Serum Matrix Metalloproteinase-3 as a Novel Marker for Risk Stratification of Patients With Nonischemic Dilated Cardiomyopathy

Abstract 

Background

Selective induction of myocardial matrix metalloproteinases (MMPs) has been reported to occur in human nonischemic dilated cardiomyopathy (DCM). We aimed to evaluate the utility of serum MMPs for risk stratification of patients with DCM.

Methods and Results

We measured serum levels of MMP-2, MMP-3, and MMP-9 using enzyme-linked immunosorbent assay in 71 patients with mild to moderate DCM (left ventricular ejection fraction = 28.3 ± 11.5%). The primary end point was the composite incidence of cardiac death and hospitalizations for worsening heart failure. During the follow-up period (mean, 28 ± 16 months), 19 patients had major cardiac events with sudden cardiac death in 6 cases and hospitalizations for worsening heart failure in 13 cases. Multivariate analysis revealed that MMP-3 and B-type natriuretic peptide were significant independent predictors of cardiac events in patients with DCM (hazard ratio 1.41, P = .012; hazard ratio 2.72, P = .048, respectively). According to the Kaplan-Meier analyses of cumulative cardiac event-free rates of the two groups that were based on the median levels of MMPs, the differences in the cardiac event-free curves were significant only for MMP-3 (P = .009). Moreover, patients with elevations of both MMP-3 and B-type natriuretic peptide were found to have the poorest prognosis.

Conclusion

Our results may address the utility of serum MMP-3 for risk stratification of patients with DCM.

Key Words: Dilated cardiomyopathy, heart failure, metalloproteinases, prognosis