Soluble ST2 in Heart Failure With Preserved Ejection Fraction

Abstract

Background Soluble ST2 is a biomarker that is elevated in certain systemic inflammatory diseases. Comorbidity‐driven microvascular inflammation is postulated to play a key role in heart failure with preserved ejection fraction ( HF p EF ) pathophysiology, but data on how sST 2 relates to clinical characteristics or inflammatory conditions or biomarkers in HF p EF are limited. We sought to determine circulating levels and clinical correlates of sST 2 in HF pEF. Methods and Results At enrollment, patients (n=174) from the Phosphodiesterase‐5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial of sildenafil in HF p EF had sST 2 levels measured. Clinical characteristics; cardiac structure and function; exercise performance; and biomarkers of neurohumoral activation, systemic inflammation and fibrosis, and myocardial necrosis were assessed in relation to sST 2 levels. Median sST 2 levels in male and female HFpEF patients were 36.7 ng/mL (range 30.9–49.2 ng/mL; reference range 4–31 ng/mL) and 30.8 ng/mL (range 25.3–39.3 ng/mL; reference range 2–21 ng/mL), respectively. Among HF p EF patients, higher sST 2 levels were associated with the presence of diabetes mellitus; atrial fibrillation; renal dysfunction; right ventricular pressure overload and dysfunction; systemic congestion; exercise intolerance; and biomarkers of systemic inflammation and fibrosis, neurohumoral activation, and myocardial necrosis ( P <0.05 for all). sST 2 was not associated with left ventricular structure or left ventricular systolic or diastolic function. Conclusions In HF p EF , sST 2 levels were associated with proinflammatory comorbidities, right ventricular pressure overload and dysfunction, and systemic congestion but not with left ventricular geometry or function. These data suggest that sST2 may be a marker of systemic inflammation in HF p EF and potentially of extracardiac origin. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00763867.