Pulsed-field ablation increases hemolysis biomarkers but not AKI; lowers major bleedingPulsed-field ablation shows lower bleeding risks for heart rhythm issues

This meta-analysis of observational studies evaluated the association between pulsed-field ablation (PFA) and thermal ablation for atrial fibrillation (AF) ablation, focusing on hemolysis biomarkers and acute kidney injury (AKI). The analysis included 5,158 adults undergoing AF ablation, with 4,884 included in the AKI analysis (2,122 PFA, 2,762 thermal). The primary outcomes were change-from-baseline hemolysis biomarkers (lactate dehydrogenase [LDH], haptoglobin, bilirubin) and AKI incidence. Secondary outcomes included major bleeding and procedure time.

PFA was associated with significantly greater hemolysis compared with thermal ablation. The mean difference (MD) in LDH change from baseline was +63.79 U/L (P <.001), haptoglobin decreased by MD -0.30 g/L (P =.036), and bilirubin increased by MD +1.91 μmol/L (P =.023). These biomarker changes indicate greater red blood cell destruction with PFA.

Despite the increased hemolysis biomarkers, AKI incidence did not differ significantly between groups (RR 1.14; 95% CI 0.42-3.12; P =.80; absolute rates 3.5% vs 3.1%). This suggests that the observed hemolysis did not translate into a measurable increase in population-level AKI, although the confidence interval is wide and a clinically meaningful difference cannot be excluded.

PFA was associated with significantly lower major bleeding (RR 0.15; 95% CI 0.04-0.62; P =.009) and shorter procedure time (MD -25.81 min; 95% CI -49.26 to -2.36; P =.031). These findings may offer procedural advantages, but they derive from observational data and should be interpreted as associations, not causal effects.

Safety findings were limited to the reported outcomes. AKI incidence did not differ, and major bleeding was lower with PFA. Serious adverse events, discontinuations, and tolerability were not reported. The analysis did not report follow-up duration, and the certainty of evidence is limited by the observational design and heterogeneity among studies.

Compared with prior evidence, this meta-analysis adds granularity on hemolysis biomarkers, which were not previously emphasized. Prior coverage indicated that PFA shows no significant difference from thermal ablation in arrhythmia freedom or safety. The current findings on AKI and major bleeding are consistent with that overall safety profile, while the hemolysis biomarker elevations are a new signal that warrants attention.

Key limitations include the observational nature of the included studies, which precludes causal inference. Heterogeneity was noted, and the magnitude of hemolysis varied by PFA platform, though specific platform data were not reported. The wide confidence interval for AKI (0.42-3.12) indicates imprecision, and the absolute difference (3.5% vs 3.1%) is small. Additionally, the analysis did not report on hydration protocols, which may influence AKI risk.

For clinical practice, these data support the use of PFA for AF ablation, given the associations with lower major bleeding and shorter procedure time. However, the increased hemolysis biomarkers suggest that dose discipline, adequate hydration, and careful platform selection remain important, particularly for high-risk patients. Clinicians should monitor renal function in patients undergoing PFA, especially those with pre-existing kidney disease, although the current data do not show a significant increase in AKI.

Several questions remain unanswered. The clinical significance of the hemolysis biomarker elevations is unclear, as they did not translate into increased AKI in this analysis. Long-term renal outcomes were not assessed. The impact of different PFA platforms and dosing protocols on hemolysis and AKI requires further investigation. Prospective randomized trials with standardized protocols and longer follow-up are needed to confirm these associations and to determine whether the hemolysis signal has clinical consequences.