Intravascular haemolysis following pulsed field ablation pulmonary vein isolation for atrial fibrillation: A systematic review.

Abstract

Background: Pulsed field ablation (PFA) has emerged as a promising non-thermal alternative to conventional atrial fibrillation (AF) ablation techniques. However, intravascular haemolysis has been increasingly recognised as a potential complication, with variable incidence and clinical significance. Objective: To systematically review the available clinical evidence on PFA-related haemolysis, focusing on biochemical markers, clinical manifestations and device-specific differences. Methods: PubMed, Embase and Cochrane databases were searched until 20 May 2025 for clinical studies evaluating primarily PFA-pulmonary vein isolation for AF that reported haemolysis, acute kidney injury (AKI) or relevant biomarker changes. The primary outcome was evaluation of incidence and biochemical evidence of PFA-related haemolysis. Secondary outcomes included incidence of AKI and its clinical consequences. Results: 12 studies (≈20 000 patients) were included. Biomarker evidence of haemolysis was consistent, with postablation lactate dehydrogenase elevations of 250–438 U/L and bilirubin 15–48 µmol/L, often accompanied by reduced haptoglobin and elevated free haemoglobin. Incidence of haemolysis varied widely (0–94.3%), reflecting heterogeneity in definitions and reporting. Clinical sequelae were uncommon: haemoglobinuria was observed in five studies, and AKI occurred in 83 patients (0.4%), 12 requiring transient dialysis. All returned to baseline renal function except one patient with severe chronic kidney disease. Procedural factors and catheter design may influence haemolysis burden. Observations of lower haemolytic biomarker changes with devices such as PulseSelect, Affera and Volt are preliminary and require confirmation, given the predominance of Farawave data. Conclusions: Haemolysis is a reproducible biochemical outcome of PFA, but clinically significant events such as AKI are rare and usually reversible. Catheter design, energy delivery and patient baseline renal function are likely to modulate haemolysis risk. Standardised haemolysis definitions and prospective head-to-head comparisons across PFA platforms are needed to clarify clinical relevance and optimise safety. PROSPERO registration number CRD420251069612.