Abstract 13055: Endotrophin is Significantly Associated With Risk of Mortality in HFpEF Patients Irrespective of Underlying Atrial Fibrillation

Abstract

Introduction: The global burden of heart failure with preserved ejection fraction (HFpEF) is increasing. HFpEF is projected to become the dominant type of HF, and atrial fibrillation (AF) is known to contribute to pathogenesis by aggravating fibrosis. Endotrophin is a bioactive molecule released from collagen type VI during its maturation, and it is a marker of fibroblast activity. The aim of this post-hoc analysis was to confirm the previously observed prognostic potential of endotrophin (measured by PRO-C6) for adverse outcome in HFpEF and to investigate the potential influence in risk stratification by AF. Methods: 166 patients with hypertensive HFpEF were included for analysis. 48.2% were NYHA Class II, 49.4% NYHA Class III and 1.2% NYHA Class IV. 50.6% of patients had a previous history of AF. Cardiac function was assessed by echocardiography and standard clinical measures. Circulating endotrophin was quantified at baseline in serum by means of an enzyme-linked immunosorbent assay, PRO-C6. Results: PRO-C6 levels increased significantly with disease severity in HFpEF patients (NYHA Class III vs II, p=0.0003), and in HFpEF patients with AF (p=0.023). PRO-C6 was able to discriminate between patients at risk of all-cause mortality (AUC=0.73, p<0.001), but no improvement in this association was observed when factoring in AF (AUC=0.72, p=0.001). When looking at patients stratified in PRO-C6 tertiles, patients in the upper tertile had a significantly higher risk of mortality (p<0.0001, hazard ratios 3 vs 1=4.1, 3 vs 2=3.5, respectively) and HF hospitalization (p<0.0001, hazard ratio 3 vs 1=4.4, 3 vs 2=1.6, respectively) compared to tertiles 1 and 2. Conclusions: In this population of hypertensive HFpEF patients, circulating endotrophin, measured by PRO-C6, was increased with increasing disease severity, and associated with a higher risk of adverse outcome in HFpEF, regardless of underlying AF. The data presented here suggest a potential role of endotrophin in HFpEF pathophysiology, associated to disease progression in HFpEF patients with or without AF. These data confirm previous observations, and strengthen the usefulness of endotrophin, measured by the PRO-C6 biomarker, as a prognostic tool aiding in assessment of HFpEF patients.