Endotrophin Could Serve as Prognostic Biomarker for Heart Failure

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Investigators from Penn Medicine have released new data they suggest provide evidence backing use of endotrophin as a prognostic biomarker for patients with heart failure.

An analysis of the TOPCAT trial followed by a patient-level meta-analysis of patients more than 800 patients from other trials and registries, results of the study suggest elevated levels of plasma endotrophin were associated with a more than 70% increase in risk of future death among patients with heart failure with preserved ejection fraction.

“HFpEF is an epidemic condition for which we needed better prognostic biomarkers, and this one could be very useful for identifying high-risk patients” said lead investigator Julio Chirinos, MD, PhD, an associate professor of Cardiovascular Medicine at Penn Medicine, in a statement.

Published by members of the Global Heart Failure Consortium (GHFC), a partnership launched in 2019 by the Perelman School of Medicine at Penn and Bristol Myers Squibb, the current study was prompted by animal models linking endotrophin as a meditator of systemic inflammation, insulin resistance, and metabolic dysregulation. With this in mind, investigators designed the study as a series of retrospective analyses of clinical trial or observational cohort data with available blood endotrophin levels to estimate their association with known clinical outcomes among patients with heart failure with preserved ejection fraction.

First, investigators planned analyses to examine the association between endotrophin and outcomes among participants within the TOPCAT trial. Results of the analysis indicated plasma endotrophin levels at baseline were associated with an increased risk of future death (HR, 1.74 [95% CI, 1.36-2.24]; P <.001) and death or heart-failure hospitalization (HR, 2.11 [95% CI, 1.67-2.67]; P <.001). Further analysis indicated Endotrophin improved the reclassification and discrimination for these outcomes beyond the MAGGIC risk score and NT-proBNP.

Next, investigators sought to validate these associations in participant-level meta-analysis that included 810 patients with HFpEF from the Dutch Public Health Foresight Study (PHFS), the PEOPLE cohort, a randomized trial of vasodilator therapy, a cohort from Donostia University Hospital and the University of Navarra, and the TRAINING-HF trial. Results of the investigators’ analyses indicated findings among this cohort were consistent with those of the TOPCAT analysis.

In additional analyses examining associations of endotrophin levels with these outcomes in patients with heart failure with reduced ejection fraction (HFrEF), results demonstrated endotrophin levels were associated with death (HR, 1.82 [95% CI, 1.66-2.00]; P <.001) and death or hospitalization for heart failure (HR, 1.40 [95% CI, 1.31-1.50]; P <.001). However, investigators pointed out the strength of the latter association was substantially lower than for the MAGGIC risk score (HR 1.93 [95% CI, 1.76-2.12]) and NT-proBNP (HR, 1.78 [95% CI, 1.66-1.92]).

“In addition to helping us gauge the risks faced by HFpEF patients, endotrophin could give us important clues to the biological processes underlying poor outcomes in this form of heart failure—and might even be a target for treatment,” Chirinos added, in the aforementioned statement.

This study, “Endotrophin, a Collagen VI Formation–Derived Peptide, in Heart Failure,” was published in NEJM Evidence.