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MicroRNA-183-3p Is a Predictor of Worsening Heart Failure in Adult Patients With Transposition of the Great Arteries and a Systemic Right Ventricle.

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.

SUBMITTER: Abu-Halima M

PROVIDER: S-EPMC8455927 | biostudies-literature |

REPOSITORIES: biostudies-literature

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MicroRNA-183-3p is a predictor of worsening heart failure in adult patients with transposition of the great arteries and a systemic right ventricle

Project description: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 arrays 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. 6 of these 106 miRNAs were significantly related to worsening HF. After validation by RT-qPCR, 4 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 and miR-183-3p were found to be independent predictors of worsening HF (P<0.001 and P=0.008, 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.

2021-09-29 | GSE179105 | GEO

MicroRNA-183-3p is a predictor of worsening heart failure in adult patients with transposition of the great arteries and a systemic right ventricle

Project description:MicroRNA-183-3p is a predictor of worsening heart failure in adult patients with transposition of the great arteries and a systemic right ventricle

| PRJNA742219 | ENA

CFC1 mutations in patients with transposition of the great arteries and double-outlet right ventricle.

Project description:Recent investigations identified heterozygous CFC1 mutations in subjects with heterotaxy syndrome, all of whom had congenital cardiac malformations, including malposition of the great arteries. We hypothesized that a subset of patients with similar types of congenital heart disease---namely, transposition of the great arteries and double-outlet right ventricle, in the absence of laterality defects---would also have CFC1 mutations. Our analysis of the CFC1 gene in patients with these cardiac disorders identified two disease-related mutations in 86 patients. The present study identifies the first autosomal single-gene defect for these cardiac malformations and indicates that some cases of transposition of the great arteries and double-outlet right ventricle can share a common genetic etiology with heterotaxy syndrome. In addition, these results demonstrate that the molecular pathway involving CFC1 plays a critical role in normal and abnormal cardiovascular development.

| S-EPMC384955 | biostudies-literature

Collagen turnover biomarkers and systemic right ventricle remodeling in adults with previous atrial switch procedure for transposition of the great arteries.

Project description:BackgroundMyocardial fibrosis is a potential pathophysiological mechanism leading to systemic right ventricular (SRV) deterioration. We hypothesize that circulating levels of collagen deposition markers are elevated in patients with SRV remodeling and this elevation may have a predictive value.MethodsWe prospectively evaluated 56 patients with D-TGA after the atrial switch procedure (mean age 25.6 ± 4.8, range 18-37 years; 67% males). Serum levels of procollagen type III amino-terminal propeptide (PIIINP), collagen type I carboxy-terminal telopeptide (CITP), procollagen type I N-terminal propeptide (PINP), matrix metalloproteinase (MMP 1, MMP 9) and a tissue inhibitor of matrix metalloproteinase (TIMP 1) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) were measured and compared with healthy controls. The relationship between these serum markers, echocardiographic and cardiac magnetic resonance parameters and the outcome at a follow-up of 61 months (range, 24-85 months) was determined.ResultsCompared with the healthy control group, the study group had significantly higher levels of TIMP1, PIIINP, CITP, PINP and NT-pro-BNP (p<0.05, each). The levels of PIIINP and CITP were significantly higher among patients with an SRV mass index above the mean value. The level of PIIINP was significantly higher among patients with an SRV EDV index above the mean value. CITP was significantly elevated in SRV late gadolinium enhanced (LGE) positive patients, compared to patients without SRV LGE. MMP9 and TIMP1 predicted an adverse clinical outcome on univariate Cox proportional hazard survival analysis in addition to well proven predictors of outcome (SRV EF and NYHA).ConclusionsWe demonstrated a pattern of altered collagen turnover adversely related with the indices of SRV remodeling and an adverse clinical outcome in patients with SRV.

| S-EPMC5540554 | biostudies-literature

The phenotypic spectrum of ZIC3 mutations includes isolated d-transposition of the great arteries and double outlet right ventricle.

Project description:Disease causing mutations for heterotaxy syndrome were first identified in the X-linked laterality gene, ZIC3. Mutations typically result in males with situs ambiguus and complex congenital heart disease; however affected females and one male with isolated d-transposition of the great arteries (d-TGA) have been reported. We hypothesized that a subset of patients with heart defects common to heterotaxy but without laterality defects would have ZIC3 mutations. We also sought to estimate the prevalence of ZIC3 mutations in sporadic heterotaxy. Patients with TGA (n = 169), double outlet right ventricle (DORV; n = 89), common atrioventricular canal (CAVC; n = 41), and heterotaxy (n = 54) underwent sequencing of ZIC3 exons. We tested 90 patients with tetralogy of Fallot (TOF) to correlate genotype with phenotype. Three potentially disease-related missense mutations were detected: c.49G > T (Gly17Cys) in a female with isolated DORV, c.98C > T (Ala33Val) in a male with isolated d-TGA, and c.841C > T (His281Tyr) in a female with sporadic heterotaxy. We also identified a novel insertion (CPFP333ins) in a family with heterotaxy. All were absent in 200 control patients and the 1000 Genomes Project (n = 629). No significant mutations were found in patients with TOF. Functional studies demonstrated reduced transcriptional activity of the ZIC3 His281Tyr mutant protein. ZIC3 mutations were rarely identified in isolated DORV and d-TGA suggesting that a subset of DORV and d-TGA may fall within the spectrum of laterality defects. ZIC3 mutations were found in 3.7% of patients with sporadic heterotaxy; therefore testing should be considered in patients with heterotaxy.

| S-EPMC3707401 | biostudies-literature

Failing systemic right ventricle in a patient with dextrocardia and complex congenitally corrected transposition of the great arteries: a case report of successful transvenous cardiac resynchronization therapy.

Project description:BackgroundPatients with congenitally corrected transposition of the great arteries (ccTGA) are prone to the development of advanced atrio-ventricular block requiring chronic ventricular pacing. The morphological right ventricle (RV) often develops systolic dysfunction as it is unable to withstand the chronic pressure overload it is exposed to when supporting the systemic circulation.Case summaryA 56-year-old woman with dextrocardia and complex ccTGA with a history of dual-chamber implantable cardioverter-defibrillator (DDD-ICD, high degree atrio-ventricular-block and syncopal ventricular tachycardia), presented with progressive heart failure and symptomatic atrial arrhythmias. She underwent a successful ablation and concomitant invasive haemodynamic evaluation of potential alternative/biventricular pacing modalities. During biventricular pacing, the QRS narrowed and the systemic RV intraventricular pressure (Dp/Dt) increased with 30%. She underwent a successful transvenous upgrade to cardiac resynchronization therapy (CRT). The electrocardiogram post-implantation showed biventricular capture and patient showed subjective and objective clinical improvement.DiscussionSystemic RV dysfunction in ccTGA can be aggravated by chronic pacing-induced dyssynchrony, contributing to progression of heart failure in this patient group. Transvenous CRT is feasible in ccTGA anatomy and may be pursued in order to improve or preserve the functional status of pacing-dependent ccTGA patients. Invasive haemodynamic contractility evaluation can help assess the potential benefit of CRT in patients with complex anatomy.

| S-EPMC8188871 | biostudies-literature

Successful hybrid cardiac resynchronization therapy in a patient with failing systemic right ventricle and significant tricuspid regurgitation in transposition of the great arteries after atrial switch procedure according to Mustard.

Project description:BackgroundPatients with a systemic right ventricle (sRV) in the context of transposition of the great arteries (TGA) late after atrial switch are prone to heart failure. Complications like tricuspid valve regurgitation (TR) can further aggravate sRV dysfunction. Tricuspid valve regurgitation is usually secondary to annular dilatation and restriction. Criteria for cardiac resynchronization therapy (CRT) in this patient group are not well defined and should be considered on a case-by-case basis.Case summaryWe present a case of a 42-year-old male with sRV failure and TR in the context of TGA after atrial switch. Patient had progressive reduction in exercise capacity. Electrocardiogram showed a wide QRS complex (right bundle branch block configuration). Echocardiography showed significant TR and signs of electromechanical dyssynchrony of the failing sRV with severely reduced systolic function. He underwent heart catheterization and invasive haemodynamic evaluation to assess the potential benefit of CRT. During sequential atrial-sRV pacing, 20% increase in Dp/Dt was measured, suggesting that he would be a CRT responder. Concomitant angiography showed no baffle leakage nor obstructive coronary artery disease. Hybrid CRT-defibrillator implantation resulted in successful resynchronization and improved sRV function, reduced TR and better exercise capacity.DiscussionInvasive haemodynamic contractility evaluation can help assess the potential benefit of CRT in patients with systemic right ventricular failure in the context of transposition of TGA after atrial switch. Successful CRT can result in improved sRV function, reduced TR and improved exercise capacity.

| S-EPMC8972821 | biostudies-literature

Left Subclavian Artery Isolation with Right Aortic Arch and D-Transposition of the Great Arteries.

Project description: Not available

| S-EPMC8712996 | biostudies-literature

Isolated Right Subclavian Artery From the Pulmonary Artery in D-Transposition of the Great Arteries

Project description:Graphical abstract Highlights • Isolated RSCA from the PA is a rare finding in d-TGA.• Atypical differential cyanosis in d-TGA may indicate abnormal aortic branching.• Fetal imaging can provide evidence of an isolated RSCA.

| S-EPMC10147546 | biostudies-literature

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

Project description:BackgroundData 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.MethodsCirculating 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.ResultsCompared 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.ConclusionsA 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.

| S-EPMC3847493 | biostudies-literature

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