Improvement in collagen metabolism after 12 weeks' cardiac resynchronization therapy in patients with ischaemic cardiomyopathy.

OBJECTIVES

To investigate the effects of cardiac resynchronization therapy (CRT) on collagen metabolism biomarkers and their relationship to cardiac function, in patients with ischaemic cardiomyopathy (ICM).

METHODS

Serum levels of matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP-9 (TIMP-1), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal telopeptide of type I collagen (ICTP) were quantified before and after 12 weeks' treatment, in patients with ICM receiving CRT and standard medical therapy (CRT group) or standard medical therapy alone (non-CRT group), and in controls. Cardiac function was measured echocardiographically.

RESULTS

MMP-9, TIMP-1, ICTP and the MMP-9/TIMP-1 ratio were significantly higher, and the PICP/ICTP ratio significantly lower, in patients with ICM (n = 27) compared with controls (n = 20). After 12 weeks' treatment, MMP-9, TIMP-1, ICTP and the MMP-9/TIMP-1 ratio were significantly higher, and the PICP/ICTP ratio significantly lower, in the non-CRT group (n = 15) compared with the CRT group (n = 12). The PICP/ICTP ratio correlated positively with TIMP-1 and negatively with MMP-9. The early/atrial ratio and left ventricular ejection fraction correlated positively and negatively, respectively, with the MMP-9/TIMP-1 ratio. Echocardiographic measurements of cardiac function were significantly worse in patients with ICM compared with controls and improved significantly after treatment in the CRT group.

CONCLUSIONS

In ICM, collagen degradation biomarkers were elevated and correlated positively with cardiac function. CRT partially reversed the deterioration in collagen metabolism and enhanced cardiac function.