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.
Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ; Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Tsung-Hsien
TH
Lin
Department of Pathology, Kaohsiung Medical University, Kaohsiung, Taiwan ; Kaohsiung Medical University Hospital, Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan ; Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Sheau-Fang
SF
Yang
Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan ; Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chaw-Chi
CC
Chiu
Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ho-Ming
HM
Su
Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ; Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Wen-Chol
WC
Voon
Department of Pathology, Kaohsiung Medical University, Kaohsiung, Taiwan ; Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Chee-Yin
CY
Chai
Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ; Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Wen-Ter
WT
Lai
Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan ; Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Sheng-Hsiung
SH
Sheu
D023381:Endpoint Determination; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000378:metabolism* / Q000601:surgery*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D013624:Taiwan; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D016896:Treatment Outcome
D019716:Tissue Inhibitor of Metalloproteinase-2