Abstract

Aims Observational data suggest that atrial cardiomyopathy can precede the clinical diagnosis of atrial fibrillation (AF) and that severe forms of atrial cardiomyopathy render rhythm control therapy futile. The aim was to quantify atrial cardiomyopathy in patients with recently diagnosed AF and to determine possible interactions between atrial cardiomyopathy and early rhythm control therapy in the EAST-AFNET 4 trial. Methods and results This prespecified analysis of the EAST-AFNET 4 trial quantified baseline atrial cardiomyopathy using left atrial (LA) size, PR interval, and NT-proBNP. Outcomes were compared between atrial cardiomyopathy categories. Interactions between early rhythm control, the randomized therapy in EAST-AFNET 4, and atrial cardiomyopathy were determined. Outcomes included the primary outcome of EAST-AFNET 4 (cardiovascular death, stroke, hospitalization for heart failure or acute coronary syndromes), recurrent AF, and safety outcomes (serious adverse events of special interest or all-cause death). In an exploratory analysis, angiopoietin-2 (ANGPT2) as well as bone morphogenetic protein 10 (BMP10) were assessed to predict atrial cardiomyopathy. Most patients showed signs of atrial cardiomyopathy at baseline [69% with at least mildly elevated LA size, 23% with prolonged PR interval (≥200 ms), 56% with NT-proBNP > 365 pg/mL]. Severe atrial cardiomyopathy, defined as the highest tertile of LA size, PR interval, and NT-proBNP, was associated with higher rates of first primary outcome [HR 7.97 (2.32, 27.37); P < 0.001]. Early rhythm control was effective with and without atrial cardiomyopathy (Pinteraction = 0.160). While ANGPT2 levels showed an association to LA diameter and to atrial cardiomyopathy severity/stage, BMP 10 was not associated with atrial cardiomyopathy. Conclusion Most patients have signs of atrial cardiomyopathy in the first year after AF diagnosis. Patients with advanced stages of atrial cardiomyopathy had a higher rate of primary outcome events and more recurrent AF. Nevertheless, early rhythm control therapy retains its efficacy across the spectrum of atrial cardiomyopathy severities. Consequently, atrial cardiomyopathy severity should not be a reason to withhold rhythm control therapy.