Acute monopolar biphasic pulsed field-mediated effects on coronary endothelial function and vascular integrity: the Vasc-PFA study
T Mohaissen, A J Gil-Ramirez, J Norup Hertel, S Dalgas Nissen, S M Chaldoupi, B Linz, J H Hansen, A Saljic, T A Jepps, T Jespersen, D LinzAbstract
Background
Reports of acute coronary vasospasm and delayed stenosis following pulsed-field ablation (PFA) have raised concerns about its vascular safety. Although coronary spasms are generally transient and responsive to nitroglycerin, the effects of PFA on endothelial function and vascular integrity remain unknown. In this respect, more knowledge is needed, especially when PFA is delivered in close proximity to coronary arteries, such as during cavotricuspid isthmus (CTI) ablation, ablation within the great cardiac vein (GCV), or epicardial PFA applications.
Aim
To evaluate the acute effect of PFA on endothelial and smooth muscle function in clinically relevant scenarios involving PFA application in close proximity to coronary arteries in a porcine model.
Methods
Landrace–Yorkshire–Duroc pigs (~50 kg, ~16 weeks old) underwent PFA using the CENTAURI generator with a focal monopolar biphasic waveform (25 A, 10 pulse trains) targeting the left anterior descending (LAD) and left circumflex (LCx) arteries through the great cardiac vein (GCV) (n = 9) and the right coronary artery (RCA) via the CTI (n= 5). After approximately 30–60 minutes, coronary artery segments were isolated post-ablation and mounted in a wire myograph to assess endothelium-dependent (using the endothelial agonist bradykinin) and endothelium-independent relaxation (using the NO donor nitroprusside). Coronary artery sections were sampled and processed in parallel for immunobiological analysis to assess vascular and endothelial integrity.
Results
In the LAD and LCx, the GCV-delivered PFA significantly reduced endothelium-dependent (bradykinin-induced) vasodilation compared with control (p < 0.05), whereas endothelium-independent (nitroprusside-induced) relaxation remained intact. Histological analysis demonstrated endothelial loss in the PFA-treated LAD/LCx segments, whereas the smooth muscle layer was still intact. In contrast, no significant alterations were observed in the structure or function of coronary arteries after CTI ablation in the RCA region. Both bradykinin-induced, endothelium-dependent vasodilation and sodium nitroprusside-induced, endothelium-independent relaxation remained intact.
Conclusion
PFA delivered near the coronary arteries from within the GCV, but not via the CTI, can induce localized endothelial dysfunction in the acute phase after the resolution of the coronary spasm. The preservation of smooth muscle cell function, which remains responsive to NO donors, explains why nitroglycerin effectively alleviates these spasms in the clinic. Further studies are needed to understand the long-term vascular consequences of endothelial damage of PFA when applied in close proximity to major coronary vessels.