Catheter ablation outshines pharmacotherapy in AF patients with heart failure

Among atrial fibrillation (AF) patients with clinically defined heart failure (HF), catheter ablation yields greater survival gains, freedom from AF recurrence, and quality of life (QoL) boost than does drug therapy, according to the results of the CABANA AF* substudy.

Specifically, there was a 43-percent relative reduction in all-cause mortality (3.1 per 100 absolute reduction at 5 years), 44-percent decrease in time to first AF recurrence, and meaningful and sustained improvements in QoL up to 5 years among AF patients with New York Heart Association (NYHA) class II or III HF at trial entry, most of whom did not have a reduced ejection fraction (EF), the investigators said.

“The morbidity of AF has been recognized for many decades, but the recognition that the development of and presence of AF is also associated with [decreased survival] is more recent,” they pointed out, adding that some of the excess mortality risk may be attributed to associated heart diseases, such as valvular or coronary disease. [J Am Coll Cardiol 2007;49:986-992; Am J Med 2002;113:359-364; Eur Heart J 2013;34:1061-1067; Eur Heart J 2016;37:2882-2889]

“If [the present] findings can be confirmed in adequately sized replication trials, clinicians would have a powerful new strategy for reducing the patient suffering and premature mortality that result when AF and HF occur together,” they pointed out.

The CABANA AF substudy included 778 AF patients (median age 68 years, 44.3 percent female) with NYHA class >II. Of these, 387 patients underwent ablation with pulmonary vein isolation, while the remaining 400 received drug therapy, including rate or rhythm control drugs.

At baseline, AF was paroxysmal in 31.6 percent of the patients, persistent in 55.3 percent, and longstanding persistent in 13.1 percent. Three-fourths of the population were taking a β-blocker, and 64 percent were on an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Of the 571 patients with baseline EF data, 79 percent had an EF ≥50 percent, 11.7 percent had an EF between 40 percent and 49 percent, and 9.3 percent had an EF <40 percent.

Over a median follow-up of 48.5 months, the primary composite endpoint (death, disabling stroke, serious bleeding, or cardiac arrest) occurred less frequently in the ablation than in the pharmacotherapy group (9.0 percent vs 12.3 percent; hazard ratio [HR], 0.64, 95 percent CI, 0.41–0.99). [Circulation 2021;143:1377-1390]

The results were similar for both all-cause mortality (6.1 percent vs 9.3 percent; HR, 0.57, 95 percent CI, 0.33–0.96) and AF recurrence (HR, 0.56, 95 percent CI, 0.42–0.74). By month 12, recurrence was documented in 37 percent and 58 percent of patients in the ablation and pharmacotherapy groups, respectively. The corresponding numbers at 5 years were 56 percent and 72 percent. There were no significant differences in HF hospitalizations.

QoL scores also favoured catheter ablation. The adjusted mean difference for the Atrial Fibrillation Effect on Quality of Life summary score averaged over the entire 60-month follow-up was 5.0 points, while that for the Mayo Atrial Fibrillation-Specific Symptom Inventory frequency score was –2.0 points.

The most common treatment-related adverse events in the ablation group were haematoma (3.2 percent), pseudoaneurysm (1.2 percent), oesophageal ulcer (1.2 percent), and severe pericardial chest pain (0.6 percent). In the pharmacotherapy group, hyper- or hypothyroidism (2.5 percent) occurred frequently, followed by gastrointestinal abnormality excluding moderate or severe diarrhoea (1.3 percent), major proarrhythmic event (0.8 percent), and liver injury or failure (0.5 percent).

“CABANA is the first large randomized trial to describe an important mortality benefit from AF treatment in HF [patients] who predominately have preserved systolic function,” according to the investigators.

While there exist several relatively small trials comparing catheter ablation with pharmacotherapy in AF patients with HF, most were limited to patients with systolic dysfunction, with predominately NYHA class II or III symptoms, and persistent AF. [BMC Cardiovasc Disord 2019;19:18; Circ Arrhythm Electrophysiol 2019;12:e007731; N Engl J Med 2018;378:417-427; Ann Intern Med 2019;171:76-77]

The investigators, however, cautioned against interpreting the results as “practice changing,” as data are still needed to be reproduced in a confirmatory trial of ablation in the same population.

*Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation