Circulating miR-423_5p fails as a biomarker for systemic ventricular function in adults after atrial repair for transposition of the great arteries

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Abstract

Background

Recently, the microRNA miR-423_5p was identified as a biomarker for left ventricular heart failure. Its role in patients with a systemic right ventricle and reduced ejection fraction after atrial repair for transposition of the great arteries has not been evaluated.

Methods

In 41 patients and 10 age- and sex-matched healthy controls circulating miR-423_5p concentration was measured and correlated to clinical parameters, cardiac functional parameters assessed by magnetic resonance imaging, and cardiopulmonary exercise testing.

Results

Levels of circulating miR-423_5p showed no difference between patients and controls. Further, there was no correlation between miR-423_5p and parameters of cardiopulmonary exercise testing or imaging findings.

Conclusions

In patients with a systemic right ventricle and reduced ejection fraction miR-423_5p levels are not elevated. Therefore, circulating miR-423_5p is not a useful biomarker for heart failure in this patient group.

Introduction

MicroRNAs are endogenous, highly conserved, noncoding RNAs that regulate the stability and subsequent translation of nascent mRNA transcripts [1]. There are estimated to be more than 1000 different miRNAs, many of which are expressed in a tissue and cell-specific manner [2]. It was discovered only recently that miRNAs are also abundantly present in blood [2]. Aberrant expression profiles of miRNAs have been identified in blood of subjects with certain forms of cancer and myocardial injury [2], [3], [4], [5].

A recent study demonstrated a number of miRNAs as putative biomarkers for heart failure [2]. Tijsen and colleagues performed miRNA arrays on RNA isolated from patients with heart failure defined by the Framingham criteria and elevated NT-proBNP levels and compared these with healthy controls and patients with dyspnea attributable to other causes. One circulating miRNA in particular, miR-423_5p, was able to distinguish heart failure cases from the other cases with an area under the curve of 0.91 [2].

In patients after atrial repair for transposition of the great arteries (D-TGA), in whom the right ventricle supports the systemic circulation, dysfunction of the right ventricle is the most important contributor to morbidity and mortality [6]. Further progressive deterioration of systemic right ventricular function is common [6]. The role of microRNAs, in particular miR-423_5p, has not been evaluated in this patient group.

Section snippets

Participants

This study is part of an exercise intervention trial, which has been registered at www.clinicaltrials.gov (No. NCT00837603) [7].

Patients with previous atrial redirection procedure (Mustard) for D-TGA who met all the inclusion criteria were eligible for the study. The inclusion criteria were: stable NYHA class I/II, unchanged medication (angiotensin converting enzyme inhibitors, beta-blockers) for the last 6 months, no physical training program at present, and the physical and mental ability to

Results

Forty-one patients and 10 age- and sex-matched healthy controls were enrolled in this study. Table 1 shows the clinical characteristics of the study population. Cardiopulmonary exercise testing, echocardiography and MRI were only performed in the patients.

Discussion

In patients with a systemic right ventricle and reduced ejection fraction miR-423_5p levels are not elevated in comparison with healthy controls. Further, there is no difference of miR-423_5p levels in patients with a more severely reduced systemic ventricular function compared to patients with a moderately reduced or even normal ventricular function. This is contrast to findings recently reported in patients with left ventricular heart failure. Tijsen and colleagues showed recently that

Acknowledgment

This work was funded by grants of the German ministry for education and research (IFB-TX 0WO0802 to TT). The authors of this manuscript have certified that they comply with the principles of ethical publishing in the International Journal of Cardiology.

References (15)

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