Abstract
Aim: MicroRNAs (miRNAs) have been shown to play an important role in the progression of heart failure (HF). The aim of our study was to analyze miRNAs in the blood of patients with transposition of the great arteries and a systemic right ventricle (TGA-RV) in order to identify those that predict worsening HF.Materials and Methods: In 36 patients with TGA-RV, SurePrint™ 8 × 60K Human v21 miRNA microarrays were used to determine the miRNA abundance profiles and compared to 35 age- and gender-matched healthy volunteers (HVs). MiRNAs that were most significantly abundant or best related to worsening HF were further validated by RT-qPCR.Results: Using miRNA array analysis, a total of 50 down-regulated and 56 up-regulated miRNAs were found to be differentially abundant in TGA-RV patients compared to HVs. Six of these 106 miRNAs were significantly related to worsening HF. After validation by RT-qPCR, four miRNAs turned out to be significantly associated with worsening HF, namely miR-150-5p, miR-1255b-5p, miR-423-3p, and miR-183-3p. In the stepwise multivariable Cox regression analysis, ejection fraction of the systemic RV, high sensitive TNT and miR-183-3p were found to be independent predictors of worsening HF (P = 0.001, P = 0.002, and P = 0.001, respectively).Conclusions: In patients with TGA-RV, miR-183-3p is an independent predictor of worsening HF and thus may be used as additional biomarker in the risk assessment of these patients.
Highlights
Transposition of the great arteries (TGA) is a rare congenital heart defect accounting for 5–7% of all congenital heart abnormalities [1]
Another and more rare form is congenitally corrected TGA that is associated with physiologically normal blood flow due to ventricular inversion and carries the risk of heart failure because the systemic ventricle is a morphologically right ventricle
In patients with congenital heart disease (CHD), those with a systemic morphological right ventricle or univentricular heart are known to be at risk for heart failure (HF) [3,4,5]
Summary
Transposition of the great arteries (TGA) is a rare congenital heart defect accounting for 5–7% of all congenital heart abnormalities [1]. The atrial switch procedure has been replaced by the arterial switch procedure nowadays, there are still a lot of patients suffering from the sequelae after the atrial switch i.e., atrial arrhythmias and heart failure [2] Another and more rare form is congenitally corrected TGA (ccTGA) that is associated with physiologically normal blood flow due to ventricular inversion and carries the risk of heart failure because the systemic ventricle is a morphologically right ventricle. In another study by Tutarel et al miR-423-5p failed to be associated with the systolic function of the systemic right ventricle as assessed by the ejection fraction via magnetic resonance imaging in TGA patients after atrial switch procedure [24] This negative result may be due to the fact that patients had only mild heart failure symptoms in that study and that the discriminative power of miR-423-5p was limited due to the lack of advanced stages of HF in the study cohort. The aim of our study, was to analyse miRNA signatures in TGA-RV patients in order to identify those miRNAs that are associated with worsening HF and may yield prognostic impact
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