Direct myocardial necrosis, but not apoptosis, is the mechanisms of myocardial cell death in pulsed-field ablation for atrial fibrillation

In in vitro studies on pulsed-field ablation (PFA), apoptosis was often described as one of the possible mechanisms of PFA-induced cell death.

This study aimed to specify the cause of cardiac cell death by comparing markers of cardiac necrosis and apoptosis during ablation for atrial fibrillation (AF) using PF and radiofrequency (RF) energy in humans.

Patients with AF indicated for pulmonary vein isolation (PVI) were enrolled and randomly assigned to undergo PVI using RF (CARTO Smart Touch, Biosense Webster) or PF (Farapulse, Boston-Scientific) energy. Markers of myocardial necrosis (troponin I) and apoptosis (soluble caspase-3, Fas ligand) were measured before and one day after the procedure.

Sixty-five patients were enrolled in the PFA (n=33) and RFA (n=32) groups. Both groups had similar baseline characteristics (age 60.5±12.7 vs. 64.0±10.7; paroxysmal AF 60.6% vs. 62.5% of patients). Compared to baseline values, no increase in Fas (98.1; 74.2-113.9 pg/mL vs. 97.1; 82.5-112.2 pg/mL, p=0.95) or caspase-3 (10172; 4113-31882 pg/mL vs. 10189; 4182-31374 pg/mL, p=0.75) concentrations were present after PFA (all values as median and interquartile ranges). No differences in the concentration of these apoptotic markers were present between PF and RF patients at 1d+. Compared to baseline, the concentrations of troponin I were higher in both groups at 1d+, but troponin I concentrations at 1d+ was substantially higher in the PFA group (10102; 8272–14207 ng/L vs. 1006 ng/L; 603–1433 ng/L, p<0.001.

In the acute setting, apoptosis does not seem to be the leading cause of cardiomyocyte death after PF ablation for AF.