Competing risks analysis defines the prevalence of the various outcomes after Norwood operation and predicts improved outcomes with successful modification of controllable risk factors.

Morphologic and functional factors can be used to predict optimal pathway and survival benefit in neonates with critical left ventricular outflow obstruction.

Characteristics of neonates with pulmonary atresia and intact ventricular septum predict type of definitive repair. A morphologically driven institutional protocol emphasizing both 2-ventricle and Fontan pathways might mitigate the negative effect of unfavorable morphology. In the current era, 85% of neonates are likely to reach a definitive surgical end point, with 2-ventricle repair achieved in an estimated 50%.

Inappropriate pursuit of biventricular repair in borderline candidates is more frequent and more consequential in survival terms than is inappropriate pursuit of univentricular repair. Use of the univentricular survival advantage tool will help identify infants for whom univentricular repair may be a better choice than attempting biventricular repair.

Background-The importance of noncoding RNAs (ncRNA), especially microRNAs (miRNAs), for maintaining stability in the developing vertebrate heart has recently become apparent; however, there is little known about the expression pattern of ncRNA in the human heart with developmental anomalies. Methods and Results-We examined the expression of miRNAs and small nucleolar RNAs (snoRNAs) in right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, 3 fetal heart samples, and 8 normally developing infants. We found 61 miRNAs and 135 snoRNAs to be significantly changed in expression in myocardium from children with TOF compared with normally developing comparison subjects. The pattern of ncRNA expression in TOF myocardium had a surprising resemblance to expression patterns in fetal myocardium, especially for the snoRNAs. Potential targets of miRNAs with altered expression were enriched for gene networks of importance to cardiac development. We derived a list of 229 genes known to be critical to heart development and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlation with 33 miRNAs, each of which also had significantly changed expression. The primary function of snoRNAs is targeting specific nucleotides of ribosomal RNAs and spliceosomal RNAs for biochemical modification. The targeted nucleotides of the differentially expressed snoRNAs were concentrated in the 28S and 18S ribosomal RNAs and 2 spliceosomal RNAs, U2 and U6. In addition, in myocardium from children with TOF, we observed splicing variants in 51% of genes that are critical for cardiac development. Taken together, these observations suggest a link between levels of snoRNA that target spliceosomal RNAs, spliceosomal function, and heart development. Conclusions-This is the first report characterizing ncRNA expression in a congenital heart defect. The striking shift in expression of ncRNAs reflects a fundamental change in cell biology, likely impacting expression, transcript splicing, and translation of developmentally important genes and possibly contributing to the cardiac defect. (Circ Cardiovasc Genet. 2012;5:279-286.)Key Words: tetralogy of Fallot Ⅲ cardiac development Ⅲ microRNA Ⅲ miRNA Ⅲ small nucleolar RNA Ⅲ snoRNA T he heart is the first major internal organ to form during embryogenesis, and it is critical for the viability of the embryo. A multitude of genes and genetic networks contribute to the spatial and temporal specification of cell lineage required for proper embryological heart formation. 1 Failure of proper cellular differentiation, migration, and apoptosis results in congenital heart defects (CHD), which are a major cause of childhood morbidity and mortality and remains a substantial challenge even in countries with advanced healthcare systems. The incidence of CHD is approximately 8 per 1000 live births, 2 making CHD the most common birth defect. Mendelian and chromosomal syndro...

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BackgroundTetralogy of Fallot (TOF) is the most commonly observed conotruncal congenital heart defect. Treatment of these patients has evolved dramatically in the last few decades, yet a genetic explanation is lacking for the failure of cardiac development for the majority of children with TOF. Our goal was to perform genome wide analyses and characterize expression patterns in cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with tetralogy of Fallot.MethodsWe employed genome wide gene expression microarrays to characterize cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with TOF (16 idiopathic and three with 22q11.2 deletions) and compared gene expression patterns to normally developing subjects.ResultsWe detected a signal from approximately 26,000 probes reflecting expression from about half of all genes, ranging from 35% to 49% of array probes in the three tissues. More than 1,000 genes had a 2-fold change in expression in the right ventricle (RV) of children with TOF as compared to the RV from matched control infants. Most of these genes were involved in compensatory functions (e.g., hypertrophy, cardiac fibrosis and cardiac dilation). However, two canonical pathways involved in spatial and temporal cell differentiation (WNT, p = 0.017 and Notch, p = 0.003) appeared to be generally suppressed.ConclusionsThe suppression of developmental networks may represent a remnant of a broad malfunction of regulatory pathways leading to inaccurate boundary formation and improper structural development in the embryonic heart. We suggest that small tissue specific genomic and/or epigenetic fluctuations could be cumulative, leading to regulatory network disruption and failure of proper cardiac development.