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

Cardiovascular magnetic resonance pulmonary perfusion for guidance of interventional treatment of pulmonary vein stenosis

Abstract Background Pulmonary vein (PV) stenosis represents a rare but serious complication following radiofrequency ablation of atrial fibrillation with a comprehensive diagnosis including morphological stenosis grading together with the assessment of its functional consequences being imperative within the relatively narrow window for therapeutic intervention. The present study determined the clinical utility of a combined, single-session cardiovascular magnetic resonance (CMR) imaging protocol integrating pulmonary perfusion and PV angiographic assessment for pre-procedural planning and follow-up of patients referred for interventional PV stenosis treatment. Methods CMR examinations (cine imaging, dynamic pulmonary perfusion, three-dimensional PV angiography) were performed in 32 consecutive patients prior to interventional treatment of PV stenosis and at 1-day and 3-months follow-up. Degree of PV stenosis was visually determined on CMR angiography; visual and quantitative analysis of pulmonary perfusion imaging was done for all five lung lobes. Results Interventional treatment of PV stenosis achieved an acute procedural success rate of 90%. Agreement between visually evaluated pulmonary perfusion imaging and the presence or absence of a ≥ 70% PV stenosis was nearly perfect (Cohen’s kappa, 0.96). ROC analysis demonstrated high discriminatory power of quantitative pulmonary perfusion measurements for the detection of ≥ 70% PV stenosis (AUC for time-to-peak enhancement, 0.96; wash-in rate, 0.93; maximum enhancement, 0.90). Quantitative pulmonary perfusion analysis proved a very large treatment effect attributable to successful PV revascularization already after 1 day. Conclusion Integration of CMR pulmonary perfusion imaging into the clinical work-up of patients with PV stenosis allowed for efficient peri-procedural stratification and follow-up evaluation of revascularization success

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