Abstract 810: Impact of Elevated Plasma Matrix Metalloproteinase-2 on Prognosis in Hypertrophic Cardiomyopathy: Evidence from Long-Term Follow-Up of Genotyped Patients
Background: Previous studies suggest that production of matrix metalloproteinase-2 (MMP-2) which is responsible for cardiac remodeling could determine prognosis of hypertrophic cardiomyopahty (HCM). However, few data exist regarding the importance of MMP-2 production in clinical settings. Therefore, we determined MMP-2 levels correlated to prognosis in HCM with sarcomere gene mutations.
Methods and Results: Echocardiography and determination of plasma MMP-2 levels by enzyme-linked immunoassay were simultaneously performed in 31 HCM patients (22 women, mean age 56±12 years) with sarcomere protein gene mutation including 22 for cardiac troponin I, 5 for cardiac myosin binding-protein C, 3 for cardiac troponin T and 1 for beta-myosin heavy chain. Major cardiac events such as hospitalization due to congestive heart failure or ventricular fibrillation and mortality were prospectively examined for follow-up period of 48.4±29.1 months. When patients were divided into two groups (Group A: MMP-2 ≥800 ng/ml n=16 and Group B: MMP-2<800ng/ml n=15), there was no differences in mean age (59.4±11.7 year vs 53.1±11.3 year, p=0.13). On echocardiograms, interventricular septal thickness in group A (11.7±4.2 mm) was smaller than that in group B (15.9±4.8 mm, p<0.05) and percent fractional shortening (FS) was significantly impaired in group A (24.8±12.5%) in comparison with that in group B (37.7±8.1%, p=0.002). There was negative correlation between the MMP-2 levels and FS (p<0.001, r=0.76). The frequency of cardiac events was significantly higher in group A (10 patients of 16 patients) than in group B (1 patient of 15 patients, p=0.0012). Importantly, 5 patients of group A died, although none of groupB patients did (p=0.018).
Conclusion: These results demonstrate that the high plasma concentration of MMP-2 (≥800 ng/ml) could be a predictor of prognosis in HCM with sarcomere mutations probably through reflecting impaired left ventricular function.