Circulating activin A is a surrogate for the incidence of diastolic dysfunction and heart failure in patients with preserved ejection fraction

Background: Diastolic dysfunction (DD) is a characteristic of heart failure with preserved ejection fraction (HFpEF), which is thought to be caused by cardiac hypertrophy or fibrosis. Activin A is involved in the inflammatory response and myocardial fibrosis, but the relationship between the activin A level and DD remains unclear. Methods and Results: A total of 209 patients with stable angina were enrolled. Serum activin A levels were assessed, and echocardiography and cross-sectional analysis were performed. Among the subjects (65% male; mean age, 70±13 years), 84 (40%) subjects had DD. The subjects were divided into tertiles based on activin A levels. Patients in the high activin A group had enhanced left ventricular mass indexes, medial E/e’ ratios, left atrial diameter, and right ventricular systolic pressure compared with those in the lower activin A groups (all P<0.001). Prevalence of DD (P=0.001), HFpEF at enrollment (P=0.007), and the composite endpoints including new-onset heart failure (HF) or death within 3 years (P<0.001) correlated positively with high activin A levels. After adjusting for confounding factors, high activin A levels remained significantly associated with DD (P=0.036) and the composite endpoints (P=0.012). Conclusions: Enhanced serum activin A levels were associated with the incidence of DD and development of HF.