Plasma Hepatocyte Growth Factor for Diagnosis and Prognosis in Light Chain and Transthyretin Cardiac Amyloidosis

Kathleen W. Zhang, Jennifer Miao, Joshua D. Mitchell, Jose Alvarez-Cardona, Kelsey Tomasek, Yan Ru Su, Mary Gordon, R. Frank Cornell, Daniel J. Lenihan

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Objectives: This study determined the diagnostic and prognostic usefulness of hepatocyte growth factor (HGF) in light chain and transthyretin cardiac amyloidosis. Background: Delays in diagnosis of cardiac amyloidosis are common, usually resulting from nonspecific findings on clinical examination and testing. A discriminatory plasma biomarker could result in earlier diagnosis and improve prognosis assessment. Methods: A total of 188 patients with cardiac amyloidosis, amyloidosis without cardiac involvement, symptomatic heart failure with left ventricular hypertrophy (LVH), or heart failure with a reduced ejection fraction (HFrEF) were enrolled prospectively. Serum biomarkers were measured at study enrollment, and all patients with amyloidosis were followed for all-cause mortality, cardiac transplantation, or left ventricular assist device implantation. Multinomial logistic regression and Kaplan-Meier survival estimates tested the association of biomarker levels with cardiac amyloidosis and clinical outcomes, respectively. Harrell's C-statistic and the likelihood ratio test compared the prognostic accuracy of plasma biomarkers. Results: HGF was significantly higher in patients with cardiac amyloidosis (p < 0.001). An HGF level of 205 pg/ml discriminated cardiac amyloidosis from LVH and HFrEF with 86% sensitivity, 84% specificity, and an area under the curve of 0.88 (95% confidence interval: 0.83 to 0.94). In patients with amyloidosis, elevated HGF levels were associated with worse event-free survival over a median follow-up of 2.6 years (p < 0.001) with incremental prognostic accuracy over N-terminal pro-B-type natriuretic peptide and troponin T (p < 0.001). Conclusions: HGF discriminates light chain and transthyretin cardiac amyloidosis from patients with symptomatic heart failure with LVH or HFrEF and is associated with worse cardiac outcomes. Confirmation of these findings in a larger, multicenter study that is enrolling suspected cases of cardiac amyloidosis is underway.

Original languageEnglish (US)
Pages (from-to)56-66
Number of pages11
JournalJACC: CardioOncology
Volume2
Issue number1
DOIs
StatePublished - Mar 2020
Externally publishedYes

Keywords

  • biomarkers
  • cardiac amyloidosis
  • hepatocyte growth factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Oncology

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