A genome-wide association study of congenital cardiovascular left-sided lesions shows association with a locus on chromosome 20.

Congenital heart defects involving left-sided lesions (LSLs) are relatively common birth defects with substantial morbidity and mortality. Previous studies have suggested a high heritability with a complex genetic architecture, such that only a few LSL loci have been identified. We performed a genome-wide case-control association study to address the role of common variants using a discovery cohort of 778 cases and 2756 controls. We identified a genome-wide significant association mapping to a 200 kb region on chromosome 20q11 [P= 1.72 × 10-8 for rs3746446; imputed Single Nucleotide Polymorphism (SNP) rs6088703 P= 3.01 × 10-9, odds ratio (OR)= 1.6 for both]. This result was supported by transmission disequilibrium analyses using a subset of 541 case families (lowest P in region= 4.51 × 10-5, OR= 1.5). Replication in a cohort of 367 LSL cases and 5159 controls showed nominal association (P= 0.03 for rs3746446) resulting in P= 9.49 × 10-9 for rs3746446 upon meta-analysis of the combined cohorts. In addition, a group of seven SNPs on chromosome 1q21.3 met threshold for suggestive association (lowest P= 9.35 × 10-7 for rs12045807). Both regions include genes involved in cardiac development-MYH7B/miR499A on chromosome 20 and CTSK, CTSS and ARNT on chromosome 1. Genome-wide heritability analysis using case-control genotyped SNPs suggested that the mean heritability of LSLs attributable to common variants is moderately high ([Formula: see text] range= 0.26-0.34) and consistent with previous assertions. These results provide evidence for the role of common variation in LSLs, proffer new genes as potential biological candidates, and give further insight to the complex genetic architecture of congenital heart disease.

Isolated coarctation of the aorta in the fetus: A diagnostic challenge.

Isolated coarctation of the aorta (CoA) is estimated by the Centers for Disease Control and Prevention to account for 4%-6% of all congenital heart disease (CHD) in the United States, with a reported prevalence of ~4 per 10 000 live births. Prenatal recognition of coarctation is important as it may improve neonatal survival and reduce morbidity. However, despite advances in imaging and the trend toward detailed aortic arch assessment as part of a comprehensive fetal echocardiogram, isolated CoA may still elude prenatal detection, with potentially lethal consequences if the diagnosis is not suspected and the patent ductus arteriosus (PDA) closes spontaneously in postnatal life. The purpose of this review is to outline the methods of antenatal aortic arch evaluation in the current era, discuss "red flags" that raise the suspicion for CoA, including associated anomalies and serve as a repository of the most up to date information regarding its diagnosis in utero and its perinatal management. Other aortic arch abnormalities, such as interrupted aortic arch, or CoA associated with complex single ventricles, are not included in this review.

The Blalock-Taussig shunt revisited: a contemporary experience.

BACKGROUND: The Blalock-Taussig shunt (BTS) was introduced 68 years ago before open repair of cyanotic congenital heart disease (CHD) was possible. The originally described technique has undergone many modifications but remains an integral component of the management of cyanotic CHD. We report our contemporary, single institution experience with the BTS. STUDY DESIGN: We performed a retrospective review of all patients treated with a BTS from June 1995 to December 2011. RESULTS: There were 730 BTS performed in 712 patients; 727 (99.6%) by interposition graft (modified). The BTS was predominantly right-sided (n = 657, 90%). Median age and weight at palliation were 8 days (range 0 days to 18.5 years) and 3.2 kg (1.5 to 51 kg). Median hospital length of stay was 16 days (range 0 to 347 days). There were 241 (33%) BTS performed as initial palliation for ultimate 2-ventricle (2V) circulation, 471 (65%) as part of staged palliation for patients with functionally univentricular lesions (1V), 6 (1%) as a part of 1.5-ventricle palliation, and 12 (1%) for Ebstein's anomaly. There were 473 (65%) BTS placed via sternotomy and the most common site of BTS was the right subclavian to right pulmonary artery (PA; n = 452, 62%). Hospital mortality was higher for BTS in 1V patients (1V 15% vs 2V 3%, p < 0.0001). Overall, 536 (73%) patients were bridged to complete repair or the second stage of 1V palliation after a median duration of 6.5 months (0 days to 15.3 years). Multivariable regression showed that sternotomy approach, use of cardiopulmonary bypass, innominate artery-PA shunt, and diagnosis of Ebstein's were risk factors for in-hospital mortality (p < 0.05). CONCLUSIONS: Although the BTS remains an important component of the surgical treatment of cyanotic congenital heart disease, patients with single ventricle circulation still face significant ongoing risk of mortality.