Faculty Bibliography

BACKGROUND:Using high-frequency jet ventilation (HFJV) to improve catheter stability with conventional energy sources during atrial fibrillation (AF) ablation is associated with higher ablation success and improved arrhythmic outcomes. The utility of HFJV with pulsed field ablation (PFA) for AF is unclear. We investigated the utility of HFJV vs. standard ventilation in PFA for AF. METHODS:We studied consecutive cases of patients with AF undergoing PFA between 5/6/24 to 10/10/24. Procedural data collected included total procedure time and major periprocedural complications. Clinical data collected included atrial tachyarrhythmia (ATA) recurrence, stroke, and major bleeding at one-year follow-up. Outcomes were compared in cases where HFJV was used vs. standard ventilation. RESULTS:A total of 512 patients were included in this study (307 standard ventilation, 205 HFJV). There was no difference in ATA recurrence by Kaplan-Meier survival analysis between standard ventilation and HFJV groups (log rank test p = 0.59). When comparing standard ventilation vs. HFJV groups, there was no difference in ATA recurrence at one year (23% vs. 26%; p = 0.43), AF burden on continuous monitoring (9 ± 5% vs. 8 ± 24%; p = 0.85), total procedure time (114 ± 38 vs. 115 ± 33 min; p = 0.78), or major periprocedural complications (3% vs. 2%; p = 0.64). There was no difference in arrhythmic outcomes when patients were stratified by AF type and whether patients presented for first-time or redo ablation. CONCLUSION/CONCLUSIONS:Using HFJV in PFA for AF produces similar sinus rhythm maintenance overall and when stratified by AF type without affecting procedure times or complication rate.

Randomized trials of ethanol infusion into the vein of Marshall (EIVOM) have shown efficacy in preventing atrial fibrillation (AF) recurrence in patients presenting for de novo ablation. The utility of EIVOM in AF patients who present for redo ablation is unclear. This meta-analysis was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Medline, Scopus, and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. Risk of bias was assessed using the Modified Newcastle-Ottawa scale. Eligible studies reported outcomes in AF patients with previous ablation who underwent redo catheter ablation (CA) alone vs. combined redo CA and EIVOM. Five observational studies comprising 568 patients were included. When comparing combined redo CA and EIVOM vs. redo CA alone, pooled results showed no difference in freedom from arrhythmia (FFA) in all patients (risk ratio [RR] 1.13; 95% confidence interval [CI] 0.96-1.33), FFA in persistent AF patients only (RR 1.08; 95% CI 0.90-1.29), total procedure time (mean difference -0.59; 95% CI -41.04-39.85), or major periprocedural complications (RR 0.81; 95% CI 0.06-11.64). Patients with AF recurrence after ablation represent a difficult-to-treat population. Salvage therapy with combined CA and EIVOM did not improve arrhythmic outcomes compared to CA alone in AF patients who presented for redo ablation.

Electrical and structural remodeling of the heart can contribute to the development of cardiac arrhythmias. Ex vivo optical mapping has been used to visualize cardiac electrophysiological properties, activation and phase maps to further elucidate the mechanisms of atrial fibrillation and ventricular fibrillation initiation and persistence. Here we show an epicardial three-dimensional panoramic optical mapping tool integrated with micro-computed tomography automatically segmented with a deep learning model relying on a convolutional neural network to provide structural and electrical activation information in a single three-dimensional volume of a mouse heart. This technique allows for the acquisition and analysis of electrical activity of the entire epicardial surface with submillimeter spatial resolution and a temporal resolution of 1 ms. We establish the use of this method in transgenic mouse hearts with spontaneous atrial fibrillation and ventricular fibrillation, and mouse surgical models of myocardial infarction and left ventricular hypertrophy.

BACKGROUND:Pulmonary vein isolation (PVI) and posterior wall isolation (PWI) are frequently used in the treatment of persistent atrial fibrillation (AF). Minimal data support adjunct PWI, possibly due to lack of durability via epicardial reconnections. OBJECTIVE:To determine the impact of very high output PW pace-capture testing in patients with persistent AF on AF/AT recurrence. METHODS:We performed a retrospective study of consecutive patients who underwent radiofrequency ablation for persistent AF and received PVI and PWI, as well as a cavotricuspid isthmus line (CTI). After the creation of three linear PW lesions (roof, carina-to-carina, and inferior PV levels), pace-capture testing was performed on the PW. The first cohort confirmed PWI using 10 mA at 2 ms (10 × 2) to pace capture. Sequentially, the second cohort utilized 20 mA at 10 ms (20 × 10). If the PW was captured, additional lesions were performed. Patients were excluded if additional lesion sets beyond PVI, PWI, and CTI were performed. RESULTS:A total of 232 patients were included. Of these, 129 (56%) patients were in the 20 × 10 group, and 103 (44%) patients were in the 10 × 2 group. The two groups did not differ in age, sex, proportion of comorbidities, presenting rhythm, left ventricular ejection fraction, or left atrial size. Despite the increase in procedure time and lesion number, in the time-to-event analysis, patients in the 20 × 10 group experienced recurrent AF/AT more frequently than those in the 10 × 2 group (log rank p = 0.01). CONCLUSION/CONCLUSIONS:Testing PWI in persistent AF with pace capture at 20 mA at 10 ms did not improve freedom from arrhythmia and may paradoxically be associated with harm. Our findings question whether PWI, regardless of durability, is effective in treating persistent AF.

Atrial fibrillation (AF) and heart failure (HF) frequently coexist and worsen one another's outcomes. To investigate shared molecular mechanisms, we compared atrial gene regulatory networks (GRNs) in the mouse Tbx5 conditional knockout (Tbx5 cKO) AF model and the transverse aortic constriction (TAC) HF model. Here we show highly correlated changes in atrial transcriptional and genomic profiles, including downregulated atrial Tbx5 expression in both mouse and human HF. More than 100 transcription factor genes were coordinately dysregulated in the atria of the Tbx5 cKO and TAC models. The wild-type atrial TBX5-driven GRN, including Klf15, a repressor of cardiomyocyte hypertrophy, was disrupted in Tbx5 cKO and TAC models. Conversely, a disease-specific network featuring Sox9 emerged in activated fibroblasts of Tbx5 cKO and TAC models. Our results identify coordinated disruption of TBX5-dependent atrial gene regulation in AF and HF, suggesting that a shared genomic injury response may underlie the reciprocal risk between these conditions.

The cardiac conduction system (CCS) has a vital role in initiating and coordinating nearly 3 billion heartbeats throughout a person's lifetime. The CCS comprises two primary tissue types: the impulse-generating, slow-conducting nodes and the fast-conducting components of the ventricular conduction system. Dysfunction in this system can give rise to a spectrum of clinical symptoms, including palpitations, syncope, heart failure and even sudden cardiac death. Owing to the limited therapeutic options other than electronic pacemakers, substantial research efforts have been aimed at uncovering the root causes of conduction system disorders. A comprehensive investigative approach integrating genetics, transcriptomics and proteomics has been used to unravel the complex biology of these diseases. Advances in single-cell genomic and transcriptomic technologies, together with spatial transcriptomics, are offering new insights into the cellular microenvironments that govern conduction system function. In this Review, we examine the latest progress in understanding the biology of the CCS, situating new findings within both established and emerging scientific paradigms. Additionally, we discuss how these insights can be leveraged to improve clinical risk assessment, expand drug discovery efforts, accelerate technology aimed at promoting CCS regeneration and foster the development of innovative therapies, including biological pacemakers.

BACKGROUND:Identifying nearfield and farfield signals is critical to mapping and ablating cardiac arrhythmias. This assessment is qualitative, depending on the "sharpness" of pulmonary vein (PV) electrograms. Electrogram peak frequency (PF) analysis is hypothesized to be a quantitative measure of signal proximity. OBJECTIVE:To confirm if PF defines nearfield versus farfield electrical signals and if it can be used during ablation to establish pulmonary vein isolation (PVI). METHODS:We created a cohort of 30 patients with AF undergoing PVI. Left atrial and PV maps of PF were generated before and after PVI. In the first 10 patients with paroxysmal AF (cohort 1), a cutoff value was selected to predict nearfield versus farfield signals. This cutoff was validated in a cohort of 10 patients with paroxysmal AF (cohort 2) and a cohort of 10 patients with persistent AF (cohort 3). RESULTS:PF was lower in farfield electrograms than nearfield electrograms. A PF cutoff of 300 Hz had a sensitivity of 93.2% (95% CI 81.3% - 98.6%) in cohort 1, 90.0% (95% CI 76.3 - 97.2) in cohort 2, and 98.6% (95% CI 90.1 - 99.7%) in cohort 3 for differentiating farfield from nearfield electrograms. The specificity was 100.0% (95% CI 98.2% - 100.0%) and the AUC was 0.99 (95% CI 0.97 - 1.00) in all patients. CONCLUSIONS:We confirmed the hypothesis that PF distinguishes nearfield from farfield electrograms. PF analysis improves the recognition of PV isolation. Mapping and ablation strategies utilizing PF should be pursued to improve ablation outcomes.

BACKGROUND:Vein of Marshall (VOM) ethanol ablation is effective in preventing recurrence in patients with persistent atrial fibrillation (AF) as a de novo strategy. There is minimal data on its use in recurrent AF. OBJECTIVE:We investigated the efficacy of VOM ethanol ablation for recurrence despite initial AF ablation. METHODS:Retrospective analysis was performed of persistent AF patients who underwent repeat ablation after an initial ablation for persistent AF. All patients had pulmonary vein isolation (PVI), posterior wall isolation (PWI), and cavotricuspid isthmus (CTI) during their previous ablation(s). At redo ablation, controls underwent confirmation and completion of previous ablation steps, substrate modification, and a search for non-PV triggers. Cases had additional VOM ethanol ablation combined with mitral isthmus ablation. RESULTS:One hundred and seven patients (49 VOM, 60 control) were included. There was no difference in AF recurrence at 1-year comparing VOM patients (47%) and controls (38%), (p = 0.39). Within the VOM group, the mean AF burden decreased from 38% preablation to 10% 12-months post (p = 0.003). The proportion of recurrent persistent AF decreased from 65% preablation to 26% post (p = 0.004). There was no significant difference in reduction in AF burden or proportion of recurrent persistent AF when comparing VOM cases and controls. Six percent of VOM patients developed intraprocedural left atrial appendage (LAA) isolation. CONCLUSIONS:In patients with previous PVI, PWI, and CTI ablation, VOM ethanol ablation did not demonstrate a reduction in AF recurrence or burden when compared with a strategy of substrate modification and trigger ablation alone and increases the risk of LAA isolation.

AIMS/UNASSIGNED:We aimed to develop and externally validate a convolutional neural network (CNN) using sinus rhythm electrocardiograms (ECGs) and CHARGE-AF features to predict incident paroxysmal atrial fibrillation (AF), benchmarking its performance against the CHARGE-AF score. METHODS AND RESULTS/UNASSIGNED:We curated 157 192 sinus ECGs from 76 986 patients within the New York University (NYU) Langone Health system, splitting data into training, validation, and test sets. Two cohorts, from suburban US outpatient practices and Greek tertiary hospitals, were used for external validation. The model utilizing the sinus ECG signal and all CHARGE-AF features achieved the highest test set area under the receiver operator curve (AUC) (0.89) and area under the precision recall curve (AUPRC) (0.69), outperforming the CHARGE-AF score alone. Model robustness was maintained in the external US cohort (AUC 0.90, AUPRC 0.67) and the European cohort (AUC 0.85, AUPRC 0.78). Subgroup analyses confirmed consistent performance across age, sex, and race strata. A CNN using ECG signals alone retained strong predictive ability, particularly when simulating missing or inaccurate clinical data. CONCLUSION/UNASSIGNED:Our CNN integrating sinus rhythm ECGs and CHARGE-AF features demonstrated superior predictive performance over traditional risk scoring alone for detecting incident paroxysmal AF. The model maintained accuracy across geographically and clinically diverse external validation cohorts, supporting its potential for broad implementation in AF screening strategies.

BACKGROUND:Pulmonary vein (PV) isolation is the cornerstone of radiofrequency (RF) ablation for atrial fibrillation (AF) and PV reconnection is a common cause of recurrent AF. The relationship between PV ostial wall thickness (WT) and durable PV isolation is a matter of ongoing investigation. Additionally, the relationship between catheter impedance and WT is not well understood. We studied the relationship between PV ostial WT, ablation lesion metrics, and PV reconnection. METHODS:16 patients were identified who underwent an initial and redo AF ablation procedure and had a cardiac CTA analyzed using ADAS-3D imaging software performed prior to the initial ablation. Ablation lesion metrics from the initial ablation procedure were collected from the electroanatomic mapping software. Reconnected and isolated PV were identified based on electroanatomic mapping data collected at the redo AF ablation procedure. Patients with reconnected PV exhibited thicker left atrial walls (1.4 mm vs 1.2 mm, P < 0.05) and reconnected veins exhibited thicker ostial walls (1.7 mm, vs 1.5 mm, P < 0.05). LA volume, number of ablation lesions, and ablation lesion time were not significantly different between reconnected and isolated PV. Impedance drop during ablation was greater in patients with reconnected PV compared to patients with isolated PV (- 9.0 Ω vs - 6.6 Ω, P < 0.05). There was no correlation between PV ostial WT and ablation lesion impedance drop. CONCLUSION/CONCLUSIONS:PV reconnection was associated with thicker LA and PV ostial WT. Future studies will examine whether targeting thicker PV ostial tissue with more aggressive lesion metrics or different ablation technology can improve PV isolation and ablationoutcomes.