Association of circulating levels of collagen turnover biomarkers with the phenotype in a population with sarcomeric hypertrophic cardiomyopathy

Abstract

Background and aim: In patients (pts) with sarcomeric hypertrophic cardiomyopathy (sHCM) and left ventricular hypertrophy (LVH), cardiac fibrosis and diastolic dysfunction are typical features. Studies suggest that collagen turnover (ColT) is increased in sHCM, but its clinical significance and relationship with cardiac LVH and function is doubtful. In order to address this question, we evaluated the association of circulating levels of biomarkers of ColT (bioColT) with clinical, morphological and functional echocardiographic (echo) features. Methods: Thirty nine sHCM pts (49±17y, 54% female) ­ major echo criteria and positive genotype, nondilated left ventricle (LV) and preserved ejection fraction ­ were enrolled, after exclusion of conditions that might influence circulating levels of bioColT. On the same day, clinical evaluation, ECG, echo study and laboratorial tests (including measurement of 6 bioColT related to collagen synthesis and degradation ­ PICP, PIIINP, CITP, MMP­1, MMP­9 and TIMP) were performed. Associations were looked for between bioColT and: 1) structural and functional parameters and indices of systolic and diastolic function evaluated by echo/tissue Doppler imaging; 2) current NYHA functional class, hospitalization due to sHCM and nonsustained ventricular tachycardia (NSVT) on Holter, during the preceding year. Associations were considered statistically significant if p<0.05. Results: Controlling for age and body mass index, TIMP­1 levels (a measure of tissue inhibition of collagentype 1 degradation) correlated with LV mass index (LVMI; r=0.49), septal thickness (ST; r=0.43), maximal wall thickness (MWT; r=0.44), LVWT score (r=0.44), lateral E' (r=−0.49), septal E/E' (r=0.55), and lateral E/E' (r=0.64); and CITP (a measure of collagen­type I degradation) levels correlated with LVMI (r=0.38), ST (r=0.36), MWT (r=0.38), LVWT score (r=0.37) and lateral E' (r=−0.45). No correlations were found between PICP or other bioColT levels and echo­data. Only TIMP­1 levels were significantly increased in the presence of symptoms and hospitalizations (p=0.031). None bioColT was associated with the occurrence of NSVT on Holter. Conclusions: In pts with sHCM and LVH, collagen turnover is active, and acts in favor of a predominance of inhibition of collagen degradation over collagen degradation. Both, TIMP1 and CITP levels were associated with the degree and extension of LVH, but only TIMP1 levels were also positively associated with echo­indices of diastolic dysfunction, left ventricular filling pressures and morbidity. Therefore, it appears in this series to be the biomarker of choice amongst ColT biomarkers, for future research.