1176Hepatocyte growth factor has prognostic utility in light chain and transthyretin cardiac amyloidosis

Abstract

Background With the advent of multiple novel therapeutics for light chain (AL) and transthyretin (ATTR) amyloidosis, there is a critical need for validated prognostic markers in cardiac amyloidosis. A discriminatory serum biomarker may improve prognostic and staging systems in AL and ATTR cardiac amyloidosis. Purpose Our objective was to test the hypothesis that hepatocyte growth factor (HGF) is associated with clinical outcomes in patients with AL and ATTR cardiac amyloidosis. Methods 102 patients with AL or ATTR and suspected cardiac involvement were prospectively enrolled. HGF, NT-proBNP, troponin-T, and eGFR were measured upon study enrollment. Cardiac involvement was established by 1) endomyocardial biopsy, or 2) non-cardiac biopsy with concentric hypertrophy on echocardiography, low voltage or pseudo-infarction on ECG, elevated NT-proBNP or troponin-T, or characteristic delayed myocardial enhancement on cardiac MRI. Patients were followed for the occurrence of all-cause mortality, cardiac transplantation, and left-ventricular assist device implantation. Results Of the total amyloidosis cohort, 72 had cardiac involvement while 30 had non-cardiac disease. HGF, NT-proBNP, and troponin-T levels were significantly higher in patients with cardiac involvement than in patients with non-cardiac disease (p<0.05 for all comparisons). Over a median follow-up period of 1.9 years there were 20 deaths, 1 cardiac transplant, and 1 left-ventricular assist device implant, all in patients with cardiac involvement. Patient stratification by cut-off levels of NT-proBNP (332 pg/mL), troponin-T (35 ng/L), and eGFR (45 mL/min/1.73m2) used in published staging models for AL and ATTR cardiac amyloidosis showed no association between abnormal biomarker level and adverse clinical outcome (p>0.05). In contrast, stratification by HGF level of 310 pg/mL (identified by the Youden Index for cardiac involvement by AL and ATTR in our cohort) showed that elevated HGF was associated with worse clinical outcomes (p=0.0211). Furthermore, event-free survival was worse in patients with elevated HGF, with survival curves diverging soon after enrollment (p=0.0730). HGF is Prognostic in Cardiac Amyloidosis Conclusions Elevated HGF is associated with worse clinical outcomes in patients with AL and ATTR cardiac amyloidosis and has potential for clinical utility.