Cardiac mechanical state matters during pulsed-field ablation: Contracture leads to larger lesions compared to relaxed state

Introduction Atrial fibrillation is a highly prevalent cardiac arrhythmia worldwide. Pulsed-Field Ablation (PFA) is a catheter-based ablation strategy using short, high-voltage electric pulses to induce irreversible electroporation and cell death, providing an efficient strategy for restoration and maintenance of sinus rhythm. Although some studies used ECG-timed ablation protocols, the role of the cardiac cycle-related mechanical state of the heart on PFA efficiency is unclear. Objective To assess whether cardiac mechanical state affects the geometry of lesions induced by PFA. Method Langendorff-perfused beating wild-type mouse hearts were stopped in relaxed state or put into contracture by perfusion of solutions containing the mechanical uncoupler BDM (30 mM), or LiCl (140 mM replacing NaCl) and caffeine (10 mM), respectively. Then, 250 V biphasic voltages were applied using a PFA generator and a monopolar linear-tip catheter (Stockert GmbH). The ablation protocol was designed to generate not fully transmural lesions, to not be limited in lesion depth measure. Every heart received two epicardial ablations per ventricle, followed by 30 min of recovery perfused by physiological solution. Hearts were stained by perfusion of 2% TTC (2,3,5-triphenyltetrazolium chloride) for 15 min, before ablated regions were excised and cryo-sectioned at 30 μm thickness, perpendicular to the epicardial surface and parallel to the lesion's long axis. Lesion morphology was assessed. Results PFA delivery on perfused hearts generated ellipsoidal lesions, clearly identifiable after TTC staining. In both ventricles, the maximal lesion area of transmural tissue sections was significantly larger when PFA was applied during contracture, compared to relaxed state: 1.4 ± 0.2 mm 2 vs 0.9 ± 0.1 mm 2 for the left and 1.3 ± 0.4 mm 2 vs 0.6 ± 0.1 mm 2 for the right ventricle ( P < 0.001 for both). In left ventricle, this was linked to significantly larger long and short axes, whereas these axes were not significantly higher in right ventricle. In both ventricles, no significant differences were observed in lesion depth. Finally, PFA delivery during contracture led to lesion volumes that were 116 ± 18% and 117 ± 39% greater for left and right ventricle ( P < 0.01 for both) compared to relaxed state. Conclusion PFA generates more than two times larger lesions when delivered during contracture, compared to relaxed hearts. Further studies will assess whether this is seen in beating hearts (physiological contractions), and in BDM-arrested hearts during passive stretch, to explore myocardial tissue tension as a possible amplifier of PFA-induced electroporation.