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

Abstract

ObjectivesThis study determined the diagnostic and prognostic usefulness of hepatocyte growth factor (HGF) in light chain and transthyretin cardiac amyloidosis. BackgroundDelays 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. MethodsA 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. ResultsHGF 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). ConclusionsHGF 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.