Circulating microRNA expression profile and systemic right ventricular function in adults after atrial switch operation for complete transposition of the great arteries

BACKGROUND Data on the use of circulating microRNAs (miRNAs) as biomarkers of cardiovascular diseases are emerging. Little, however, is known on the expression profile of circulating of microRNAs in congenital heart malformations with a systemic right ventricle that is prone to functional impairment. We aimed to test the hypothesis that circulating miRNA profile is altered in patients late after atrial switch operation for complete transposition of the great arteries (TGA) and further explored possible relationships between alteration of circulating miRNAs and systemic ventricular contractility. METHODS Circulating miRNA expression profiling of serum samples from 5 patients and 5 healthy controls was performed. The results were validated in 26 patients and 20 controls using real-time quantitative reverse-transcription polymerase chain reaction for candidate miRNAs with fold changes >3 by expression profiling. Systemic ventricular myocardial acceleration during isovolumic contraction (IVA) was determined by colour tissue Doppler echocardiography. RESULTS Compared with controls, patients had significantly lower systemic ventricular IVA (p = 0.002). Of the 23 upregulated miRNAs identified by profiling, 11 were validated to be increased in patients compared with controls: miR-16, miR-106a, miR-144*, miR-18a, miR-25, miR-451, miR-486-3p, miR-486-5p, miR-505*, let-7e and miR-93. Among the validated 11 miRNAs, miR-18a (r = -0.45, p = 0.002) and miR-486-5p (r = -0.35, p = 0.018) correlated negatively with systemic ventricular IVA for the whole cohort. CONCLUSIONS A distinct serum miRNA expression signature exists in adults with complete TGA after atrial switch operation, with serum miR-18a and miR-486-5p being associated with systemic ventricular contractility.