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Background: Radiofrequency ablation (RFA) of cavotricuspid isthmus (CTI)-dependent atrial flutter requires ablation of the tricuspid annulus overlying the right coronary artery (RCA). While considered safe, reports of acute and subacute RCA injury in human and animal studies raise the possibility of late RCA stenosis., Objective: To compare the incidence and severity of angiographic RCA stenoses in patients who have undergone CTI RFA to a control group to assess the long-term risk of RCA damage., Methods: A two-center retrospective case-cohort study was performed including all patients from 2002-2018 undergoing atrial fibrillation (AF) with CTI ablation (CTI+AF) or AF ablation alone with subsequent coronary angiography (CAG). The AF alone group served as controls due to anticipated similarity of baseline characteristics. Coronary arteries that are anatomically remote to the CTI were examined as prespecified falsification endpoints. CAG was scored by a blinded observer., Results: 156 patients who underwent PVI with subsequent CAG (CTI+AF, n=81; AF alone, n=75) had no difference in baseline characteristics including age, sex, comorbidities, and medications. Mean time from ablation to CAG was similar (CTI+AF 5.0±3.7 years vs AF alone 5.4 ±3.9 years, p=0.5). The mid and distal RCA showed no difference in the average number of angiographic stenoses or lesion severity. In regression analysis, CTI ablation was not a predictor of RCA stenosis severity (p=0.6). There was no difference in coronary disease at sites remote to the CTI ablation (p=NS for all)., Conclusion: There was no observed relationship between CTI RFA and the number or severity of angiographically apparent RCA stenoses in long-term follow up., (Copyright © 2024. Published by Elsevier Inc.)

Background: Pectoral nerve (PECs) blocks are established regional anesthesia techniques that can provide analgesia to the anterior chest wall. Although commonly performed preoperatively by anesthesiologists, the feasibility of electrophysiologist-performed PECs blocks from within cardiac implantable electronic device (CIED) pockets at the time of implantation has not been established. The objective of this study is to assess the feasibility of routine PECs blocks performed by the electrophysiologist from within the exposed device pocket at the time of CIED procedures., Methods: Patients undergoing CIED procedures underwent a PECs I block (15 cc of 1% lidocaine/0.25% bupivacaine) injected between the pectoralis major and minor muscles guided by ultrasound placed in the device pocket, or PECs II block, which included a second injection (15 cc) between pectoralis minor and serratus anterior muscles. Postoperatively, pain was assessed on a numeric scale (0-10) at 1, 2, 4, and 24 h, and 2 weeks after the procedure., Results: Among 20 patients (age 65 ± 16 years, 70% male, 55% with history of chronic pain), PECs I (75%) and PECs II (25%) blocks were performed. The procedures were de novo implantation (n = 17) or device revision (n = 3). The average pain score in the first 4 h was 0.4 ± 0.8 and 0.3 ± 0.6 at 24 h after the procedure. During the 24-h postoperative period, 4 patients received opioids. Two patients were discharged with opioids for pain unrelated to the procedure., Conclusions: Intraoperative PECs blocks can be feasibly performed from within an exposed pocket at the time of CIED procedures with minimal postoperative pain., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cardiac implantable electronic device (CIED) procedures can cause significant postoperative pain. Opioid use for postoperative pain is associated with risk of persistent use. The benefits of pectoral nerve (PECs) blocks have been established for other chest wall surgeries, but adoption in electrophysiology has been limited., Objectives: The purpose of this study was to evaluate the efficacy of intraoperative ultrasound-guided PECs blocks performed at the time of CIED procedures by the implanting physician from within the device pocket., Methods: Patients undergoing a pectoral CIED procedure at 7 centers from 2022-2023 were included. Patients underwent intraoperative PECs blocks and subcutaneous local anesthetic vs subcutaneous local anesthetic only at the discretion of the operator. Patients were prospectively evaluated for postoperative pain., Results: Six hundred ten patients (age 67 ± 15 years old; 63% male) were enrolled. and half (n = 305) underwent PECs block. Patients who underwent PECs block were more likely to have a history of chronic pain (32% vs 11%, P <.001). PECs block was associated with lower pain scores in the 4 hours after the procedure (1.5 ± 2.1 vs 4.5 ± 2.5, P <.001). Pain scores were not different after 24 hours (2.8 ± 1.7 vs 3.1 ± 2.2) and 2 weeks (0.9 ± 1.4 vs 0.9 ± 1.2). PECs block patients were less likely to receive inpatient opioids (10% vs 48%, P <.001) and to be discharged with an opioid prescription (15% vs 59%, P <.001). In multivariable linear regression, PECs block (P <.001), age (P = .002), and absence of chronic pain (P = .009) were associated with lower acute postoperative pain., Conclusion: Intraoperative PECs block can reduce postoperative pain and opioid use. This procedure can be readily performed by the implanting physician from within the device pocket., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The importance of nonpulmonary vein (PV) triggers for the initiation/recurrence of atrial fibrillation (AF) is well established., Objectives: This study sought to assess the incremental benefit of provocative maneuvers for identifying non-PV triggers., Methods: We included consecutive patients undergoing first-time AF ablation between 2020 and 2022. The provocation protocol included step 1, identification of spontaneous non-PV triggers after cardioversion of AF and/or during sinus rhythm; step 2, isoproterenol infusion (3, 6, 12, and 20-30 μg/min); and step 3, atrial burst pacing to induce AF followed by cardioversion during residual or low-dose isoproterenol infusion or induce focal atrial tachycardia. Non-PV triggers were defined as non-PV ectopic beats triggering AF or sustained focal atrial tachycardia., Results: Of 1,372 patients included, 883 (64.4%) underwent the complete stepwise provocation protocol with isoproterenol infusion and burst pacing, 334 (24.3%) isoproterenol infusion only, 77 (5.6%) burst pacing only, and 78 (5.7%) no provocative maneuvers (only step 1). Overall, 161 non-PV triggers were found in 135 (9.8%) patients. Of these, 51 (31.7%) non-PV triggers occurred spontaneously, and the remaining 110 (68.3%) required provocative maneuvers for induction. Among those receiving the complete stepwise provocation protocol, there was a 2.2-fold increase in the number of patients with non-PV triggers after isoproterenol infusion, and the addition of burst pacing after isoproterenol infusion led to a total increase of 3.6-fold with the complete stepwise provocation protocol., Conclusions: The majority of non-PV triggers require provocative maneuvers for induction. A stepwise provocation protocol consisting of isoproterenol infusion followed by burst pacing identifies a 3.6-fold higher number of patients with non-PV triggers., Competing Interests: Funding Support and Author Disclosures This work was supported by the Leducq Foundation FANTASY Network and the Richard T and Angela Clark Innovation Fund in Cardiovascular Medicine. Dr Marchlinski serves as a consultant for Abbott Medical, Biosense Webster, and Medtronic Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Epicardial (Epi) access is commonly required during ventricular tachycardia ablation. Conventional Epi (ConvEpi) access targets a "dry" pericardial space presenting technical challenges and risk of complications. Recently, intentional puncture of coronary venous branches with Epi carbon dioxide insufflation (EpiCO 2 ) has been described as a technique to improve Epi access. The safety of this technique relative to conventional methods remains unproven., Objectives: The authors sought to compare the feasibility and safety of EpiCO 2 to ConvEpi access., Methods: All patients at a high-volume center undergoing Epi access between January 2021 and December 2023 were included and grouped according to ConvEpi or EpiCO 2 approach. Access technique was according to the discretion of the operator., Results: Epi access was attempted in 153 cases by 17 different operators (80 ConvEpi vs 73 EpiCO 2 ). There was no difference in success rate whether the ConvEpi or EpiCO 2 approach was used (76 [95%] cases vs 67 [91.8%] cases; P = 0.4). Total Epi access time was shorter in the ConvEpi group compared with the EpiCO 2 group (16.3 ± 11.6 minutes vs 26.9 ± 12.7 minutes; P < 0.001), though the total procedure duration was similar. Major Epi access-related complications occurred in only the ConvEpi group (6 [7.5%] ConvEpi vs 0 [0%] EpiCo 2 ; P = 0.02). Bleeding ≥80 mL was more frequently observed following ConvEpi access (14 [17.5%] cases vs 4 [5.5%] cases; P = 0.02). After adjusting for age, repeat Epi access, and antithrombotic therapy, EpiCO 2 was associated with a reduction in bleeding ≥80 mL (OR: 0.27; 95% CI: 0.08-0.89; P = 0.03)., Conclusions: EpiCO 2 access is associated with lower rates of major complication and bleeding when compared with ConvEpi access., Competing Interests: Funding Support and Author Disclosures Drs Oraii, Marchlinski, and Hyman are supported by the Leducq Foundation (TNE FANTASY 19CV03). Dr Chaumont also acknowledges the “Fédération Française de Cardiologie,” the “Fondation Charles Nicolle-Normandie,” the “GSC G4,” the “Working Group of Pacing and Electrophysiology of the French Society of Cardiology,” and the “Philippe Foundation.” Dr Hyman has been a consultant for Asahi Intecc, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. All rights reserved.)

Background: Although the epicardial predominance of substrate abnormalities has been well demonstrated in early stages of arrhythmogenic right ventricular cardiomyopathy (ARVC), endocardial (ENDO) ablation may suffice to eliminate ventricular tachycardia (VT) in some patients., Objectives: This study aimed to report the long-term outcomes of ENDO-only ablation in ARVC patients and factors that predict VT-free survival., Methods: We included consecutive patients with Task Force Criteria diagnosis of ARVC undergoing a first ENDO-only VT ablation between 1998 and 2020. Ablation was predominantly guided by activation/entrainment mapping for mappable VTs and pace mapping/targeting abnormal electrograms for unmappable VTs. The primary endpoint was freedom from any recurrent sustained VT after the last ENDO-only ablation., Results: Seventy-four ARVC patients underwent ENDO-only VT ablation. VT noninducibility was achieved in 49 (66%) patients. During median follow-up of 6.6 years (Q1-Q3: 3.4-11.2 years), 40 (54.1%) patients remained free from any VT recurrence with rare VT ≤2 episodes in additional 12.2%. Among patients with noninducibility, VT-free survival was 75.5% during long-term follow-up. In multivariable analysis, >45 y of age at diagnosis (HR: 0.41; 95% CI: 0.17-0.98) and VT noninducibility (HR: 0.36; 95% CI: 0.16-0.80) were predictors of VT-free survival., Conclusions: Long-term VT-free survival can be achieved in over half of ARVC patients following ENDO-only VT ablation, increasing to over 75% if VT noninducibility is achieved. Our results support consideration of a stepwise ENDO-only approach before proceeding to epicardial ablation if VT noninducibility can be achieved particularly in older patients., Competing Interests: Funding Support and Author Disclosures This work was supported by the Winkelman Family Fund in Cardiovascular Innovation, Katherine J. Miller EP Research Fund, Bogle Family Fund in Cardiac Electrophysiology, and F. Harlan Batrus EP Research Fund. Dr Chaumont acknowledges the Fédération Française de Cardiologie, Fondation Charles Nicolle-Normandie, GSC G4, Working Group of Pacing and Electrophysiology of the French Society of Cardiology, and Philippe Foundation. Dr Nazarian has served as a consultant for and received research funding from Biosense Webster Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures Dr Hyman is a consultant for Asahi Intecc, Inc. All other authors have no conflicts of interest to disclose.

Introduction: Identifying the origin of nonpulmonary vein atrial fibrillation (AF) triggers (NPVTs) after pulmonary vein isolation (PVI) can be challenging. We aimed to determine if noninvasive electrocardiographic imaging (ECGi) could localize pacing from common NPVT sites. ECGi combines measured body surface potentials with heart-torso geometry acquired from computed tomography (CT) to generate an activation map., Methods: In 12 patients with AF undergoing first time ablation, the ECGi vest was fitted for preprocedural CT scan and worn during the procedure. After PVI, we performed steady-state pacing from 15 typical anatomic NPVT sites at a cycle length of 700-800 ms. We co-registered the invasive anatomic map with the CT-based ECGi epicardial activation map to compare ECGi predicted to true pacing origin., Results: In the study cohort (67% male, 58% persistent AF, and 67% with left atrial dilation), 148 (82%) pacing sites had both capture and adequate anatomy acquired from the three-dimensional mapping system to co-register with ECGi activation map. Median distance between true pacing sites and point of earliest epicardial activation derived from the ECGi maps for all sites was 17 mm (interquartile range, 10-22 mm). Assuming paced sites treated as regions with a radius of 2.5 cm, the earliest activation site on ECGi map falls within the region with 94% accuracy., Conclusion: ECGi can approximate the origin of paced beats from common NPVT sites to within a median distance of 17 mm. A rapidly identified region may then be the focus of more detailed catheter-based mapping techniques to facilitate successful localization and ablation of NPVTs., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: Targeting non-pulmonary vein triggers (NPVTs) after pulmonary vein isolation may reduce atrial fibrillation (AF) recurrence. Isoproterenol infusion and cardioversion of spontaneous or induced AF can provoke NPVTs but typically require vasopressor support and increased procedural time., Objective: The purpose of this study was to identify risk factors for the presence of NPVTs and create a risk score to identify higher-risk subgroups., Methods: Using the AF ablation registry at the Hospital of the University of Pennsylvania, we included consecutive patients who underwent AF ablation between January 2021 and December 2022. We excluded patients who did not receive NPVT provocation testing after failing to demonstrate spontaneous NPVTs. NPVTs were defined as non-pulmonary vein ectopic beats triggering AF or focal atrial tachycardia. We used risk factors associated with NPVTs with P <.1 in multivariable logistic regression model to create a risk score in a randomly split derivation set (80%) and tested its predictive accuracy in the validation set (20%)., Results: In 1530 AF ablations included, NPVTs were observed in 235 (15.4%). In the derivation set, female sex (odds ratio [OR] 1.40; 95% confidence interval [CI] 0.96-2.03; P = .080), sinus node dysfunction (OR 1.67; 95% CI 0.98-2.87; P = .060), previous AF ablation (OR 2.50; 95% CI 1.70-3.65; P <.001), and left atrial scar (OR 2.90; 95% CI 1.94-4.36; P <.001) were risk factors associated with NPVTs. The risk score created from these risk factors (PRE 2 SSS 2 score; [PRE]vious ablation: 2 points, female [S]ex: 1 point, [S]inus node dysfunction: 1 point, left atrial [S]car: 2 points) had good predictive accuracy in the validation cohort (area under the receiver operating characteristic curve 0.728; 95% CI 0.648-0.807)., Conclusion: A risk score incorporating predictors for NPVTs may allow provocation of triggers to be performed in patients with greatest expected yield., Competing Interests: Disclosures Dr Marchlinski has served as consultant for Abbott Medical, Biosense Webster, Biotronik, and Medtronic Inc. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Substantial data support a heritable basis for supraventricular tachycardias, but the genetic determinants and molecular mechanisms of these arrhythmias are poorly understood. We sought to identify genetic loci associated with atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular accessory pathways or atrioventricular reciprocating tachycardia (AVAPs/AVRT)., Methods: We performed multiancestry meta-analyses of genome-wide association studies to identify genetic loci for AVNRT (4 studies) and AVAP/AVRT (7 studies). We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and examining prior genome-wide association studies., Results: Analyses comprised 2384 AVNRT cases and 106 489 referents, and 2811 AVAP/AVRT cases and 1,483 093 referents. We identified 2 significant loci for AVNRT, which implicate NKX2-5 and TTN as disease susceptibility genes. A transcriptome-wide association analysis supported an association between reduced predicted cardiac expression of NKX2-5 and AVNRT. We identified 3 significant loci for AVAP/AVRT, which implicate SCN5A , SCN10A , and TTN/CCDC141 . Variant associations at several loci have been previously reported for cardiac phenotypes, including atrial fibrillation, stroke, Brugada syndrome, and electrocardiographic intervals., Conclusions: Our findings highlight gene regions associated with ion channel function (AVAP/AVRT), as well as cardiac development and the sarcomere (AVAP/AVRT and AVNRT) as important potential effectors of supraventricular tachycardia susceptibility., Competing Interests: Disclosures Dr Lubitz is a full-time employee of Novartis as of July 2022. Previously, Dr Lubitz received research support from Bristol Myers Squibb/Pfizer, Bayer AG, Boehringer Ingelheim, Fitbit, IBM, Medtronic, and Premier, Inc, and consulted for Bristol Myers Squibb/Pfizer, Bayer AG, Blackstone Life Sciences, and Invitae. Dr Ellinor receives research support from Bayer AG, IBM, and Bristol Myers Squibb/Pfizer and has consulted for Novartis, MyoKardia, and Bayer AG. Dr Damrauer receives research support for RenalytixAI and has consulted for Calico Labs. Dr Svendsen is a member of Medtronic advisory boards and has received speaker honoraria and research grants from Medtronic outside this work. Dr Cutler has consulted for Janssen Scientific. Dr Roselli is supported by a grant from Bayer AG to the Broad Institute focused on the development of therapeutics for cardiovascular disease. The other authors report no conflicts.

Background: There is growing interest in the possibility of discontinuing oral anticoagulation following successful catheter ablation of atrial fibrillation (AF). However, it remains unknown whether patients can accurately detect arrhythmia recurrences following ablation. We therefore sought to characterize the accuracy of pulse checking and arrhythmia symptoms for the identification of AF following ablation., Methods: This prospective cohort study included patients at the Hospital of the University of Pennsylvania with an insertable cardiac monitor (ICM) treated with catheter ablation for AF who recorded the results from minimum twice daily pulse checks and additionally with arrhythmia symptoms into a diary for 2 months following their procedure. Accuracy of this self-assessment protocol was determined by comparison to ICM-detected AF., Results: A total of 55 patients (age 69 ± 8 years, 30 (55%) male, CHA 2 DS 2 VASc score 3.2 ± 1. 5) were included. Patients recorded a total of 5911 pulse checks, and there were 280 episodes of ICM-documented AF among 26 patients with an average duration of 2.5 ± 3.3 h. Among 362 episodes of patient-suspected AF, 134 correlated with ICM-identified AF (37% true positive rate). Of the 5549 pulse checks that did not identify AF, 196 correlated with ICM-identified AF (4% false negative rate). Twice daily pulse checking had a sensitivity of 47% and a specificity of 96% for identifying each episode of AF., Conclusions: Our data indicate that a strategy of pulse checks and symptom assessment is insufficient to identify all episodes of AF in many patients following catheter ablation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The use of a multi-electrode Optrell mapping catheter during ventricular tachycardia (VT) or premature ventricular complex (PVC) ablation procedures has not been widely reported., Objectives: We aim to describe the feasibility and safety of using the Optrell multipolar mapping catheter (MPMC) to guide catheter ablation of VT and PVCs., Methods: We conducted a single-center, retrospective evaluation of patients who underwent VT or PVC ablation between June and November 2022 utilizing the MPMC., Results: A total of 20 patients met the inclusion criteria (13 VT and 7 PVC ablations, 80% male, 61 ± 15 years). High-density mapping was performed in the VT procedures with median 2753 points [IQR 1471-17,024] collected in the endocardium and 12,830 points [IQR 2319-30,010] in the epicardium. Operators noted challenges in manipulation of the MPMC in trabeculated endocardial regions or near valve apparatus. Late potentials (LPs) were detected in 11 cases, 7 of which had evidence of isochronal crowding demonstrated during late annotation mapping. Two patients who also underwent entrainment mapping had critical circuitry confirmed in regions of isochronal crowding. In the PVC group, high-density voltage and activation mapping was performed with a median 1058 points [IQR 534-3582] collected in the endocardium., Conclusions: This novel MPMC can be used safely and effectively to create high-density maps in LV endocardium or epicardium. Limitations of the catheter include a longer wait time for matrix formation prior to starting point collection and challenges in manipulation in certain regions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Long-term rhythm monitoring to detect atrial fibrillation (AF) following a cryptogenic stroke (CS) is well established. However, the burden of organized atrial arrhythmias in this population is not well defined., Objective: The purpose of this study was to assess the incidence and risk factors for organized atrial arrhythmias in patients with CS., Methods: We evaluated all patients with CS who received an insertable cardiac monitor (ICM) between October 2014 and April 2020. All ICM transmissions categorized as AF, tachycardia, or bradycardia were reviewed. We evaluated the time to detection of organized AF and the combination of either organized atrial arrhythmia or AF., Results: A total of 195 CS patients with ICMs were included (51% men; mean age 66 ± 12 years; mean CHA 2 DS 2 -VAS C score 4.6). Over mean follow-up of 18.9 ± 11.2 months, organized atrial arrhythmias lasting ≥30 seconds were detected in 45 patients (23%), of whom 62% did not have AF. Seventeen patients had both organized atrial arrhythmia and AF, and another 21 patients had AF only. Compared to those with normal left atrial size, patients with left atrial enlargement had a higher adjusted risk for development of atrial arrhythmias (mild left atrial enlargement: hazard ratio 1.99; 95% confidence interval 1.06-3.75; moderate/severe left atrial enlargement: hazard ratio 3.06; 95% confidence interval 1.58-5.92)., Conclusion: Organized atrial arrhythmias lasting ≥30 seconds are detected in nearly one-fourth of CS patients. Two-thirds of these patients did not have AF. Further studies are required to evaluate the impact of organized atrial arrhythmias on recurrent stroke risk., (© 2023 Heart Rhythm Society. Published by Elsevier Inc.)

Background: Entrainment and pace mapping are used to identify critical components (CCs) of ventricular tachycardia (VT) circuits. In patients with dense myocardial scarring, VT circuits may elude capture at standard high pacing outputs (up to 10 mA at a 2-millisecond pulse width)., Objectives: The purpose of this study was to assess the utility of very high-output pacing (V-HOP, 50 mA at 2 milliseconds) for identifying CCs of VT circuits after standard high pacing output failed to elicit capture in densely scarred myocardial tissue., Methods: Our standard VT ablation approach included electroanatomic mapping for substrate characterization and entrainment and/or pace mapping to identify CCs of VT circuits. Patients that required V-HOP to capture sites of interest comprised the study cohort. Ablation endpoints were VT termination and noninducibility., Results: Twenty-five patients (71 ± 10 years of age, all males) undergoing 26 VT ablations met the inclusion criteria. The mean left ventricular ejection fraction was 30% ± 14%, and 85% had ischemic cardiomyopathy. V-HOP was used to successfully entrain VT in 17 patients, yielding central isthmus sites in 10 and entrance/exit sites in 4. VT terminated with radiofrequency ablation at these sites in 15 patients. In 9 patients, V-HOP identified scar locations with a delayed exit. Acute procedural success was achieved in 24 patients without any adverse events. Over a follow-up period of 16 ± 21 months, 2 patients experienced VT recurrence requiring repeat ablation during which the same location was targeted successfully in 1 patient., Conclusions: In VT patients with a dense scar that is traditionally inexcitable, V-HOP can identify CCs of the re-entrant circuit and guide successful ablation., Competing Interests: Funding Support and Author Disclosures This study was supported by the Bogle Family Fund in Cardiac Electrophysiology and the Katherine J. Miller EP Research Fund. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Targeting nonpulmonary vein triggers (NPVTs) of atrial fibrillation (AF) after pulmonary vein isolation can be challenging. NPVTs are often single ectopic beats with a surface P-wave obscured by a QRS or T-wave., Objectives: The goal of this study was to construct an algorithm to regionalize the site of origin of NPVTs using only intracardiac bipolar electrograms from 2 linear decapolar catheters positioned in the posterolateral right atrium (along the crista terminalis with the distal bipole pair in the superior vena cava) and in the proximal coronary sinus (CS)., Methods: After pulmonary vein isolation in 42 patients with AF, pacing from 15 typical anatomic NPVT sites was conducted. For each pacing site, the electrogram activation sequence was analyzed from the CS catheter (simultaneous/chevron/inverse chevron/distal-proximal/proximal-distal) and activation time (ie, CSCTAT) between the earliest electrograms from the 2 decapolar catheters was measured referencing the earliest CS electrogram; a negative CSCTAT value indicates the crista terminalis catheter electrogram was earlier, and a positive CSCTAT value indicates the CS catheter electrogram was earlier. A regionalization algorithm with high predictive value was defined and tested in a validation cohort with AF NPVTs localized with electroanatomic mapping., Results: In the study patient cohort (71% male; 43% with persistent AF, 52% with left atrial dilation), the algorithm grouped with high precision (positive predictive value 81%-99%, specificity 94%-100%, and sensitivity 30%-94%) the 15 distinct pacing sites into 9 clinically useful regions. Algorithm testing in a 98 patient validation cohort showed predictive accuracy of 91%., Conclusions: An algorithm defined by the activation sequence and timing of electrograms from 2 linear multipolar catheters provided accurate regionalization of AF NPVTs to guide focused detailed mapping., Competing Interests: Funding Support and Author Disclosures This work was supported by the Richard T. and Angela Clark Innovation Fund in Cardiovascular Medicine, the Mark S. Marchlinski EP Research and Education Fund, the Winkelman Family Fund in Cardiovascular Innovation, and the Leducq Foundation Fantasy Network. Dr Marchlinski has served as consultant for Abbott Medical, Biosense Webster, Biotronik, Boston Scientific, and Medtronic Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Although efficacious, catheter ablation (CA) of ventricular arrhythmias (VAs) originating from left ventricular (LV) papillary muscles (PAPs) has the potential to affect mitral valve (MV) function., Objectives: The aim of this study was to determine whether lesions delivered during CA of VAs from LV PAPs affected MV function., Methods: Consecutive patients undergoing CA of LV PAP VAs from January 2015 to December 2020 in whom both preprocedural and postprocedural transthoracic echocardiography was performed were included. Radiofrequency ablation was performed with an irrigated-tip catheter with or without contact force sensing and intracardiac echocardiographic guidance. The PAPs were delineated into segments: tip, body, and base. Pre- and post-CA transthoracic echocardiograms were reviewed to assess MV regurgitation, which was graded 0 (none), 1 (mild), 2 (moderate), or 3 (severe). A change of ≥2 grades from baseline was considered significant., Results: A total of 103 patients (mean age 63 ± 15 years, 78% men) were included. VAs were ablated from the anterolateral PAP in 35% (n = 36), posteromedial PAP in 55% (n = 57), and both PAPs in 10% (n = 10). Lesion distribution was as follows: PAP tip in 52 (50%), PAP base in 34 (33%), PAP body in 13 (13%), and entire PAP in 4 (4%). The mean number of lesions delivered was 16 ± 13 (median 14). Of 103 patients, 102 (99%) showed no change in MV function., Conclusions: Using intracardiac echocardiographic guidance, lesions can be safely delivered on various aspects of this structure without adverse impact on MV function., Competing Interests: Funding Support and Author Disclosures This work was supported by the Richard T and Angela Clark Innovation Fund in Cardiovascular Medicine. Dr Lin has received a speaker honorarium from Abbott. Dr Frankel is a scientific advisory board member for Biosense Webster. Dr Santangeli has received a research grant from Biosense Webster; and is an advisory board member for Biosense Webster and Abbott. Dr Nazarian has received a research grant from Biosense Webster. Dr Hyman has given educational lectures for Biosense Webster. Dr Epstein is an advisory board and events committee member for Abbott; and is an events committee member for Boston Scientific and Medtronic. Dr Callans is an advisory board member for Abbott and Biosense Webster; and has received honoraria for lectures from Biosense Webster. Dr Marchlinski has received a lecture honorarium from and is a scientific advisory board member for Abbott; and is a scientific advisory board member for and has received a lecture honorarium and research support from Biosense Wesbet. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Guidelines recommend that initial trial of a "pill-in-the-pocket" (PIP) Class 1C antiarrhythmic drug (AAD) for cardioversion of atrial fibrillation (AF) be performed in a monitored setting because of the potential for adverse reactions., Objectives: This study sought to characterize real-world, contemporary use of the PIP approach, including the setting of initiation and incidence of adverse events., Methods: This retrospective cohort study included all patients at the Hospital of the University of Pennsylvania treated with a PIP approach for AF between 2007 and 2020., Results: A total of 273 patients (age 56 ± 13 years; 182 [67%] male; CHA 2 DS 2 VASc score 1.1 ± 1.2) took a first dose of PIP AAD. Flecainide was used in 151 (55%) and propafenone in 122 (45%). The first dose of PIP AAD was taken in a monitored setting in 167 (62%). Significant adverse events occurred in 7 patients (3%), 2 of whom had taken the dose in a monitored setting. Significant adverse events included unexplained syncope (1 of 7), symptomatic bradycardia/hypotension (4 of 7), and 1:1 atrial flutter (2 of 7). All occurred in patients taking 300 mg of flecainide (n = 4) or 600 mg of propafenone (n = 3). Electrical cardioversion was performed in 29 (11%) patients because of failure of the AAD to terminate AF. One patient required intravenous fluids and vasopressors for 2 hours because of persistent hypotension and bradycardia. Two patients required permanent pacemakers for bradycardia. The remaining patients required no intervention., Conclusions: Our data support the current recommendation to initiate PIP AAD in a monitored setting because of rare significant adverse reactions that can require urgent intervention., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Pharmacologic activation of branched-chain amino acid (BCAA) catabolism is protective in models of heart failure (HF). How protection occurs remains unclear, although a causative block in cardiac BCAA oxidation is widely assumed. Here, we use in vivo isotope infusions to show that cardiac BCAA oxidation in fact increases, rather than decreases, in HF. Moreover, cardiac-specific activation of BCAA oxidation does not protect from HF even though systemic activation does. Lowering plasma and cardiac BCAAs also fails to confer significant protection, suggesting alternative mechanisms of protection. Surprisingly, activation of BCAA catabolism lowers blood pressure (BP), a known cardioprotective mechanism. BP lowering occurred independently of nitric oxide and reflected vascular resistance to adrenergic constriction. Mendelian randomization studies revealed that elevated plasma BCAAs portend higher BP in humans. Together, these data indicate that BCAA oxidation lowers vascular resistance, perhaps in part explaining cardioprotection in HF that is not mediated directly in cardiomyocytes., Competing Interests: Declaration of interests Z.A. received consulting fees from Pfizer. J.W.E. received consulting fees, unassociated with this work, from Jannsen Pharmaceuticals and Mitobridge, Inc. J.D.R. is an advisor and stockholder in Colorado Research Partners, Empress Therapeutics, L.E.A.F. Pharmaceuticals, Bantam Pharmaceuticals, Barer Institute, and Rafael Holdings; a founder, director, and stockholder of Farber Partners, Serien Therapeutics, and Sofro Pharmaceuticals; a founder and stockholder in Toran Therapeutics; inventor of patents held by Princeton University; and a director of the Princeton University-PKU Shenzhen collaboration., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability ([Formula: see text]) was estimated from 0.13 to 0.28 (s.e., 0.10-0.13) in European ancestries, with 35-74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5-4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] was estimated from 0.03 to 0.33 (s.e., 0.09-0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The right ventricle (RV) is uncommonly implicated in postinfarction ventricular tachycardia (VT). The prevalence and features of the RV substrate participating in postinfarction VT are undefined., Objectives: The purpose of this study was to characterize critical right ventricular substrate (CRVS) involvement in patients with postinfarction VT., Methods: We retrospectively reviewed 1279 patients with postinfarction VT undergoing catheter ablation at our center from January 2000 through May 2020. Cases with CRVS defined by conclusive demonstration of participation in VT with activation, entrainment, and/or pacemapping during sinus rhythm were identified., Results: CRVS was identified in 27 of 1279 patients (2.1%): age 65 ± 13 years, 96% male, median left ventricular (LV) ejection fraction 25%, and 93% with left bundle branch block (LBBB) morphology VT. CRVS was identified by RV activation and/or entrainment mapping (n = 19) or by the presence of low-voltage abnormal electrograms with excellent pacemap for the targeted VT and noninducibility after ablation (n = 8). VT termination during RV ablation occurred in 15 patients. After median follow-up of 20 months (interquartile range 9-53 months) and median of 2 procedures (interquartile range 1-3), 22 of 27 patients (80%) had no VT recurrence and 11 (41%) died., Conclusion: The RV contains critical substrate elements of postinfarction VT in at least 2.1% of cases. RV mapping should be considered in cases in which LV mapping fails to demonstrate adequate targets, particularly in patients with LBBB morphology VT., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: This study sought to explore whether prolonged duration (PD) radiofrequency ablation (RFA) from adjacent endocardial locations can improve catheter ablation (CA) outcomes of left ventricular summit (LVS) ventricular arrhythmias (Vas)., Background: CA of VAs originating from the LVS region can be challenging., Methods: Patients undergoing CA of LVS VAs from January 1, 2015, to December 31, 2019, were included. Standard RFA approach involved incremental power titration (20-45 W) over 60-120 seconds with irrigated tip catheter to achieve 10%-12% impedance drop. Prolonged duration RFA involved similar power titration; however, lesion application was extended beyond 120 seconds (maximum 5 minutes). Lesions were confined to lowest aspect of aortic cusps and/or subvalvular LV outflow tract region (≤0.5 cm from the valve). Procedural success was defined as suppression of VA ≥30 minutes postablation and clinical success as no arrhythmia symptoms on follow-up and >80% reduction of VA burden on postprocedure monitor., Results: This study included 102 patients (60±14 years old, 62% male): standard RFA in 80 and PD RFA in 38. Procedural success was achieved in 54 patients with standard and 32 patients with PD RFA (68% vs 84%; P = 0.05). Short-term clinical success was achieved in 48 patients (60%) with standard and 30 patients (79%) with PD RFA (P = 0.04). Two pericardial effusions occurred (1 in each group) and no steam pops were noted. Patients in whom standard RFA was successful were more likely to have R/S ratio >1 or absence of qS in lead I (odds ratio: 3.35; 95% CI: 1.20-9.35; P = 0.03)., Conclusions: Prolonged duration RFA from adjacent endocardial locations is a safe and effective technique for successfully targeting challenging LVS VAs that fail standard RFA., Competing Interests: Funding Support and Author Disclosures Supported by the Richard T. and Angela Clark Innovation Fund in Cardiovascular Medicine. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The type 1 electrocardiographic (ECG) pattern diagnostic of Brugada syndrome (BrS) can be dynamic. Limited studies have rigorously evaluated the temporal stability of the Brugada ECG pattern., Objective: We sought to evaluate fluctuations of the Brugada pattern in serial resting ECGs from BrS patients managed within a large health care system., Methods: In our cohort of BrS patients with at least 2 standard, resting ECGs recorded on separate clinical encounters, we evaluated serial changes in the Brugada pattern and categorized patients into 1 of 3 groups: dynamic was defined as the presence of both type 1 and non-type 1 patterns in available ECGs; the provoked-only group was defined as having a non-type 1 Brugada pattern across resting ECGs; and the persistent group was defined as having a type 1 pattern on all ECGs. We also evaluated the clinical risk in this cohort according to the Shanghai risk score., Results: In 72 patients with BrS (mean age 46 ± 15 years, 69% male), 828 standard, resting ECGs were recorded over a median duration of 30.2 (interquartile range 6.3-68.1) months. The dynamic group comprised 50 (69% of the cohort) patients, the provoked-only group consisted of 17 patients (24% of the cohort), and the persistent group included 5 patients. No significant differences were detected in the total number of ECGs evaluated during the follow-up period between any of the groups. Only sinus node dysfunction and a prior cardiac arrest were associated with the persistent type 1 group. The majority of patients had a low annualized risk of lethal arrhythmic events., Conclusion: Most BrS patients have a dynamic Brugada pattern noted on longitudinal, resting ECGs. Expert consensus statements should provide clarity on the frequency of obtaining resting ECGs in patients suspected of having BrS during follow-up., (© 2022 Heart Rhythm Society. Published by Elsevier Inc.)

Background: Severe endoscopically detected esophageal thermal lesions (EDELs) have been associated with higher risk of progression to atrio-esophageal fistula (AEF) following radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). We sought to evaluate safety and feasibility of active esophageal cooling using the Attune Medical Esophageal Heat Transfer Device (EnsoETM) to limit frequency or severity of EDELs., Objective: We sought To evaluate safety and feasibility of active esophageal cooling using the Attune Medical Esophageal Heat Transfer Device (EnsoETM) to limit frequency or severity of EDELs METHODS: Consecutive patients undergoing first-time RFCA were randomized in a 1:1 fashion to esophageal cooling (device group) or standard temperature monitoring (control group). Ablation on the posterior wall was performed with a maximum power of 30W for up to 20s. All patients underwent EGD within 48 h. Endoscopy findings were classified as 1, erythema-mild injury; 2, superficial ulceration-moderate injury; 3, deep ulceration-significant injury; and 4, fistula/perforation. Severe EDELs were defined as grade 3 or 4 lesions., Results: Forty-four patients completed the study (22 device group, 22 control group). Adjunctive posterior wall isolation was performed more frequently in the device group (11/22, 50% vs. 4/22, 18%). EDELs were detected in 5/22 (23%) control group patients, with mild or moderate injury in 2/5 patients (40%) and severe thermal injury in 3/5 patients (60%). In the device group, EDELs were detected in 8/22 (36%) patients, with mild or moderate injury in 7/8 (87%) patients and severe thermal injury in 1/8 (12%) patients. There was no acute perforation or AEF during follow-up., Conclusions: Active esophageal cooling may reduce the occurrence of severe EDELs. A larger randomized study is warranted to further evaluate the benefit of this strategy., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The substrate for ventricular tachycardia (VT) in left ventricular (LV) nonischemic cardiomyopathy may be epicardial. We assessed the prevalence, location, endocardial electrograms, and VT ablation outcomes in LV nonischemic cardiomyopathy with isolated epicardial substrate., Methods: Forty-seven of 531 (9%) patients with LV nonischemic cardiomyopathy and VT demonstrated normal endocardial (>1.5 mV)/abnormal epicardial bipolar low-voltage area (LVA, <1.0 mV and signal abnormality). Abnormal endocardial unipolar LVA (≤8.3 mV) and endocardial bipolar split electrograms and predictors of ablation success were assessed., Results: Epicardial bipolar LVA (27.3 cm 2 [interquartile range, 15.8-50.0]) localized to basal (40), mid (8), and apical (3) LV with basal inferolateral LV most common (28/47, 60%). Of 44 endocardial maps available, 40 (91%) had endocardial unipolar LVA (24.5 cm 2 [interquartile range, 9.4-68.5]) and 29 (67%) had characteristic normal amplitude endocardial split electrograms opposite the epicardial LVA. At mean of 34 months, the VT-free survival was 55% after one and 72% after multiple procedures. Greater endocardial unipolar LVA than epicardial bipolar LVA (hazard ratio, 10.66 [CI, 2.63-43.12], P =0.001) and number of inducible VTs (hazard ratio, 1.96 [CI, 1.27-3.00], P =0.002) were associated with VT recurrence., Conclusions: In patients with LV nonischemic cardiomyopathy and VT, the substrate may be confined to epicardial and commonly basal inferolateral. LV endocardial unipolar LVA and normal amplitude bipolar split electrograms identify epicardial LVA. Ablation targeting epicardial VT and substrate achieves good long-term VT-free survival. Greater endocardial unipolar than epicardial bipolar LVA and more inducible VTs predict VT recurrence.

Background: Prescription opioids are a major contributor to the ongoing epidemic of persistent opioid use (POU). The incidence of POU among opioid-naïve patients after cardiac implantable electronic device (CIED) procedures is unknown., Methods: This retrospective cohort study used data from a national administrative claims database from 2004 to 2018 of patients undergoing CIED procedures. Adult patients were included if they were opioid-naïve during the 180-day period before the procedure and did not undergo another procedure with anesthesia in the next 180 days. POU was defined by filling an additional opioid prescription >30 days after the CIED procedure., Results: Of the 143 400 patients who met the inclusion criteria, 15 316 (11%) filled an opioid prescription within 14 days of surgery. Among these patients, POU occurred in 1901 (12.4%) patients 30 to 180 days after surgery. The likelihood of developing POU was increased for patients who had a history of drug abuse (odds ratio, 1.52; P =0.005), preoperative muscle relaxant (odds ratio, 1.52; P <0.001) or benzodiazepine (odds ratio, 1.23; P =0.001) use, or opioid use in the previous 5 years (OR, 1.76; P <0.0001). POU did not differ after subcutaneous implantable cardioverter defibrillator or other CIED procedures (11.1 versus 12.4%; P =0.5). In a sensitivity analysis excluding high-risk patients who were discharged to a facility or who had a history of drug abuse or previous opioid, benzodiazepine, or muscle relaxant use, 8.9% of the remaining cohort had POU. Patients prescribed >135 mg of oral morphine equivalents had a significantly increased risk of POU., Conclusions: POU is common after CIED procedures, and 12% of patients continued to use opioids >30 days after surgery. Higher initially prescribed oral morphine equivalent doses were associated with developing POU.

Background: Interatrial septal tachycardias (IAS-ATs) following atrial fibrillation (AF) ablation or cardiac surgery are rare, and their management is challenging., Objective: The purpose of this study was to investigate the electrophysiological features and outcomes associated with catheter ablation of IAS-AT., Methods: We screened 338 patients undergoing catheter ablation of ATs following AF ablation or cardiac surgery. Diagnosis of IAS-AT was based on activation mapping and analysis of response to atrial overdrive pacing., Results: Twenty-nine patients (9%) had IAS-AT (cycle length [CL] 311 ± 104 ms); 16 (55%) had prior AF ablation procedures (median 3; range 1-5), 3 (10%) had prior surgical maze, and 12 (41%) had prior cardiac surgery (including atrial septal defect surgical repair in 5 and left atrial myxoma resection in 1). IAS substrate abnormalities were documented in all patients. Activation mapping always demonstrated a diffuse early IAS breakout with centrifugal biatrial activation, and atrial overdrive pacing showed a good postpacing interval (equal or within 25 ms of the AT CL) only at 1 or 2 anatomically opposite IAS sites in all cases. Ablation was acutely successful in 27 patients (93%) (from only the right IAS in 2, only the left IAS in 9, both IAS sides with sequential ablation in 13, and both IAS sides with bipolar ablation in 3). After median follow-up of 15 (6-52) months, 17 patients (59%) remained free from recurrent arrhythmias., Conclusion: IAS-ATs are rare and typically occur in patients with evidence of IAS substrate abnormalities and prior cardiac surgery. Catheter ablation can be challenging and may require sequential unipolar ablation or bipolar ablation., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: It remains unclear whether additional left atrial posterior wall isolation (LAPWI) beyond pulmonary vein reisolation (PVRI) is beneficial in atrial fibrillation (AF) patients undergoing repeat ablation., Objective: We sought to assess impact of LAPWI on arrhythmia outcomes in patients undergoing repeat AF ablation., Methods: All AF patients that underwent repeat ablation between January 2016 and December 2018 were included. Those undergoing PVRI only served as control, whereas those undergoing LAPWI (with or without PVRI) were the study group. Primary endpoint was freedom from atrial arrhythmias (AA) off antiarrhythmic drugs (AADs) at 1 year follow-up. Secondary endpoint was freedom from AA on/off AADs at 1 year follow-up., Results: One hundred ninety-six patients (61% paroxysmal AF, 39% persistent AF) participated; 93 underwent PVRI and 103 underwent LAPWI±PVRI. Patients in the LAPWI group were older, had more hypertension and persistent AF, and had lower rates of PV reconnection (52.4% vs 100%, P < .001). LAPWI was performed empirically in 79.6% and to target triggers in 20.4%. It was accomplished by linear lesions across the LA floor and roof alone in 65% and additional LAPW lesions in 35%. The primary and secondary endpoints were similar between patients undergoing LAPWI and those undergoing PVRI (43.7% vs 69.9%, P = .50 and 66% vs 77.4%, P = .36, respectively). There was no difference in adverse events between the 2 groups., Conclusion: LAPWI did not improve freedom from atrial arrhythmias on or off AADs at 1 year beyond PVRI in AF patients undergoing repeat ablation. Differences in patient demographics and AF type may underlie the observed lack of benefit of LAPWI, and further study is warranted., (© 2021 Heart Rhythm Society. Published by Elsevier Inc.)

Objective: To evaluate the prognosis of patients with ischemic stroke according to the timing of an atrial fibrillation (AF) diagnosis, we created an inception cohort of incident stroke events and compared the risk of death between patients with stroke with (1) sinus rhythm, (2) known AF (KAF), and (3) AF diagnosed after stroke (AFDAS)., Methods: We used the Penn AF Free study to create an inception cohort of patients with incident stroke. Mortality events were identified after linkage with the National Death Index through June 30, 2017. We also evaluated initiation of anticoagulants and antiplatelets across the study duration. Cox proportional hazards models evaluated associations between stroke subtypes and death., Results: We identified 1,489 individuals who developed an incident ischemic stroke event: 985 did not develop AF at any point during the study period, 215 had KAF before stroke, 160 had AF detected ≤6 months after stroke, and 129 had AF detected >6 months after stroke. After a median follow-up of 4.9 years (interquartile range 1.9-6.8), 686 deaths occurred. The annualized mortality rate was 8.8% in the stroke, no AF group; 12.2% in the KAF group; 15.8% in the AFDAS ≤6 months group; and 12.7% in the AFDAS >6 months group. Patients in the AFDAS ≤6 months group had the highest independent risk of all-cause mortality even after multivariable adjustment for demographics, clinical risk factors, and the use of antithrombotic therapies (hazard ratio 1.62 [1.22-2.14]). Compared to the stroke, no AF group, those with KAF had a higher mortality risk that was rendered nonsignificant after adjustment., Conclusions: The AFDAS group had the highest risk of death, which was not explained by comorbidities or use of antithrombotic therapies., (© 2021 American Academy of Neurology.)

Importance: In patients with mechanical valves in the aortic and mitral positions, percutaneous access to the left ventricle (LV) via a transfemoral approach for catheter ablation of ventricular tachycardia (VT) has been considered infeasible., Objective: To describe the outcomes of a novel percutaneous trans-right atrial (RA) access to the LV via a femoral venous approach for catheter ablation of VT in patients with mechanical aortic and mitral valves., Design, Setting, and Participants: This observational study included consecutive patients with mechanical valves in the aortic and mitral positions and recurrent monomorphic drug-refractory VT associated with an LV substrate. Percutaneous LV access was performed from a transfemoral venous route with the aid of a deflectable sheath and a radiofrequency wire by creating an iatrogenic Gerbode defect with direct puncture of the inferior and medial aspect of the RA, adjacent to the inferior-septal process of the LV (ISP-LV), under intracardiac echography guidance. Once the wire crossed to the LV, balloon dilatation of the ventriculotomy site (with a noncompliant balloon; diameter, 8 to 10 mm) was performed to facilitate passage of the sheath within the LV., Exposures: Percutaneous trans-RA access to the LV via puncture of the ISP-LV to perform catheter ablation of VT in patients with mechanical aortic and mitral valves., Main Outcomes and Measures: Feasibility and safety of a trans-RA access to the LV for catheter ablation of VT., Results: A total of 4 patients (mean [SD] age, 60 [7] years; mean [SD] LV ejection fraction, 31% [9%]) with recurrent VT associated with an LV substrate (ischemic cardiomyopathy, 3 patients; nonischemic cardiomyopathy, 1 patient) and mechanical valves in the aortic and mitral position underwent trans-RA access through the ISP-LV for catheter ablation of VT. The time to obtain LV access ranged from 60 minutes (first case) to 22 minutes (last case) (mean [SD], 36 [15] minutes). No complications associated with the access occurred. In particular, in the 3 patients with preserved atrioventricular conduction at baseline, no new conduction abnormalities were observed after the access. Complete VT noninducibility at programmed ventricular stimulation was achieved in 3 cases, and no patient had VT recurrence at a median follow-up of 14 months (range, 6-21 months)., Conclusions and Relevance: A percutaneous trans-RA access to the LV via a femoral venous approach for catheter ablation of VT in patients with mechanical aortic and mitral valves is feasible and appears safe. This novel technique may allow for catheter ablation of VT in a population of patients in whom conventional LV access via retrograde aortic or atrial transseptal routes is not possible.

Importance: Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk., Objective: To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy., Design, Setting, and Participants: This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants., Interventions: Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks., Main Outcomes and Measures: The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2-positive participants., Results: Of the 132 randomized participants (median age, 33 years [range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%]; P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%; P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, -9 to 17; vs placebo: 3 milliseconds; 95% CI, -5 to 11; P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered., Conclusions and Relevance: In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19., Trial Registration: ClinicalTrials.gov Identifier: NCT04329923.

Observational studies have shown an association between hypertension and atrial fibrillation (AF). Aggressive blood pressure management in patients with known AF reduces overall arrhythmia burden, but it remains unclear whether hypertension is causative for AF. To address this question, this study explored the relationship between genetic predictors of blood pressure and risk of AF. We secondarily explored the relationship between genetically proxied use of antihypertensive drugs and risk of AF. Two-sample Mendelian randomization was performed using an inverse-variance weighted meta-analysis with weighted median Mendelian randomization and Egger intercept tests performed as sensitivity analyses. Summary statistics for systolic blood pressure, diastolic blood pressure, and pulse pressure were obtained from the International Consortium of Blood Pressure and the UK Biobank discovery analysis and AF from the 2018 Atrial Fibrillation Genetics Consortium multiethnic genome-wide association studies. Increases in genetically proxied systolic blood pressure, diastolic blood pressure, or pulse pressure by 10 mm Hg were associated with increased odds of AF (systolic blood pressure: odds ratio [OR], 1.17 [95% CI, 1.11-1.22]; P =1×10 -11 ; diastolic blood pressure: OR, 1.25 [95% CI, 1.16-1.35]; P =3×10 -8 ; pulse pressure: OR, 1.1 [95% CI, 1.0-1.2]; P =0.05). Decreases in systolic blood pressure by 10 mm Hg estimated by genetic proxies of antihypertensive medications showed calcium channel blockers (OR, 0.66 [95% CI, 0.57-0.76]; P =8×10 -9 ) and β-blockers (OR, 0.61 [95% CI, 0.46-0.81]; P =6×10 -4 ) decreased the risk of AF. Blood pressure-increasing genetic variants were associated with increased risk of AF, consistent with a causal relationship between blood pressure and AF. These data support the concept that blood pressure reduction with calcium channel blockade or β-blockade could reduce the risk of AF.

Introduction: Data on the mechanisms of atrial arrhythmias (AAs) and outcomes of catheter ablation (CA) in lung transplantation (LT) patients are insufficient. We evaluated the electrophysiologic features and outcomes of CA of AAs in LT patients. METHODS AND RESULTS: We conducted a retrospective study of all the LT patients who underwent CA for AAs at our institution between 2004 and 2019. A total of 15 patients (43% males, age: 61 ± 10 years) with a history of LT (60% bilateral and 40% unilateral) were identified. All patients had documented organized AA on surface electrocardiogram and seven patients also had atrial fibrillation (AF; 47% with >1 clinical arrhythmia). At electrophysiological study, 19 organized AAs were documented (48% focal and 52% macro-re-entrant). Focal atrial tachycardias/flutters were targeted along the pulmonary vein (PV) anastomotic site at the left inferior PV (n = 2), ridge and carina of the left superior PV (n = 2), left atrium (LA) posterior wall (n = 3), LA roof (n = 1), and tricuspid annulus (n = 1). Macro-re-entrant AAs included cavotricuspid isthmus-dependent flutter (n = 2), incisional LA flutter (n = 4), LA roof-dependent flutter (n = 1), and mitral annular flutter (n = 3). In patients with LA mapping (n = 13), PV reconnection on the side of the LT was found in six patients (40%, all with clinically documented AF), with a mean of 2.1 ± 0.9 PVs reconnected per patient. Patients with AF underwent successful PV isolation. After a median follow-up of 19 months (range: 6-86 months), 75% of patients remained free from recurrent AAs. No procedural major complications occurred., Conclusion: In patients with prior LT, recurrent AAs are typically associated with substrate surrounding the surgical anastomotic lines and/or chronically reconnected PVs. CA of AAs in this population is safe and effective to achieve long-term arrhythmia control., (© 2020 Wiley Periodicals LLC.)

Background: First pass pulmonary vein isolation (PVI) is associated with durable isolation and reduced recurrence of atrial fibrillation (AF)., Objective: We sought to investigate the relationship between left atrial electrogram voltage using multielectrode fast automated mapping (ME-FAM) and first pass isolation with radiofrequency ablation., Methods: We included consecutive patients (pts) undergoing first time ablation for paroxysmal AF (pAF), and compared the voltage characteristics between patients with and without first pass isolation. Left atrium (LA) adjacent to PVs was divided into 6 regions, and mean voltages obtained with ME-FAM (Pentaray, Biosense Webster) in each region and compared. LA electrograms with marked low voltage (<0.5 mV) were identified and the voltage characteristics at the site of difficult isolation was compared to the voltage in adjacent region., Results: Twenty consecutive patients (10 with first pass and 10 without) with a mean age of 63.3 ± 6.2 years, 65% males, were studied. Difficult isolation occurred on the right PVs in eight pts and left PVs in three pts. The mean voltage in pts without first pass isolation was lower in all 6 regions; posterior wall (1.93 ± 1.46 versus 2.99 ± 2.19; p < 0.001), roof (1.83 ± 2.29 versus 2.47 ± 1.99; p < 0.001), LA-LPV posterior (1.85 ± 3.09 versus 2.99 ± 2.19, p < 0.001), LA-LPV ridge (1.42 ± 1.04 versus 1.91 ± 1.61; p < 0.001), LA-RPV posterior (1.51 ± 1.11 versus 2.30 ± 1.77, p < 0.001) and LA-RPV septum (1.55 ± 1.23 versus 2.31 ± 1.40, p < 0.001). Patients without first pass isolation also had a larger percentage of signal with an amplitude of <0.5 mV for each of the six regions (12.8% versus 7.5%). In addition, the mean voltage at the site of difficult isolation was lower at 8 out of 11 sites compared to mean voltage for remaining electrograms in that region., Conclusion: In patients undergoing PVI for paroxysmal AF, failure in first pass isolation was associated with lower global LA voltage, more marked low amplitude signal (<0.5 mV) and lower local signal voltage at the site with difficult isolation. The results suggest that a greater degree of global and segmental fibrosis may play a role in ease of PV isolation with radiofrequency energy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Garg, Pothineni, Daw, Hyman, Arkles, Tschabrunn, Santangeli and Marchlinski.)

Background: Randomized trials evaluating cardiac resynchronization therapy (CRT) have excluded patients with a pre-existing implantable cardioverter-defibrillator (ICD). The association of CRT upgrade with clinical outcomes in patients with a pre-existing ICD is unclear., Objective: The purpose of this study was to examine a CRT-eligible population to evaluate clinical outcomes associated with CRT upgrade compared to patients who did not undergo CRT., Methods: Using the National Cardiovascular Data Registry (NCDR) ICD Registry between April 2010 and December 2014, we created a hierarchical logistic regression model to identify predictors of CRT upgrade in a CRT-eligible ICD population. In the subpopulation of patients with Medicare-linked claims data, differential outcomes were determined with censoring at 3 years. The primary endpoint of this study was all-cause mortality, with secondary endpoints of rates of hospitalization and procedural complications., Results: CRT upgrade was performed in 75.5% of CRT-eligible patients with pre-existing ICD (n = 15,803). Presence of left bundle branch block conduction was the strongest predictor of CRT upgrade (odds ratio [OR] 4.56; 95% confidence interval [CI] 4.08-5.11; P <.0001). In both unadjusted and adjusted analyses, CRT upgrade was associated with a reduction in mortality at 3 years (unadjusted hazard ratio [HR] 0.80; 95% CI 0.70-0.92; P = .001; adjusted HR 0.84; 95% CI 0.72-0.98; P = .02, respectively). Compared to patients with ICD generator replacement only, patients who underwent CRT upgrade experienced no different 3-year rates of hospitalization (adjusted HR 1.01; 95% CI 0.91-1.12; P = .81) or 1-year periprocedural complication rates (adjusted HR 1.07; 95% CI 0.79-1.45; P = .66)., Conclusion: In a national registry of CRT-eligible patients with pre-existing ICD, upgrade to CRT was associated with lower rates of mortality than continued medical management., (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to address whether technological innovations such as contact force sensing (CFS) can improve acute and long-term ablation outcomes of left ventricular papillary muscle (LV PAP) ventricular arrhythmias (VAs)., Background: Catheter ablation of LV PAP VAs has been less efficacious than another focal VAs. It remains unclear whether technological innovations such as CFS can improve acute and long-term ablation outcomes of LV PAP VA., Methods: From January 2015 to December 2019, a total of 137 patients underwent LV PAP VA ablation. VA site of origin (SOO) was identified using activation and pace-mapping guided by intracardiac echocardiography. Radiofrequency energy (20 to 50 W for 60 to 90 s) was delivered by irrigated catheter with or without CFS. We defined acute success as complete suppression of targeted VA ≥30 min post ablation and clinical success as ≥80% VA burden reduction at outpatient follow-up., Results: VA manifested as premature ventricular complexes in 98 (71%), nonsustained ventricular tachycardia in 18 (13%), sustained ventricular tachycardia in 12 (9%) and premature ventricular complexes induced ventricular fibrillation in 9 (7%). VA SOO was anterolateral PAP in 51 (37%), posteromedial PAP in 73 (53%), and both PAPs in 13 (10%). VAs were targeted using CFS in 97 (71%) and non-CFS in 40 (29%). After a single procedure, acute success was achieved in 130 (95%) and clinical success was achieved in 112 (82%); neither was impacted by VA SOO and/or CFS. Complications occurred in 5 patients (3.6%)., Conclusion: Independent of CFS technology, intracardiac echocardiography-guided catheter ablation is highly efficacious and may be considered as first-line therapy in the management of LV PAP VA., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)