper, Shijie Zhou and Associates tested an automated localization system to identify the site of origin of left ventricular [LV] activation in real time using 12-lead ECG. The automated site of origin, solo system, consists of three steps: (1) localization of ventricular segment based on population templates, (2) population-based localization within a segment, and, (3) patient-specific site localization. Localization error was assessed by the distance between the known reference site and the estimated site. In 19 patients undergoing 21 catheter ablation procedures of scar related VT, solo accuracy was estimated using 552 LV left endocardial pacing sites pooled together and 25 VT-exit sites identified by contact mapping. For the 25 VT-exit sites, localization error of the population-based localization steps was within 10 mm. Patient-specific site localization achieved accuracy of within 3.5 mm after including up to 11 pacing (training) sites. Using 3 remotes (67.8 mm from the reference VT-exit site), and then 5 close pacing sites, resulted in localization error of 7.2 mm for the 25 identified VT-exit sites. In 2 emulated clinical procedure with 2 induced VT's, the solo system achieved accuracy within 4 mm.

In our next paper, Ryan Koene and associates examined outcomes of use of dofetilide in atrial fibrillation [AF] patients with left ventricular ejection fraction [LVEF]≤35% without prior implantable cardioverter defibrillator [ICD] cardiac resynchronization therapy [CRT], or AF ablation. An analysis of 168 consecutive patients from 2007 to 2016 was performed. Incidences of adverse events, drug discontinuation, ICD, or CRT implementation, LVEF improvement (>35%) and recovery (50% or greater), AF recurrence, and AF ablation were determined. Multi-variate regression analysis to identify predictors of LVEF improvement/recovery was performed. The mean age was 64 years. Dofetilide was discontinued prior to hospital discharge in 46 (27%) because of QT prolongation (14%), torsades de pointe or polymorphic ventricular tachycardia/ventricular fibrillation (6% [sustained 3%, nonsustained 3%]), in effectiveness (5%), and other causes (3%). At one year 43% remained on dofetilide. Freedom from AF was 42% at 1 year and 40% underwent future AF ablation. LVEF recovered to 50% or greater in 45% and an improved to greater than 35% in 73%. Predictors of LVEF improvement included presence of AF during echocardiogram (odds ratio 4.22, P=0.002), coronary artery disease (odds ratio 0.35, P=0.01), left atrial diameter (odds ratio, 0.52 per 1 cm increase, P=0.01), and LVEF (odds ratio, per 1% increase, 1.09, P=0.006). The C statistic was 0.78.

Our next paper is a research letter by Giuseppe Ciliberti, Gherardo Finocchiaro, and Associates. Myocardial infarction with nonobstructive coronary arteries, MINOCA, accounts for one to 10% of all causes of acute myocardial infarction [MI]. The authors examine 37, that is 0.7% of the entire study population, sudden cardiac death cases of MINOCA. The majority of decedents were male (N=23, 62%), mean age at death was 34 years, age range 13 to 96 years. Death occurred at rest or during daily activities in 36, that is 97% of individuals. Coronary thrombosis was found at 9 out of 13 at a 69% with nonobstructive atherosclerosis. Drug use was reported in 10 or 27%.

Our next paper is a special report entitled HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for tele-health and arrhythmia monitoring during and after a pandemic. This document discusses how digital health may facilitate electrophysiology practice in patients with arrhythmia. Electrophysiology is well placed for virtual consultation. Digital tools such as direct to consumer mobile ECG and wireless blood pressure devices can be used to further compliment the tele-health visit without in-person contact C-I-E-D wearable mobile health and clinical data can be integrated into clinician workflow. Wearable and smart flow based devices allow convenient real-time monitoring for arrhythmias. Remote CID monitoring has a continue important role. Our special report is entitled Guidance for Rebooting Electrophysiology Through COVID-19 Pandemic from the Heart Rhythm Society and the American Heart Association, Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology endorsed by the American College of Cardiology. Dhanunjaya Lakkireddy, Mina Chung and Associates in this joint document for representatives of the Heart and Society, American Heart Association, American College of Cardiology, provide guidance for clinicians, institutions establishing safe electrophysiological care. To achieve the same they address regional and local COVID-19 disease status, the role of viral screening, and serologic testing, return to work considerations for exposed and infected healthcare workers, risk stratification and management strategy based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures and development of outpatient and periprocedural care pathways.

In a special report, Philip Krisai and Associates reported the results of CONVERT-AF (Canakinumab for the Prevention of Recurrences After Electrical Cardioversion in Patients With Persistent Atrial Fibrillation) is a randomized double blind placebo control trial enrolling patients with persistent A-Fib, atrial fibrillation, AF undergoing electrical cardioversion, or ECV with HS CRP levels of two mg/L or greater. Age, greater than 50 years of age women needed to be post-menopausal. After sinus rhythm restoration, patients were randomly assigned within 60 minutes to a single subcutaneous injection of 150 mg of Canakinumab or matching placebo. 11 and 13 patients were randomized to Canakinumab and placebo rest respectively mean overall age was 66 years, 24% women. AF recurrence in six months occurred in 10 (77%) and four (36%) in patients with the placebo or Canakinumab groups, respectively (hazard ratio 0.36, P=0.09). At one month AF recurred in six (46%) and four (36%); at three months in eight (62%) and four (36%) patients respectively. The hazard ratios for first time redo ECV and hospitalization-free survival were 0.29 (P=0.27) and 0.74 (P=0.75) respectively and antiarrhythmic drug use at 6 months were used in 7 (54%) and 9 (82%) of patients in the placebo and the Canakinumab group respectively. Odds ratio 3.86 P equals 0.16 log transform high sensitivity CRP was 31% lower in the Canakinumab group. At six months, adverse events occurred in 3 (23%) and 3 (27%) in the placebo and Canakinumab groups, respectively. Infections occurred in 2 (15%) and 2 (18%) in the placebo and Canakinumab groups respectively.

In a special report Amr Barakat and associates reported that the number of implants of SelectSecure 3830 [SS3830] increase greater than 4-fold in 2017 (9,145) and 2018 (9,895) compared to 2016 (1,972 implants). The yearly number of his bundle pacing related publications increased approximately 4-fold in 2015 and approximately 25-fold in 2018, compared to 2014. 140 medical device reports related to SS3830 lead use were made for permanent his bundle pacing.

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, 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

In our next, paper Hirosuke Yamaji and associates conducted a randomized control trial to examine the impact of electrophysiological evaluation of the left atrium on atrial fibrillation [AF] outcome. They examined consecutive persistent and patients with, in 33, and without, 111 patients left atrial [LA] low voltage areas [LA-LVA]. Patients without LA-LVA were randomly assigned to EP test-guided (n=57) and control (n=54). In the EP test-guided group, an adjunctive posterior wall isolation [PWI] was performed in those with positive results (PWI subgroup; n=24) but not those with negative results (n=33). The criteria for positive EP tests were an effective refractory period ≤180 ms, ERP > 20 ms shorter than the other sites, and/or induction of AF/atrial tachycardia during measurements. LVA ablation was performed in the LA-LVA patients during the follow-up period of a mean of 62 weeks, the EP test-guided group had a significantly lower recurrence rate (19%,11/57 versus 41%, 22/54, P=0.012) and a higher Kaplan-Meier AF/AT-free survival curve compared with controls (P=0.01). No significant differences in the recurrence, and AF/AT-free survival curves between PWI (positive EP test) and non-PWI (negative EP test) subgroups were observed. Therefore, PWI for positive EP tests reduced the AF/AT recurrence in the EP test-guided group. A stepwise Cox proportional hazard analysis identified EP test-guided ablation as a factor, reducing recurrence rates. The recurrence rates in LA-LVA ablation group and EP test-guided group were similar.

In our next study, Jinxuan Lin and associates assess whether simultaneous pacing of the left and right bundle branch areas may achieve more synchronous ventricular activation than just bundle pacing alone. In symptomatic bradycardia patients, the distal electrode of the bipolar pacing lead was placed at the left bundle branch area via a transventricular-septal approach. This was used to pace the left bundle branch area, while the ring electrode was used to pace the right bundle branch area. Bilateral bundle branch area pacing [BBBP] was achieved by stimulating the cathode and anode in various configurations. BBBP was successfully performed in 22 out of 36 patients. Compared with LBBP, BBBP resulted in greater shortening of QRS duration (109.3 vs 118.4 ms, P

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

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

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

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

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

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

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

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]

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

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

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

In our next paper, Henry Chubb and associates examine the outcomes of cardiac resynchronization therapy studies in pediatric and or congenital heart disease patients using a propensity score match analysis. They examined 63 matched CRT control pairs. Heart transplant or death occurred in 12 subjects or 19% or 37 controls or 59% with a median follow-up of 2.7 years. Cardiac resynchronization therapy was associated with markedly reduced risk of heart transplant or death. Hazard ratio is 0.24 P

In our next paper Pachon-M and associates examined whether AF nest ablation eliminates the atropine response and decreases RR variability suggesting that they're related to vagal innervation. The authors perform prospective control longitudinal randomized study enrolling 62 patients in two groups, AF nest group that is 32 patients with functional or reflex Bradyarrhythmias or vagal AF treated with AF Nest ablation and a control group, 30 patients with anomalous bundles, ventricular prematures, atrial flutter, AV nodal reentry and atrial tachycardias who were treated with a conventional ablation approach.

In the AF nest group, ablation was delivered at the AF nest detected by fragmentation or fractionation of the endocardial electrograms and by 3D anatomical location of the ganglionated plexus. Vagal response was evaluated before, during and post ablation by five seconds non-contact vagal stimulation at the jugular foramen through the internal jugular veins, analyzing 15 seconds mean heart rate, longest RR pauses and AV block. A pre-ablation non-contact vagal stimulation due sinus pauses, asystole, and transient AV block in both groups showing a strong vagal response.

Post-ablation non-contact vagal stimulation in the AF nest showed complete abolishment of the cardiac vagal response in all cases, P

In our next paper, Domingo Uceda and Xiang-Yang Zhu and associates examined whether progressive increases in pericardial fat volume and inflammation, prospectively dampens the heart rate variability in hypercholesterolemic pigs. The author studied wild type or PCSK9 gain-of-function Ossabaw mini-pigs in-vivo before and after three and six months of a normal diet. Four in the wild type group and six in the PKSK9 group. Or high-fat diet, wild type three, in PCSK9, six.

At diet completion, they found that the hypercholesterolemic PCSK9 had significantly depressed heart rate variability, and both high fat diet groups had higher sympathovagal balance compared to the normal diet. P

In our next paper, Konstantinos Aronis and Rheeda Ali and associates examined myocardial conduction velocity and myocardial fibrosis density on late gadolinium enhanced cardiac magnetic resonance imaging in patients with ischemic cardiomyopathy. The author studied six patients with ischemic cardiomyopathy undergoing VT ablation, and five with structurally normal left ventricle serving as controls. All patients underwent late gadolinium enhanced cardiac magnetic resonance, and electroatomic mapping in sinus rhythm. Median conduction velocity in ischemic cardiomyopathy patients and controls was 0.41 meters per second and 0.65 meters per second respectively. In ischemic cardiomyopathy patients conduction velocity in areas with no visible fibrosis was 0.81 meters per second. For each 25% increase in normalized late gadolinium-enhanced intensity conduction velocity decreased by 1.34 fold. Dense scar areas have an average of 1.97 to 2.66 fold slower conduction velocity compared to areas without dense scar. Ablation lesions that terminate at VT were localized in areas of slow conduction on conduction velocity maps. The authors found that conduction velocity is inversely associated with late gadolinium enhanced cardiac magnetic resonance fibrosis density in patients with ischemic cardiomyopathy.

In our next paper, Bence Hegyi and associates examined whether the IKR current or the sodium L-type current play counterbalancing roles in the ventricular action potential. The authors found that a comparable amount of net charge carried by these two currents during the physiological action potential, suggesting that the outward potassium current via IKR and the inward sodium current via the sodium L-type current are in balance during physiological repolarization. These two current integrals in control myocytes were highly correlated, but this close correlation was lost in heart failure myocytes. Pretreatment with E-4031 to block IKR mimicking long QT syndrome 2, or ATX II to impair a sodium channel inactivation mimicking long QT3 prolong the action potential duration. However, using GS-967 to inhibit sodium L-type current sufficiently restored action potential control to control in both cases.

Furthermore, the sodium L-type inhibition significantly reduced the beat to beat and short-term variabilities of action potential duration. Sodium L-type current inhibition also restored action potential duration in repolarization stability in heart failure. Conversely, pretreatment with GS-967 shortened action potential duration mimicking short QT syndrome and E-4031 reverted APD shortening. Furthermore, the amplitude of action potential alternans occurring at high pacing frequency was decreased by sodium L-type inhibition, increased by IKR inhibition and restored by a combination of sodium L-type and IKR inhibitions. The author suggests that targeting these two ionic currents to normalize or balance may have significant therapeutic potential in heart diseases with repolarization abnormalities.

In our next paper, Derek Chew and associates examine the impact of the duration between first diagnosis of atrial fibrillation and ablation or diagnosis to ablation time on AF recurrence following catheter ablation by conducting a systematic review and meta analysis of observational studies. They found six studies that met inclusion criteria with a total of 4,950 participants undergoing atrial fibrillation ablation for symptomatic AF. A shorter diagnosis to ablation time of one year or less was associated with a lower relative risk of AF recurrence compared to diagnose to the ablation time greater than one year. Relative risk 0.73 P

The authors concluded that the duration between time to first day of AF and AF ablation is associated with an increased likelihood of atrial fibrillation ablation procedural success.

In a research letter by Kapuaola Gellert and associates, 48 hour continuous ECG was found to have an association between sleep apnea and atrial fibrillation in the community-based population study, the ARIC study.

In a special report, Francesco Notaristefano reported that the risk of device pocket hematoma 10 days after CIED surgery showed an independent association with the type of interventional procedure such as device implementation, odds ratio 3.5, implantable cardioverter defibrillator 4.4, cardiac resynchronization therapy, odds ratio 11.7, and antithrombotic treatment, but not with novel oral anticoagulants.

In an interesting review article Nicholas Tan and associates describe the current and future perspectives of left bundle branch block.

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.

Copyright American Heart Association 2020.

Paul J. Wang:

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

Elizabeth Wang and Associates examined the relationship between acute precipitants of atrial fibrillation and long-term recurrence of atrial fibrillation, AF, from a multi-institutional, longitudinal electronic medical record database. Among 10,723 patients with newly diagnosed Afib, age 67.9 years, 41% women, the authors found that 19% had an acute AF precipitant, the most common of which were cardiac surgery in 22%, pneumonia in 20% and non-cardiothoracic surgery in 15%. The cumulative incidence of AF recurrence at five years was 41% among individuals with a precipitant, compared to 52% in those without a precipitant. Adjusted hazard ratio 0.75 P

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

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

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 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 P = 0.03, and left atrial high-resolution late gadolinium enhancement coefficient 0.035, P

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 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

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

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

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.