TWEAK and NT-proBNP levels predict exercise capacity in hypertrophic cardiomyopathy

Abstract

Background Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate hypertrophy, myocyte disarray and increased interstitial fibrosis. The tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is a cell surface cytokine with biological activities including stimulation of cell growth, induction of inflammatory cytokines and stimulation of apoptosis. There are controversial data about the potential role of TWEAK in different cardiovascular pathologies. NT-proBNP is an established biomarker of myocardial wall stress, associated with poor functional class in HCM. We hypothesized that effort capacity in patients with HCM could be related to serum levels of these biomarkers.

Materials and methods We included 40 haemodynamic stable HCM patients and 53 healthy controls with similar sex and age. We studied exercise capacity by maximal oxygen consumption in a limited treadmill exercise test. TWEAK and NT-proBNP were assayed by ELISA method and automated Elecsys® platform, respectively. We obtained 46 samples of myocardial tissues by septal myectomy in patients with HCM and evaluated myocardial fibrosis, immunoreaction with TWEAK antibody and apoptosis with TUNEL assay.

Results We found raised TWEAK and NT-proBNP serum levels in patients when compared with control levels (both P < 0·001). In a multivariate analysis, TWEAK and NT-proBNP levels, as well as sex, remained independently associated with the effort capacity (all P < 0·05). We found an association between immunoreaction degree and the degree of myocardial fibrosis (P = 0·021), as well as apoptosis (P = 0·002) in the tissue samples from patients undergoing septal myectomy.

Conclusions TWEAK and NT-proBNP levels are biomarkers of disease severity independently associated with the effort capacity in patients with HCM.