Low-dose digoxin improves cardiac function in patients with heart failure, preserved ejection fraction and atrial fibrillation - the RATE-AF randomized trial.

Aims: To compare the effect of digoxin versus beta-blockers on left ventricular function, in patients with permanent atrial fibrillation (AF) and symptoms of heart failure within the RATE-AF randomized trial.

Methods and results: Blinded echocardiograms were performed at baseline and 12-month follow-up using a pre-defined imaging protocol and the index-beat approach. The change in systolic and diastolic function was assessed, stratified by left ventricular ejection fraction (LVEF). Overall, 145 patients completed follow-up, with median age 75 years (interquartile range 69-82) and 44% women. In 119 patients with baseline LVEF ≥50%, a significantly greater improvement in systolic function was noted in patients randomized to low-dose digoxin versus beta-blockers: adjusted mean difference for LVEF 2.3% (95% confidence interval [CI] 0.3-4.2; p = 0.021), s' 1.1 cm/s (95% CI 1.0-1.2; p = 0.001) and stroke volume 6.5 ml (95% CI 0.4-12.6; p = 0.037), with no difference in global longitudinal strain (p = 0.11) or any diastolic parameters. There were no significant differences between groups for patients with LVEF 40-49% and <40%. Digoxin reduced N-terminal pro-B-type natriuretic peptide compared to beta-blockers (geometric mean difference 0.77; 95% CI 0.64-0.92; p = 0.004), improved New York Heart Association functional class (odds ratio [OR] 11.3, 95% CI 4.3-29.8; p < 0.001) and modified European Heart Rhythm Association arrhythmia symptom class (OR 4.91, 95% CI 2.36-10.23; p < 0.001), with substantially less adverse events (incident rate ratio 0.21, 95% CI 0.13-0.31; p < 0.001). There were no interactions between treatment effects and baseline LVEF for these outcomes (interaction p = 0.62, 0.49, 0.07 and 0.13, respectively).

Conclusions: Low-dose digoxin in patients with symptoms of heart failure, preserved LVEF and permanent AF leads to a significantly greater improvement in systolic function compared to treatment with beta-blockers.