Faculty Bibliography

Ca²⁺ is a fundamental second messenger in all cell types and is required for numerous essential cellular functions, including cardiac and skeletal muscle contraction. The intracellular concentration of free Ca²⁺ ([Ca²⁺]) is regulated primarily by ion channels, pumps (ATPases), exchangers and Ca²⁺-binding proteins. Defective regulation of [Ca²⁺] is found in a diverse spectrum of pathological states that affect all the major organs. In the heart, abnormalities in the regulation of cytosolic and mitochondrial [Ca²⁺] occur in heart failure (HF) and atrial fibrillation (AF), two common forms of heart disease and leading contributors to morbidity and mortality. In this Review, we focus on the mechanisms that regulate ryanodine receptor 2 (RYR2), the major sarcoplasmic reticulum (SR) Ca²⁺-release channel in the heart, how RYR2 becomes dysfunctional in HF and AF, and its potential as a therapeutic target. Inherited RYR2 mutations and/or stress-induced phosphorylation and oxidation of the protein destabilize the closed state of the channel, resulting in a pathological diastolic Ca²⁺ leak from the SR that both triggers arrhythmias and impairs contractility. On the basis of our increased understanding of SR Ca²⁺ leak as a shared Ca²⁺-dependent pathological mechanism in HF and AF, a new class of drugs developed in our laboratory, known as rycals, which stabilize RYR2 channels and prevent Ca²⁺ leak from the SR, are undergoing investigation in clinical trials.

BACKGROUND:The COVID-19 pandemic has greatly altered the practice of cardiac electrophysiology around the world for the foreseeable future. Professional organizations have provided guidance for practitioners, but real-world examples of the consults and responsibilities cardiac electrophysiologists face during a surge of COVID-19 patients is lacking. METHODS:In this observational case series we report on 29 consecutive inpatient electrophysiology consultations at a major academic medical center in New York City, the epicenter of the pandemic in the United States, during a 2 week period from March 30-April 12, 2020, when 80% of hospital beds were occupied by COVID-19 patients, and the New York City metropolitan area accounted for 10% of COVID-19 cases worldwide. RESULTS:Reasons for consultation included: Atrial tachyarrhythmia (31%), cardiac implantable electronic device management (28%), bradycardia (14%), QTc prolongation (10%), ventricular arrhythmia (7%), post-transcatheter aortic valve replacement conduction abnormality (3.5%), ventricular pre-excitation (3.5%), and paroxysmal supraventricular tachycardia (3.5%). Twenty-four patients (86%) were positive for COVID-19 by nasopharyngeal swab. All elective procedures were canceled, and only one urgent device implantation was performed. Thirteen patients (45%) required in-person evaluation and the remainder were managed remotely. CONCLUSION/CONCLUSIONS:Our experience shows that the application of a massive alteration in workflow and personnel forced by the pandemic allowed our team to efficiently address the intersection of COVID-19 with a range of electrophysiology issues. This experience will prove useful as guidance for emerging hot spots or areas affected by future waves of the pandemic.

OBJECTIVES/OBJECTIVE:We investigated characteristics of left atrial conduction in patients with HCM, paroxysmal AF and normal bipolar voltage. BACKGROUND:Patients with hypertrophic cardiomyopathy (HCM) exhibit abnormal cardiac tissue arrangement. The incidence of atrial fibrillation (AF) is increased fourfold in patients with HCM and confers a fourfold increased risk of death. Catheter ablation is less effective in HCM, with twofold increased risk of AF recurrence. The mechanisms of AF perpetuation in HCM are poorly understood. METHODS:We analyzed 20 patients with HCM and 20 controls presenting for radiofrequency ablation of paroxysmal AF normal left atrial voltage(> 0.5 mV). Intracardiac electrograms were extracted from the CARTO mapping system and analyzed using Matlab/Python code interfacing with Core OpenEP software. Conduction velocity maps were calculated using local activation time gradients. RESULTS: = 0.13, p = 0.03). CONCLUSIONS:Atrial conduction velocity is significantly reduced in patients with HCM and paroxysmal AF, possibly contributing to arrhythmia persistence after catheter ablation.

BACKGROUND:Established electroanatomic mapping techniques for substrate mapping for ventricular tachycardia (VT) ablation includes voltage mapping, isochronal late activation mapping (ILAM), and fractionation mapping. Omnipolar mapping (Abbott Medical, Inc.) is a novel optimized bipolar electrogram creation technique with integrated local conduction velocity annotation. The relative utilities of these mapping techniques are unknown. OBJECTIVE:The purpose of this study was to evaluate the relative utility of various substrate mapping techniques for the identification of critical sites for VT ablation. METHODS:Electroanatomic substrate maps were created and retrospectively analyzed in 27 patients in whom 33 VT critical sites were identified. RESULTS:. CONCLUSION/CONCLUSIONS:ILAM, fractionation, and CV mapping each identified distinct critical sites and provided a smaller area of interest than did voltage mapping alone. The sensitivity of novel mapping modalities improved with greater local point density.

INTRODUCTION/BACKGROUND:Radiofrequency ablation (RFA) slow pathway modification for catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT) is traditionally performed using a 4-mm nonirrigated (NI) RF ablation catheter. Slow pathway modification using irrigated, contact-force sensing (ICFS) RFA catheters has been described in case reports, but the outcomes have not been systematically evaluated. METHODS:Acute procedural outcomes of 200 consecutive patients undergoing slow pathway modification for AVNRT were analyzed. A 3.5-mm ICFS RFA catheter (ThermoCool SmartTouch STSF, Biosense Webster, Inc.) was utilized in 134 patients, and a 4-mm NI RFA catheter (EZ Steer, Biosense Webster, Inc.) was utilized in 66 patients. Electroanatomic maps were retrospectively analyzed in a blinded fashion to determine the proximity of ablation lesions to the His region. RESULTS:The baseline characteristics of patients in both groups were similar. Total RF time was significantly lower in the ICFS group compared to the NI group (5.53 ± 4.6 vs. 6.24 ± 4.9 min, p = 0.03). Median procedure time was similar in both groups (ICFS, 108.0 (87.5-131.5) min vs. NI, 100.0 (85.0-125.0) min; p = 0.2). Ablation was required in closer proximity to the His region in the NI group compared to the ICFS group (14.4 ± 5.9 vs. 16.7 ± 6.4 mm, respectively, p = 0.01). AVNRT was rendered noninducible in all patients, and there was no arrhythmia recurrence during follow-up in both groups. Catheter ablation was complicated by AV block in one patient in the NI group. CONCLUSION/CONCLUSIONS:Slow pathway modification for catheter ablation of AVNRT using an ICFS RFA catheter is feasible, safe, and may facilitate shorter duration ablation while avoiding ablation in close proximity to the His region.

INTRODUCTION/BACKGROUND:Radiofrequency ablation technology for treating atrial fibrillation (AF) has evolved rapidly over the past decade. We investigated the impact of technological and procedural advances on procedure times and ablation outcomes at a major academic medical center over a 10-year period. METHODS:Clinical data was collected from patients who presented to NYU Langone Health between 2011 and 2021 for a first-time AF ablation. Time to redo AF ablation or direct current cardioversion (DCCV) for recurrent AF during a 3-year follow-up period was determined and correlated with ablation technology and practices, antiarrhythmic medications, and patient comorbid conditions. RESULTS:From 2011 to 2021, the cardiac electrophysiology lab adopted irrigated-contact force ablation catheters, high-power short duration ablation lesions, steady-pacing, jet ventilation, and eliminated stepwise linear ablation for AF ablation. During this time the number of first time AF ablations increased from 403 to 1074, the percentage of patients requiring repeat AF-related intervention within 3-years of the index procedure dropped from 22% to 14%, mean procedure time decreased from 271 ± 65 to 135 ± 36 min, and mean annual major adverse event rate remained constant at 1.1 ± 0.5%. Patient comorbid conditions increased during this time period and antiarrhythmic use was unchanged. CONCLUSION/CONCLUSIONS:Rates of redo-AF ablation or DCCV following an initial AF ablation at a single center decreased 36% over a 10-year period. Procedural and technological changes likely contributed to this improvement, despite increased AF related comorbidities.

INTRODUCTION/BACKGROUND:Patients with HIV infection have increased risk of atrial fibrillation, but the pathophysiologic mechanisms and the utility of catheter ablation in this population are not well-studied. We aimed to characterize outcomes of atrial fibrillation ablation and left atrial substrate in patients with HIV. METHODS:The study was a retrospective propensity score-matched analysis of patients with and without HIV undergoing atrial fibrillation ablation. A search was performed in the electronic medical record for all patients with HIV who received initial atrial fibrillation ablation from 2011 to 2020. After calculating propensity scores for HIV, matching was performed with patients without HIV by using nearest-neighbor matching without replacement in a 1:2 ratio. The primary outcome was freedom from atrial arrhythmia and secondary outcomes were freedom from atrial fibrillation, freedom from atrial tachycardia, and freedom from repeat ablation, compared by log-rank analysis. The procedures of patients with HIV who underwent repeat ablation at our institution were further analyzed for etiology of recurrence. To further characterize the left atrial substrate, a subsequent case-control analysis was then performed for a set of randomly chosen 10 patients with HIV matched with 10 without HIV to compare minimum and maximum voltage at nine pre-specified regions of the left atrium. RESULTS:Twenty-seven patients with HIV were identified. All were prescribed antiretroviral therapy at time of ablation. These patients were matched with 54 patients without HIV by propensity score. 86.4% of patients with HIV and 76.9% of controls were free of atrial fibrillation or atrial tachycardia at 1 year (p = .509). Log-rank analysis showed no difference in freedom from atrial arrhythmia (p value .971), atrial fibrillation (p-value .346), atrial tachycardia (p value .306), or repeat ablation (p value .401) after initial atrial fibrillation ablation in patients with HIV compared to patients without HIV. In patients with HIV with recurrent atrial fibrillation, the majority had pulmonary vein reconnection (67%). There were no significant differences in minimum or maximum voltage at any of the nine left atrial regions between the matched patients with and without HIV. CONCLUSIONS:Ablation to treat atrial fibrillation in patients with HIV, but without overt AIDS is frequently successful therapy. The majority of patients with recurrence of atrial fibrillation had pulmonary vein reconnection, suggesting infrequent nonpulmonary vein substrate. In this population, the left atrial voltage in patients with HIV is similar to that of patients without HIV. These findings suggest that the pulmonary veins remain a critical component to the initiation and maintenance of atrial fibrillation in patients with HIV.

BACKGROUND:Prior studies have shown that addition of posterior wall isolation (PWI) may reduce atrial fibrillation recurrence in patients with persistent atrial fibrillation. No data on PWI in paroxysmal AF (pAF) patients with normal left atrial voltage is available, to date. OBJECTIVE:This study sought to evaluate the efficacy of PWI in addition to pulmonary vein isolation (PVI) in patients presenting with pAF and normal left atrial voltage. METHODS:Consecutive patient registry analysis was performed on all patients with pAF and normal left atrial voltage undergoing initial radiofrequency ablation from November 1, 2018 to November 15, 2019. Primary endpoint was recurrence of atrial arrhythmia including AF, atrial tachycardia (AT) or atrial flutter (AFL). RESULTS:A total of 321 patients were studied, 214 in the PVI group and 107 in the PWI+PVI group. Recurrence of any atrial arrhythmia occurred in 18.2% of patients in the PVI group and 16.8% in the PVI+PWI cohort (p=0.58). At one year, recurrence was 14.0% in the PVI group and 15.0% in the PWI+PVI group (p=0.96). There was a lower AT/AFL recurrence in the PVI+PWI group, not reaching significance (3.7% in the PWI+PVI group vs. 7.9% in PVI group, p=0.31). Need for carina lesions predicted recurrence in the PVI-only group. CONCLUSIONS:Addition of PWI to PVI in pAF patients undergoing their first ablation did not reduce the frequency of atrial arrhythmia recurrence. This warrants further study in a prospective trial. This article is protected by copyright. All rights reserved.

PURPOSE/OBJECTIVE:Catheter ablation procedures for atrial fibrillation (AF) were significantly curtailed during the peak of coronavirus disease 2019 (COVID-19) pandemic to conserve healthcare resources and limit exposure. There is little data regarding peri-procedural outcomes of medical procedures during the COVID-19 pandemic. We enacted protocols to safely reboot AF ablation while limiting healthcare resource utilization. We aimed to evaluate acute and subacute outcomes of protocols instituted for reboot of AF ablation during the COVID-19 pandemic. METHODS:Perioperative healthcare utilization and acute procedural outcomes were analyzed for consecutive patients undergoing AF ablation under COVID-19 protocols (2020 cohort; n=111) and compared to those of patients who underwent AF ablation during the same time period in 2019 (2019 cohort; n=200). Newly implemented practices included preoperative COVID-19 testing, selective transesophageal echocardiography (TEE), utilization of venous closure, and same-day discharge when clinically appropriate. RESULTS:Pre-ablation COVID-19 testing was positive in 1 of 111 patients. There were 0 cases ablation-related COVID-19 transmission and 0 major complications in either cohort. Pre-procedure TEE was performed in significantly fewer 2020 cohort patients compared to the 2019 cohort patients (68.4% vs. 97.5%, p <0.001, respectively) despite greater prevalence of persistent arrhythmia in the 2020 cohort. Same-day discharge was achieved in 68% of patients in the 2020 cohort, compared to 0% of patients in the 2019 cohort. CONCLUSIONS:Our findings demonstrate the feasibility of safe resumption of complex electrophysiology procedures during the COVID-19 pandemic, reducing healthcare utilization and maintaining quality of care. Protocols instituted may be generalizable to other types of procedures and settings.