Faculty Bibliography

BACKGROUND:Genetic testing is a cornerstone in the assessment of many cardiac diseases. However, variants are frequently classified as variants of unknown significance, limiting the utility of testing. Recently, the DeepMind group (Google) developed AlphaMissense, a unique artificial intelligence-based model, based on language model principles, for the prediction of missense variant pathogenicity. We aimed to report on the performance of AlphaMissense, accessed by VarCardio, an open web-based variant annotation engine, in a real-world cardiovascular genetics center. METHODS AND RESULTS/RESULTS:<0.001). Genotype-phenotype concordance was highly aligned using VarCard.io predictions, at 95.9% (95% CI, 92.8-97.9) concordance rate. For 109 variants classified as pathogenic, likely pathogenic, benign, or likely benign by ClinVar, concordance with VarCard.io was high (90.5%). CONCLUSIONS:AlphaMissense, accessed via VarCard.io, may be a highly efficient tool for cardiac genetic variant interpretation. The engine's notable performance in assessing variants that are classified as variants of unknown significance in ClinVar demonstrates its potential to enhance cardiac genetic testing.

BACKGROUND/UNASSIGNED:Catheter ablation (CA) for ventricular tachycardia (VT) can be a useful treatment strategy, however, few studies have compared CA to medical therapy (MT) in the sarcoidosis population. OBJECTIVE/UNASSIGNED:To assess in-hospital outcomes and unplanned readmissions following CA for VT compared to MT in patients with sarcoidosis. METHODS/UNASSIGNED:Data was obtained from the Nationwide Readmissions Database between 2010 and 2019 to identify patients with sarcoidosis admitted for VT either undergoing CA or MT during elective and non-elective admission. Primary endpoints were a composite endpoint of inpatient mortality, cardiogenic shock, cardiac arrest and 30-day hospital readmissions. Procedural complications at index admission and causes of readmission were also identified. RESULTS/UNASSIGNED: = 0.343). The most common cause of readmission were ventricular arrhythmias (VA) in both groups, however, those undergoing elective CA were less likely to be readmitted for VA compared to non-elective CA. The most common complication in the CA group was cardiac tamponade (4.8 %). CONCLUSION/UNASSIGNED:VT ablation is associated with similar rates of 30-day readmission compared to MT and does not confer increased risk of harm with respect to inpatient mortality, cardiogenic shock or cardiac arrest. Further research is warranted to determine if a subgroup of sarcoidosis patients admitted with VT are better served with an initial conservative management strategy followed by VT ablation.

BACKGROUND:Many patients with mildly to moderately reduced left ventricular ejection fraction (LVEF) who require permanent pacemaker (PPM) implantation do not have a concurrent indication for implantable cardioverter-defibrillator (ICD) therapy. However, the risk of ventricular tachycardia/ventricular fibrillation (VT/VF) in this population is unknown. OBJECTIVE:The aim of this study was to describe the risk of VT/VF after PPM implantation in patients with mildly to moderately reduced LVEF. METHODS:Retrospective analysis was performed of 243 patients with LVEF between 35% and 49% who underwent PPM placement and did not meet indications for an ICD. The primary end point was occurrence of sustained VT/VF. Competing risks regression was performed to calculate subhazard ratios for the primary end point. RESULTS:Median follow-up was 27 months; 73% of patients were male, average age was 79 ± 10 years, average LVEF was 42% ± 4%, and 70% were New York Heart Association class II or above. Most PPMs were implanted for sick sinus syndrome (34%) or atrioventricular block (50%). Of 243 total patients, 11 (4.5%) met the primary end point of VT/VF. Multivessel coronary artery disease (CAD) was associated with significantly higher rates of VT/VF, with a subhazard ratio of 5.4 (95% CI, 1.5-20.1; P = .01). Of patients with multivessel CAD, 8 of 82 (9.8%) patients met the primary end point for an annualized risk of 4.3% per year. CONCLUSION:Patients with mildly to moderately reduced LVEF and multivessel CAD undergoing PPM implantation are at increased risk for the development of malignant ventricular arrhythmias. Patients in this population may benefit from additional risk stratification for VT/VF and consideration for upfront ICD implantation.

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 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:Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiomyopathy. Implantable Cardioverter Defibrillator (ICD) is important for prevention of sudden cardiac death (SCD) in patients at high risk. In recent years the subcutaneous ICD (S-ICD) has emerged as a viable alternative to the transvenous ICD (TV-ICD). The S-ICD does not require intravascular access, but cannot provide antitachycardia pacing therapy (ATP). OBJECTIVE:To assess the real world incidence of ICD therapy in patients with HCM implanted with TV-ICD versus S-ICD. METHODS:We compared the incidence of ATP and shock therapies between all HCM patients with S-ICD and TV-ICD enrolled in the Boston Scientific ALTITUDE database. Cumulative Kaplan Meier incidence was used to compare therapy free survival and Cox proportional hazard ratios were calculated. We performed an unmatched as well as propensity match analysis. RESULTS:We included 2047 patients with TV-ICD and 626 patients with S-ICD followed for an average of 1650.5±1038.5 and 933.4±550.6 days, respectively. Patients with HCM and TV-ICD had significantly higher rate of device therapy as compared to those with S-ICD (32.7 vs. 14.5 therapies /100 patient year; p<0.001), driven by a high incidence of ATP therapy in the TV-ICD group which accounted for more than 67% of therapies delivered. Shock incidence was similar between groups, both in the general and in the matched cohorts. CONCLUSIONS:Patients with HCM and S-ICD had significantly lower therapy rate than patients with TV-ICD without difference in shock therapy, suggesting potentially unnecessary ATP therapy. Empiric ATP programing in patients with HCM may be unbeneficial.

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.

Background/UNASSIGNED:There is limited information on the long-term outcomes of ICDs in patients with inherited arrhythmia syndromes. Methods/UNASSIGNED:Prospective registry study of inherited arrhythmia patients with an ICD. Incidence of therapies and complications were measured as 5-year cumulative incidence proportions and analyzed with the Kaplan-Meier method. Incidence was compared by device indication, diagnosis type and device type. Cox-regression analysis was used to identify predictors of appropriate shock and device complication. Results/UNASSIGNED:123 patients with a mean follow up of 6.4 ± 4.8 years were included. The incidence of first appropriate shock was 56.52% vs 24.44%, p < 0.05 for cardiomyopathy and channelopathy patients, despite similar ejection fraction (61% vs 60%, p = 0.6). The incidence of first inappropriate shock was 13.46% vs 56.25%, p < 0.01 for single vs. multi-lead devices. The incidence of first lead complication was higher for multi-lead vs. single lead devices, 43.75% vs. 17.31%, p = 0.04. Patients with an ICD for secondary prevention were more likely to receive an appropriate shock than those with primary prevention indication (HR 2.21, CI 1.07-4.56, p = 0.03). Multi-lead devices were associated with higher risk of inappropriate shock (HR 3.99, CI 1.27-12.52, p = 0.02), with similar appropriate shock risk compared to single lead devices. In 26.5% of patients with dual chamber devices, atrial sensing or pacing was not utilized. Conclusion/UNASSIGNED:The rate of appropriate therapies and ICD complications in patients with inherited arrhythmia is high, particularly in cardiomyopathies with multi-lead devices. Risk-benefit ratio should be carefully considered when assessing the indication and type of device in this population.