Does Ejection Fraction Make or Break Afib Ablation in Heart Failure Patients?

The efficacy of catheter ablation for heart failure (HF) patients with atrial fibrillation (Afib or AF) hinged on the phenotype of disease, researchers reported based on a meta-analysis.

Compared with conventional rate or rhythm control, pulmonary vein isolation (PVI)-based catheter ablation was associated with reduced risk of HF events in HF with reduced ejection fraction, or HFrEF (RR 0.59, 95% CI 0.48-0.72), while this benefit did not apply to patients with HF with preserved ejection fraction, or HFpEF (RR 0.93, 95% CI 0.65-1.32). This HF event effect tested significant for interaction by ejection fraction (P=0.03), according to Jorge Wong, MD, MPH, of the Population Health Research Institute in Hamilton, Ontario, and colleagues.

Catheter ablation was also associated with reduced risk of cardiovascular death compared with conventional therapies in HFrEF (RR 0.49, 95% CI 0.34-0.70) but not in HFpEF (RR 0.91, 95% CI 0.46-1.79). Improvement in all-cause mortality was similarly detected in the HFrEF (RR 0.63, 95% CI 0.47-0.86) but not the HFpEF (RR 0.95, 95% CI 0.39-2.30) group.

Given the scant mortality outcomes data for catheter ablation in HFpEF, however, these latter endpoints had wide confidence intervals and were ultimately not enough to support significant treatment interaction by ejection fraction, Wong's group reported in JAMA Cardiology.

"The currently available randomized evidence suggests that catheter ablation for AF was associated with reduced risk of HF events in patients with HFrEF but with no or limited efficacy in patients with HFpEF," study authors concluded.

"These observations indicate lack of sufficient power for drawing definitive conclusions about differential mortality benefit with catheter ablation according to HF phenotype," they noted. "[Randomized clinical trials] are needed to reach definitive conclusions about the role of catheter ablation in patients with HFpEF."

Such ongoing trials include the German CABA-HFPEF and China's STABLE-SR IV. Both studies are evaluating catheter ablation compared with conventional therapy in patients with Afib and concomitant HFpEF for more conclusive data on cardiovascular outcomes.

Steadily increasing in prevalence, HFpEF is expected to be the more common form of HF in the future, Wong and colleagues noted. They added that Afib is a coexisting condition in the majority of HFpEF patients, and cited that Afib is associated with an estimated 30-40% increase in HF hospitalizations and mortality.

CASTLE-AF and AATAC were the major trials that established that Afib ablation procedures can reduce all-cause mortality and worsening HF hospitalizations in some patients, relative to medical therapy alone.

Since 2022, American guidelines have given Afib ablation a class IIa recommendation for symptomatic HF patients regardless of ejection fraction, based on these two trials. Similarly, European guidelines also endorse catheter ablation for better HF outcomes in people with HFrEF and Afib, a class IIa recommendation starting in 2020.

"AF ablation in HF is an established standard of care. However, we concur with [Wong and colleagues] 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," cautioned JAMA Cardiology editors Kristen Patton, MD, of University of Washington School of Medicine in Seattle, and Clyde Yancy, MD, MSc, of Northwestern University Feinberg School of Medicine in Chicago.

Patton and Yancy recalled the controversy over CASTLE-AF and its limited robustness of outcome data, high loss to follow-up, and baseline imbalances between groups.

"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," the duo wrote in an editor's note.

For their present report, Wong's group conducted a meta-analysis pooling 12 randomized trials of HF patients with a New York Heart Association functional class II or worse and a history of paroxysmal or persistent Afib.

Included studies had parallel groups randomized to either PVI ablation (with or without posterior left atrial wall isolation, additional linear lesions, or trigger modulation) or conventional rate/rhythm control strategies (e.g., rate-lowering medications, atrioventricular junction ablation followed by pacemaker or cardiac resynchronization therapy device implantation, antiarrhythmic medications, and electrical cardioversion).

The total cohort counted 2,465 people averaging age 65.3 years, with 26.7% women. Patients were split between the 20.3% who had paroxysmal Afib and 79.7% with persistent or long-standing persistent Afib.

HFrEF and HFpEF accounted for 63.0% and 37.0% of patients, respectively. Study authors acknowledged a major limitation of these estimates, however, as the 12 trials differed in how they defined HFpEF.

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