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

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.

To determine the diagnostic and prognostic utility of hepatocyte growth factor (HGF) in light chain and transthyretin cardiac amyloidosis.

188 patients with cardiac amyloidosis, amyloidosis without cardiac involvement, or symptomatic heart failure with left ventricular hypertrophy (LVH) or 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 transplant, or left ventricular assist device implant. 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.

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% CI 0.83-0.94). In patients with amyloidosis, elevated HGF levels were associated with worse event-free survival over a median follow-up period of 2.6 years (p<0.001) with incremental prognostic accuracy over NT-proBNP and troponin-T (p<0.001).

HGF discriminates light chain and transthyretin cardiac amyloidosis from patients with symptomatic HF with LVH or HFrEF, and is associated with worse cardiac outcomes. Confirmation of these findings in a larger, multi-center study enrolling confirmed and suspected cases of cardiac amyloidosis is underway.