Neurodegenerative biomarkers and heart failure: is there a neurodegenerative cardiomyopathy? a systematic review and meta-analysis

Heart failure (HF) and cognitive impairment (CI) frequently coexist. The objective of this meta-analysis was to synthesize evidence on the association between circulating biomarkers of neurodegenerative diseases and (1) the incidence of HF; (2) cognitive dysfunction in patients with HF; and (3) adverse HF outcomes.

A comprehensive search of MEDLINE and EMBASE identified 17 studies assessing plasma levels of amyloid beta (Aβ), tau protein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), triggering receptor expressed on myeloid cells 2 (TREM2), ubiquitin C-terminal hydrolase L1 (UCHL1), and YKL-40 in relation to HF-related outcomes.

Elevated Aβ40 and YKL-40 levels were significantly associated with all-cause mortality in HF, with respective hazard ratios (HR) of 1.34 (95% CI: 1.01–1.79; P = 0.0434) and 1.081 (95% CI: 1.002–1.166; P = 0.0443). There was a positive, but not significant, trend between elevated plasma tau levels and HF hospitalization, with HR of 1.21 (95% CI: 0.94–1.55; P = 0.1383). A pooled analysis of all biomarkers across various adverse outcomes demonstrated a significant association, with a HR of 1.20 (95% CI: 1.10–1.30; P < 0.0001). pTau-181, NfL, GFAP, and TREM2 demonstrated associations with memory impairment in HF. Aβ40, pTau-181, NfL, and YKL-40 were linked to incident HF in individual studies.

Neurodegenerative biomarkers, particularly Aβ40 and YKL-40, are indicators of risk in HF populations. These data highlight the need to validate their clinical utility and elucidate shared potentially causative mechanistic pathways linking HF and neurodegenerative conditions, defining a neurodegenerative cardiomyopathy.