In this episode of the EP Edge Newsletter Podcast, we analyze the pivotal clinical trials that established pulsed field ablation (PFA) as a major technological advancement in atrial fibrillation ablation. We examine the foundational FDA-approval studies, including the PULSED AF trial evaluating the Medtronic PulseSelect system and the ADVENT randomized trial comparing FARAPULSE pulsed field ablation with conventional radiofrequency and cryoballoon ablation. These trials demonstrated that pulsed field ablation achieves high rates of acute pulmonary vein isolation with freedom from atrial arrhythmia recurrence comparable to thermal ablation, while maintaining a favorable safety profile and procedural efficiency. Importantly, these studies defined modern clinical endpoints for catheter ablation success, including composite measures incorporating arrhythmia recurrence, antiarrhythmic drug use, cardioversion, and repeat ablation.

PFA Part II

We also explore next-generation pulsed field ablation platforms, including the Sphere-9 lattice-tip catheter, VARIPULSE system, and VOLT balloon-in-basket catheter, each designed to improve lesion durability, catheter stability, and procedural reproducibility. These studies demonstrate consistently high rates of pulmonary vein isolation, favorable safety outcomes, and evolving workflow advantages, including reduced fluoroscopy use and efficient lesion delivery. We then examine the latest randomized and investigational trials, including INSIGHT, which compared nanosecond pulsed field ablation with optimized ablation-index guided radiofrequency ablation, and the PULSAR IDE trial evaluating spherical array catheter design for durable pulmonary vein isolation. These trials highlight a critical reality in atrial fibrillation ablation: long-term success is determined not only by energy source, but by catheter design, tissue contact, lesion geometry, and pulmonary vein isolation durability.

PFA Part II

Full references, detailed discussion, figures, and graphical summaries are available on the EP Edge Newsletter on LinkedIn, as well as the complete long-form article on Substack at epedge.substack.com. If you have questions, suggestions, or feedback, please contact epedgecast@gmail.com.

In this foundational episode of the EP Edge Newsletter Podcast, we examine the scientific and engineering principles underlying pulsed field ablation (PFA), a transformative advance in catheter ablation for atrial fibrillation. Unlike radiofrequency or cryoablation, which rely on thermal injury, pulsed field ablation produces myocardial lesions through irreversible electroporation, a non-thermal mechanism that disrupts the cell membrane by applying precisely controlled electric fields. This represents a fundamental shift in ablation biology, where lesion formation is governed not by heat, but by transmembrane voltage thresholds, membrane destabilization, and controlled cellular injury.

This episode traces the history of electroporation, from its origins in physics and industrial biotechnology to its adoption in oncology as a non-thermal tumor ablation modality and eventual translation into cardiac electrophysiology. We then explore the Engineering Trinity of pulsed field ablation—the waveform, catheter, and pulse generator—and how these components interact to determine lesion size, safety profile, tissue selectivity, and procedural effectiveness. Understanding this integrated engineering system is essential to interpreting differences between pulsed field ablation platforms and explains why voltage alone does not define lesion durability or procedural success.

We also examine the cellular and molecular mechanisms of PFA lesion formation, including nanopore creation within the lipid bilayer, calcium influx, ATP depletion, mitochondrial dysfunction, and regulated cell death pathways. These membrane-driven injury mechanisms produce lesions that differ fundamentally from thermal ablation, preserving extracellular architecture while eliminating cardiomyocytes. This unique biology underlies one of the most important advantages of pulsed field ablation—tissue selectivity, where myocardial cells demonstrate greater susceptibility to irreversible electroporation compared with surrounding structures such as the esophagus, nerves, and vasculature, enabling effective ablation with reduced collateral injury risk.

Finally, we review the histopathology and structural evolution of pulsed field ablation lesions, including sharply demarcated injury zones, preserved tissue scaffolding, and progressive fibrocellular remodeling over time. These distinctive lesion characteristics explain both the safety profile and long-term behavior of pulsed field ablation and provide critical insight into how electrophysiologists should interpret acute procedural endpoints and long-term durability.

Full references, detailed discussion, figures, and visual summaries are available on the EP Edge Newsletter on LinkedIn, as well as the full long-form edition on Substack at epedge.substack.com.

If you have questions, suggestions, or feedback, please email epedgecast@gmail.com

In this EP-EDGE podcast episode, Dr. Niraj Sharma, cardiac electrophysiologist, breaks down the latest evidence linking modern high-THC cannabis to cardiovascular and electrophysiologic risk. Drawing from large real-world datasets, mechanistic studies, and global meta-analyses, this episode explains how today’s cannabis products—vapes, edibles, dabs, and synthetic cannabinoids—are very different from the low-potency marijuana of the past.

We explore the science behind CB1 receptor activation, autonomic imbalance, endothelial dysfunction, platelet activation, and how these mechanisms translate into real-world clinical outcomes—including:

• Atrial fibrillation and supraventricular tachycardia
• Premature atrial and ventricular beats
• Ventricular tachycardia and ventricular fibrillation
• Myocardial infarction and stroke in young adults
• Endothelial dysfunction as an early vascular warning sign
• Why high-potency THC and route of use (vaping, edibles, dabs) matter

This episode reviews landmark studies from JACC Advances, Heart, JAMA Cardiology, European Heart Journal, and Heart Rhythm, including massive EHR-based cohorts involving millions of patients. We also address common misconceptions, including why some older studies show neutral risk—and why those findings do not apply to modern high-potency cannabis use.

Whether you are a cardiologist, electrophysiologist, primary care clinician, or an informed patient, this episode provides a clear, evidence-based framework to understand why modern cannabis is not cardiovascularly benign and how it should be discussed in clinical practice—especially in patients with atrial fibrillation, ventricular arrhythmias, or unexplained cardiac events.

References, infographics, and detailed study breakdowns are available in the EP-EDGE LinkedIn Newsletter (December 2025 issue).