Not all energy is equal: time-course of haemolysis and myocardial injury biomarkers after pulmonary vein isolation with pulsed-field versus thermal ablation

Background Pulsed-field ablation (PFA) has been associated with intravascular haemolysis, but comparative time-course data for myocardial injury across ablation energies unclear. Hemolysis and cardiomyocyte injury may represent partially different biological processes, and their temporal differences may shed light on the mechanisms. Objective To compare the magnitude and temporal profiles of haemolysis and myocardial injury after pulmonary vein isolation (PVI) using PFA versus thermal ablation (radiofrequency [RFA], cryoballoon [CBA]). Methods We analyzed a single-center cohort of consecutive atrial fibrillation patients undergoing first-time PVI with one of three PFA systems—basket-array (n=73), variable-loop (n=49), fixed-loop (n=92)—or with RFA (n=11) or CBA (n=23). Biomarkers were obtained at three predefined time points: pre-procedure (T1), immediately post-procedure (T2), and the following day (T3). Haptoglobin indexed intravascular haemolysis; lactate dehydrogenase (LDH) and creatine kinase (CK) indexed myocardial injury. Application counts adhered to each device’s instructions for use. Primary outcomes were the trajectories of haptoglobin, LDH and CK across T1–T3. Analyses compared within- and between-group changes across time points. Results PVI was completed in all patients without major complications. Across all PFA systems, haptoglobin declined from T1 to T2 and from T2 to T3; at T3 it was lowest with the basket-array versus the fixed-loop system (median 29 [16–50] vs 50 [25–84] mg/dL, P<0.01), with the variable-loop intermediate. After PFA, LDH increased at T2 and remained elevated at T3; no significant LDH increase occurred after RFA. CBA showed an LDH rise at T2 without further increase at T3. CK did not increase from T1 to T2 with any PFA system but increased from T2 to T3; by contrast, CK rose from T1 to T2 with CBA and continued to rise at T3, while statistically CK rise was not observed with RFA. Application counts differed between PFA systems (overall P<0.001), reflecting device-specific workflows; biomarker patterns were consistent after accounting for these differences. No clinically significant renal impairment or acute kidney injury occurred in any group. Conclusions Ablation energy and PFA system type were associated with distinct biomarker kinetics. PFA showed a delayed CK rise and system-dependent haemolysis magnitude. In RFA and CBA, CK tended to increase from T1 to T2, showing different dynamics from PFA. These patterns align with electroporation versus thermal mechanisms and support peri-procedural monitoring using haemolysis indices and serial biomarkers.