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Background: Congenital heart disease (CHD) is a common birth defect affecting approximately 1% of newborns. Great progress has been made in elucidating the genetic aetiology of CHD with advances in genomic technology, which we leveraged in recovering a new pathway affecting heart development in humans previously known to affect heart development in an animal model., Methods: Four hundred and sixteen individuals from Thailand and the USA diagnosed with CHD and/or congenital diaphragmatic hernia were evaluated with chromosomal microarray and whole exome sequencing. The DECIPHER Consortium and medical literature were searched for additional patients. Murine hearts from ENU-induced mouse mutants and transgenic mice were evaluated using both episcopic confocal histopathology and troponin I stained sections., Results: Loss of function ROBO1 variants were identified in three families; each proband had a ventricular septal defect, and one proband had tetralogy of Fallot. Additionally, a microdeletion in an individual with CHD was found in the medical literature. Mouse models showed perturbation of the Slit-Robo signalling pathway, causing septation and outflow tract defects and craniofacial anomalies. Two probands had variable facial features consistent with the mouse model., Conclusion: Our findings identify Slit-Robo as a significant pathway in human heart development and CHD., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Heart rate variability (HRV) has been used as a reliable method to detect cardiac autonomic nervous system activity. Peak oxygen uptake (VO(2) peak) has been a predictor of death for adults with repaired tetralogy of Fallot (TOF). This study investigated the correlation between HRV and exercise capacity in 30 patients with TOF after surgery for total correction. The median age of the patients was 14 years (range, 9-25 years), and the median follow-up period was 11.6 months (range, 5.3-20.2 months). Low- and high-frequency-domain HRV significantly correlated with VO(2) peak (r = 0.56, P = 0.001 and r = 0.44, P = 0.02, respectively). After the 1-year follow-up evaluation, VO(2) peak and HRV analysis did not differ from those at entry to the study. However, low- and high-frequency-domain HRV still correlated significantly with VO(2) peak (r = 0.43, P = 0.03 and r = 0.52, P = 0.007, respectively). Left ventricular early diastolic myocardial velocity was most closely correlated with the VO(2) peak (r = 0.51, P = 0.005). Impaired cardiovascular autonomic control and left ventricular diastolic dysfunction may be responsible for exercise intolerance in patients with repaired TOF. Long-term follow-up evaluation with exercise testing and 24-h Holter monitoring are warranted.

Background: Tissue Doppler imaging has been recently used to evaluate ventricular function. Peak oxygen uptake (V•O2peak) has been demonstrated as a predictor for death in adults with repaired tetralogy of Fallot (TOF). The aim of this study was to determine which Doppler parameters correlated with V•O2peak in patients with repaired TOF., Method and Results: Doppler echocardiography, tissue Doppler imaging, and exercise test were performed in 30 patients with TOF after surgical repair. In 30 patients with repaired TOF (median age 14 years, range 9-25 years), 11 patients (37%) were female. Seven patients (median age 12 years) had normal left ventricular diastolic function, whereas the rest of the patients were classified as diastolic dysfunction grade II (median age 15 years; n=15) and III and IV (median age 18 years; n=8). The oxygen uptake at anaerobic threshold (V•O2AT) and peak exercise in patients with left ventricular diastolic dysfunction was significantly lower than that in those with normal diastolic function. Also, V•O2AT and V•O2 peak in patients with diastolic dysfunction grade III and IV were significantly lower than that in those with diastolic dysfunction grade II. Left ventricular early diastolic myocardial velocity was most closely correlated to V•O2peak (r=0.51; P=0.005). Peak early ventricular filling velocity to early diastolic myocardial velocity ratio was significantly correlated with V•O2peak (r=-0.50; P=0.006)., Conclusion: Left ventricular diastolic dysfunction is correlated with V•O2peak. Left ventricular diastolic function should be a routine echocardiographic assessment in patients with repaired TOF., (© 2011, Wiley Periodicals, Inc.)

The authors report a pseudoaneurysm in a 2-year-old boy presenting with fever, increasing cyanosis and right upper lung shadowing on a chest radiograph at six weeks following modified Blalock-Taussig shunt surgery. Echocardiography and a CT scan of the chest revealed a large pseudoaneurysm originating from the right subclavian artery at the proximal insertion of modified Blalock-Taussig shunt. The patient underwent aneurysmal resection, Blalock-Taussig shunt removal, right subclavian artery ligation and the creation of a central shunt between the ascending aorta and main pulmonary artery. Unfortunately, the patient died 3 hours after the operation.