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

Abstract

AimDilated 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 resultsOne 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).ConclusionsIncreased myocardial TNC expression was associated with worse LV remodeling and long‐term outcome in DCM.

Plasminogen Activator Inhibitor Type I Controls Cardiomyocyte Transforming Growth Factor-β and Cardiac Fibrosis

“…36 The most highly upregulated transcript in the PAI-1 −/− heart encodes Tenascin C, which is transiently expressed in fibrotic myocardium after multiple modes of injury, and has been studied as a circulating biomarker for heart failure and remodeling in humans. 49,50 …”

Clinical impact of the presence of macrophages in endomyocardial biopsies of patients with dilated cardiomyopathy

“…Immunohistochemistry on formalin‐fixed paraffin‐embedded sections was performed using a Leica Bond‐III autostainer (Leica Biosystems, Wetzlar, Germany) as previously described . Commercially available antibodies were used as primary antibodies to detect each inflammatory cell infiltrate.…”

Evolving concepts in dilated cardiomyopathy

“…While there is a general appreciation that DCM can be caused by many different disease processes, in everyday clinical practice it is often considered under the catch‐all heading of ‘non‐ischaemic HF’ with reduced ejection fraction. However, the concept that DCM represents a family of diseases characterized by complex interactions between environment and genetic predisposition is gaining prominence as the clinical impact of a precise diagnosis is better appreciated …”

“…However, the concept that DCM represents a family of diseases characterized by complex interactions between environment and genetic predisposition is gaining prominence as the clinical impact of a precise diagnosis is better appreciated. 8,9 The term 'idiopathic DCM' is often used in clinical practice and in some series accounts for 20-30% of non-ischaemic HF. However, the approach to a patient with non-ischaemic DCM rarely seeks reversible factors other than hypertension, valve disease, and congenital heart disease (Figure 1).…”