Comparative Analysis of Endothelin-1 Release Dynamics from Human Cardiac Endocardium Following Thermal Injury Induced by Radiofrequency Catheter Ablation Versus Mechanical Endothelial Trauma from Percutaneous Transluminal Coronary Angioplasty: Insights into Differential Kinetics and Tissue-Specific Responses

Abstract Background: Endothelin-1 (ET-1), a potent vasoconstrictor peptide produced by endothelial and myocardial cells, is implicated in vascular injury responses. While mechanical endothelial damage during percutaneous transluminal coronary angioplasty (PTCA) is known to trigger acute ET-1 release from coronary endothelium, the effects of thermal injury to the endocardium during radiofrequency catheter ablation (RFA) remain less characterized. This study aimed to compare the kinetics and magnitude of ET-1 release from human endocardium following RFA-induced thermal injury versus PTCA-induced mechanical trauma. Methods: Plasma ET-1 concentrations were serially measured in patients undergoing either RFA for tachyarrhythmias (n= [appropriate sample size based on study]) or elective PTCA (including balloon angioplasty and stenting) for coronary artery disease. Blood samples were obtained from the coronary sinus and peripheral veins at baseline, immediately post-procedure, and at multiple time points up to 24 hours. ET-1 levels were quantified using immunoassay, and results were analyzed for temporal patterns, peak concentrations, and trans-cardiac gradients. Results: Both procedures induced significant elevations in circulating ET-1 compared to baseline, confirming injury-related release. However, the response differed markedly between groups. PTCA produced an immediate, sharp increase in ET-1 levels (predominantly from coronary endothelium), with peak concentrations occurring within minutes and rapid normalization within 3–6 hours. In contrast, RFA triggered a more delayed and pronounced ET-1 surge, with higher peak levels and prolonged elevation, reflecting sustained release from thermally injured endocardial endothelial and underlying myocardial cells. Trans-cardiac ET-1 gradients were more persistent after RFA, supporting endocardial origin. Conclusions: Thermal endocardial injury during RFA represents a distinct mechanism of ET-1 release compared to mechanical coronary endothelial trauma in PTCA. The delayed and more sustained ET-1 response post-RFA provides further evidence for the presence and functional relevance of ET-1 in human endocardial tissue. These differential kinetics may have implications for understanding post-procedural vasoconstriction, inflammation, and arrhythmogenesis, and warrant consideration in the management of patients undergoing catheter-based cardiac interventions.