Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.

Congenital heart defects (CHDs) have a neonatal incidence of 0.8-1% (refs. 1,2). Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (∼2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD

Influence of a 100-mile ultramarathon on heart rate and heart rate variability

Aims This study aimed to investigate the impact of an ultramarathon (UM) with a distance of 100 miles on heart rate (HR) and heart rate variability (HRV).Methods 28 runners (25 men and 3 women) underwent 24-hour Holter ECG monitoring 1 week before the UM, immediately after the UM and after a week of recovery. The influence of age, body mass index (BMI), HR and HRV on the run time and recovery was investigated.Results A rise in the baseline HR (18.98%) immediately after the run accompanied by a significant drop in the SD of all normal RR intervals (7.12%) 1 week after. Except for the runners’ age, BMI, HR and HRV showed no influence on the competition time. Full return of HRV to the athletes’ baseline did not occur within 1 week. There were no significant differences between finishers and non-finishers in the analysed parameters.Conclusion The present results show that a 100-mile run leads to an increase in sympathetic activity and thus to an increase in HR and a decrease in HRV. Also, HRV might be a suitable parameter to evaluate the state of recovery after a 100-mile run but does not help to quantify the status of recovery, as the damage to the tendomuscular system primarily characterises this after completing a UM

Retrospective study of complete atrioventricular canal defects: Anesthetic and perioperative challenges

Objective: The objective of this study was to highlight anesthetic and perioperative management and the outcomes of infants with complete atrioventricular (AV) canal defects. Design: This retrospective descriptive study included children who underwent staged and primary biventricular repair for complete AV canal defects from 1999 to 2013. Setting: A single-center study at a university affiliated heart center. Participants: One hundred and fifty-seven patients with a mean age at surgery of 125 ± 56.9 days were included in the study. About 63.6% of them were diagnosed as Down syndrome. Mean body weight at surgery was 5.6 ± 6.3 kg. Methods: Primary and staged biventricular repair of complete AV canal defects. Measurements and main results: A predefined protocol including timing of surgery, management of induction and maintenance of anesthesia, cardiopulmonary bypass, and perioperative intensive care treatment was used throughout the study. Demographic data as well as intraoperative and perioperative Intensive Care Unit (ICU) data, such as length of stay in ICU, total duration of ventilation including reintubations, and total length of stay in hospital and in hospital mortality, were collected from the clinical information system. Pulmonary hypertension was noted in 60% of patients from which 30% needed nitric oxide therapy. Nearly 2.5% of patients needed permanent pacemaker implantation. Thorax was closed secondarily in 7% of patients. In 3.8% of patients, reoperations due to residual defects were undertaken. Duration of hospital stay was 14.5 ± 4.7 days. The in-hospital mortality was 0%. Conclusion: Protocolized perioperative management leads to excellent outcome in AV canal defect repair surgery

Fetal hemodynamic response to aortic valvuloplasty and postnatal outcome: a European multicenter study

Objective: Fetal aortic stenosis may progress to hypoplastic left heart syndrome. Fetal valvuloplasty (FV) has been proposed to improve left heart hemodynamics and maintain biventricular (BV) circulation. The aim of this study was to assess FV efficacy by comparing survival and postnatal circulation between fetuses that underwent FV and those that did not. Methods: This was a retrospective multicenter study of fetuses with aortic stenosis that underwent FV between 2005 and 2012, compared with contemporaneously enrolled natural history (NH) cases sharing similar characteristics at presentation but not undergoing FV. Main outcome measures were overall survival, BV-circulation survival and survival after birth. Secondary outcomes were hemodynamic change and left heart growth. A propensity score model was created including 54/67 FV and 60/147 NH fetuses. Analyses were performed using logistic, Cox or linear regression models with inverse probability of treatment weighting (IPTW) restricted to fetuses with a propensity score of 0.14–0.9, to create a final cohort for analysis of 42 FV and 29 NH cases. Results: FV was technically successful in 59/67 fetuses at a median age of 26 (21–34) weeks. There were 7/72 (10%) procedure-related losses, and 22/53 (42%) FV babies were delivered at < 37 weeks. IPTW demonstrated improved survival of liveborn infants following FV (hazard ratio, 0.38; 95% CI, 0.23–0.64; P = 0.0001), after adjusting for circulation and postnatal surgical center. Similar proportions had BV circulation (36% for the FV cohort and 38% for the NH cohort) and survival was similar between final circulations. Successful FV cases showed improved hemodynamic response and less deterioration of left heart growth compared with NH cases (P ≤ 0.01). Conclusions: We report improvements in fetal hemodynamics and preservation of left heart growth following successful FV compared with NH. While the proportion of those achieving a BV circulation outcome was similar in both cohorts, FV survivors showed improved survival independent of final circulation to 10 years' follow-up. However, FV is associated with a 10% procedure-related loss and increased prematurity compared with the NH cohort, and therefore the risk-to-benefit ratio remains uncertain. We recommend a carefully designed trial incorporating appropriate and integrated fetal and postnatal management strategies to account for center-specific practices, so that the benefits achieved by fetal therapy vs surgical strategy can be demonstrated clearly. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd