Mitral Tissue Inhibitor of Metalloproteinase 2 Is Associated with Mitral Valve Surgery Outcome

Background: Matrix metalloproteinases play a role in regulating cardiac remodeling. We previously reported an association between tissue inhibitor of metalloproteinase 2 (TIMP-2) expression and mitral valve (MV) disease. However, the determinants and prognostic value of mitral TIMP2 after MV surgery are unknown. Methods: This retrospective study of 164 patients after MV surgery in a tertiary medical center in Taiwan assessed mitral TIMP2 on a semiquantitative scale (0–2) by immunohistochemical staining. The primary endpoints were the composite of cardiovascular death and heart failure admission. Results: Mean age was 50.4±13.7 years. After a mean follow-up period of 101±59 months, primary endpoints had occurred in 25 (15.2%) subjects. Patients with and without primary endpoint events significantly differed in terms of age (56.6±14.4 vs. 49.2±13.4 years, respectively; p = 0.013) and left ventricular end-systolic diameter (LVESD) (39.7±8.2 vs. 35.5±7.5 mm, p = 0.010) at surgery. The TIMP2 had a significant dose-dependent association with development of a primary endpoint (p = 0.002). Kaplan–Meier analysis showed that TIMP2 expression has a significant positive association with primary endpoint-free survival (log-rank test; p = 0.004). Cox regression analysis showed that independent predictors of primary endpoints were TIMP2 (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.12–0.65; p = 0.003), age (HR 1.05; 95% CI 1.02–1.09; p = 0.003) and LVESD (HR 1.05; 95% CI 1.01–1.10; p = 0.020). Conclusions: The lack of mitral TIMP2 expression is associated with increases in cardiovascular death and heart failure following MV surgery.