Plasma active matrix metalloproteinase 9 and indices of diastolic function in patients with preserved systolic function

Background: This study aimed to investigate whether the endogenous active levels of MMP-9 or tissue inhibitor of metalloproteinases-1 (TIMP-1) were related to indices of diastolic dysfunction (DD) in the setting of contemporary treatment of coronary artery disease (CAD).

Methods and results: We prospectively studied 116 patients with CAD and preserved left ventricular LV systolic function (ejection fraction ≥ 45%). All patients were free of heart failure symptoms at recruitment and underwent percutaneous intervention (PCI) of culprit lesions. Demographic and angiographic characteristics were collected. Plasma samples were analysed for the active form of MMP-9 and TIMP-1 using enzyme-linked immunosorbent assay-based isoform sensitive assays. Conventional and tissue Doppler-echocardiographic assessment of diastolic filling was undertaken with measurements of maximal early (E) and late (A) transmitral velocities in diastole, E/A ratio, E-wave deceleration time, isovolumic relaxation time, peak systolic (S), diastolic (D) and atrial reversal velocities of pulmonary venous flow, S/D fraction, time difference between A and duration of atrial reversal flow, early diastolic peak velocities of the lateral mitral annulus (E') and E/E'. Active MMP-9 level was higher in patients with more severe phases of DD (normal [n=22]: median 0.57 ng/ml; mild [n=19] 0.83 ng/ml; mild-moderate [n=41] 0.64 ng/ml; moderate or severe [n=34] 1.63 ng/ml; p<0.0001 for trend). Three month post-PCI elevated levels of active MMP-9 had an adjusted odds ratio of 11.2 (2.3-56.0, p<0.004) for association with moderate or severe DD.

Conclusion: Elevated active MMP-9 level is associated with more severe DD in patients with CAD and preserved systolic function, which may indicate abnormal extracellular matrix metabolism in myocardial ischaemia.