# The Role of GDF-15 in Heart Failure and Biomarker Potential—From Basic Science to Clinical Praxis

## TL;DR

GDF-15 is a promising biomarker for predicting outcomes in heart failure patients but has limitations in diagnosis and therapeutic targeting.

## Contribution

This paper reviews recent evidence on GDF-15's role in heart failure prognosis and highlights gaps in its clinical utility.

## Key findings

- GDF-15 is an independent predictor of adverse outcomes in heart failure patients.
- Adding GDF-15 to traditional biomarker-based risk scores improves prognostic accuracy.
- Diagnostic use is limited by GDF-15's lack of tissue specificity.

## Abstract

Despite state-of-the-art management heart failure prognosis remains poor, resulting in a tremendous burden on health-care systems. Growth differentiation factor-15, a member of the transforming growth factor-beta superfamily, emerges as a promising biomarker to refine heart failure management. We performed a review focusing on its role in heart failure management based on contemporary evidence (i.e., after the latest updates of the guidelines by major Scientific Societies), and on previous articles (for purposes of historical contextualization or due to its indubitable importance). An extensive body of evidence supports this stress cytokine as an independent prognosticator of adverse outcomes throughout the wide spectrum of heart failure patients. Moreover, its incorporation into several risk scores based on traditional biomarkers has further improved their accuracy. Regarding diagnostic purposes, its lack of tissue specificity hinders its utility. Tailored treatment based on growth differentiation factor-15 variations during follow-up and its application as a therapeutic target are still hypothetical, as the effect that evidence-based heart failure drugs exert on growth differentiation factor-15 concentrations is poorly understood, and clinical trials targeting growth differentiation factor-15 have failed. Large-scale prospective studies are urged to confirm the trustworthiness of this biomarker, in order to enable its general routine clinical usage.

Heart failure (HF) prognosis, particularly readmission and mortality, remains poor irrespective of advances in its management. Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-beta (TGF-β) superfamily that arises as a promising biomarker to improve HF management, still despite two decades of extensive investigation some issues remain controversial. We performed a search in PubMed using the following Medical Subject Headings (MeSH) to identify relevant studies published in the last five years (after the latest updates of the guidelines by major Scientific Societies): “Growth differentiation factor-15 (GDF-15)”, “heart failure”, “prognosis” and “diagnosis”. The search was supplemented by data previous to this period, considered of utmost importance. A total of 115 articles written in English were retrieved. Extensive evidence supports GDF-15 as an independent predictor of adverse outcomes across the heterogeneous HF spectrum and its addition to risk scores based on traditional biomarkers improves prognostic power. However, limited tissue specificity restricts its diagnostic value. Tailored treatment strategies and its role as a therapeutic target remain speculative, as the effect of HF therapies on GDF-15 levels is unclear and clinical trials have been unsuccessful. Large prospective studies are needed to validate its reliability for routine clinical use.