Background
Congenital heart defects (CHDs) are the most common group of major birth defects. Half of the affected children require at least one operation during childhood. A substantial reason for the high post-operative morbidity rate in pediatric cardiac surgeries, is the consequential myocardial damage, which leads to cardiac dysfunction and heart failure. Lacatate and troponin blood levels are well established biomarkers in that population, but still have their limitations. Circulating Micro-RNAs (miRNAs) have emerged as potential diagnostic markers due to their organ-specific expression pattern and their high biostability when released into plasma. Recently, it has been shown that cardiac-specific miRNA-208a,-208b,-499 could be used as reliable biomarkers for acute myocardial infarction and myocardial damage in adults
Hypothesis and purpose
We hypothesized that the plasma levels of miRNA-208a,-208b,-499 rise in the first 24 hours after cardiac surgery in children, and that their levels correlate with the extent of the myocardial damage and clinical course.
Methods
After institutional review board approval and informed consent, blood samples from 30 children with CHDs were obtained preoperatively, 12hrs and 24hrs after surgery. Plasma levels of miRNAs of interest were quantified using exogenous Caenorhabditis elegans miRNA-39 for normalization, and relative quantitative PCR. Patients were categorized into 2 groups defined by their median miRNAs values, in the specific time points. Demographic and clinical data was collected and compared between the two groups.
Results
12hr after heart surgery, plasma levels of cardiac-enriched miRNAs were highly elevated: miRNA-208a showed a 3740-fold increase, miRNA-208b showed a 2269 fold increase, and miRNA-499 was elevated by 750 fold (p<0.01 for miRNA-208a,-499, and p<0.05 for miRNA-208b). At 24hr, their plasma levels decreased, however still remained higher than seen before surgery. Increased miRNAs concentrations were associated with higher Troponin levels (p<0.05), longer cardio-pulmonary bypass and aortic cross clamp times and delayed hospital discharge.
Conclusions
We have shown, for the first time, that miRNA-208a,-208b,-499 may serve as novel biomarkers for myocardial damage and post operative clinical course in children with CHDs.
