Matrix metalloproteinase-9 in pediatric rheumatic heart disease with and without heart failure

Abstract

In cardiovascular disorders, the myocardium may be subjected to the breakdown and remodeling of collagen by metalloproteinase-9 (MMP-9). We hypothesized that the serum MMP-9 concentration may be elevated in pediatric patients with rheumatic heart disease (RHD) and heart failure (HF), and its level can be correlated with the HF severity. Thus, in the present study, we aimed to evaluate the sensitivity and accuracy of MMP-9 to predict HF in children with RHD and to determine its effectiveness as an indicator of the degree of HF. This study included 98 consecutive children admitted to the Department of Pediatrics, Zagazig University Hospital, Al Sharqia Governorate, Egypt with newly diagnosed RHD. Their ages ranged from 8.5 to 16 years. Fifty-eight children had RHD without HF while 40 children were complicated with HF which was diagnosed clinically and by echocardiography. A total of 44 healthy children were enrolled as a control group. MMP-9 serum levels were estimated by enzyme-linked immunosorbent assay. The serum MMP-9 concentration was higher in the RHD without HF and RHD with HF groups than this level noted in the control (P<0.001). MMP-9 was a significant predictor of HF; area under the curve (AUC)=0.85 [95% confidence interval (CI), 0.76-0.94]. At the level of 386.9 ng/ml, MMP-9 detected HF with a sensitivity 95% (95% CI, 83.08-99.39), specificity 74.14% (95% CI, 60.96-84.74), positive predictive value 71.70% (95% CI, 61.96-79.75), negative predictive value 95.56% (95% CI, 84.67-98.82) and accuracy 82.65% (95% CI, 73.69-89.56). In addition, MMP-9 showed a significant negative correlation with ejection fraction and fractional shortening (P=0.01 and P=0.02, respectively). In conclusion; MMP-9 may be an independent sensitive marker with which to detect HF in children with RHD and it can predict the prognoses of these patients as it correlates with the severity of HF. Further studies considering MMP-9 in the detection of 'silent' RHD in school aged children and asymptomatic HF in children with known RHD especially in rural areas, are highly recommended.

Keywords: ejection fraction; heart failure; matrix metalloproteinase 9; rheumatic heart disease.

Figure 1

ROC curve for MMP-9 in the detection of HF in RHD. Serum MMP-9 concentration as a significant predictor of HF in children with RHD. Area under curve=0.85 (0.76-0.94) at 95% CI. ROC, receiver operating characteristic curve; MMP-9 matrix metalloproteinase-9; RHD, rheumatic heart disease; CI, confidence interval.

Figure 2

Scatter plot with line chart for the correlation between MMP-9 and EF. MMP-9 levels increased significantly with the deterioration of EF in the RHD with HF group. MMP-9 matrix metalloproteinase-9; EF ejection fraction; RHD, rheumatic heart disease; HF, heart failure.