Early Rhythm Control Beneficial in Patients With AF and Heart Failure

Researchers determined the effects of early rhythm control therapy in patients diagnosed with atrial fibrillation with signs and symptoms of heart failure.

When initiated within 1 year of atrial fibrillation (AF) diagnosis, rhythm control therapy confers clinical benefit to patients with signs or symptoms of heart failure, according to research results published in Circulation.

Results of the EAST-AFNET 4 trial (ClinicalTrials.gov Identifier: NCT01288352) demonstrated the clinical benefit of early rhythm control therapy delivered via a combination of antiarrhythmic drugs and AF ablation. However, it remains unclear with these clinical benefits can be extrapolated to patients with stable heart failure, particularly heart failure with preserved ejection fraction (HFpEF), and whether these effects can be replicated by early rhythm control via antiarrhythmic drugs or AF ablation.

EAST-AFNET 4, an investigational, investigator initiated, parallel group, randomized, open, blinded-outcome assessment trial, included adults aged 75 years and older with early AF who met 2 of the study inclusion criteria.

Primary outcomes included a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome, and the number of nights spent in the hospital per year. Secondary outcomes included heart rhythm, left ventricular ejection fraction (LVEF), quality of life, AF-related symptoms, and cognitive function.

Overall, 2789 patients were randomly assigned 1:1 to receive either early rhythm control or standard care. A total of 798 patients with stable heart failure were included in the analysis: 442 (56.3%) with HFpEF, 211 (26.9%) with heart failure with moderately reduced ejection fraction (HFmrEF), and 132 (16.8%) with heart failure with reduced ejection function (HFrEF). Patient characteristics were similar between groups.

In total, 94 and 130 patients in the early rhythm control and standard care group, respectively, met the primary outcome (univariable hazard ratio [HR], 0.74; P =.03). The outcome was similar among patients with normal left ventricular function without signs of heart failure (HR, 0.81; P =.06). Patients with and without ischemic cardiomyopathy had a similar risk for both primary outcomes.

Patients with preserved LVEF had a lower risk for the first primary outcome —composite of death — compared with those with reduced LVEF; patients with preserved and mid-range LVEF also had a similar risk for the first primary outcome. Total nights spent in the hospital —the second primary outcome — were higher in the early rhythm control vs standard care group (8.36±27.85 vs 7.46±23.9 nights, respectively).

Early rhythm control improved the combined outcome of death or hospitalization for worsening heart failure, with 91 vs 123 patients in the rhythm control vs standard care group, respectively, experiencing an outcome of death or hospitalization for worsening heart failure. Composite outcome of death, disabling stroke, serious bleeding, and cardiac arrest was numerically lower in patients in the early rhythm control vs standard care group.

Rhythm control therapy was initiated in 93.9% (n=367/391) of patients in the early rhythm control group. Most patients received flecainide, dronedarone, or amiodarone. At baseline, sinus rhythms were recorded more often in patients in the early rhythm control vs standard care group.

Catheter ablation was performed among 140 patients with heart failure: 88 and 52 in the early rhythm control and standard care group, respectively.

In both the early rhythm control therapy and standard care group, LVEF improved (mean improvement, 5.3%±11.6 vs 4.9%±11.6, respectively). The LVEF improved primarily in patients with reduced or mid-range LVEF, with no differences between the randomized groups. A total of 24 and 26 patients in each group, respectively, experienced a complete recovery of initially reduced LVEF.

At the end of follow-up, a similar number of patients without AF symptoms were seen in the rhythm control therapy and standard care group (69.54% vs 64.65%, respectively). Outcomes regarding quality of life were also similar. In both groups, AF symptoms improved at 24 months (56.4% vs 54.2%, respectively).

The majority of patients (approximately 90%) received guideline-recommended oral anticoagulation throughout the follow-up period; vitamin K antagonists and novel oral anticoagulants were distributed evenly between the groups. Therapy for concomitant cardiovascular conditions was also evenly balanced, and heart failure medications did not show differences between the randomized groups at discharge.

New York Heart Association (NYHA) class at baseline showed “some association” with primary and secondary outcomes. At 24 months, NYHA class improved in both groups, with a slightly higher improvement in the early rhythm control group (53.2% vs 45.3%, respectively). Patients with preserved ejection fraction experienced the highest improvement in NYHA class.

Results of a multivariable analysis showed that adjusted effects of the first primary outcome were associated with sex (female vs male hazard ratio [HR], 0.65), ejection fraction (reduced LVEF vs preserved LVEF HR, 1.76), and NYHA class 3 (NYHA class 3 vs no heart failure HR, 3.93).

Study limitations included the lack of blinding and the lack of data on LVEF function and quality of life after the 2-year follow-up.

“This subanalysis…demonstrates that early rhythm control therapy using antiarrhythmic drugs or atrial fibrillation ablation is safe and reduced cardiovascular events in patients with heart failure,” the researchers concluded. “Clinical benefit is observed across the spectrum of heart failure subtypes, suggesting that restoring and maintaining sinus rhythm via rhythm control therapy conveys the clinical benefit.”

“All patients with signs or symptoms of heart failure should be considered for rhythm control therapy within a year of being diagnosed with atrial fibrillation,” they concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Rillig A, Magnussen C, Ozga A-K, et al. Early rhythm control therapy in patients with atrial fibrillation and heart failure. Circulation. Published online July 30, 2021. doi:10.1161/CIRCULATIONAHA.121.056323