Atrial Myopathy and Ischemic Stroke in Heart Failure With Preserved Ejection Fraction

Recent studies suggested an association between atrial myopathy and stroke independent of atrial fibrillation (AF). We examined the hypothesis that atrial myopathy may be associated with ischemic stroke in patients with heart failure with preserved ejection fraction. This is an exploratory, post hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Patients with sinus rhythm documented at baseline electrocardiogram and without known AF were included in this analysis. Atrial myopathy was defined by echocardiographic evidence of left atrial (LA) enlargement (LA diameter >46 mm or LA volume index >36 ml/m²) or elevated natriuretic peptides (brain natriuretic peptide >100 pg/ml or N-terminal Pro-B-type natriuretic peptide >400 pg/ml). We used Cox regression to investigate the effect of atrial myopathy on incident ischemic stroke over the study period. In 3,445 patients in the TOPCAT trial, 2,225 (mean age 67.5 ± 4.9 years; female 54.8%) had normal sinus rhythm at baseline and no history of AF. Atrial myopathy was present in 756 patients (34.0%). During a median follow-up of 2 years, 56 patients (2.5%) developed ischemic stroke, including 25 with atrial myopathy. Atrial myopathy was associated with increased risk of stroke (hazard ratio = 1.74, 95% confidence interval 1.01 to 2.98, p = 0.04) in multivariate analysis. Diabetes mellitus (hazard ratio = 2.02, 95% confidence interval 1.19 to 3.43 p = 0.01) was the only other independent predictor of stroke. In patients with heart failure with preserved ejection fraction, atrial myopathy increases the risk of ischemic stroke, in the absence of AF. Further investigations are needed to better characterize this association and implement stroke prevention strategies.