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Background: Covered stent implantation for treatment of coarctation of the aorta (CoA) is effective and can prevent aortic wall injury. Prospective studies with long-term follow-up, including imaging, are lacking. We report the acute and long-term outcomes for use of the Large Diameter Advanta V12 covered stent for treatment of native and recurrent CoA., Methods: A prospective, multicenter, nonrandomized study was performed including 70 patients (43 male), median age 17 years, median weight 57.4 kg with CoA who underwent implantation of the Large Diameter Advanta V12 covered stent. Annual follow-up for 5 years included Doppler echocardiography to calculate diastolic velocity: systolic velocity ratio., Results: CoA diameter increased from 5.6±3.6 to 14.9±3.9 mm ( P <0.0001) and the pressure gradient decreased from 35.8±16.2 to 5.6±7.9 mm Hg ( P <0.0001). Preimplantation diastolic velocity:systolic velocity of 0.6±0.16 dropped to 0.34±0.13 ( P <0.0001) and was maintained at 5 years. Computed tomography angiograms at 12 months postimplantation demonstrated the stent:transverse arch diameter to be similar, 0.91±0.09 to postprocedure 0.86±0.14. Major adverse vascular events at 30 days and 12 months were 1.4% and 4.3%, respectively. Significant adverse events included three patients who required stent implantation to treat infolding. There were no mortalities., Conclusions: The Large Diameter Advanta V12 covered stent is safe and effective for the treatment of CoA with an immediate and sustained reduction of the pressure gradient over 12 months and 5 years as assessed by preimplantation and postimplantation Doppler echocardiography and 12-month computed tomography angiography. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00978952. URL: http://www.anzctr.org.au; Unique identifier: ACTRN12612000013864.

Systematic data are lacking on pediatric long COVID. This study prospectively assessed 90 children with persistent symptoms who presented to a designated multidisciplinary clinic for long COVID. In nearly 60%, symptoms were associated with functional impairment at 1-7 months after the onset of infection. A comprehensive structured evaluation revealed mild abnormal findings in approximately half the patients, mainly in the respiratory aspect., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Vascular rings cause respiratory symptoms in children. Treatment consists of surgical division; however, data regarding mid-term results are scarce. The purpose of this study was to evaluate clinical results of vascular ring surgery., Methods: Retrospective chart review of consecutive patients who underwent vascular ring surgery. Mid-term follow-up consisted of clinic visits and telephone questionnaire over a 1-year period sampling at five points in time., Results: Follow-up of 85 patients who underwent vascular rings surgery revealed significant symptomatic improvement within 6 months. In total, 50% were symptomatic to some degree at their last documented clinic visit complaining of stridor (36.8%), cough (34.2%), wheezing (10.5%), dyspnoea on exertion (10.5%), or recurrent respiratory infections (23.7%). By telephone questionnaires, 83% described a significant improvement in respiratory symptoms, 63.4% had some residual symptoms, 36.6% stridor, 38.8% chronic cough, 32.4% bronchodilator use,18.3% had at least one episode of pneumonia per year, 31% of children had dyspnoea or respiratory limitation, and 12.7% while doing physical activities. We found no association between the age at surgery or anatomic variant to the presence of symptoms at mid-term follow-up., Conclusions: Surgical division of vascular rings results in significant clinical improvement within 1 year; nevertheless, some patients remain symptomatic to some degree. We found no association between the age at surgery or anatomic variant to the presence of symptoms at mid-term follow-up. Further evaluation is warranted to assess the nature of residual symptoms and explore whether anatomical causes can be identified leading to surgical modifications.

Objective: To explore factors that influence parents' decisions regarding the termination of pregnancy after the detection of fetal congenital heart disease (CHD)., Design: A prospective descriptive study., Setting: The Institute of Pediatric Cardiology in the Schneider Children's Medical Center., Participants: One hundred twenty couples (240 participants) with fetuses prenatally diagnosed with CHD, which was defined as conditions requiring surgical treatment., Methods: We obtained data from a structured questionnaire for the pediatric cardiologist, the medical records, and structured self-report questionnaires for the participants., Results: Thirty-six of 120 couples (30%) decided to terminate the pregnancy after a prenatal diagnosis of fetal CHD. The main factors associated with the decision to terminate were low gestational age (OR = 0.83 per week, 95% confidence interval [CI] [0.75, 0.96]), severe cardiac malformation (OR = 2.23, 95% CI [1.40, 3.53]), religious affiliation (OR = 10.0 for secular participants vs. others, 95% CI [4.61, 22.46], population group (OR = 2.96 for Jewish participants vs. others, 95% CI [1.63, 11.3]), and education (OR = 1.34 per year of education, 95% CI [1.15, 1.55])., Conclusions: Our findings describe the profiles of couples who decided to terminate their pregnancies after a prenatal diagnosis of fetal CHD. Early identification of the couple's decision can help health care providers provide adequate support, counseling, and guidance. Future research is needed to understand parents' needs for support through the process of decision-making, with attention to their religious and cultural values and contexts., (Copyright © 2021 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

This is the first published case, as far as we know, of a term neonate with refractory chylothorax secondary to diastolic dysfunction in the cardiac postoperative period, where extracorporeal membrane oxygenation (ECMO) was used to improve the physiologic derangements, thus allowing resolution of the chylous effusion. The infant was prenatally diagnosed with d-transposition of the great arteries. He was started on prostaglandin infusion and underwent balloon atrial septostomy followed by arterial switch operation. After surgery, he developed anasarca and high-volume chylothorax that did not respond to medical management and fasting. Cardiac catheterization demonstrated severe diastolic dysfunction and pulmonary hypertension. On postoperative day 19, he was placed on veno-arterial (VA) ECMO and had gradual regression of the chylothorax and edema. After 13 days on ECMO support, he was decannulated with small, self-limiting, reaccumulation of chylous effusion. He was discharged home on postoperative day 57, and has since been thriving with no evidence of reaccumulation of the chylous effusion. In summary, VA ECMO support could be considered as a rescue modality for patients with uncontrollable refractory high-volume chylous effusion, after other treatment options have been pursued., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2021 by the ASAIO.)

The purpose of this stuy is to prospectively assess the reliability of the ultrasound cardiac output monitor (USCOM™) for measuring stroke volume index and predicting left ventricular outflow tract diameter in adolescents with heart disease. Sixty consecutive adolescents with heart disease attending a tertiary medical center underwent USCOM™ assessment immediately after cardiac magnetic resonance imaging. USCOM™ measured stroke volume index and predicted left ventricular outflow tract diameter were compared to cardiac magnetic resonance imaging-derived values using Bland-Altman analysis. Ten patients with an abnormal left ventricular outflow tract were excluded from the analysis. An adequate USCOM™ signal was obtained in 49/50 patients. Mean stroke volume index was 46.1 ml/m 2 by the USCOM™ (range 22-66.9 ml/m 2 ) and 42.9 ml/m 2 by cardiac magnetic resonance imaging (range 24.7-59.9 ml/m 2 ). The bias (mean difference) was 3.2 ml/m 2 ; precision (± 2SD of differences), 17 ml/m 2 ; and mean percentage error, 38%. The mean (± 2SD) left ventricular outflow tract diameter was 0.445 ± 0.536 cm smaller by the USCOM™ algorithm prediction than by cardiac magnetic resonance imaging. Attempted adjustment of USCOM™ stroke volume index using cardiac magnetic resonance imaging left ventricular outflow tract diameter failed to improve agreement between the two modalities (bias 28.4 ml/m 2 , precision 44.1 ml/m 2 , percentage error 77.3%). Our study raises concerns regarding the reliability of USCOM™ for stroke volume index measurement in adolescents with cardiac disease, which did not improve even after adjusting for its inaccurate left ventricular outflow tract diameter prediction.

Kingella spp. have emerged as an important cause of invasive pediatric diseases. Data on Kingella infective endocarditis (KIE) in children are scarce. We compared the clinical features of pediatric KIE cases with those of Streptococcus species IE (StIE) and Staphylococcus aureus IE (SaIE). A total of 60 patients were included in the study. Throughout the study period, a rise in incidence of KIE was noted. KIE patients were significantly younger than those with StIE and SaIE, were predominately boys, and had higher temperature at admission, history of oral aphthae before IE diagnosis, and higher lymphocyte count (p<0.05). Pediatric KIE exhibits unique features compared with StIE and SaIE. Therefore, in young healthy children <36 months of age, especially boys, with or without a congenital heart defect, with a recent history of oral aphthae, and experiencing signs and symptoms compatible with endocarditis, Kingella should be suspected as the causative pathogen.

Björk conduit failure is a common reason for reintervention after a Björk modification of the Fontan procedure. We describe a first performed in human percutaneous procedure for the treatment of a failing Björk circuit in an adult with congenital heart disease and complex anatomic features. ( Level of Difficulty: Advanced. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

Epistaxis is a common debilitating manifestation in hereditary hemorrhagic telangiectasia (HHT), due to mucocutaneous telangiectases. The epistaxis can be difficult to control despite available treatments. Dysregulated angiogenesis has been shown to be associated with telangiectases formation. Topical propranolol has demonstrated antiangiogenic properties. We performed a two-phase study, i.e., a double-blind placebo-controlled phase, followed by an open-label phase. The aim of the study was assessment of safety and efficacy of nasal propranolol gel in HHT-related epistaxis. Twenty participants with moderate-severe HHT-related epistaxis were randomized to eight weeks of propranolol gel 1.5%, or placebo 0.5 cc, applied to each nostril twice daily; and continued propranolol for eight weeks in an open-label study. For the propranolol group, the epistaxis severity score (ESS) improved significantly (-2.03 ± 1.7 as compared with -0.35 ± 0.68 for the placebo group, p = 0.009); hemoglobin levels improved significantly (10.5 ± 2.6 to 11.4 ± 2.02 g/dL, p = 0.009); and intravenous iron and blood transfusion requirement decreased. The change in nasal endoscopy findings was not significant. During the open-label period, the ESS score improved significantly in the former placebo group (-1.99 ± 1.41, p = 0.005). The most common adverse event was nasal mucosa burning sensation. No cardiovascular events were reported. Our results suggest that topical propranolol gel is safe and effective in HHT-related epistaxis.

There is limited data on the cost-effectiveness of continuous-flow left ventricular assist devices (LVAD) in the United States particularly for the bridge-to-transplant indication. Our objective is to study the cost-effectiveness of a small intrapericardial centrifugal LVAD compared with medical management (MM) and subsequent heart transplantation using the respective clinical trial data. We developed a Markov economic framework. Clinical inputs for the LVAD arm were based on prospective trials employing the HeartWare centrifugal-flow ventricular assist device system. To better assess survival in the MM arm, and in the absence of contemporary trials randomizing patients to LVAD and MM, estimates from the Seattle Heart Failure Model were used. Costs inputs were calculated based on Medicare claim analyses and when appropriate prior published literature. Time horizon was lifetime. Costs and benefits were appropriately discounted at 3% per year. The deterministic cost-effectiveness analyses resulted in $69,768 per Quality Adjusted Life Year and $56,538 per Life Year for the bridge-to-transplant indication and $102,587 per Quality Adjusted Life Year and $87,327 per Life Year for destination therapy. These outcomes signify a substantial improvement compared with prior studies and re-open the discussion around the cost-effectiveness of LVADs.

Aberrant regulation of myocardial force production represents an early biomechanical defect associated with sarcomeric cardiomyopathies, but the molecular mechanisms remain poorly defined. Here, we evaluated the pathogenicity of a previously unreported sarcomeric gene variant identified in a pediatric patient with sporadic dilated cardiomyopathy, and we determined a molecular mechanism. Trio whole-exome sequencing revealed a de novo missense variant in TNNC1 that encodes a p.I4M substitution in the N-terminal helix of cardiac troponin C (cTnC). Reconstitution of this human cTnC variant into permeabilized porcine cardiac muscle preparations significantly decreases the magnitude and rate of isometric force generation at physiological Ca 2+ -activation levels. Computational modeling suggests that this inhibitory effect can be explained by a decrease in the rates of cross-bridge attachment and detachment. For the first time, we show that cardiac troponin T (cTnT), in part through its intrinsically disordered C terminus, directly binds to WT cTnC, and we find that this cardiomyopathic variant displays tighter binding to cTnT. Steady-state fluorescence and NMR spectroscopy studies suggest that this variant propagates perturbations in cTnC structural dynamics to distal regions of the molecule. We propose that the intrinsically disordered C terminus of cTnT directly interacts with the regulatory N-domain of cTnC to allosterically modulate Ca 2+ activation of force, perhaps by controlling the troponin I switching mechanism of striated muscle contraction. Alterations in cTnC-cTnT binding may compromise contractile performance and trigger pathological remodeling of the myocardium., (© 2019 Johnston et al.)

Background: Accessory pathways (APs) are a common reason for supraventricular tachycardia in small children. Trans-septal puncture (TSP) approach is commonly used for the ablation of left-sided APs, however it may be challenging in small children. The aim of this study was to assess the efficacy and safety of trans-septal approach radiofrequency (RF) ablation of left-sided APs in children weighing up to 30 kg., Methods: Of the 658 children who underwent catheter ablation of APs since 06/2002, 86 children had left-sided AP and weighed less than 30 kg. TSP approach guided with TEE and fluoroscopy was used for left atrium access., Results: The mean age, height, and body weight were 7.6 ± 1.9 years, 122.4 ± 9.3 cm and 24.0 ± 4.2 kg, respectively. Forty-three children (50%) were male, 46 of 86 (53%) had manifest AP, 17 of 86 (20%) weighed less than 20 kg and in 24 of 86 children (28%) a three-dimensional system (3DS) was used to reduce fluoroscopy time. The acute success rate was 98.8% (85/86), with a recurrence rate of 2.4% (2/85) in a mean follow-up of 66.2 ± 42.7 (9.1-184.2) months. The mean procedure time and fluoroscopy time were significantly lower for the 3DS group compared to the standard fluoroscopy group 131 ± 41 (55-262) and 2.4 ± 1.5 (1-6) minutes vs 164 ± 51 (62-249) and 27 ± 13 (8-77) minutes, P  < 0.01 and P  < 0.0001, respectively. There were no ablation-related complications., Conclusions: RF ablation of left-sided APs using TSP approach in small children had an excellent efficacy and safety profile. The use of 3DS significantly reduces the procedure and fluoroscopy time., Competing Interests: Authors declare no conflict of interests for this article., (© 2019 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

Infective endocarditis (IE) in the pediatric population can present as a life-threatening condition. Optimal timing for surgical intervention should consider surgical risks versus the risk of neurologic complications. We herein report our experience with this group of critically ill children. Retrospective analysis of patient charts of all patients who underwent urgent surgical treatment of aortic IE from 1994 to 2014 was performed. Nine patients with acute storming IE of the aortic valve or the ascending aorta were urgently operated (eight normal heart, one congenital aortic stenosis), age ranged from 8 weeks to 4.2 years. Causative organisms were Staphylococcus aureus (2), Staphylococcus coagulase negative (1), Kingella kingae (2), Streptococcus pneumoniae (2), or culture negative (2). Presenting symptoms other than hemodynamic instability were neurologic decompensation (5) coronary embolization (1) and cardiogenic shock due to scalded skin syndrome (1). CT and MRI demonstrated significant brain infarcts in four patients. Operations performed were the Ross operation (7) and ascending aortic reconstruction (2). There were no operative deaths. At a median follow-up of 6 years (range 2-196 months), all patients are alive and well. Re-intervention included homograft replacement (2) and transcatheter Melody valve implantation (1). At their last follow-up, the neo-aortic valve was functional in all patients with minimal regurgitation and all had full resolution of the neurological deficits. Urgent surgical treatment for aortic valve IE in infants is challenging. Although surgery is complex and pre-disposing conditions such as sepsis, neurologic and cardiac decompensations are prevalent, operative results are excellent and gradual and significant neurologic improvement was noted over time.

Background: Sudden Infant Death Syndrome (SIDS) mechanisms of death remains obscured. SIDS' Triple Risk Model assumed coexistence of individual subtle vulnerability, critical developmental period and stressors. Prone sleeping is a major risk factor but provide no clues regarding the mechanism of death. The leading assumed mechanisms of death are either an acute respiratory crisis or arrhythmias but neither one is supported with evidence, hence both are eventually speculations. Postmortem findings do exist but are inconclusive to identify the mechanism of death. WHAT DOES THE PROPOSED HYPOTHESIS BASED ON?: 1. The stressors (suggested by the triple risk model) share a unified compensatory physiological response of decrease in systemic vascular resistant (SVR) to facilitate a compensatory increase in cardiac output (CO). 2. The cardiovascular/cardiorespiratory control of the vulnerable infant during a critical developmental period may be impaired. 3. A severe decrease in SVR is associated with hyper-dynamic state, high output failure and distributive shock., The Hypothesis: Infant who is exposed to one or more stressors responds normally by decrease in SVR which increases CO. In normal circumstances once the needs are met both SVR and CO are stabilized on a new steady state. The incompetent cardiovascular control of the vulnerable infant fails to stabilize SVR which decreases in an uncontrolled manner. Accordingly CO increases above the needs to hyper-dynamic state, high output heart failure and hyper-dynamic shock., Conclusions: The proposed hypothesis provides an appropriate alternative to either respiratory crises or arrhythmia though both speculations cannot be entirely excluded., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Influenza is a major cause of respiratory morbidity worldwide. It poses a risk of complications in children with cardiac disease. Influenza vaccine is considered the most effective and safe means of preventing the disease. The aims of this study were to determine the rate of influenza vaccination in children with cardiac disease and to identify the reasons for failure to vaccinate in this patient population., Methods: The study group included 186 children and their parents who attended the cardiology institute of a tertiary pediatric medical center between September and October 2012. Parents were asked to complete a questionnaire covering demographics, clinical features, influenza vaccination, receipt of advice from medical professionals regarding vaccination and personal knowledge about and attitude toward the influenza vaccine., Results: Median age of the children was 7.6 years. Thirty-six percent had been vaccinated in the previous influenza season. Vaccination was unrelated to the child's age or sex or the parents' education. Factors significantly affecting the decision of the parents to have their child vaccinated were their knowledge, beliefs and conceptions about the vaccine and their receipt of a recommendation to do so from the pediatrician or cardiologist (P < 0.001)., Conclusions: The rate of vaccination against influenza is low in children with heart disease. Major factors encouraging vaccination are proper parental knowledge and the recommendation of the primary physician or cardiologist. Medical professionals caring for this patient population should be alerted to the need to routinely counsel parents on the importance of influenza vaccination.

Background: Limited fluoroscopy ablation using 3D electro-anatomical system (3DS) has been used for arrhythmias in children, however it is not a common practice. We aimed to facilitate a fluoroscopy limited approach for ablation of accessory pathways (AP) in children., Methods: Following electrophysiologic (EP) catheter placement a single dual-plane fluoroscopic image (right anterior oblique-30° and left anterior oblique-60° views) was acquired and the 3DS views were rotated to be a perfect match to the fluoroscopy. Ninety-four consecutive pediatric patients [mean age 11.8±4.1 (4.2-18) years, 61.7% males] with Wolf-Parkinson-White syndrome underwent ablation of an AP. Fifty-seven had manifest AP, 54 had left-sided AP (LSAP) and 40 had right-sided AP (RSAP)., Results: The acute success rate was 95.7% (90/94), with a recurrence rate of 1.1% (1/90) at a mean follow-up of 13±5.5 (4.4-22.9) months. Mean procedure and fluoroscopy times were 144±45 (55-262)min and 1.8±1.4 (0.1-5.6)min, respectively. Comparison of the first 20 procedures to the next 74 procedures demonstrated an extended procedure time (171±53min vs 135±38min, p<0.005), however the fluoroscopy time, the number of long applications, the time to effect, and the acute success rate were similar. There were no permanent ablation-related complications., Conclusions: A limited fluoroscopy approach for ablation of AP in children using 3DS is easily acquired, adapted, reduces the fluoroscopy time, and has an excellent efficacy and safety profile., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: To assess the use of thyroid-stimulating hormone (TSH) tests for identifying primary hypothyroidism in 2 academic family medicine settings., Design: Descriptive study involving a retrospective electronic chart review of family medicine patients who underwent TSH testing., Setting: Two academic family practice sites: one site is within a tertiary hospital in Toronto, Ont, and the other is within a community hospital in Newmarket, Ont., Participants: A random sample of 205 adult family medicine patients who had 1 or more TSH tests for identifying potential primary hypothyroidism between July 1, 2009, and September 15, 2013. Exclusion criteria included a previous diagnosis of any thyroid condition or abnormality, as well as pregnancy or recent pregnancy within the year preceding the study period., Main Outcome Measures: The proportion of normal TSH test results and the proportion of TSH tests that did not conform to test-ordering guidelines., Results: Of the 205 TSH test results, 200 (97.6%, 95% CI 94.4% to 99.2%) showed TSH levels within the normal range. All 5 patients with abnormal TSH test results had TSH levels above the upper reference limits. Nearly one-quarter (22.4%, 95% CI 16.9% to 28.8%) of tests did not conform to test-ordering guidelines. All TSH tests classified as not conforming to test-ordering guidelines showed TSH levels within normal limits. There was a significant difference ( P < .001) between the proportions of nonconforming TSH tests at the tertiary site (14.3%, 95% CI 8.2% to 22.5%) and the community site (31.0%, 95% CI 22.1% to 41.0%). Preliminary analyses examining which variables might be associated with abnormal TSH levels showed that only muscle cramps or myalgia ( P = .0286) and a history of an autoimmune disorder ( P = .0623) met or approached statistical significance., Conclusion: In this study, the proportion of normal TSH test results in the context of primary hypothyroidism case finding and screening was high, and the overall proportion of TSH tests that did not conform to test-ordering guidelines was relatively high as well. These results highlight a need for more consistent TSH test-ordering guidelines for primary hypothyroidism and perhaps some educational interventions to help curtail the overuse of TSH tests in the family medicine setting., (Copyright© the College of Family Physicians of Canada.)

Background: Limited fluoroscopy cryo-ablation using a 3D electro-anatomical system (3DS) has been used for AVNRT in children. We aimed to facilitate a fluoroscopy limited approach of RF ablation of AVNRT in children., Methods: A retrospective study was performed of procedure parameters in children undergoing RF ablation of AVNRT in 75 consecutive children (June 2011 to November 2013 - Group A) using standard fluoroscopy techniques compared to those of 64 consecutive children (December 2013 to May 2015 - Group B), using a fluoroscopy limited approach with 3DS., Results: The acute success rate was 98.7% (74/75) and 98.4% (63/64) for groups A and B, respectively. The recurrence rate was 2.7% (2/74) and 0% (0/63) with a mean follow-up period of 45.5±12.1 and 14.3±6.1months for group A and group B, respectively. The mean procedure and fluoroscopy times were significantly lower for group B compared to group A (119±37 (43-203) and 0.83±1.04 (0.05-3.83) minutes versus 146±53 (72-250) and 16.1±8.9 (4.39-55) minutes, p<0.003 and p<0.0001, respectively). There were no ablation-related complications., Conclusions: A fluoroscopy limited approach for RF ablation of AVNRT in children using a 3DS is easily acquired and adapted, and significantly reduces the fluoroscopy and procedure time with excellent efficacy, safety and low recurrence rate., Condensed Abstract: This study confirmed that a 3D mapping system (3DS) to guide ablations of AVNRT in children reduces radiation exposure. Combined, limited fluoroscopy and 3DS in a methodology that resembles the familiar conventional fluoroscopy approach for RF ablation of AVNRT in children is proposed. Combined limited fluoroscopy and RF-energy in children with AVNRT are associated with a shorter procedure time, minimal fluoroscopy time, a high success rate and a low recurrence rate., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: When bronchopulmonary dysplasia (BPD) is complicated by pulmonary hypertension (PH), morbidity and mortality are significantly increased. BPD-associated PH is not included in the current indications for PH medications. However, limited data demonstrate hemodynamic improvement and decreased mortality with PH-specific treatment. This report describes our 6-year experience treating BPD-associated PH with PH medications, mainly sildenafil., Study Design: The medical records of 20 infants diagnosed with BPD-associated PH at a tertiary pediatric pulmonary hypertension clinic in 2008-2014 were reviewed. Clinical improvement was defined as a decrease in Ross functional class by at least one degree. PH severity was classified by echocardiography as mild, moderate, or severe. Hemodynamic improvement was defined as a decrease in PH severity by at least one level., Results: Eighteen out of 20 patients were treated with PH medications: 12 sildenafil, 5 sildenafil and bosentan, and 1 bosentan. Median follow-up time was 2 years. Mean functional class significantly decreased from 3.2 ± 0.9 at diagnosis to 1.7 ± 0.9 at the last follow-up. Improvement in functional class was observed in 15/16 children (94%). Moderate or severe PH was found in 13/18 children (72%) at diagnosis, and in three (17%, all moderate PH) at the last follow-up. Improvement in PH class by echocardiography was demonstrated in 14/18 children (78%). The survival rate was 95%., Conclusion: Treatment of BPD complicated by PH with PH-specific medications, mainly sildenafil, is associated with improvement in both clinical and hemodynamic parameters and a low mortality rate. Pediatr Pulmonol. 2017;52:77-83. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: neonatal cardiac surgery has evolved over the last 50 years with a large percentage of the patients achieving complete physiological repair in the neonatal period. The remaining patients achieve staged palliation with an increasing amount of success., Objectives: To report our experience with 1000 neonatal cardiac surgical procedures performed in the last 10 years., Methods: We conducted a retrospective analysis of surgical outcome in all neonatal patients who underwent cardiac surgery between January 2007 and July 2016 at Schneider Children's Medical Center of Israel., Results: A total of 1003 neonates aged < 30 days underwent surgery for congenital heart defects at our center. Neonatal surgery accounted for 22.5% of all cardiac surgeries. Neonatal operative mortality was 7.3%, Operative mortality for individual lesions were: simple aortic coarctation (CoA) (198 patients, 2.5%), CoA with hypoplastic arch (24, 4%), CoA with ventricular septal defect (VSD) (84, 2.3%), transposition of the great arteries (TGA, simple and complex, 185, 6.3%), TGA with VSD (37, 0%), truncus arteriosus (26, 3.8%), interrupted aortic arch (25, 4%), Norwood Sano (71, 19.7%), neonatal tetralogy of Fallot (41, 0%), and shunt (131 patients, 12%)., Conclusions: Neonatal surgical capabilities have improved substantially over the last decades. Excellent results can be expected for lesions that can be repaired to create biventricular circulation. Improved results can be attributed in part to the evolution of surgical strategies and assistive technologies, but essential is the collaborative effort of surgeons, cardiologists, anesthesiologists, and intensive care specialists acting as a cohesive team whose performance far exceeds the sum of its individual members' contributions.

Aims: Assessment of the feasibility of creating real-time interactive 3D digital holograms in a standard catheterization laboratory. 3D medical images are typically displayed and interacted with on 2D screens limiting their usefulness. A digital computer-generated real-time holographic display of patient's 3D data could provide a spatially accurate image with all the depth cues and afford interaction within the image., Methods and Results: We performed a feasibility study of creating real-time interactive 3D digital holograms with a purpose-built prototype using intraprocedural data from 3D rotational angiography and live 3D transesophageal echocardiography. The primary objective was to demonstrate that all the anatomical landmarks identified on standard imaging can be similarly identified using dynamic and static holographic images. The secondary objective was to demonstrate the usability of interactions with the image. Parameters were assessed by a rating scale. Eight patients were enrolled of whom five underwent transcatheter ASD closure using 3DTEE and three patients were evaluated by 3D rotational angiography. In all cases dynamic real-time and static 3D holograms were created in standard cath lab conditions. Four individual observers identified all anatomical landmarks on the holographic display independently from the 2D display. Interactions with the hologram including marking, cropping and rotation were performed. There were no adverse events., Conclusions: This study demonstrates, for the first time, the feasibility of generating high quality, clinically relevant, 3D real-time colour dynamic holograms in a standard clinical setting with real patient volumetric data. The impact of computer-generated holography needs to be evaluated in controlled clinical trials., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Purpose: Coil embolization of pulmonary arteriovenous malformations (PAVMs) has a high re-canalization/re-perfusion rate. Embolization with Amplatzer plugs has been previously described, but the long-term efficacy is not established. This study reports the experience of a referral medical center with the use of coils and Amplatzer plugs for treating PAVMs in patients with hereditary hemorrhagic telangiectasia., Methods: The study was approved by the Institutional Review Board with waiver of informed consent. The cohort included all patients who underwent PAVM embolization in 2004-2014 for whom follow-up imaging scans were available. The medical files were retrospectively reviewed for background data, embolization method (coils, Amplatzer plugs, both), and complications. Re-canalization of treated PAVMs was assessed from intrapulmonary angiograms (following percutaneous procedures) or computed tomography angiograms. Fisher's exact test and Pearson Chi-squared test or t test were used for statistical analysis, with significance at p < 0.05., Results: 16 patients met the study criteria. Imaging scans were available for 63 of the total 110 PAVMs treated in 41 procedures. Coils were used for embolization in 37 PAVMs, Amplatzer plugs in 21, and both in five. Median follow-up time was 7.7 years (range 1.4-18.9). Re-canalization was detected in seven vessels, all treated with coils; there were no cases of re-canalization in plug-occluded vessels (p = 0.0413)., Conclusion: The use of Amplatzer plugs for the embolization of PAVMs in patients with hemorrhagic telangiectasia is associated with a significantly lower rate of re-canalization of feeding vessels than coils. Long-term prospective studies are required to confirm these findings.

Background: Ice, or freezing rain storms have the potential to affect human health and disrupt normal functioning of a community. The purpose of this study was to assess acute health impacts of an ice storm that occurred in December 2013 in Toronto, Ontario, Canada., Methods: Data on emergency department visits were obtained from the National Ambulatory Care Reporting System. Rates of visits in Toronto during the storm period (December 21, 2013 - January 1, 2014) were compared to rates occurring on the same dates in the previous five years (historical comparison) and compared to those in a major unaffected city, Ottawa, Ontario (geographic comparison). Overall visits and rates for three categories of interest (cardiac conditions, environmental causes and injuries) were assessed. Rate ratios were calculated using Poisson regression with population counts as an offset. Absolute counts of carbon monoxide poisoning were compared descriptively in a sub-analysis., Results: During the 2013 storm period, there were 34 549 visits to EDs in Toronto (12.46 per 1000 population) compared with 10 794 visits in Ottawa (11.55 per 1000 population). When considering year and geography separately, rates of several types of ED visits were higher in the storm year than in previous years in both Toronto and Ottawa. Considering year and geography together, rates in the storm year were higher for overall ED visits (RR: 1.10, 95 % CI: 1.09-1.11) and for visits due to environmental causes (RR: 2.52, 95 % CI: 2.21-2.87) compared to previous years regardless of city. For injuries, visit rates were higher in the storm year in both Toronto and Ottawa, but the increase in Toronto was significantly greater than the increase in Ottawa, indicating a significant interaction between geography and year (RR: 1.23, 95 % CI: 1.16-1.30)., Conclusions: This suggests that the main health impact of the 2013 Ice Storm was an increase in ED visits for injuries, while other increases could have been due to severe weather across Ontario at that time. This study is one of the first to use a population-level database and regression modeling of emergency visit codes to identify acute impacts resulting from ice storms.

Purpose: To compare the effective doses of needle biopsies based on dose measurements and simulations using adult and pediatric phantoms, between cone beam c-arm CT (CBCT) and CT., Method: Effective doses were calculated and compared based on measurements and Monte Carlo simulations of CT- and CBCT-guided biopsy procedures of the lungs, liver, and kidney using pediatric and adult phantoms., Results: The effective doses for pediatric and adult phantoms, using our standard protocols for upper, middle and lower lungs, liver, and kidney biopsies, were significantly lower under CBCT guidance than CT. The average effective dose for a 5-year old for these five biopsies was 0.36 ± 0.05 mSv with the standard CBCT exposure protocols and 2.13 ± 0.26 mSv with CT. The adult average effective dose for the five biopsies was 1.63 ± 0.22 mSv with the standard CBCT protocols and 8.22 ± 1.02 mSv using CT. The CT effective dose was higher than CBCT protocols for child and adult phantoms by 803 and 590% for upper lung, 639 and 525% for mid-lung, and 461 and 251% for lower lung, respectively. Similarly, the effective dose was higher by 691 and 762% for liver and 513 and 608% for kidney biopsies., Conclusions: Based on measurements and simulations with pediatric and adult phantoms, radiation effective doses during image-guided needle biopsies of the lung, liver, and kidney are significantly lower with CBCT than with CT.

Background: In contrast to axial hiatus hernias, paraesophageal hernias are rare but can lead to chronic iron deficiency anemia and severe acute complications. Treatment is manifold and consistent standards are lacking., Objectives: The aim of this study was to describe our experiences of 286 patients with paraesophageal hernias, who underwent surgery from 2003 to 2014 at a tertiary referral center. The study was particularly concerned with morbidity, mortality, quality of life and recurrence rates., Material and Methods: In 12 years a total of 286 paraesophageal hernias were surgically treated, 255 with a minimally invasive procedure and 31 with an open approach. In 138 patients (48 %) the suture-based hiatoplasty was reinforced by means of a lightweight mesh, which was fixed with fibrin glue in 90 cases. Abdominal fixation of the stomach consisted of a gastropexy and anterior (n = 244) or posterior (n = 42) fundoplication., Results: Complications arose in 8.4 % of the patients. The mean hospital stay was 5.3 (± 2.8) days for elective surgery and 24.7 (± 17.8) days for emergency operations. The gastrointestinal quality of life index according to Eypasch significantly increased from mean preoperative values of 92.8 (± 22.5) to 109.6 (± 20.2) in the postoperative course (p < 0.001). Of the patients 20 (7 %) suffered a recurrence requiring surgery, including 7 early and 13 late recurrences. During the immediate postoperative period radiographically detected recurrences were promptly revised. The strategy of late recurrences in the long-term course was based on patient symptoms and asymptomatic hernias were treated conservatively while symptomatic hernias were surgically treated. Symptomatic late recurrences developed in 4.6 % of the patients, including 7.4 % (11 out of 148) without and 1.4 % (2 out of 138) with primary mesh repair., Conclusion: The repair of paraesophageal hernias in 286 patients provided excellent patient satisfaction and symptom improvement with low perioperative morbidity and mortality. Mesh reinforcement reduced the recurrence rate. The quality of life index is a suitable clinical course parameter for evaluation of paraesophageal hernias.

αMUPA transgenic mice spontaneously consume less food compared with their wild type (WT) ancestors due to endogenously increased levels of the satiety hormone leptin. αMUPA mice share many benefits with mice under caloric restriction (CR) including an extended life span. To understand mechanisms linked to cardiac aging, we explored the response of αMUPA hearts to ischemic conditions at the age of 6, 18, or 24 months. Mice were subjected to myocardial infarction (MI) in vivo and to ischemia/reperfusion ex vivo. Compared to WT mice, αMUPA showed functional and histological advantages under all experimental conditions. At 24 months, none of the WT mice survived the first ischemic day while αMUPA mice demonstrated 50% survival after 7 ischemic days. Leptin, an adipokine decreasing under CR, was consistently ~60% higher in αMUPA sera at baseline. Leptin levels gradually increased in both genotypes 24h post MI but were doubled in αMUPA. Pretreatment with leptin neutralizing antibodies or with inhibitors of leptin signaling (AG-490 and Wortmannin) abrogated the αMUPA benefits. The antibodies also reduced phosphorylation of the leptin signaling components STAT3 and AKT specifically in the αMUPA myocardium. αMUPA mice did not show elevation in adiponectin, an adipokine previously implicated in CR-induced cardioprotection. WT mice treated for short-term CR exhibited cardioprotection similar to that of αMUPA, however, along with increased adiponectin at baseline. Collectively, the results demonstrate a life-long increased ischemic tolerance in αMUPA mice, indicating the attenuation of cardiac aging. αMUPA cardioprotection is mediated through endogenous leptin, suggesting a protective pathway distinct from that elicited under CR.

Endocarditis is an uncommon presentation of Kingella kingae infection in children. A previously healthy 17 month old child was referred to our emergency department for evaluation of fever lasting eleven days, aphthous stomatitis and a new systolic murmur. Within a few hours of admission, antibiotic therapy was initiated for a presumptive diagnosis of bacteremia and within 24 hours after admission, gram negative coccobacilli were growing in the blood culture. In addition, echocardiography demonstrated a mycotic aneurysm of the ascending aorta with a mobile vegetation. The presumptive diagnosis of Kingella kingae endocarditis was made. Further evaluation by MRI revealed frontal and occipital cerebral infarcts. Due to the presence of presumed septic emboli in conjunction with progressive left ventricular dysfunction, the child was urgently taken to the operating room where aggressive debridement of the infected tissue was performed and the aortic aneurysm was repaired. The patient had an uneventful post-operative course. This case emphasizes the need for a high index of suspicion when evaluating children with community acquired infection. In addition, it also demonstrates the importance of early diagnosis and appropriate treatment of K. kingae endocarditis.

Background: Because of its safety profile, cryoablation has become an alternative therapy for septal arrhythmias, including parahisian accessory pathways (APs). Data regarding its efficacy, safety, and late outcome for parahisian APs in children are limited., Objective: The purpose of this study was to evaluate the safety and efficacy of cryoablation of parahisian APs in children., Methods: Fifty-nine cryoablations of parahisian APs were performed in 50 patients [76% males; median age 16.5 years (range 5.3-20 years)]. Thirty-three had manifest APs and 17 had concealed APs. The time to effect was defined as the duration of time from reaching -30°C to the disappearance of AP during the cryomapping phase. The acute success rate for the first ablation was 94% (47/50)., Results: Mean fluoroscopy time and number of cryoablations were 28.5 ± 23.3 minutes and 2.6 ± 1.2 seconds, respectively. The time to effect was 8.5 ± 7.1 seconds. The overall recurrence rate was 14.9%, decreasing from 40% in the first 10 cases to 8.1% in the next 37 (P <.02). Multivariate analysis showed that the only independent predictor for recurrence rate was time to effect <10 seconds (P <.001). A high recurrence rate was also associated with concealed APs and ablation during supraventricular tachycardia (P <.03 and P <.05, respectively). The patients who had recurrence underwent a second successful cryoablation. During median follow-up of 59.7 months (range 6-102 months), a long-term success rate of 94% was achieved. No permanent ablation-related complications occurred., Conclusion: Cryoablation of parahisian APs has excellent short- and long-term efficacy and safety profile. Increased physician experience is associated with a reduced recurrence rate., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Right aortic arch (RAA) is usually associated with the presence of a significant congenital heart disease, usually a conotruncal defect, which determines the postnatal outcome. In the absence of such cardiac defects, the significance of RAA has not been determined. The aims of this study were to evaluate the significance of recognizing RAA in fetuses with normal or near normal intracardiac anatomy and to determine which associations may be present., Methods: A retrospective study was completed of all fetuses diagnosed with RAA with normal or near normal intracardiac anatomy between 1999 and 2011. The aim was to evaluate the presence of RAA with complete ultrasonic evaluation using two-dimensional imaging complemented by the Doppler color flow technique, paying particular attention to the three-vessel and tracheal view. We compared the prenatal findings with the postnatal outcomes and management of this cohort of fetuses., Results: Among 16,450 fetal echocardiograms, 58 fetuses (0.35%) were diagnosed with RAA with normal or near normal intracardiac anatomy. Gestational age at diagnosis ranged from 19 to 34 weeks (mean, 23 weeks). Isolated RAAs were found in 50 fetuses, and double aortic arches (DAAs) were recognized in eight other cases. The postnatal cohort consisted of 44 newborns with RAAs and eight with DAAs (two were lost to follow-up, and four pregnancies were terminated). Postnatal echocardiography confirmed the prenatal diagnosis of RAA in 41 of 45 children, and four were found to have DAAs. Three of seven fetuses diagnosed prenatally as having DAAs were found to have only RAAs. Fourteen fetuses underwent karyotyping; two had 22q11 deletion and two had 47xxy. Eleven infants (21%) had respiratory symptoms, eight with DAAs, one with RAA, mirror-image head and neck vessels, and two with RAAs and aberrant left subclavian arteries. Surgery was indicated in all symptomatic patients except one, whose symptoms resolved. One asymptomatic patient underwent operation for significant compression of the trachea., Conclusions: RAA on fetal ultrasonography may indicate vascular and chromosomal abnormalities that may complicate postnatal management. When RAA is identified, fetal karyotype analysis (including the integrity of chromosome 22) is warranted. RAA may herald an occult DAA and may be a clue to a tight vascular ring. Hence, it seems essential to conduct a careful postnatal evaluation of fetuses with RAAs on prenatal ultrasound., (Copyright © 2014 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objectives: To present our initial experience with the Amplatzer Duct Occluder II Additional Sizes (ADOIIAS) device., Background: The ADOIIAS is a modified PDA closure device of various lengths and widths with small disks to avoid flow disturbance in the pulmonary arteries and descending aorta., Patient Population: All patients who underwent attempted closure with an ADOIIAS device at our institution CATHETERIZATION: Following aortography the PDA was closed using a 4-5Fr delivery system from the pulmonary or aortic side with an ADOIIAS. Aortography to confirm position and leak was performed before and after device release. Echocardiography was performed before discharge the following day., Results: Between June 2011 and December 2012, 60 patients [33 female], median age 3.3 yrs [0.6-15.8 years], and weight 14.5 kg [4-79] underwent attempted PDA closure with an ADOIIAS device. 56/60 [93.3%] ADOIIAS devices were successfully deployed [52 aortic side]. In 55/56 [98.2%], the PDA was closed on follow up echocardiogram usually on the next day. In one case, there was a small residual PDA of no hemodynamic significance on follow up. In four cases, the ADOIIAS was unstable, including one device embolization which was retrieved with no sequelae, and the PDA was closed in all cases with an alternative device in the same procedure. The mean ratio of ADOIIAS height:PDA pulmonary diameter was 2.4 ± 0.5:1., Conclusions: We report a large single-center experience with the new ADOIIAS device which proved to be versatile, safe, effective, and easy to use in the appropriate ductal anatomy., (Copyright © 2014 Wiley Periodicals, Inc.)

Objective: Ascitic fluid in the peritoneal cavity may severely impair respiratory and renal function following neonatal heart surgery. It has been our practice to liberally insert percutaneous peritoneal catheters (PPCs) in order to manage fluid balance and thereby improve ventilatory function. We herein report our experience with PPC., Methods: Retrospective analysis of charts of all surviving neonates that underwent PPC insertion from January 2007 through March 2010. Charts were reviewed for demographic and clinical variables from the preoperative, operative, and postoperative periods., Results: A total of 1268 patients underwent surgery, 292 (23%) were neonates. 17 (5.8%) patients required PPC. Mean age and weight were 16 days and 3.1 kg, respectively. Mean amount drained upon insertion was 55 ± 46 ml. Catheters were maintained for a mean of 5 days and drained an average of 201 ml on the first postinsertion day. Ventilatory settings did not change significantly prior to and postcatheter insertion (respiratory rate [29 ± 3.8 vs 28.7 ± 3.9; P = .93], inspiratory pressures [26.3 ± 3.6 vs 26.1 ± 3.3 cm H2O; P = .34], and fraction of inspired oxygen [0.66 ± 0.21 vs 0.63 ± 0.18; P = .53]). Carbon dioxide values decreased significantly (43.2 ± 9.7 vs 37 ± 4.9 mm Hg; P = .01), and PO2 values increased (78 ± 69 vs 104 ± 57 mm Hg; P = .05)., Conclusions: The PPC insertion can be easily performed at the bedside with minimal complications. Fluid balance management is facilitated, and ventilation is improved. The PPC insertion is a valuable addition to the armamentarium of the physician treating neonates in the intensive care unit after complex congenital heart surgery.

Purpose: Congenital portosystemic shunts (CPSS) with portal venous hypoplasia cause hyperammonemia. Acute shunt closure results in portal hypertension. A transcatheter method of staged shunt reduction to afford growth of portal vessels followed by shunt closure is reported., Methods: Pressure measurements and angiography in the CPSS or superior mesenteric artery (SMA) during temporary occlusion of the shunt were performed. If vessels were diminutive and the pressure was above 18 mmHg, a staged approach was performed, which included implantation of a tailored reducing stent to reduce shunt diameter by ~50 %. Recatheterization was performed approximately 3 months later. If the portal pressure was below 18 mmHg and vessels had developed, the shunt was closed with a device., Results: Six patients (5 boys, 1 girl) with a median age of 3.3 (range 0.5-13) years had CPSS portal venous hypoplasia and hyperammonemia. Five patients underwent staged closure. One patient tolerated acute closure. One patient required surgical shunt banding because a reducing stent could not be positioned. At median follow-up of 3.8 (range 2.2-8.4) years, a total of 21 procedures (20 transcatheter, 1 surgical) were performed. In all patients, the shunt was closed with a significant reduction in portal pressure (27.7 ± 11.3 to 10.8 ± 1.8 mmHg; p = 0.016), significant growth of the portal vessels (0.8 ± 0.5 to 4.0 ± 2.4 mm; p = 0.037), and normalization of ammonia levels (202.1 ± 53.6 to 65.7 ± 9.6 μmol/L; p = 0.002) with no complications., Conclusion: Staged CPSS closure is effective in causing portal vessel growth and treating hyperammonemia.

Structural heart disease, intravascular catheters, and invasive procedures are predisposing factors for infective endocarditis (IE). Data on IE in children with structurally normal hearts and no predisposing factors are limited. We aim to characterize IE (definite or possible by Duke criteria) in such a subgroup of pediatric patients (age <18 years) who were treated at our medical center. Of 51 events of IE in 50 children, 9 (18 %) had no predisposing factors. These infections were all community-acquired and presented with fever, a newly detected heart murmur, diagnostic echocardiographic findings, and left-sided infection. Clinical course was characterized by acute onset (n = 8 of 9) with a 100 % complication rate (heart failure or embolic phenomena). Emergency cardiac surgery was performed in 7 children (Ross surgery [n = 4], mitral valve replacement [MVR; n = 2], and valve repair [n = 1]). Causative organisms were S. aureus (n = 3), S. pneumoniae (n = 2), H. parainfluenzae (n = 1), and K. kingae (n = 1). In contrast, IE in children with predisposing factors (42 of 51 [82 %]) was frequently health care-associated (30 of 42), right-sided (20 of 42, p = 0.041), and with lower rates of diagnostic echocardiographic findings (28 of 42, p = 0.041), complications (16 of 42, p < 0.001), and surgical intervention (9 of 42, p = 0.002). Causative organisms were mainly viridans streptococci (n = 9), Candida species (n = 8), coagulase-negative staphylococci (n = 6), enteric Gram-negative bacilli (n = 6), S. aureus (n = 5), and K. kingae (n = 3). Mortality was 11 % in both groups. We conclude that pediatric IE in children with and without predisposing factors differs significantly. Due to the acute and complicated course of the latter, high awareness among pediatricians and prompt diagnosis are crucial.

Background: B-type natriuretic peptide (BNP) has been shown to have prognostic value for morbidity and mortality after cardiac surgery. Less is known about its prognostic value in infants., Objectives: To investigate the predictive value of BNP levels regarding the severity of the postoperative course in infants undergoing surgical repair of congenital heart disease., Methods: We conducted a prospective comparative study. Plasma BNP levels in infants aged 1-12 months with congenital heart disease undergoing complete repair were measured preoperatively and 8, 24 and 48 hours postoperatively. Demographic and clinical data included postoperative inotropic support and lactate level, duration of mechanical ventilation, intensive care unit (ICU) and hospitalization stay., Results: Cardiac surgery was performed in 19 infants aged 1-12 months. Preoperative BNP level above 170 pg/ml had a positive predictive value of 100% for inotropic score > or = 7.5 at 24 hours (specificity 100%, sensitivity 57%) and 48 hours (specificity 100%, sensitivity 100%), and was associated with longer ICU stay (P = 0.05) and a trend for longer mechanical ventilation (P = 0.12). Similar findings were found for 8 hours postoperative BNP above 1720 pg/ml. BNP level did not correlate with measured fractional shortening., Conclusions: In infants undergoing heart surgery, preoperative and 8 hour BNP levels were predictive of inotropic support and longer ICU stay. These findings may have implications for preplanning ICU loads in clinical practice. Further studies with larger samples are needed.

Background: Antegrade cerebral perfusion (ACP) is performed in neonates either by direct cannulation (DC) or indirect cannulation (IC) of the innominate artery. IC is achieved by a graft sutured to the innominate artery or advancement of a cannula through the ascending aorta into the innominate artery, whereas DC is performed by directly cannulating the innominate artery. These techniques may be limited by technical problems that can compromise perfusion. The purpose of the present study was to evaluate the flow measurements and safety of DC when compared with IC., Methods: This was a retrospective chart review of consecutive neonates who underwent ACP from January 2007 to December 2010. Patient characteristics, surgical and hemodynamic measurements, and postoperative neurologic findings were recorded., Results: Seventy neonates underwent ACP during the study period (46 using DC and 24 using IC). The groups were similar in age and weight. Operative variables were similar regarding cardiopulmonary bypass (CPB), cross-clamp times, maximal flow at full CPB, minimal temperature, ACP time, flow and flow index, and upper extremity blood pressure and proximal cannula pressure during ACP. There was a significantly higher flow index at full CPB in the DC group (217 ± 40 mL/kg/min versus 190 ± 46 mL/kg/min; p = 0.013), which correlated with higher proximal cannula pressures at full CPB (172 ± 27 mm Hg versus 158 ± 26 mm Hg; p = 0.04). Sixty-two of the 65 survivors (95%) had normal neurologic evaluations on discharge., Conclusions: ACP using DC is comparable to that using IC, with appropriate pressures in the proximal aortic line at full CPB and adequate upper extremity pressures during ACP, reflecting suitable flows in the cerebral circulation., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Congenital disorders of glycosylation are a growing group of inborn errors of protein glycosylation. Cardiac involvement is frequently observed in the most common form, PMM2-CDG, especially hypertrophic cardiomyopathy. Dilated cardiomyopathy, however, has been only observed in a few CDG subtypes, usually with a lethal outcome. We report on cardiac pathology in nine patients from three unrelated Israeli families, diagnosed with dolichol kinase deficiency, due to novel, homozygous DK1 gene mutations. The cardiac symptoms varied from discrete, mild dilation to overt heart failure with death. Two children died unexpectedly with acute symptoms of heart failure before the diagnosis of DK1-CDG and heart transplantation could take place. Three other affected children with mild dilated cardiomyopathy at the time of the diagnosis deteriorated rapidly, two of them within days after an acute infection. They all went through successful heart transplantation; one died unexpectedly and 2 others are currently (after 1-5 years) clinically stable. The other 4 children diagnosed with mild dilated cardiomyopathy are doing well on supportive heart failure therapy. In most cases, the cardiac findings dominated the clinical picture, without central nervous system or multisystem involvement, which is unique in CDG syndrome. We suggest to test for DK1-CDG in patients with dilated cardiomyopathy. Patients with discrete cardiomyopathy may remain stable on supportive treatment while others deteriorate rapidly. Our paper is the first comprehensive study on the phenotype of DK1-CDG and the first successful organ transplantation in CDG syndrome.

Although some evidence suggests benefit of steroid supplementation after pediatric cardiac surgery, data correlating adrenal function with the postoperative course is scarce. This study sought to determine if adrenal insufficiency (AI) after cardiac surgery is associated with a more complicated postoperative course in children. A prospective study was performed during a 6-month period at a pediatric medical center. Included were 119 children, 3 months and older, who underwent heart surgery with cardiopulmonary bypass. Cortisol levels were measured before and 18 h after surgery. Patients were divided into two groups by procedure complexity (low or high), and clinical and laboratory parameters were compared between patients with and without AI within each complexity group. In the low-complexity group, 45 of the 65 patients had AI. The normal adrenal function (NAF) subgroup had greater inotropic support at 12, 24, and 36 h after surgery and a higher lactate level at 12 and 24 h after surgery. There were no significant differences between subgroups in duration of ventilation, sedation, intensive care unit (ICU) stay, or urine output. In the high-complexity group, 27 patients had AI, and 27 did not. There were no significant differences between subgroups in inotropic support or urine output during the first 36 h or in mechanical ventilation, sedation, or ICU stay duration. Children with AI after heart surgery do not have a more complex postoperative course than children with NAF. The adrenal response of individual patients seems to be appropriate for their cardiovascular status.

Objective: The LIM-homeobox transcription factor Isl1 plays a crucial role during heart embryogenesis and later on gives rise to adult resident cardiac stem cells. In this study, we aimed to discover new extra cardiac populations of Isl1 stem cells. We then investigated endogenous Isl1 kinetics after myocardial infarction (MI), and the effect of intra-myocardial gene transfer of naked DNA encoding Isl1 on functional recovery after MI., Methods: We used the transgenic mice Isl1/cre/Z/EG for lineage tracing of extra cardiac Isl1 stem cells. Non transgenic mice were used to study Isl1 kinetics post-MI by RT-PCR and FACS analysis. MI was induced in non transgenic mice by permanent ligation of the left anterior descending coronary artery (LAD). Naked DNA encoding Isl1 was injected to the peri-infarct region. Evaluation of cardiac performance was conducted by echocardiogram. Analysis of myocardial fibrosis and number of vessels was performed on histological cryosections., Results and Conclusions: Isl1 gives rise to subpopulations of progenitors in both the bone marrow and spleen, and is re-expressed in the spleen and left ventricle following MI. Intramyocardial gene transfer of Isl1 to the border zone of the infarcted hearts resulted in partial salvage of left ventricular function, enhanced vascularization, and reduced myocardial fibrosis. The Isl1 gene appears to be an attractive reparative target for future management of myocardial dysfunction., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Introduction: The characteristics of pediatric infective endocarditis (IE) are continuously changing., Objectives: To describe trends in pediatric IE over a period of 25 years., Study Methods: Children (< 18 years old] treated at Schneider Children's Medical Center during 1992-2004 who met Duke criteria for definite or possible IE were included in the study. Demographic, clinical and laboratory data were collected and compared to data gathered during 1980-1991., Results: Compared to 1980-1991, during 1992-2004 we noted a decrease in the mean age from 6.5 to 4 years and in the incidence of congenital heart defects from 96% to 61% (p = 0.001). Incidence of significant underlying diseases and non-cardiac predisposing factors rose from 4% to 43%. Significantly Less children presented with fever, splenomegaly and murmur during 1992-2004; a 4-fold increase in surgical intervention [p = 0.024) and a 3-fold increase in mortality p = 0.257 were observed. Viridans streptococci (37.5%), Staphylococcus aureus (20.8%) and gram-negative bacilli 2.5%] caused most of IE during 1980-1992, whereas viridians streptococci (19.1%), Candida spp (17%), S. aureus (17%) and coagulase-negative staphylococci (12.8%) were the common causes during 1992-2004., Conclusions: Considerable changes in pediatric IE were observed., Discussion and Summary: Pediatric IE became an infection of young children, especially those with significant noncardiac underlying diseases. It is less commonly caused by viridans streptococci and is increasingly caused by Candida spp and coagulase-negative staphylococci. These trends may affect the management of pediatric IE.

Objective/aim: To compare hemodynamic parameters in infants with congenital heart disease (CHD) undergoing noncardiac surgery (NCS) under awake spinal anesthesia (SA) with controls without CHD also undergoing SA., Background: NCS poses a twofold higher mortality risk in infants with CHD. SA might be a good alternative to general anesthesia (GA) in this setting., Methods: The files of 84 infants were reviewed; 42 had CHD and 42 were controls without CHD. Primary outcome measures were percent decrease in mean arterial pressure (%MAP decrease) and heart rate (%HR decrease)from baseline to the lowest intraoperative value. One-way analysis of variance(ANOVA), ANOVA with repeated measures, Pearson chi-square test, Fisher's exact test, and Pearson correlation were used for statistical analysis.Time to discharge was analyzed with the nonparametric Mann–Whitney U-test., Results: There were no significant between-group differences in %MAP decrease and %HR decrease; no significant associations and correlations between %MAP decrease or %HR decrease and other variables; and no correlation between %MAP decrease and %HR decrease. A %MAP decrease of >20% was documented in 11 patients with CHD (26.2%) and 10 controls (23.8%); a lowest intraoperative HR of <100 b.min)1 was recorded in two study patients (4.8%) and four controls (9.5%) (P = NS for both). There were no cases of high SA or conversion to GA and no need for mechanical ventilation or inotropic support intra/postoperatively., Conclusions: These preliminary findings show that hemodynamic parameters in infants with CHD undergoing NCS under awake SA are not different from controls without CHD and that SA appears to be safe in infants with CHD.

Postnatal microcephaly is defined as normal head circumference at birth, which progressively declines to more than 2 standard deviations below the average for the patient's age and sex. We describe four patients from three consanguineous families of Arab Bedouin origin who presented with autosomal recessive inheritance of progressive microcephaly, spasticity, thin corpus callosum, pyramidal signs, and intellectual disability. Homozygosity mapping (Human Mapping NspI 250K arrays, Affymetrix, Santa Clara, CA) placed the disease locus at 8q23.2-q24.12. The candidate region includes 22 known or predicted genes, including RAD21, which is related to the cohesion complex EIF3H, which is involved in translation initiation, and TAF2, which may be involved in intellectual disability. Identification of the causative gene in our reported family will shed light on the pathogenesis of this severe condition., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Pyrimidine nucleotides are signaling molecules, which activate G protein-coupled membrane receptors of the P2Y family. P2Y(2) and P2Y(4) receptors are part of the P2Y family, which is composed of 8 subtypes that have been cloned and functionally defined. We have previously found that uridine-5'-triphosphate (UTP) reduces infarct size and improves cardiac function following myocardial infarct (MI). The aim of the present study was to determine the role of P2Y(2) receptor in cardiac protection following MI using knockout (KO) mice, in vivo and wild type (WT) for controls. In both experimental groups used (WT and P2Y(2)(-/-) receptor KO mice) there were 3 subgroups: sham, MI, and MI+UTP. 24h post MI we performed echocardiography and measured infarct size using triphenyl tetrazolium chloride (TTC) staining on all mice. Fractional shortening (FS) was higher in WT UTP-treated mice than the MI group (44.7±4.08% vs. 33.5±2.7% respectively, p<0.001). However, the FS of P2Y(2)(-/-) receptor KO mice were not affected by UTP treatment (34.7±5.3% vs. 35.9±2.9%). Similar results were obtained with TTC and hematoxylin and eosin stainings. Moreover, troponin T measurements demonstrated reduced myocardial damage in WT mice pretreated with UTP vs. untreated mice (8.8±4.6 vs. 12±3.1 p<0.05). In contrast, P2Y(2)(-/-) receptor KO mice pretreated with UTP did not demonstrate reduced myocardial damage. These results indicate that the P2Y(2) receptor mediates UTP cardioprotection, in vivo., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In the United States, duloxetine has been approved for the treatment of major depressive disorder, diabetic peripheral neuropathic pain and fibromyalgia in the adult population. Data regarding the use of duloxetine in the pediatric population, however, are very limited. Femoral nerve injury is a rare complication of cardiac catheterization. In the case described, duloxetine contributed to a successful multimodal treatment program for peripheral neuropathic pain due to femoral neuropathy in an adolescent with 'reactive depression' and conversion symptoms. To the best of the authors' knowledge, the present article is only the third such report on this dual use of duloxetine in children and adolescents, and the first report of such treatment following femoral neuropathy induced by cardiac catheterization.

We describe a consanguineous Israeli Arab kindred with five males in two interrelated families with intellectual disabilities, alacrima, achalasia, and mild autonomic dysfunction. Adrenal function is normal. Their phenotype is similar to the phenotype observed in autosomal recessive Triple A syndrome except for the presence of mental retardation in all affected individuals. The pedigree is compatible with either X-linked or autosomal recessive inheritance. Sequencing of the AAAS gene causing autosomal recessive Triple A syndrome did not reveal mutations. Genotyping of affected family members identified a 16.4 Mb continuous segment of identical alleles shared by the patients between markers rs2748314 and rs5906782 on Xp11.23-p21, establishing linkage to chromosome X. This study further confirms genetic heterogeneity in Triple A syndrome and points to a clinically different subtype including significant cognitive impairment., (Copyright © 2011 Wiley-Liss, Inc.)

Background: Infective endocarditis (IE) in children is continuously changing in regard to underlying conditions, predisposing factors, etiologic agents, clinical manifestations, treatment, and outcome. We describe current characteristics and compare healthcare-associated and community-associated disease., Patients and Methods: All children (<18 years) who were treated at our center between January 1992 through June 2004 and met the Duke criteria for definite or possible IE were included. Demographic, clinical, and laboratory data were collected. Cases were categorized as healthcare- or community-associated., Results: A total of 50 children with IE were identified (51 events; 0.32/1000 hospitalizations). Twenty children (41%) had an isolated congenital heart disease, 13 (25%) had an underlying chronic disease, 9 (18%) were previously healthy, and 8 (16%) were preterm. Mortality rate was 12% (6/51). Compared with the community-associated cases (21/51, 41%), the healthcare-associated cases (30/51, 59%) showed female preponderance, younger age, 1.7-fold longer hospitalization, 1.6-fold longer time to pathogen eradication, and 3.4-fold higher mortality. The leading causes of healthcare-associated IE were Candida sp (8/30, 27%), coagulase-negative staphylococci (6/30, 20%), and Gram-negative bacilli (5/30, 16%). By contrast, the leading causes of community-associated IE were viridans streptococci (8/21, 38%) and Staphylococcus aureus (4/21, 19%)., Conclusions: A high proportion of pediatric IE is healthcare-associated that occurs in younger and sicker children. Healthcare-associated IE differs from community-associated IE in the patients' age, causative pathogens, and mortality. These trends and the different etiologies may affect future antibiotic management of this important pediatric infection.

Background: This study reports on a hitherto undescribed autosomal recessive syndrome characterised by dysmorphic features and multiple congenital anomalies together with severe neurological impairment, chorea and seizures leading to early death, and the identification of a gene involved in the pathogenesis of the disease., Methods: Homozygosity mapping was performed using Affymetrix Human Mapping 250k NspI arrays. Sequencing of all coding exons of the candidate genes was performed with primer sets designed using the Primer3 program. Fluorescence activated cell sorting was performed using conjugated antibody to CD59. Staining, acquisition and analysis were performed on a FACSCalibur flow cytometer., Results: Using homozygosity mapping, the study mapped the disease locus to 18q21.32-18q22.1 and identified the disease-causing mutation, c.2126G→A (p.Arg709Gln), in PIGN, which encodes glycosylphosphatidylinositol (GPI) ethanolamine phosphate transferase 1, a protein involved in GPI-anchor biosynthesis. Arginine at the position 709 is a highly evolutionarily conserved residue located in the PigN domain. The expression of GPI linked protein CD59 on fibroblasts from patients as compared to that in a control individual showed a 10-fold reduction in expression, confirming the pathogenic consequences of the mutation on GPI dependent protein expression., Conclusions: The abundant expression of PIGN in various tissues is compatible with the diverse phenotypic features observed in the patients and with the involvement of multiple body systems. The presence of developmental delay, hypotonia, and epilepsy combined with multiple congenital anomalies, especially anorectal anomalies, should lead a clinician to suspect a GPI deficiency related disorder.