AMSTERDAM — Catheter ablation conferred large clinical benefits to people with end-stage heart failure and symptomatic atrial fibrillation (Afib) in the small CASTLE HTx randomized trial that was terminated prematurely for efficacy.

The trial, originally planned for 2 years, was brought to a halt upon the discovery that these patients undergoing catheter ablation had fewer composite adverse events a median 1.5 years later compared with peers staying on medications alone (8% vs 30%, HR 0.24, 95% CI 0.11-0.52).

Broken down individually, the three components of the primary endpoint largely favored catheter ablation on intention-to-treat analysis:

• All-cause death (6% vs 20%, HR 0.09, 95% CI 0.12-0.72), a reduction in cardiovascular deaths accounting for much of the difference
• Left ventricular assist device (LVAD) implantation (1% vs 10%, HR 0.09, 95% CI 0.01-0.70)
• Urgent heart transplant (1% vs 6%, HR 0.15, 95% CI 0.02-1.25)

Christian Sohns, MD, of Herz- und Diabeteszentrum Nordrhein-Westfalen, Ruhr-Universität Bochum (HDZ NRW) in Bad Oeynhausen, Germany, presented CASTLE HTx at the European Society of Cardiology (ESC) congress. The findings also were published in the New England Journal of Medicine.

Safety data suggest few, minor adverse events related to catheter ablation in end-stage heart failure, according to the report.

“Afib ablation should be considered as part of the standard therapy options in advanced heart failure patients. Afib ablation has beneficial effects on mortality during the waiting time for heart transplant and prolongs the time span until necessity for surgical interventions,” Sohns said.

CASTLE HTx was designed as a follow-up to 2017’s CASTLE-AF, which had shown catheter ablation to be successful in Afib patients with impaired left ventricular ejection fraction (LVEF). Some have since surmised that the benefits of reduced hospitalization and mortality may have been driven by lower Afib burden and improved LVEF in that trial.

Indeed, the CASTLE HTx investigators reported that LVEF rose by 6.4 percentage points and Afib burden was reduced by more than 20% compared with controls at 12 months following catheter ablation.

Although the 194 patients in CASTLE HTx are fewer than the original CASTLE’s sample of over 350, the quality of the data in the present report nevertheless “is enough to affect guidelines,” said study co-author Philipp Sommer, MD, also of HDZ NRW, during an ESC press conference.

Rod Passman, MD, of Northwestern University Feinberg School of Medicine in Chicago, suggested caution, however.

“It is worth noting that this is a single-center study where ablation was performed by a limited number of experienced operators. If less experienced centers and operators took on these cases with increasing frequency, it will be important to ensure that the success rates and complication rates can be reproduced in the ‘real world,'” he told MedPage Today.

The trial’s results are nevertheless “very impressive” and provide “a compelling argument” for Afib ablation in patients with end-stage heart failure and symptomatic Afib, he said.

“If a patient is a candidate for ablation, it will be critical to perform the procedure in a timely manner so as not to delay the work up for transplant. However, if a reduction in Afib burden achieved through ablation can improve the ejection fraction and delay or avoid the need for LVAD or transplant, perhaps ablation should be considered before someone is actually listed,” noted Passman, who was not involved with the study.

Importantly, he said the question remains whether end-stage heart failure patients should be put on amiodarone or go straight to ablation for their Afib.

CASTLE HTx was a single-center trial that enrolled patients with symptomatic Afib and end-stage heart failure who had been referred for heart transplantation or LVAD placement. They agreed to be randomized to guideline-directed medical therapy with or without catheter ablation.

The 194 participants averaged just below age 65, and were approximately 80% men.

Over half were in New York Heart Association class III and approximately one-third were class II. The 6-minute walk test result was around 300 meters at baseline, average LVEF was 27%, and the cause of heart failure was most commonly nonischemic. Afib was persistent or long-standing persistent for around 70% of people and paroxysmal in the remaining 30%.

Background drug therapy was “very complete” in this group, according to Sommer. Two-thirds of people were on sacubitril/valsartan (Entresto) and 45% on amiodarone.

Catheter ablation was performed in 84% of the ablation group and in 16% in the medical-therapy group.

Sommer acknowledged that he and his collaborators had been concerned about potential complications in people with end-stage heart failure undergoing ablation. By procedural duration and complication rates, however, it ended up being “like a normal patient population … nothing really special,” he said.

Procedure-related complications were all vascular access site problems: three in the ablation group and one in the medical therapy group.

That is in experienced hands at just one center, however, and not every ablationist would consider the procedure for the “very sick” end-stage heart failure population, Sommer acknowledged. “This should change,” he said. “We need more of those skilled hands.”

Other limitations of CASTLE HTx include its open-label design, early termination, and exclusion of people with asymptomatic Afib. Additionally, it is unknown how pulsed field ablation would fare in this kind of population, according to Passman.

Please enable JavaScript to view the

comments powered by Disqus.