A faster, optimized pulsed field timing sequence demonstrates safety under aggressive lesion stacking without evidence of electrode heating

Background The Variable Loop Circular Catheter (VLCC) is a pulsed-field ablation (PFA) device for treatment of atrial fibrillation (AF) that has demonstrated a favorable safety and efficacy profile in clinical use. A novel pulse protocol, Sequence 2, which shortens ablation delivery from the ~20.6 second pulse delivery of Sequence 1 to ~3.8 seconds, is untested for its ability to be safe under excessive use conditions. Because the shorter delivery time increases instantaneous pulse density, it is pertinent to assess if Sequence 2 creates a risk of focal electrode heating or energy stacking during repeated applications. Purpose The objective of this study was to assess the safety and efficacy of the new VLCC Sequence 2 pulse recipe, when used outside the bounds of the recommended clinical workflow. Methods A total of eight porcine subjects were randomized into two test groups: 2X nominal dose and 4X nominal dose, corresponding to two or four consecutive PFA applications per site, respectively. PFA was performed with intentional lesion stacking and nominal electrode irrigation (30ml/min). Subsequent coronary angiography, blood chemistry panels, and evaluation of VLCC electrode charring was also performed. Animals were survived for 30±3 days post ablation to undergo follow-up remapping procedures before being euthanized to allow for gross necropsy and histopathology. Results For all animals, 100% acute and chronic effectiveness was observed for pulmonary vein isolation (PVI). Safety metrics were met, no incidence of phrenic nerve injury, esophageal injury, or catheter charring were observed. Transient asymptomatic coronary spasm could be induced and was detected following cavotricuspid ablation in both the 2X and 4X dose groups, whereas spasm following mitral isthmus ablation only occurred in the 2X group. All coronary spasms resolved following administration of a nitroglycerin dose and no hemodynamic compromise was observed. The 4X group exhibited greater transient increases in hemolysis (e.g., plasma-free hemoglobin, LDH) and myocardial injury markers (e.g., CK/troponins) compared with the 2X group, with all values returning to or near baseline by the survival endpoint. The 4X treatment group showed more marked changes in hemolysis and myocardial injury markers than the 2X treatment group, with all markers returning to or near baseline by the survival endpoint (Figure 1). Conclusion In this study, Sequence 2 maintained a favorable safety profile even when applied at 2X and 4X nominal dosing with no evidence of charring or excessive electrode heating at nominal irrigation and only transient elevations in hemolysis and myocardial injury markers. PFA applications near coronary arteries, under these excessive use conditions, resulted in self-limiting spasm. These findings suggest that the accelerated pulse protocol preserves PFA’s non-thermal safety characteristics and remains well-tolerated even during excessive use conditions.