A subgroup analysis of the EAST – AFNET 4 study population revealed: Early initiation of rhythm control therapy is associated with clinical benefit in patients with heart failure and recently diagnosed atrial fibrillation. The new findings were presented by Dr. Andreas Rillig, UKE Hamburg, at the HRS congress on 30.07.2021 , .
Atrial fibrillation (AF) and heart failure (HF) are two cardiovascular epidemics which often appear together. Approximately 30 % of patients with atrial fibrillation suffer from heart failure. These patients with both conditions are at particular risk of cardiovascular complications including death, stroke, and worsening of heart failure. Recent studies suggest that rhythm control therapy using atrial fibrillation ablation could improve left ventricular function in patients with atrial fibrillation and heart failure, and that this may lead to improved outcomes. However, further evidence illustrating these effects in different HF subtypes is needed.
The EAST – AFNET 4 trial investigated whether rhythm control therapy – with antiarrhythmic drugs or ablation – delivered within one year after AF diagnosis improves outcomes. The main study result, published last year , demonstrated a clinical benefit of early rhythm control therapy for all patients: Early rhythm control therapy with antiarrhythmic drugs and/or AF ablation reduced a composite of cardiovascular death, stroke, and hospitalization for worsening heart failure or acute coronary syndrome in 2789 patients with early AF and cardiovascular risk factors compared to usual care over a 5-year follow-up time.
Now the EAST – AFNET 4 investigators studied whether the beneficial effects of early rhythm control can be transferred to the subgroup of HF patients. Principal investigator Professor Paulus Kirchhof of the University Heart and Vascular Centre UKE Hamburg, Germany, explains: “Rhythm control is an important component of AF management in HF patients. However, it is not clear, whether rhythm control therapy conveys clinical benefit in patients with moderately reduced or preserved left ventricular ejection fraction (LVEF). To answer this question, we analyzed the effect of early rhythm control in patients with HF enrolled into the EAST – AFNET 4 trial.”
The analysis includes 798 patients with HF (785 with known LVEF at baseline). The majority, 442 patients, had HF with preserved LVEF (LVEF≥50%), 211 HF with mid-range LVEF (LVEF40-49%), and 132 HF with reduced LVEF (LVEF<40%). 396 patients were randomized to early rhythm control, 402 to usual care.
Over the 5.1-year median follow-up, the composite primary outcome of cardiovascular death, stroke or hospitalization for worsening of HF or for acute coronary syndrome occurred less frequently in HF patients randomized to early rhythm control (94/396; 5.7 per 100 patient-years) compared to HF patients randomized to usual care (130/402; 7.9 per 100 patient-years).
Early rhythm control therapy was safe in patients with HF. The primary safety outcome – defined as a composite of death, stroke, or serious adverse events of rhythm control therapy – occurred in 71/396 (17.9%) HF patients on early rhythm control and in 87/402 (21.6%) on usual care. Left ventricular function improved in both groups.
Dr. Rillig concludes: “The results of this analysis demonstrate a clinical benefit of early rhythm control therapy for all HF patients of the EAST – AFNET 4 trial. Early rhythm control based on either antiarrhythmic drug therapy or catheter ablation should be offered to all patients with AF and symptoms of HF or reduced LVEF.”
 Rillig A, Ozga A, Magnussen C, Brandes A, Breithardt G, Camm AJ, Crijns HJGM, Eckardt L, Elvan A, Gulizia M, Haegeli LM, Heidbuchel H, Kuck KH, Ng GA, Szumowski L, van Gelder IC, Wegscheider K, Kirchhof P. Early rhythm control therapy in patients with atrial fibrillation and heart failure. Abstract HRS congress 2021
 Rillig A, Magnussen C, Ozga, Suling A, Brandes A, Breithardt G, Camm AJ, Crijns HJGM, Eckardt L, Elvan A, Goette A, Gulizia M, Haegeli LM, Heidbuchel H, Kuck KH, Ng GA, Szumowski L, van Gelder IC, Wegscheider K, Kirchhof P. Early rhythm control therapy in patients with heart failure. Circulation. 2021; (published ahead of print). DOI: 10.1161/CIRCULATIONAHA.121.056323
 Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, Fetsch T, van Gelder IC, Haase D, Haegeli LM, Hamann F, Heidbüchel H, Hindricks G, Kautzner J, Kuck K-H, Mont L, Ng GA, Rekosz J, Schön N, Schotten U, Suling A, Taggeselle J, Themistoclakis S, Vettorazzi E, Vardas P, Wegscheider K, Willems S, Crijns HJGM, Breithardt G, for the EAST–AFNET 4 trial investigators. Early rhythm control therapy in patients with atrial fibrillation. N Engl J Med 2020; 383:1305-1316.
Angelika Leute, PhD
Phone: +49 202 2623395
Follow us on Twitter @afnet_ev and hashtag #EASTtrial. @AndreasRillig
Funding: AFNET, BMBF, DZHK, EHRA, Deutsche Herzstiftung, Abbott, Sanofi
About the EAST – AFNET 4 trial
EAST – AFNET 4 is an investigator initiated trial (IIT) that compared two different treatment strategies in atrial fibrillation. The EAST – AFNET 4 trial tested whether an early, comprehensive rhythm control therapy can prevent adverse cardiovascular outcomes in patients with atrial fibrillation (AF) compared to usual care.
A total of 2789 patients with early AF (diagnosed less than a year ago) and at least two cardiovascular conditions (approximating a CHA₂DS₂-VASc score >=2) were enrolled by 135 sites in 11 countries during 2011 to 2016. Patients were randomized 1:1 to early rhythm control therapy or usual care, stratified by sites. Patients in both groups received guideline-recommended treatment for underlying cardiovascular conditions, anticoagulation, and rate control.
All patients in the early rhythm control group received antiarrhythmic drugs or catheter ablation after randomization (chosen by the local study teams). Rhythm control therapy was escalated with AF ablation and/or antiarrhythmic drugs when recurrent AF was documented clinically or by ECG, including monitoring with patient-operated ECG devices.
Patients in the usual care group were initially managed with rate control. Rhythm control therapy was only used to improve atrial fibrillation-related symptoms despite optimal rate control, following current guidelines.
About the Atrial Fibrillation NETwork (AFNET)
The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK).