Circulating Brain-Derived Neurotrophic Factor Levels and Heart Failure: A Systematic Review and Meta-Analysis

Biomarkers are paramount for managing heart failure (HF) patients as prognostic and therapeutic efficacy index tools. Systemic levels of brain-derived neurotrophic factor (BDNF) can add to the HF biomarker scenario, allowing for potentiated efficacy in diagnosis, prognostic stratification, and prediction of patient response to a given therapeutic intervention because BDNF is one of the primary rulers of myocardial function. Yet, whether BDNF is a reliable clinical biomarker awaits clinical validation. Hence, we aimed to answer this relevant question via a systematic review and meta-analysis of existing studies.

International databases, including PubMed, Scopus, Embase, and the Web of Science, were comprehensively searched for studies assessing BDNF levels in patients with HF versus non-HF controls or as a prognostic factor for HF complications. Data were extracted and analysed by random-effect meta-analysis. Standardized mean difference (SMD) and 95% confidence intervals (CIs) were computed to pool the results of studies. We included 11 studies in the final review, among which six underwent meta-analysis. These studies analysed 1420 HF patients, with a mean age of 65.4 ± 11.2 years. Meta-analysis revealed that patients with HF had significantly lower circulating BDNF levels than healthy controls (SMD −2.47, 95% CI −4.39 to −0.54, P-value = 0.01). Moreover, patients with higher New York Heart Association functional classification had lower levels of BDNF. Adverse clinical outcomes such as all-cause mortality and HF rehospitalization were also associated with lower levels of BDNF in individual studies.

BDNF levels are decreased in patients with HF. Most importantly, we observed an association between lower BDNF levels and poor prognosis in patients with HF. Our study supports BDNF as an easy-to-dose diagnostic and prognostic biomarker to be implemented in clinical practice for HF. Further studies are warranted to address this ability specifically.