Circulating miR208a: A Post-operative Biomarker for Predicting Complications after Cardiac Surgery in Pediatric Patients

Micro-RNAs (miRNAs), a class of short non-coding RNA molecules that repress gene expression, are involved in virtually all biological processes. Cardiac tissue, as many other tissues, displays `signature expression` pattern of miRNAs. Due to their tissue-specific expression pattern, rapid-release kinetics and stability in plasma, they have been shown to be promising biomarkers for several clinical conditions including cardiovascular disease. Current clinical risk assessment strategies have poor accuracy for identifying patients who will suffer adverse perioperative events. Therefore there is a need for properly validated biomarkers for more precise and earlier prediction of complications after pediatric cardiac surgery.

Hypothesis:
We hypothesize that miRNA-208a, previously shown to be elevated in adults with acute myocardial infarction (AMI), can serve as a sensitive and specific circulating non-invasive biomarker for the post-operative clinical course and predict complications in pediatric patients with CHD that have undergone cardiac surgery. Additionally, we hypothesize that this miRNA will outperform conventional biomarkers used currently.

Results:
miRNA-208a was quantified in samples obtained from 79 patients undergoing cardiac surgery preoperatively and at 6, 12 and 24h post-op. The amount of miRNA-208a rises sharply at 6h after the operation, remains high at 12h and then declines. The amount at 6h and 12h correlates with the length of CPB and ACC during the operation and with laboratory parameters of the patients such as Troponin and Lactate. The amount of miR208a at 6h and 12h was found to correlate with post-operative complications, length of hospitalization and to be associated with longer than 48h of ventilation.

Conclusions:
Our results show that the levels of post-operative circulating miRNA-208a in pediatric patients with CHD are indicative of myocardial damage. Moreover we show that as early as at 6h after the operation, miR-208a is a suitable biomarker for predicting the future post-operative course and the complications in these patients.