Circulating Matrix Metalloproteinases in Infective Endocarditis: A Possible Marker of the Embolic Risk

BACKGROUND: Embolic events (EE) in infective endocarditis (IE) are caused by fragmentation of vegetations or valvular tissue. Vegetation length is considered to be the most potent predictor of EE, but does not take into account the degree of friability of the vegetation and of the surrounded infected tissue. Matrix metalloproteinases (MMPs) are enzymes involved in degradation of matrix extracellular components and play a role in the pathophysiology of IE. We aimed to determine whether, in addition to the vegetation size, circulating MMPs could provide accurate predictive value of embolism in IE. METHODS: Among 145 patients referred for a native valve IE, we prospectively included 16 patients who experienced EE during antibiotic therapy (new-EE) and 30 patients without new-EE and treated without valvular surgery. A control group of 38 patients with a degenerative valvular heart disease was also included. In addition to clinical, microbiological and echocardiographic assessment, blood MMPs and their inhibitors were assayed in all patients at admission. RESULTS: MMP-9 serum level was significantly higher in patients with new-EE compared to controls (median [interquartile range]; 250 ng/mL [175–455] vs. 111 ng/mL [70–144], respectively; p<0.0001) and patients with no new-EE (250 ng/mL [175–455] vs. 138 ng/mL [95–232]; p<0.01). A higher MMP-9 activity in patients who experienced new-EE was further confirmed by gelatin zymography analysis. Circulating MMP-9 remains a predictor of new-EE after adjustment for vegetation length and other potential confounders. This parameter provided incremental predictive value over vegetation measurements. CONCLUSIONS: MMP-9 serum level is associated with the risk of embolism during IE. This marker might help physicians in the management of the disease, but further propspective studies are need to confirm these preliminary results.