Significance of myocardial tenascin-C expression in left ventricular remodelling and long-term outcome in patients with dilated cardiomyopathy

Eur J Heart Fail. 2016 Apr;18(4):375-85. doi: 10.1002/ejhf.464. Epub 2016 Jan 13.

Abstract

Aim: Dilated cardiomyopathy (DCM) has a variety of causes, and no useful approach to predict left ventricular (LV) remodelling and long-term outcome has yet been established. Myocardial tenascin-C (TNC) is known to appear under pathological conditions, possibly to regulate cardiac remodelling. The aim of this study was to clarify the significance of myocardial TNC expression in LV remodelling and the long-term outcome in DCM.

Methods and results: One hundred and twenty-three consecutive DCM patients who underwent endomyocardial biopsy for initial diagnosis were studied. Expression of TNC in biopsy sections was analysed immunohistochemically to quantify the ratio of the TNC-positive area to the whole myocardial tissue area (TNC area). Clinical parameters associated with TNC area were investigated. The patients were divided into two groups based on receiver operating characteristic analysis of TNC area to predict death: high TNC group with TNC area ≥2.3% (22 patients) and low TNC group with TNC area <2.3% (101 patients). High TNC was associated with diabetes mellitus. Comparing echocardiographic findings between before and 9 months after endomyocardial biopsy, the low TNC group was associated with decreased LV end-diastolic diameter and increased LV ejection fraction, whereas the high TNC group was not. Survival analysis revealed a worse outcome in the high TNC group than in the low TNC group (P < 0.001). Multivariable Cox regression analysis revealed that TNC area was independently associated with poor outcome (HR = 1.347, P = 0.032).

Conclusions: Increased myocardial TNC expression was associated with worse LV remodeling and long-term outcome in DCM.

Keywords: Dilated cardiomyopathy; Heart failure; Left ventricular remodelling; Prognosis; Tenascin-C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Cardiomyopathy, Dilated / diagnostic imaging
  • Cardiomyopathy, Dilated / drug therapy
  • Cardiomyopathy, Dilated / metabolism*
  • Cardiomyopathy, Dilated / mortality
  • Collagen / metabolism
  • Comorbidity
  • Diabetes Mellitus / epidemiology
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardium / metabolism*
  • Prognosis
  • Proportional Hazards Models
  • Sodium Potassium Chloride Symporter Inhibitors / therapeutic use
  • Stroke Volume
  • Survival Analysis
  • Tenascin / metabolism*
  • Time Factors
  • Ventricular Remodeling*

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Sodium Potassium Chloride Symporter Inhibitors
  • Tenascin
  • Collagen