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Matrix metalloproteinase-9 in pediatric rheumatic heart disease with and without heart failure
Ahmed A Elhewala1, Mohammed Sanad1, Alshimaa M Soliman1
1Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Al Sharqia Governorate 44519, Egypt.
Insights
Elevated serum matrix metalloproteinase-9 (MMP-9) levels accurately predict heart failure (HF) in children with rheumatic heart disease (RHD). MMP-9 also correlates with HF severity, offering a potential prognostic marker.
Area of Science:
- Cardiovascular Research
- Pediatric Cardiology
- Biomarker Discovery
Background:
- Collagen breakdown and remodeling in cardiovascular disorders involve matrix metalloproteinase-9 (MMP-9).
- Serum MMP-9 levels may be elevated in pediatric patients with rheumatic heart disease (RHD) and heart failure (HF).
- The correlation between MMP-9 concentration and HF severity in RHD requires investigation.
Purpose of the Study:
- To evaluate the sensitivity and accuracy of MMP-9 in predicting HF in children with RHD.
- To determine MMP-9's effectiveness as an indicator of HF degree in pediatric RHD patients.
- To assess the correlation between serum MMP-9 levels and HF severity.
Main Methods:
- A study involving 98 children (8.5-16 years) with newly diagnosed RHD, including 40 with HF and 58 without HF.
- A control group of 44 healthy children was included.
- Serum MMP-9 levels were quantified using enzyme-linked immunosorbent assay (ELISA).
Main Results:
- Serum MMP-9 concentrations were significantly higher in RHD patients (with and without HF) compared to controls (P<0.001).
- MMP-9 demonstrated significant predictive value for HF with an Area Under the Curve (AUC) of 0.85.
- At 386.9 ng/ml, MMP-9 showed 95% sensitivity and 74.14% specificity for detecting HF, with 82.65% overall accuracy. Negative correlation observed with ejection fraction and fractional shortening (P=0.01, P=0.02).
Conclusions:
- MMP-9 may serve as an independent and sensitive biomarker for detecting HF in pediatric RHD.
- Serum MMP-9 levels correlate with HF severity, suggesting its utility as a prognostic indicator.
- Further research is recommended for MMP-9's role in detecting 'silent' RHD and asymptomatic HF in children, particularly in rural areas.
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.
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