Samuel Asirvatham

Pulsed field ablation (PFA) is a paradigm shift in the field of cardiac electrophysiology. The well-demonstrated success with atrial PFA is generating enthusiasm for ventricular applications of PFA, for which the clinical experience is still in its infancy, however. This study is a systematic review and critical appraisal of the published preclinical and clinical evidence on ventricular PFA, involving a total of 111 primary articles (55 preclinical and 56 clinical). An increasing number of PFA platforms and catheters are being used in the ventricle in clinical practice. This appraisal evaluates the impact of ablation parameters in association with lesion depth and volume, and synthesises the available studies of safety and efficacy outcomes for ablation of ventricular tachycardia and premature ventricular complexes with PFA, as reported in case reports and case series from around the world. The cumulative published evidence amounts to a total of 434 patients ablated with PFA for ventricular arrhythmias, with generally favourable acute and long-term results, while the understanding of safety constraints continues to be explored.

Pulsed field ablation (PFA) has rapidly emerged as a major development in catheter ablation, with increasing clinical adoption driven by procedural efficiency and a favorable safety profile compared with thermal energies. This article summarizes the future directions of PFA in electrophysiology, focusing on technological innovation, and how these advances are expected to expand PFA clinical indications. Additionally, this article provides a perspective on current gaps and future challenges of PFA. A perspective on future developments in new waveforms, catheter architectures, and integration with electroanatomical mapping systems for PFA is summarized. The document discusses novel waveform configurations and catheter design concepts that may improve lesion quality, procedural versatility, and safety. Additionally, this article also reviews how parallel advances in electroanatomical mapping integration, artificial intelligence, and robotic navigation are expected to enhance procedural guidance and enable individualized therapy. This manuscript summarizes the potential applications of PFA beyond pulmonary vein isolation and how emerging evidence supports its feasibility for linear atrial lesions, substrate modification, treatment of complex atrial tachycardias, and ventricular arrhythmia ablation. In addition, this article provides insights on how PFA may facilitate catheter ablation in new patient populations including elderly patients and those with higher procedural risks. Finally, this manuscript provides an outlook at major remaining challenges and knowledge gaps for PFA. The lack of homogenous procedural endpoints definitions and lesion durability assessment are discussed. Furthermore, this article highlights the need for standardized terminology and reporting in an environment where the high heterogeneity between available commercial systems complicates comparison across technologies.

Aims: Pulsed field ablation (PFA) has emerged as a novel ablation modality for the treatment of cardiac arrhythmias and has rapidly reshaped contemporary electrophysiology practice. This article provides a comprehensive analysis on the mechanisms underlying the specific effects of PFA on myocardial, neural tissue structures, and the cardiac conduction system, integrating biophysical principles with preclinical and clinical evidence relevant to contemporary electrophysiology practice. Methods and results: This document provides an exhaustive mechanistic explanation for the preferential effects of PFA on myocardium and the limits of the ‘tissue-selectivity’ concept. The complex interplay between cellular and tissue-level biophysics, biological responses, and tissue regenerative capacity that determines differential susceptibility to electroporation across tissues is analysed. Distinct patterns of lesion formation and maturation following PFA are also reviewed, highlighting the temporal and histopathological differences compared with radiofrequency ablation. Additionally, lesion formation in heterogeneous substrates is analysed, including fibrotic and adipose-rich myocardium, where local electric field distribution critically influences lesion durability. Conclusion: The article further examines the interaction between pulsed electric fields and neural tissue, with emphasis on the phrenic nerve and intrinsic cardiac autonomic nervous system. While nerve stimulation and transient reversible conduction disturbances produced by reversible electroporation can occur during ablation, permanent neural injury appears extremely rare in current clinical experience. Finally, this manuscript examines current understanding regarding the specific effects of PFA on the cardiac conduction system, which according to the limited available evidence appear strongly dependent on electric field dose and anatomical proximity.

Pulsed field ablation (PFA) has rapidly emerged as a promising ablation modality for the treatment of cardiac arrhythmias because of its myocardial tissue preferential ablation and favourable safety profile. However, procedural control of lesion formation and reliable assessment of lesion durability remain important challenges. This review summarizes the main determinants of PFA efficacy and current approaches for intraprocedural lesion assessment. Experimental and clinical studies indicate that PFA lesion formation results from the interaction between delivered electrical energy, catheter design, tissue coupling, and application strategy. Lesion size and geometry are primarily determined by electric field distribution and cumulative electroporation exposure, while excessive energy delivery may induce unwanted thermal or electrochemical effects. Procedural efficacy also depends on stable catheter positioning, adequate tissue proximity, and sufficient lesion overlap. Unlike thermal ablation technologies, conventional procedural markers such as electrogram attenuation, impedance changes, and pacing threshold variation correlate poorly with durable irreversible electroporation. Multiparametric lesion estimation models integrating electrical, mechanical, and positional data have shown encouraging preclinical results, although clinical validation remains limited. Emerging strategies combining electroanatomical mapping, imaging, and automated electrogram analysis may improve real-time evaluation of lesion continuity and durability. Current PFA workflows rely mainly on standardized energy delivery protocols, optimized catheter positioning, and lesion overlap rather than real-time titration of energy. Although robust intraprocedural markers of irreversible electroporation are still lacking, ongoing advances in catheter technology, imaging, and lesion assessment tools are expected to improve procedural reproducibility and long-term lesion durability. Further studies are needed to establish validated endpoints for durable PFA lesion formation.

BACKGROUND: Ventricular fibrillation (VF) remains a leading cause of sudden cardiac death with an incompletely characterized electrophysiological substrate. Traditional large-animal VF models are limited by hemodynamic collapse and myocardial ischemia. This study establishes a reproducible swine model using dual mechanical circulatory devices to enable high-density electroanatomic mapping under nonischemic conditions. METHODS: Five Yorkshire swine (55–65 kg) underwent sustained VF supported by venoarterial extracorporeal membrane oxygenation (2.5–3.0 L/min) and percutaneous left ventricular unloading (Impella CP, P-2–P-4). High-density electroanatomic mapping using CARTO 7 was performed at baseline and after defibrillation. Bipolar voltage was acquired from 7 predefined ventricular regions (21 measurements per animal per time point; n=210 paired observations). Unipolar voltage mapping and continuous surface ECG monitoring were used to assess acute ischemic injury. Systemic perfusion was maintained at systolic arterial pressure ≥80 mm Hg. Linear mixed-effects modeling was used to analyze voltage changes from pre-VF to post-VF. RESULTS: Sustained VF (10±1 minutes) was reproducibly induced and maintained with consistent hemodynamics (systolic arterial pressure, 90±5 mm Hg; extracorporeal membrane oxygenation flow, 2.5±0.5 L/min). All animals were successfully defibrillated. High-density mapping was feasible in all experiments (1000±300 points per chamber). Bipolar voltage showed no change from pre-VF (5.86±2.56 mV) to post-VF (6.53±2.22 mV; mean difference, 0.67 mV [95% CI, –0.31 to 1.65]; P =0.15). Both left ( P =0.17) and right ventricles ( P =0.08) demonstrated voltage preservation. Regional analysis showed no significant changes (all P >0.05); post-VF voltages remained above viability thresholds (>1.5 mV). Unipolar voltage maps recovered toward baseline, with no ECG injury pattern identified after defibrillation. CONCLUSIONS: Dual mechanical circulatory support with venoarterial extracorporeal membrane oxygenation and Impella CP enables reproducible, high-fidelity electroanatomic mapping and preserves myocardial substrate after sustained VF in a large-animal model. This platform overcomes key technical barriers in VF research, providing a nonischemic foundation for future mechanistic and translational studies.

Background: Bicuspid aortic valve (BAV) is the most common congenital heart defect, associated with a lifetime morbidity burden exceeding 80% and an estimated 7% probability of transmission to first-degree relatives. Hence, echocardiographic screening of relatives is recommended. The aim of our study is to develop an artificial intelligence-enabled electrocardiogram (AI-ECG) model for the detection of BAV. Methods: Between January 1, 1990, and June 30, 2023, the Mayo Clinic healthcare system database was searched for patients aged ≥18 years with echocardiograms performed for family history of BAV, abnormal auscultation, a BAV-related diagnosis, or to rule out the condition, and with an electrocardiogram (ECG) obtained within 6 months. Cases were patients with a confirmed BAV diagnosis, and controls were those with normal aortic valves. ECGs were randomly assigned into training (80%), internal validation (10%), and test (10%) groups. The AI-ECG model was built using Keras under TensorFlow. Results: A total of 13,065 valid ECG–echocardiogram pairs were included (mean [SD] age, 58 [17] years; 44% women), with a median time of 1 day (interquartile range, 0–3 days) between studies. With a 45% BAV prevalence in the test group ( n = 1301), the area under the curve was 0.704, positive predictive value (PPV) 60.1%, and negative predictive value (NPV) 69.4%. At a prevalence of 7%, the NPV increased to 96.1%, but the PPV decreased to 12.2%. Conclusions: In this retrospective cohort and using the current AI-ECG model, BAV detection showed modest diagnostic performance and limited standalone clinical utility, suggesting that ECG-only screening for BAV may require additional modalities or more refined phenotyping.

Background: Pulsed field ablation (PFA) is an emerging non‐thermal ablation modality with proven safety in atrial arrhythmia ablation. However, data on its performance for ventricular arrhythmias (VA) remain limited. Objective: To evaluate the feasibility, safety, and efficacy of PFA for complex VA in a multicenter real‐world US registry. Methods: This retrospective study included consecutive patients undergoing PFA for ventricular tachycardia (VT) or premature ventricular contractions (PVCs) at three Mayo Clinic centers (April 2024 to July 2025). The primary feasibility outcome was the successful delivery of PFA lesions to the intended target substrate. Primary efficacy outcomes included acute procedural success; sustained VT recurrence requiring implantable cardioverter‐defibrillator (ICD) shocks or multiple antitachycardia pacing therapies; and ≥ 80% reduction in PVC burden. Safety outcomes included procedural complications, valvular function, thromboembolic events, renal function, and conduction disturbances. Results: Twenty‐six patients were included (13 PVC, 13 VT). Acute success was achieved in all VT ablations (69.2% complete; 30.8% partial) and in 92.3% of PVC ablations. Complications occurred in 11.5% of patients (transient LBBB [ n = 1] and vascular complications [ n = 2]). No thromboembolic events, intracardiac thrombus, or acute kidney injury were observed. Lesions near the mitral valve apparatus did not worsen mitral regurgitation, including in patients with pre‐existing valve disease. After a median follow‐up of 365 days, one patient experienced VT recurrence requiring ICD shocks. Estimated recurrence‐free survival after VT ablation was 61.5% at 12 months; 58.3% of PVC patients achieved ≥ 80% burden reduction. Conclusion: PFA for VA appears feasible and acutely effective, with a low rate of procedure‐related complications. While acute success was high, long‐term outcomes were acceptable for VT ablation and relatively modest for PVC ablation, highlighting the need for continued refinement of technology and energy‐delivery strategies. Larger prospective studies are warranted.

BACKGROUND: It is unknown whether cardiac resynchronization therapy (CRT) improves systemic metabolomic profile by enhancing left ventricular function. The observational cohort study aimed to investigate the effect of CRT on left ventricular ejection fraction (LVEF) and circulating plasma metabolites in patients who had heart failure with reduced LVEF. METHODS: We prospectively screened patients with ischemic cardiomyopathy and nonischemic cardiomyopathy who received CRT with a defibrillator for LVEF ≤35% according to current guidelines. Clinical assessment included echocardiography and device interrogation. Blood samples for metabolomic analysis were collected before CRT and at 6-month follow-up. Plasma was subjected to gas chromatography-mass spectrometry and ¹ H nuclear magnetic resonance-based metabolomic analysis. RESULTS: Totally 92 patients were enrolled, with a mean age of 67.3±11.3 years (37.0% female). LVEF was significantly improved from 28.9±7.6% at baseline to 36.0±11.3% at 6 months ( P P P P =0.01), were reduced. A branched-chain amino acid, isoleucine, was also decreased after CRT ( P =0.01). These metabolomic changes were mainly observed in the nonischemic cardiomyopathy group, while the metabolomic profile in the ischemic cardiomyopathy group was characterized by enhanced amino acid oxidation and elevated levels of lactate and pyruvate. The improvement in LVEF positively correlated with the ratio of changes in ketone bodies and isoleucine. CONCLUSIONS: CRT may modulate the systemic plasma metabolomic profile, which correlated with improvement in left ventricular function in patients with severe heart failure with reduced ejection fraction.