Hepatocyte Growth Factor: A Marker of Cardiac Function, Mortality, and Disease Subtype in Cardiac Amyloidosis.

BACKGROUND

It is important to reduce diagnostic delays for patients with cardiac amyloidosis (CA). Plasma biomarkers could streamline the diagnostic process and enhance prognostic accuracy.

OBJECTIVES

The authors aimed to identify circulating biomarkers capable of differentiating patients with CA from patients with heart failure (HF) and no amyloidosis. Additionally, we assessed whether these markers were associated with patient outcomes.

METHODS

We performed focused protein screening in 12 patients with transthyretin CA, 5 patients with HF, and 16 healthy controls (HCs). To validate the findings, we used immunoassays to measure levels of differentially regulated proteins in a larger sample of 86 patients with transthyretin CA, 15 patients with light-chain CA, 16 patients with HF, and HCs. We compared protein levels between groups using multivariable general linear models. Associations between protein levels and all-cause mortality were assessed by receiver operating characteristic analysis.

RESULTS

We identified 99 candidate proteins by proteomic screening. In the validation sample, 4 of these markers were higher in CA than in HCs. Levels of C-X-C motif chemokine ligand 9 and hepatocyte growth factor (HGF) were also higher in CA than in HF. HGF correlated with measures of cardiac function in patients with transthyretin and light chain CA. HGF had a good discriminatory ability for predicting all-cause mortality (area under the curve = 0.80, P < 0.001), similar to those of N-terminal pro-B-type natriuretic peptide and troponin T.

CONCLUSIONS

Plasma HGF is a promising screening tool for CA. Higher levels of HGF are associated with more severe HF and worse prognosis in patients with CA.