A Randomized Ablation-based atrial Fibrillation rhythm control versus rate control Trial in patients with heart failure and high burden Atrial Fibrillation - RAFT-AF

Contribution To Literature:

The RAFT-AF trial showed that a rhythm-control strategy (via AF ablation) is not superior to a rate-control strategy for CV outcomes at 5 years among patients with AF and HF. This is in the context of early termination of the trial; event rates were numerically lower in the rhythm-control arm, particularly for patients with pre-existing systolic HF (EF ≤45%).


The goal of the trial was to compare the safety and efficacy of catheter ablation-based rhythm control compared with rate control for the treatment of patients with atrial fibrillation (AF) and heart failure (HF).

Study Design

Patients were randomized in a 1:1 fashion to either rhythm control (n = 214) or rate control (n = 197). For patients undergoing ablation, pulmonary vein isolation was the required minimum lesion set to be delivered; those with persistent AF underwent additional ablation that may have included ablation of complex fractionated atrial electrograms, roof line, mitral isthmus line, left atrial (LA) posterior wall isolation, or a combination of the above. Antiarrhythmic medications used were amiodarone or dofetilide in patients with reduced left ventricular (LV) function and amiodarone or sotalol in patients with preserved LV function. For patients randomized to rate-control, beta-blockers, calcium channel blockers (if not contraindicated), digitalis, or in combination were used to achieve a resting heart rate <80 bpm and <110 bpm during a 6-minute walk).

  • Total number of enrollees: 411
  • Duration of follow-up: 37.4 months
  • Mean patient age: 67 years
  • Percentage female: 25%

Inclusion criteria:

  • Patients with one of the following AF type (≥1 electrocardiogram of AF):
    • High burden paroxysmal AF: ≥4 episodes of AF in the last 6 months, and ≥1 episode >6 hours (not required cardioversion) and was <7 days
    • Persistent AF 1: AF episodes <7 days but requires cardioversion
    • Persistent AF 2: ≥1 episode of AF >7 days but not >1 year
    • Long-term persistent AF: ≥1 episode >1 year, but not <3 years
  • Optimal therapy for HF of ≥6 weeks
  • HF with New York Heart Association (NYHA) class II or III symptoms
  • Either impaired LV function (left ventricular ejection fraction [LVEF] ≤45%) or preserved LV function (LVEF >45%) determined within 12 months prior to enrollment
  • Suitable candidate for catheter ablation or rate control for the treatment of AF
  • Age ≥18 years
  • N-terminal pro–B-type natriuretic peptide (NT-proBNP)/BNP levels above predetermined levels based on prior hospitalization and baseline rhythm

Exclusion criteria:

  • LA dimension >5.5 cm
  • Rheumatic heart disease
  • Severe aortic or mitral valve disease
  • Life expectancy <1 year

Other salient features/characteristics:

  • Cardiomyopathy: 9%
  • Underlying nonischemic heart disease: 69%
  • Existing cardiovascular implantable electronic devices (CIED): 33%
  • Baseline medications: beta-blockers: 92%, mineralocorticoid receptor antagonists: 25%
  • Left atrial diameter: 4.6 cm
  • Median LVEF: 58%; LVEF ≤45%: 58%

Principal Findings:

The trial was terminated early due to futility concerns. The primary outcome, death and HF events for rhythm vs. rate control, was: 23.4% vs. 32.5% (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.49-1.03, p = 0.066).

  • Death: 13.6% vs. 17.3% (p = 0.35)
  • HF events: 24.4% vs. 17.8% (p = 0.12)

Among patients with EF ≤45% at baseline: 22.6% vs. 37.1% (HR 0.63, 95% CI 0.39-1.02, p = 0.059)

  • EF >45% at baseline: 24.4% vs. 25.9% (HR 0.88, 95% CI 0.48-1.61, p = 0.67; p for interaction = 0.4)
  • At the end of 60 months, 18.9% of patients in the rhythm-control arm were in AF/atrial flutter compared with 91.2% in the rate-control arm.

Secondary outcomes for rhythm vs. rate control:

  • Minnesota Living With Heart Failure Questionnaire: change from baseline to 24 months: -17.4 vs. -14.8 (p = 0.0036)
  • Change in 6-minute walk distance to 24 months: 44.9 vs. 27.5 meters (p = 0.025)
  • % reduction of geometric mean in NT-proBNP at 24 months: 77.1 vs. 39.2 (p < 0.0001)
  • Change in LVEF from baseline at 24 months: 10.1 vs. 3.8% (p = 0.017)
  • Ablation-related events: 10.8% vs. 0.5% (p < 0.0001)


The results of this important trial indicate that a rhythm-control strategy (via AF ablation) is not superior to a rate-control strategy for cardiovascular (CV) outcomes at 5 years among patients with AF and HF. This is in the context of early termination of the trial; event rates were numerically lower in the rhythm-control arm, particularly for patients with pre-existing systolic HF (EF ≤45%). Significant improvements were, however, noted in functional and serum biomarkers, including NT-proBNP. AF was significantly reduced with rhythm-control strategy, although periprocedural complication rates including perforation and bleeding were high.

Although this is technically a “negative” trial, the results are more similar to EAST-AFNET 4, which showed an improvement in CV outcomes with AF ablation among patients with AF and concomitant CV conditions (HF in 29%). Similarly, although CABANA-AF was negative, a benefit with rhythm control was noted among patients with ≥ NYHA class II HF at baseline. Like most of these trials, the current trial is only single-blinded (not to intervention received). That can confound assessment of the various endpoints. Based on recent experiences from important sham-controlled trials (SYMPLICITY, ORBITA), these findings should prompt consideration for a sham-controlled trial to assess the true efficacy of catheter ablation in modulating CV outcomes among patients with AF and HF.


Highlighted text has been updated as of June 10, 2022.

Parkash R, Wells GA, Rouleau J, et al. Randomized Ablation-Based Rhythm-Control Versus Rate-Control Trial in Patients With Heart Failure and Atrial Fibrillation: Results From the RAFT-AF Trial. Circulation 2022;145:1693-1704.

Editorial: Pokorney SD, Granger CB. Evidence Builds for Catheter Ablation for Atrial Fibrillation and Heart Failure. Circulation 2022;145:1705-7.

Presented by Dr. Anthony Tang at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 17, 2021.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: ACC21, ACC Annual Scientific Session, Arrhythmias, Cardiac, Atrial Fibrillation, Atrial Flutter, Cardiomyopathies, Catheter Ablation, Electric Countershock, Electrocardiography, Heart Failure, Natriuretic Peptide, Brain, Percutaneous Coronary Intervention, Stroke Volume, Ventricular Function, Left

< Back to Listings