Abstract 13676: Circulating Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Cardiac Amyloidosis
Background: Cardiac amyloidosis (CA) is characterized by amyloid infiltration resulting in extracellular matrix (ECM) disruption. Cardiomyopathy (CMP) and symptomatic heart failure (HF) due to cardiac deposition of immunoglobulin light chain (AL) has a median survival of <6 months if untreated. CMP due to deposition of wildtype or mutant TTR (ATTR) has a more indolent course. The ECM is regulated by metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). In non-amyloid HF, MMPs and TIMPs are associated with cardiac remodeling and prognosis. We hypothesized that the different rates of progression of CMP might be reflected by differences in circulating levels of MMPs and TIMPs in AL vs. ATTR.
Methods: Between 2000-2010, patients with biopsy-proven amyloidosis were enrolled at first visit to the Amyloid Clinic at Boston Medical Center. Routine laboratory tests, physical examination, and echocardiography were performed. We studied 100 CA patients: 50 with AL-CMP and 50 with ATTR-CMP. Serum MMP-2 and -9 and TIMP-1 and -2 levels were measured by ELISA.
Results: ATTR-CMP patients had significantly greater left ventricular (LV) thickness, LV mass index, and lower LV ejection fraction (LVEF). However BNP, Troponin I (TnI), MMP-2, and TIMP-1 were more elevated in AL-CMP. There were insignificant correlations between these biomarkers and echocardiographic parameters. The 1-year survival rate in AL-CMP was 60% vs. 92% (p<0.01 vs. ATTR-CMP). Multivariate analysis showed NYHA (HR 6.48, p<0.01), BNP (HR 1.001, p<0.01), and TIMP-1 (HR 1.006, p<0.05) were significant predictors of prognosis in AL-CMP.
Conclusions: Despite increased LV hypertrophy and decreased LVEF with ATTR-CMP, AL-CMP showed higher BNP, TnI, MMP-2, and TIMP-1. In addition, poor prognosis in AL-CMP is associated with NYHA, BNP and TIMP-1. These results suggest that TIMP-1 may serve as a potential prognostic and therapeutic target in CA.
- © 2011 by American Heart Association, Inc.