Background:
Tenascin-C (TN-C) is an extracellular matrix protein, and may regulate matrix organization during tissue remodeling. Although serum TN-C is reported as a prognostic biomarker in patients with dilated cardiomyopathy (DCM), the clinical significance of myocardial expression of TN-C remains undetermined. The objective of this study is to clarify the significance of myocardial TN-C expression on left ventricular (LV) remodeling and long-term prognosis in patients with DCM.
Methods:
Eighty consecutive patients in 2005 and 2006, who were diagnosed with DCM by excluding ischemic cardiomyopathy and secondary cardiomyopathy by coronary angiography and right ventricular endomyocardial biopsy, were analyzed. Those patients were followed up to 73±34 months, and their clinical data were obtained. Immunohistochemistry for TN-C was performed on stored biopsy specimens to examine the association of TN-C deposition with the occurrence of LV reverse remodeling as well as long-term mortality. Immunostained area of myocardial TN-C was measured densitometrically and calculated in percent by the fraction of TN-C stained area to the whole myocardium (TN-C area). LV reverse remodeling was defined as LV end-diastolic dimension ≤55 mm and fractional shortening ≥25% by 60 months after diagnosis.
Results:
TN-C area was 1.2±1.6% on average. Twenty-two patients (28%) underwent LV reverse remodeling. Patients with LV reverse remodeling showed less TN-C area at diagnosis than those without (TN-C area; 0.6±0.5 vs. 1.5±1.8%, p=0.021). Patients were divided into two groups according to the extent of TN-C area; high TN-C group (TN-C area≥1.5%, n=19) and low TN-C group (TN-C area<1.5%, n=61). LV reverse remodeling occurred less frequently in high TN-C group compared with low TN-C group (5% vs 33%, p=0.01). Eleven patients (14%) died during the observation period. Kaplan-Meier analysis revealed high TN-C group had worse prognosis than low TN-C group (p=0.009).
Conclusions:
Patients with higher immunohistological expression of myocardial TN-C in DCM were characterized with lower occurrence of later LV reverse remodeling and poorer long-term prognosis. Myocardial TN-C may have some crucial role in LV remodeling process in patients with DCM.
Predictors of Left Ventricular Reverse Remodeling and Subsequent Outcome in Nonischemic Dilated Cardiomyopathy
