Plasma metalloproteinase levels and left ventricular remodeling in hypertrophic cardiomyopathy in patients with an identical mutation

Abstract

Background and purpose: Although it has been reported that matrix metalloproteinases (MMPs) are associated with left ventricular (LV) remodeling in patients with hypertrophic cardiomyopathy (HCM), the impact of plasma MMP levels in patients with HCM is somewhat vague.

Methods and subjects: Plasma levels of MMP-2, MMP-9, and clinical/echocardiographic findings were evaluated in 16 HCM patients with preserved LV ejection fraction (defined as LV ejection fraction more than 50%) caused by an identical frameshift mutation (S593fs: a one-base deletion of a thymidine at nucleotide 11,645) in the cardiac myosin-binding protein C gene.

Results: MMP-2 levels were inversely related to LV ejection fraction (r(2)=-37, p=0.01). MMP-9 levels were inversely related to LV end-diastolic dimension (r(2)=-0.24, p=0.06) and positively related to the maximum LV wall thickness (r(2)=0.25, p=0.04). During follow-up period of 4.1 ± 1.2 years, LV ejection fraction decreased from 68.5 ± 7.4% to 64.9 ± 9% (p=0.03). Among clinical, echocardiographic findings at baseline and levels of biomarkers, high MMP-9 levels were only related to the decrease of LV ejection fraction from baseline to follow-up (r(2)=0.39, p=0.009).

Conclusions: MMP-2 levels are related to reduced LV systolic function in HCM patients with preserved LV ejection fraction caused by an identical cardiac myosin-binding protein C gene abnormality. On the other hand, MMP-9 levels are associated with small LV size and the degree of LV hypertrophy and related to the deterioration in LV systolic function during follow-up. These results suggest that MMPs are important in the process of LV remodeling in HCM.