Catheter Ablation for AFib Shows Little to No Benefit in HFpEF, Despite Positive Effect in HFrEF

Alireza Oraii, MD
Credit: LinkedIn

An analysis of data from a dozen randomized clinical trials encompassing more than 2400 patients offers an overview of the comparative effects of catheter ablation for atrial fibrillation among patients with heart failure with reduced ejection fraction (HFrEF) relative to their counterparts with heart failure with preserved ejection fraction (HFpEF).

Results of the study suggested use of catheter ablation for atrial fibrillation was associated with a reduced risk of heart failure events among those with HFrEF, but this benefit was not observed among those with HFpEF.¹

“To our knowledge, this systematic review and meta-analysis has for the first time pooled the most up-to-date randomized evidence to compare the differential efficacy of catheter ablation in the reduction of [heart failure]-related outcomes according to [heart failure] phenotype,” wrote investigators.¹ “The currently available randomized evidence suggests that catheter ablation for [atrial fibrillation] was associated with reduced risk of [heart failure] events in patients with HFrEF but with no or limited efficacy in patients with HFpEF.”

Management of heart failure has undergone a transformation since the turn of the century thanks to advancements in understanding of pathophysiology and therapeutics, including the ARNI and SGLT2 inhibitor classes, which have been examined in both HFrEF and HFpEF. Still, despite having new medications with specific indications for HFpEF, management has proven difficult.

Citing a lack of studies comprehensively summarizing and comparing randomized evidence on differential efficacy of ablation on heart failure outcomes for people with HFpEF relative to their counterparts with HFrEF, a team of investigators led by Alireza Oraii, MD, of Penn Medicine, launched the current study to fill this knowledge gap. Oraii and colleagues designed their systematic review and meta-analysis to leverage data obtained from a literature search in the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for studies published from inception to September 3, 2023.¹

The primary outcome of interest for the systematic review and meta-analysis was difference in risk of heart failure events with catheter ablation relative to conventional rate or rhythm control therapies in those with HFrEF and HFpEF. Investigators defined heart failure events as heart failure hospitalization, clinically significant worsening of heart failure, or unscheduled visits to a clinician for treatment intensification. Secondary outcomes of interest included cardiovascular and all-cause mortality.¹

Studies of interest for the systematic review and meta-analysis included parallel-group randomized clinical trials comparing catheter ablation with conventional rate or rhythm control therapies in patients with heart failure, New York Heart Association functional class II or greater, and a history of paroxysmal or persistent atrial fibrillation. From their initial search, 7531 titles and abstracts were identified for review. Among these, 12 randomized clinical trials and 4 substudies met inclusion criteria.¹

These 12 studies included 2465 participants, with 1552 having HFrEF and 913 having HFpEF. The overall cohort had a mean age of 65.3 (Standard Deviation [SD], 9.7) years and 26.7% were female.¹

Results of the meta-analysis indicated catheter ablation was associated with a reduced risk of heart failure events in HFrEF compared to use of conventional rate or rhythm control (Risk Ratio [RR], 0.59; 95% Confidence Interval [CI], 0.48 to 0.72). However, this benefit was not observed among those with HFpEF (RR, 0.93; 95% CI, 0.65 to 1.32; P for interaction = .03). Analysis of cardiovascular death revealed catheter ablation associated with reduced risk compared with conventional therapies in HFrEF (RR, 0.49; 95% CI, 0.34 to 0.70), but no such benefit observed in HFpEF (RR, 0.91; 95% CI, 0.46 to 1.79; P for interaction = .12). For all-cause mortality, there was no difference observed for benefit of catheter ablation relative to conventional therapies in those with HFrEF (RR, 0.63; 95% CI, 0.47 to 0.86) and HFpEF (RR, 0.95; 95% CI, 0.39-2.30; P for interaction = .39).¹

Before concluding investigators called specific attention to limitations of their study to consider when interpreting results, including an elevated level of heterogeneity observed with pooled effect estimates, variable definitions for HFpEF across the studies, and limited available randomized evidence published to date in patients with HFpEF.¹

In an editorial comment, Kristen Patton, MD, of the University of Washington, and Clyde Yancy, MD, MSc, of Northwestern University, commended investigators for their contributions and noted how their calls for more research are echoed by others in the community.²

“AF ablation in [heart failure] is an established standard of care. However, we concur with the authors and further assert that the durability of the mortality benefit per se in HFrEF and the evidence of important clinical benefit, including mortality, in HFpEF remain uncertain,” wrote the pair.² “Clearly, more outcomes from rigorous, randomized clinical trials better elucidating the role of ablation in patients with both HFrEF and HFpEF are warranted. Simply put, we need more data.”

References:

1. Oraii A, McIntyre WF, Parkash R, et al. Atrial Fibrillation Ablation in Heart Failure With Reduced vs Preserved Ejection Fraction: A Systematic Review and Meta-Analysis. JAMA Cardiol. Published online April 24, 2024. doi:10.1001/jamacardio.2024.0675
2. Patton KK, Yancy CW. Atrial Fibrillation Ablation in Heart Failure—More Data Are Needed. JAMA Cardiol. Published online April 24, 2024. doi:10.1001/jamacardio.2024.0684