JACC. CardioOncology (Mar 2020)

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

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

Journal volume & issue
Vol. 2, no. 1
pp. 56 – 66

Abstract

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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.

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