Characterization of a novel assay for full-length endotrophin in heart failure with preserved ejection fraction

Endotrophin is a matrikine released from the C-terminus of the alpha-3 chain of type VI collagen, gaining increasing attention both as a biomarker and as a therapeutic target in the cardiometabolic space. So far, it has been quantified in circulation by the PRO-C6 assay, which detects different-sized proteolytic fragments of the C-terminus, including endotrophin. Here, we developed and evaluated a novel immunoassay targeting the full-length endotrophin, explored its biological relevance in two clinical cohorts of HFpEF, and investigated its potential as a prognostic biomarker. Increased circulating Endotrophin levels were associated with cardiovascular and all-cause mortality in both cohorts. When adjusting for relevant confounders, Endotrophin remained independently associated with both endpoints only in cohort 1. This work emphasizes the importance of the extracellular matrix in disease, confirms the prognostic value of endotrophin, and provides a novel tool for further exploration of its biological role.