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Heart failure patients had better long-term outcomes when they were randomized to catheter ablation instead of medical therapy to treat their atrial fibrillation (Afib), the CASTLE-AF investigators reported.

The rate of combined death from any cause or hospitalization for worsening heart failure reached (HR 0.62, 95% CI 0.43-0.87) after a median 37.8 months. Both endpoints individually also significantly favored catheter ablation.

Also, fewer ablation-treated patients died from cardiovascular causes (11.2% versus 22.3%, HR 0.49, 95% CI 0.29-0.84), Nassir Marrouche, MD, of University of Utah Health in Salt Lake City, and colleagues reported in the Feb. 1 issue of the New England Journal of Medicine.

Top-line findings of CASTLE-AF were previously reported at the European Society of Cardiology meeting in 2017.

"This is a remarkable trial that should strongly move the needle to change practice. This trial rigorously confirms what many of us ablationists have suspected all along -- that there is benefit in heart failure -- particularly in moderate LV [left ventricular] dysfunction that is not past the point of no return," commented Mintu Turakhia, MD, of Stanford University and VA Palo Alto Healthcare System.

"The mortality benefit is striking," he added, "and appears to track along with reduction in cardiovascular death, improvement in EF [ejection fraction], reduction in Afib, and decrease in heart failure severity – these data make sense and are compelling."

"The greatest treatment benefit appears to be in earlier-stage heart failure -- NYHA class II, and EFs that are not severely depressed. However, there was no treatment interaction with Afib severity, and ischemic cardiomyopathy patients also had benefit. Therefore, ablation seems appropriate in situations where there is a reasonable chance of the EF improving, few competing causes of death, and low procedural risk," continued Turakhia, who was not involved in the trial.

In an , Mark Link, MD, of UT Southwestern Medical Center in Dallas, agreed that "it seems reasonable to be more aggressive in offering ablation for Afib in patients who also have congestive heart failure."

The mortality benefit of ablation emerged after 3 years, Marrouche and colleagues noted. In addition to the advantages in survival and reduced rehospitalization for heart failure, heart failure patients also had LVEF increase by 8% after catheter ablation compared with 0.2% in medical-therapy group (P=0.005). Moreover, 63.1% and 21.7% of the groups, respectively, were in sinus rhythm at 60-month follow-up (P<0.001).

Patients with both paroxysmal and persistent Afib benefited from catheter ablation, according to Marrouche's group. "We avoided mandating a specific strategy (rate control versus rhythm control) or choice of antiarrhythmic drugs in the medical-therapy group, since previous studies had not shown one strategy or drug to be superior to another," they said.

CASTLE-AF enrolled patients with heart failure with LVEF below 35%, and all had cardiac resynchronization therapy defibrillators or implantable cardioverter defibrillators with automatic daily remote-monitoring capabilities. They either didn't respond to or didn't want to take antiarrhythmic drugs.

The bulk of more than 3,000 recruits had been excluded after a 5-week run-in period to adjust heart failure medication. Afterward, a baseline assessment was performed and patients were randomized to catheter ablation (n=179) or medical therapy (n=184).

One caveat to the trial was that a greater number of patients in the ablation group than in the medical-therapy group crossed over to the other treatment group, the investigators acknowledged, though they said their results held up similarly in per-protocol and as-treated analyses.

"The study was underpowered in women even though the investigators did all they could to enroll. Based on the totality of evidence, I would expect similar treatment effects in women," Turakhia added. "Future studies may be helpful to solidify this."

"These findings must be interpreted conservatively given the relatively small sample size, specific criteria for patient selection, lack of blinded randomization, and treatment allocation, and the fact that the procedures were performed by experienced operators in high-volume medical centers, a circumstance that probably reduced complication rates," according to Link.

"Despite these limitations, this trial builds on and adds to the accumulating evidence that the use of ablation to maintain normal sinus rhythm in patients with Afib and congestive heart failure not only results in fewer admissions for heart failure and decreased mortality but also leads to reverse remodeling, as indicated by an improvement in LVEF," he wrote.

Link noted that ablation did not completely eliminate Afib, but decreased the time in Afib to 25% (versus 60% for the medical therapy group). This suggests, he said, that an outright "'cure' of Afib is not necessary to improve outcomes in heart failure."

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