Characterization and clinical significance of hemolysis after pulsed-field ablation for atrial fibrillation: insights from a multicentric analysis

Pulsed-field ablation is a novel non-thermal ablation modality which is being increasingly used in clinical practice for the treatment of atrial fibrillation (AF). While the susceptibility of erythrocytes to electroporation is well-established, the effect of cardiac PFA technologies on erythrocyte destruction has not been described so far.

The aim of this study was to investigate whether PFA induces clinically significant hemolysis.

We included 187 patients undergoing AF catheter ablation with either PFA (n=145) or RFA (n=42) at four high-volume centers. PFA was performed using a pentaspline catheter (biphasic, bipolar pulses of 2kV) and RFA with a 3.5 mm irrigated-tip catheter (40-60 W). The lesion set comprised pulmonary vein isolation (PVI) for paroxysmal AF and PVI ± additional lesions/lines for persistent AF. Established biomarkers of hemolysis, anemia and renal function were analyzed in blood samples obtained at baseline (T1), at the end of ablation (T2) and 24 hours after the procedure (T3).

Baseline characteristics were well-balanced between groups (65.5 ± 9.6 years, 72.7% male, p>0.05). The ablation procedures comprised a mean of 61.4 ± 27.2 deliveries (PFA group) and a mean RF duration of 31.0 ± 16.3 min (RFA group). Atrial ablation in addition to PVI was performed in 55.2% vs. 61.9% patients, respectively (p=0.469). The direct hemolysis marker free plasma hemoglobin was significantly higher with PFA (592.8 ± 330.6 mg/dl) than with RFA (186.6 ± 215.8 mg/dl, p<0.001) at the end of ablation. A strong correlation was found between free plasma hemoglobin and PFA deliveries (Pearson r=0.615, p<0.001). PFA was further associated with a 2.2-fold increase in bilirubin (21.3 ± 11.3 vs. 9.6 ± 4.7 µmol/l), a 2.4-fold decrease in haptoglobin (0.5 ± 0.4 vs. 1.2 ± 0.4 g/l) and a 1.8-fold increase in LDH (352.7 ± 115.7 vs. 192.2 ± 51.6 U/l, T3 vs. T1, all p<0.001). There were no significant changes in bilirubin and haptoglobin in the RFA group (p>0.05). A slight decrease in red blood cells, hemoglobin and hematocrit was detected after both PFA and RFA (Abstract Figure), with no significant differences between groups (all p>0.05). While mean creatinine levels and glomerular filtration rates did not significantly change after ablation in either group, acute kidney injury occurred in 4/124 (3.2%) with PFA vs. 0/32 (0%) with RFA (p=0.303).

Intravascular hemolysis is a frequent finding after PFA for AF and increases with the number of PFA deliveries. While PFA was not associated with clinically significant anemia, the incidence of acute kidney injury in the present study warrants future large-scale investigations assessing the biological impact and nephrotoxicity of PFA-induced hemolysis.

Abstract Figure