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Hepatocyte Growth Factor: A Marker of Cardiac Function, Mortality, and Disease Subtype in Cardiac Amyloidosis
Margrethe Flesvig Holt1, Annika E Michelsen2, August Flø3
1Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Insights
Hepatocyte growth factor (HGF) in plasma shows promise for diagnosing cardiac amyloidosis (CA) and predicting patient outcomes. Elevated HGF levels correlate with heart failure severity and poorer prognosis in CA patients.
Area of Science:
- Cardiology
- Biomarker Discovery
- Proteomics
Background:
- Cardiac amyloidosis (CA) diagnosis is often delayed, impacting patient prognosis.
- Plasma biomarkers offer a potential solution to expedite diagnosis and improve prognostic accuracy.
Purpose of the Study:
- To identify circulating protein biomarkers differentiating CA from heart failure (HF) without amyloidosis.
- To assess the association of identified biomarkers with patient outcomes, including all-cause mortality.
Main Methods:
- Focused proteomic screening was conducted on patients with transthyretin CA, HF, and healthy controls (HCs).
- Immunoassays validated protein levels in a larger cohort including transthyretin CA, light-chain CA, HF, and HCs.
- Multivariable general linear models and receiver operating characteristic analysis were used for comparisons and outcome associations.
Main Results:
- Proteomic screening identified 99 candidate proteins; 4 were elevated in CA versus HCs.
- Hepatocyte growth factor (HGF) and C-X-C motif chemokine ligand 9 were higher in CA than in HF.
- HGF levels correlated with cardiac function and demonstrated strong discriminatory ability for predicting all-cause mortality (AUC = 0.80).
Conclusions:
- Plasma HGF serves as a potential screening biomarker for cardiac amyloidosis.
- Elevated HGF levels indicate more severe heart failure and a worse prognosis in CA patients.
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.
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