Mortality Falls After AF Ablation in Heart Failure: CASTLE-AF in Print

February 02, 2018

BOSTON — Catheter ablation of AF, as opposed to rhythm- or rate-control medical therapy, was followed by a significantly reduced rate of death or HF hospitalization in patients with both AF and HF and reduced ejection fraction in the randomized CASTLE-AF trial.[1]

Ablation was also associated with significantly improved LV function and reductions in all-cause and cardiovascular mortalities, as well as HF hospitalization over the 363-patient trial's median follow-up, which exceeded 3 years. This is longer than most other AF ablation trials.

CASTLE-AF was published January 31 in the New England Journal of Medicine with essentially the same outcomes reported at the August 2017 European Society of Cardiology (ESC) Congress, which | Medscape Cardiology covered at the time.

A majority of patients in the ablation group, about 63%, were in sinus rhythm at the 60-month follow-up, compared with only 22% (P<0.001) in the group with medically managed AF, "which suggests that maintenance of sinus rhythm is beneficial when achieved without the use of antiarrhythmic drugs," write the authors, led by Dr Nassir F Marrouche (University of Utah Health, Salt Lake City).

As invited discussant after the CASTLE-AF presentation at last year's ESC sessions, Dr Carina Blomstrom-Lundqvist (Uppsala University, Sweden), who was not involved in the study, pointed out ways the trial differs from prior AF studies comparing ablation to medical rate control or rhythm control.

"The CASTLE-AF trial is novel, because it's the first time we use as a primary end point mortality and hospitalization, which both combined and separately showed reduction of these events in the AF-ablation arm compared with conventional treatment, and the follow-up was long term," she said, as previously reported by | Medscape Cardiology.

"One unexpected finding I think was that the maintenance of sinus rhythm was very high in the ablation arm even after 5 years, which is usually not the pattern you see."

According to an editorial accompanying the new publication,[2] "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."

Still, writes Dr Mark S Link (University of Texas Southwestern Medical Center, Dallas), "this trial builds on and adds to the accumulating evidence that the use of ablation to maintain normal sinus rhythm in patients with atrial fibrillation and congestive heart failure not only results in fewer admissions for heart failure and decreased mortality but also leads to reverse remodeling."

The trial had randomly assigned patients with symptomatic paroxysmal or persistent AF, NYHA class 2 to 4 heart failure, an LVEF less than 35%, and an implanted defibrillator: 179 to undergo AF ablation and 184 to guidelines-based rate- or rhythm-control medical management.

Over a median of 37.8 months, the adjusted hazard ratio (HR) was 0.62 (95% CI, 0.43–0.87; P=0.007, ablation vs medical therapy), for the primary endpoint of death from any cause or hospitalization for worsening HF. 

Significant HR reductions also favored the ablation group for death from any cause (by 47%; P=0.01), hospitalization for worsening HF (by 44%; P=0.004), cardiovascular death (by 51%; P=0.009), and cardiovascular hospitalization (by 28%; P=0.04). No significant difference was seen in the rate of stroke.

In his editorial, Link writes, "For the present, it seems reasonable to be more aggressive in offering ablation for atrial fibrillation in patients who also have congestive heart failure."

As discussant at the ESC sessions, Blomstrom-Lundqvist questioned whether the CASTLE-AF results would appear as favorable for ablation had the patients overall been older or with more severe HF (noting that most were in NYHA class 2), or if it had not been restricted to symptomatic patients.

"The take-home message is it's time to offer AF ablation procedures at an early stage in CHF patients with AF," she concluded. But, she added, "we'll be careful to select the patients, and that selection should reflect the populations included in the trial."

CASTLE AF was supported by Biotronik. Marrouche discloses receiving grant support and consulting for Abbott, Wavelet Health, Medtronic, Vytronus, Biosense Webster, Boston Scientific, GE Health Care, and Siemens; consulting for Preventice; and holding equity in Marrek and Cardiac Design. Link had no disclosures. At the ESC sessions, Blomstrom-Lundqvist had reported no relevant financial relationships.

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