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The ductus arteriosus is important to fetal circulation. Failure to close at birth is a common event. In this educational pictorial essay, we illustrate the association of the ductus arteriosus with a variety of congenital cardiac, vascular and pulmonary lesions. These lesions can impact the systemic circulation, the pulmonary circulation or the airway and include coarctation of the aorta, ductal origin of the pulmonary artery and vascular rings.

Objective To evaluate the relative incidence of cardiogenic and septic shock in term neonates and identify findings that help differentiate the two entities. Study Design We conducted a retrospective chart review of term neonates presenting to British Columbia Children’s Hospital (BCCH) with decompensated shock of an undiagnosed etiology between January 1, 2008 and January 1, 2013. Charts were reviewed to determine the underlying diagnoses of all neonates meeting our inclusion criteria. Patients were categorized as having septic, cardiogenic, or other etiologies of shock. We then evaluated potential demographic, clinical, and biochemical parameters that could help differentiate between septic and cardiogenic shock. Results Cardiogenic shock was more common than septic shock (relative risk=1.53). A history of cyanosis was suggestive of cardiogenic shock (positive likelihood ratio, LR+=3.2 and negative likelihood ratio, LR−=0.4). Presence of a murmur or gallop (LR+=5.4, LR−=0.3), or decreased femoral pulses (LR+=5.1, LR−=0.5) on physical exam were also suggestive of cardiogenic shock as was cardiomegaly on chest x-ray (LR+=4.9, LR−=0.5). Notably, temperature instability (LR+=0.7, LR−=1.8) and white blood cell count elevation or depression (LR+=0.8, LR−=1.1) were all poor predictors of septic shock. Conclusion Cardiogenic shock is a more common cause of decompensated shock than septic shock. A history of cyanosis, murmur or gallop, or decreased femoral pulses on exam and cardiomegaly on chest x-ray are useful indicators of cardiogenic shock. In evaluating the neonate with decompensated shock, early consideration for Cardiology consultation and interventions to treat the underlying condition is warranted.

INTRODUCTION Pediatric heart transplant (HTx) recipients have reduced exercise capacity typically two-thirds of predicted values, the mechanisms of which are not fully understood. We sought to assess the cardiorespiratory responses to progressive exercise in HTx relative to controls matched for age, sex, body size, and work rate. METHODS Fourteen HTx recipients and matched controls underwent exercise stress echocardiography on a semisupine cycle ergometer. Hemodynamics, left ventricular (LV) dimensions, and volumes were obtained and indexed to body surface area. Oxygen consumption (V˙O2) was measured, and arteriovenous oxygen difference was estimated using the Fick Principle. RESULTS At rest, LV mass index (P = 0.03) and volumes (P < 0.001) were significantly smaller in HTx, whereas wall thickness (P < 0.01) and LV mass-to-volume ratio (P = 0.01) were greater. Differences in LV dimensions and stroke volume persisted throughout exercise, but the pattern of response was similar between groups as HR increased. As exercise progressed, heart rate and cardiac index increased to a lesser extent in HTx. Despite this, V˙O2 was similar (P = 0.82) at equivalent work rates as HTx had a greater change in arteriovenous oxygen difference (P < 0.01). CONCLUSIONS When matched for work rate, HTx had similar metabolic responses to controls despite having smaller LV chambers and an attenuated increase in hemodynamic responses. These findings suggest that HTx may increase peripheral O2 extraction as a compensatory mechanism in response to reduced cardiovascular function.

The objective of this study was to describe hypersensitivity reactions with and without the use of in-line filters during intravenous etoposide therapy in pediatric oncology patients. This was a retrospective review of all patients treated in the Division of Oncology/Hematology/Bone Marrow Transplant at British Columbia Children's Hospital with intravenous etoposide between December 1, 2013 and February 1, 2018. Hypersensitivity reactions and anaphylaxis associated with etoposide infusions were compared over time, including 12 months prior to, 27 months during the use of, and for 12 months after the discontinuation of in-line filtration. There were 192 patients (median age 6.0 (IQR 2.8-13.0) years treated with etoposide and 486 etoposide infusions including 137 (28%) before, 261 (54%) during and 88 (18%) after use of in-line filters at our center. Twenty-six of 486 (5%) and 13/486 (3%) of infusions resulted in a type I hypersensitivity reaction and anaphylaxis, respectively. There were 2/137 (1%), 36/261 (14%) and 1/88 (1%) infusion reactions prior to, during and after in-line filter use, respectively. Infusion reactions during the in-line filter period were higher than during the pre-filter (Z = 3.978; p 0.001) and post-filter (Z = 3.335; p 0.001) periods of the study. These data suggest that the use of in-line filtration may be associated with increased frequency of hypersensitivity reactions to etoposide in pediatric cancer patients.

Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) is a syndrome of unknown etiology characterized by profound fatigue exacerbated by physical activity, also known as post-exertional malaise (PEM). Previously, we did not detect evidence of immune dysregulation or virus reactivation outside of PEM periods. Here we sought to determine whether cardiopulmonary exercise stress testing of ME/CFS patients could trigger such changes. ME/CFS patients (n = 14) and matched sedentary controls (n = 11) were subjected to cardiopulmonary exercise on 2 consecutive days and followed up to 7 days post-exercise, and longitudinal whole blood samples analyzed by RNA-seq. Although ME/CFS patients showed significant worsening of symptoms following exercise versus controls, with 8 of 14 ME/CFS patients showing reduced oxygen consumption ([Formula: see text]) on day 2, transcriptome analysis yielded only 6 differentially expressed gene (DEG) candidates when comparing ME/CFS patients to controls across all time points. None of the DEGs were related to immune signaling, and no DEGs were found in ME/CFS patients before and after exercise. Virome composition (P = 0.746 by chi-square test) and number of viral reads (P = 0.098 by paired t-test) were not significantly associated with PEM. These observations do not support transcriptionally-mediated immune cell dysregulation or viral reactivation in ME/CFS patients during symptomatic PEM episodes.

AIMS: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an ion channelopathy characterized by ventricular arrhythmia during exertion or stress. Mutations in RYR2-coded Ryanodine Receptor-2 (RyR2) and CASQ2-coded Calsequestrin-2 (CASQ2) genes underlie CPVT1 and CPVT2, respectively. However, prognostic markers are scarce. We sought to better characterize the phenotypic and genotypic spectrum of CPVT, and utilize molecular modelling to help account for clinical phenotypes. METHODS AND RESULTS: This is a Pediatric and Congenital Electrophysiology Society multicentre, retrospective cohort study of CPVT patients diagnosed at

Background The authors used semisupine cycle ergometry stress echocardiography to assess cardiac function and unmask baffle stenosis in patients with d-transposition of the great arteries after atrial redirection surgery. Methods This was a retrospective review of semisupine cycle ergometry stress echocardiography performed in 53 patients (64% male; mean age, 24.0 years; 90% Mustard procedure) and 56 healthy control subjects. Incremental exercise to volitional fatigue was performed. Hemodynamic data, echocardiographic cardiac dimensions, area change, tissue Doppler velocities, strain, ventricular synchronization, and superior vena cava flow velocities before and immediately after exercise are reported. Results Patients had lower exercise capacity (870 vs 1,854 J/kg, P P 2 , P = .400). Cardiac index increased in both groups with exercise (3.0 vs 6.1 and 2.9 vs 7.0 L/min/m 2 , P P = .006). Right ventricular diastolic and systolic areas decreased significantly with exercise in both the short-axis and four-chamber views. Right and left ventricular contraction time shortened with exercise (405 vs 247 and 338 vs 217 msec, P P = .020) and normalized after catheter intervention (1.49 vs 1.46 m/sec, P = .800). Conclusions Patients with d-transposition of the great arteries have lower exercise capacity and peak heart rates. The systemic right ventricle presents a lesser but qualitatively normal systolic response and decreased diastolic filling. Semisupine cycle ergometry stress echocardiography unmasked SVC obstruction.

Using noninvasive techniques, we sought to assess arterial stiffness, impedance, hydraulic power, and efficiency in children with postoperative tetralogy of Fallot (TOF), coarctation of the aorta (COA), and transposition of the great arteries (TGAs). Results were compared with those of healthy peers. Fifty-five children with repaired congenital heart disease (24 TOFs, 20 COAs, and 11 TGAs) were compared with 55 age-matched control subjects (CTRL). Echocardiographic Doppler imaging and carotid artery applanation tonometry were preformed to measure aortic flow, dimensions, and calculate pulse wave velocity, vascular impedance and arterial stiffness indexes, hydraulic power (mean and total), and hydraulic efficiency (HE) which were calculated using standard fluid dynamics equations. All congenital heart disease subgroups had higher pulse wave velocity than CTRL. Only the COA group had higher characteristic impedance. Mean power was higher in TGA than in CTRL and TOF, and total power was higher in TGA than in CTRL and TOF. Hydraulic efficiency was higher in TOF than in COA and TGA. In conclusion, children with TOF, COA, and TGA have stiffer aortas than CTRL. These changes may be related to intrinsic aortic abnormalities, altered integrity of the aorta due to surgical repair, and/or acquired postsurgery. These patients may be at increased long-term cardiovascular risk, and long-term follow-up is important for monitoring and assessment of efforts to reduce risk.

6040 Background: FRα is overexpressed on > 90% of high-grade EOC. We conducted a randomized double-blind multicenter phase II clinical trial to evaluate the safety and efficacy of TPIV200 (a multi-epitope FRα peptide vaccine admixed with GM-CSF adjuvant) versus GM-CSF alone as a control in patients with stage III-IV high-grade platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal carcinoma in first complete or partial remission, irrespective of baseline level of FRα expression. Methods: Patients with stage III-IV high-grade serous, high-grade endometrioid, carcinosarcoma or poorly differentiated EOC who had previously completed standard upfront therapy without evidence of disease progression and who were within a year of last platinum were randomized 1:1 to intradermal vaccination of TPIV200 versus intradermal GM-CSF alone. The vaccination period included 6 administrations of the study drug at 4-week intervals. Up to 6 booster vaccinations at 12-week intervals were permitted for patients who did not have disease progression. AEs were assessed using CTCAE. Tumor response was assessed via RECIST every 12 weeks. The primary endpoint, progression free survival (PFS), was calculated from date of first vaccination to the date of progression, death or study termination. Results: Of 120 patients randomized, 63 (53%) were treated on the TPIV200 arm. The median age at study entry was 63 years (range 37-88). AEs were generally mild. Injection site reaction was more frequent in the TPIV200 (63%) versus GM-CSF arm (39%). The other most common AEs, abdominal pain (25%) and fatigue (23%), were comparable in both arms. At study termination with a median follow-up of 15.2 months (range: 1.2-28.3 months), 68 of 119 intention-to-treat patients had progressed (55% in the TPIV200 arm and 59% in the GM-CSF arm). The median PFS was 11.1 months (95% CI: 8.3-16.6 months) and there was no statistically significant difference in median PFS between the arms (10.9 months with TPIV200 versus 11.1 months with GM-CSF, HR = 0.85 [upper 90% CI = 1.17]). Conclusions: Although TPIV200 had a manageable safety profile, the study was terminated for futility after the planned interim analysis. Future development of FRα-targeted therapy will likely focus on the careful selection of patients whose cancers show high FRα expression. Clinical trial information: NCT02978222.

OBJECTIVES Radiographic survey of the entire aerodigestive tract (nares to anus) is common practice in children presenting to the emergency department following coin ingestion. The purpose of our study was to determine the optimal protocol for radiographic survey post-coin ingestion. We hypothesized that for children presenting with a clear history of coin ingestion a frontal chest radiograph including the entire esophagus is adequate to guide treatment. METHODS We reviewed the clinical history and radiographic surveys of 134 patients presenting with suspected or witnessed coin ingestion to the emergency department of a tertiary care pediatric hospital between January 2012 and June 2016. Patient demographics, presenting symptoms, anatomic coverage of survey, type, number and location of radiopaque foreign bodies, intervention, and follow-up were recorded. RESULTS Coins were identified on radiographic surveys in 109 of 134 patients; 25 of 134 patients had no coin. Of those with coins, none of 109 had coin(s) in the airway, 42 of 109 had coin(s) in the esophagus, and 67 of 109 had coin(s) distal to the esophagus. Of those with esophageal coins, 35 of 42 reported symptoms, 7 of 42 were asymptomatic, 40 of 42 underwent endoscopic coin removal, and 2 of 42 had no intervention. Of 92 of 134 surveyed patients with no coin or coin distal to the esophagus, 30 of 92 reported symptoms, 62 of 92 were asymptomatic, 90 of 92 had no further intervention, and 2 of 92 eventually underwent endoscopic coin removal for specific indications (abdominal pain, delayed passage). When there was no coin found in the esophagus, the negative predictive value for intervention was 97.8%. CONCLUSIONS Following a clear history of coin ingestion, a frontal chest radiograph including the entire length of the esophagus provides sufficient information to direct patient management.

BackgroundFemales with Turner syndrome (TS) carry an elevated risk of aortic dissection. The objective of the study was to assess the biophysical properties of the aorta and ambulatory blood pressure (BP) in females with TS and compare these findings to those in healthy female age-matched controls.MethodsThis was a prospective cohort study including subjects aged 8–25 years. Utilizing two-dimensional (2D) echocardiography and Doppler, proximal aortic dimensions were measured and biophysical properties of the aorta were calculated including pulse wave velocity (PWV), arterial pressure-strain elastic modulus and stiffness index. Resting BP was measured and ambulatory blood pressure monitoring (ABPM) was performed.ResultsOf 23 TS patients and 46 controls (median age 16.3 years), aortic annulus, sinus of Valsalva and sinotubular (ST) junction diameters, as well as left ventricular (LV) mass, were significantly greater in TS patients compared with controls when scaled for height2.7, but not for body surface area (BSA), although ascending aorta diameter was greater when scaled for both. Median PWV was faster in TS patients compared to controls (451 vs. 360 cm/s) while arterial pressure-strain elastic modulus and stiffness index were similar. Resting BP was abnormal in seven out of 22 patients and ABPM was abnormal in 16 out of 21 patients.ConclusionsYoung patients with TS had dilated proximal aortas when scaled for height2.7and stiffer aortas when compared with healthy female age-matched controls. Moreover, resting BP underdiagnosed pre-hypertension and hypertension compared to ABPM. These findings are consistent with the presence of a primary aortopathy in TS.

Whether the large lungs of swimmers result from intensive training or genetic endowment has been widely debated. Given that peak lung growth velocities occur during puberty, this study examined if competitive swimming during puberty affected lung growth. Eleven‐ to fourteen‐year‐old healthy female competitive swimmers and controls were assessed before (PRE) and after (POST) one swimming season (7.4 ± 0.5 months). Pulmonary function testing included lung volumes, spirometry, diffusion capacity (DL , CO), and maximal inspiratory (PIMAX) and expiratory (PEMAX) pressures. Ventilatory constraints, including end‐expiratory lung volume, expiratory flow limitation, and utilization of ventilatory capacity, were assessed during an incremental cycling test. Swimmers (n = 11) and controls (n = 10) were of similar age, size, and sexual maturity (P > 0.05). However, swimmers compared to controls had a greater total lung capacity (PRE 4.73 ± 0.73 vs. 3.93 ± 0.46, POST 5.08 ± 0.68 vs. 4.19 ± 0.64 L; P 0.05). Changes over time were not different between groups (P > 0.05). At the initial measurement, pubertal female swimmers had greater lung size, expiratory flows, and indices of respiratory muscle strength, but similar ventilatory constraints while cycling. One competitive swimming season did not further accentuate this enhanced lung size and function or alter ventilatory mechanics, suggesting that competitive swimming during puberty did not affect lung growth.

Background— Patients with anorexia nervosa exhibit abnormal myocardial repolarization and are susceptible to sudden cardiac death. Exercise testing is useful in unmasking QT prolongation in disorders associated with abnormal repolarization. We characterized QT adaptation during exercise in anorexia. Methods and Results— Sixty-one adolescent female patients with anorexia nervosa and 45 age- and sex-matched healthy volunteers performed symptom-limited cycle ergometry during 12-lead ECG monitoring. Changes in the QT interval during exercise were measured, and QT/RR-interval slopes were determined by using mixed-effects regression modeling. Patients had significantly lower body mass index than controls; however, resting heart rates and QT/QTc intervals were similar at baseline. Patients had shorter exercise times (13.7±4.5 versus 20.6±4.5 minutes; P P P P =0.54), the QTc interval had prolonged significantly more in patients than controls (37±28 versus 24±25 ms; P P P =0.026). Conclusions— Despite the absence of manifest QT prolongation, adolescent anorexic females have impaired repolarization reserve in comparison with healthy controls. Further study may identify impaired QT dynamics as a risk factor for arrhythmias in anorexia nervosa.

Objective This retrospective case–control study investigated cardiac dimensions and ventricular function in female adolescents with anorexia nervosa (AN) compared with controls. Methods Echocardiographic measurements of left ventricular (LV) dimensions, LV mass index, left atrial size and cardiac index were made. Detailed measures of systolic and diastolic ventricular function were made including tissue Doppler imaging. Patients were stratified by body mass index ≤10th percentile (AN ≤ 10th) and >10th percentile (AN > 10th). Results Ninety-five AN patients and 58 controls were included. AN and AN ≤ 10th groups had reduced LV dimensions, LV mass index, left atrial size and cardiac index compared with controls. There were no differences between groups in measures of systolic function. Measures of diastolic tissue Doppler imaging were decreased in AN and AN ≤ 10th. No differences in echocardiographic measurements existed between controls and AN > 10th. Discussion Female adolescents with AN have preserved systolic function and abnormalities of diastolic ventricular function. AN ≤ 10th may be a higher risk group. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Background Patients with Marfan (MFS) and Loeys-Dietz (LDS) syndromes have been shown to have abnormal aortic biophysical properties. The purpose of this study was to compare the effects of 12-months of therapy with atenolol or losartan on vascular function in young patients with MFS and LDS. Methods Seventeen patients with MFS or LDS were recruited and randomized to treatment with atenolol, 25-50mg, or losartan, 25mg daily. Prior to treatment and following therapy, echocardiography for left ventricular size, function and aortic root size was performed. Pulse wave velocity (PWV), input (Zi, ZiF) and characteristic (Zc, ZcF) impedances, arterial stiffness (Ep and β-index), total arterial compliance (TAC), mean (Wm) and total (Wt) hydraulic power, efficiency, power cost per unit of forward flow (Wt/CI) and brachial artery flow-mediated dilation (FMD) were measured. Results The atenolol group consisted of 9 females (17.6years) and the losartan group 7 males and 1 female (17.0years). Their height, weight, BSA, BMI, systolic and diastolic blood pressures were similar. Baseline to 12-month changes for atenolol and losartan were PWV (20% vs -14%), Zi (-2% vs -27%), Zc (-20% vs -27%), Ep (1%, vs -13%), β-index (10% vs 14%), FMD (11% vs 20%), TAC (3% vs 42%), Wm (-24% vs 15%), Wt (-24% vs 17%), and Wt/CI (3% vs 21%). There was a trend for losartan to decrease PWV and stiffness indexes while atenolol decreased power and power/unit flow. Conclusion This pilot study suggests that atenolol and losartan may have different mechanisms of action on vascular function. A larger clinical trial is needed to confirm these effects.Clinical trials registration NCT00593710 (ClinicalTrials.gov).

Background Exercise testing in children is widely recommended for a number of clinical and prescriptive reasons. Many institutions continue to use the Bruce protocol for treadmill testing; however, with its incremental changes in speed and grade, it has challenges for practical application in children. We have developed a novel institutional protocol (British Columbia Children’s Hospital (BCCH)), which may have better utility in paediatric populations. Aim To determine if our institutional protocol yields similar peak responses in minute ventilation (VE), oxygen consumption (VO 2 ), carbon dioxide production (VCO 2 ), respiratory exchange ratio (RER), metabolic equivalents (METS) and heart rate (HR) when compared with the traditional Bruce protocol. Methods On two different occasions, 70 children (boys=33; girls=37) aged 10–18 years completed an exercise test on a treadmill using each of the protocols. During each test, metabolic gas exchange parameters were measured. HR was monitored continuously during exercise using an HR monitor. Results Physiological variables were similar between the two protocols (median (IQR); r s ): VE (L/min) (BCCH=96.7 (72.0–110.2); Bruce=99.2 (75.6–120.0); r s =0.95), peak VO 2 (mL/min) (BCCH=2897 (2342–3807); Bruce=2901 (2427–3654); r s =0.94) and METS (BCCH=16.2 (14.8–17.7); Bruce=16.4 (14.7–17.9); r s =0.89). RERs were similar (BCCH=1.00 (0.96–1.02); Bruce=1.03 (0.99–1.07); r s =0.48). Total exercise time (in seconds) was longer for the BCCH protocol: BCCH=915 (829–1005); Bruce=810 (750-919); r s =0.67. Conclusion The BCCH protocol produces similar peak exercise responses to the Bruce protocol and provides an alternative for clinical exercise testing in children.

ObjectiveWe sought to determine the feasibility and assess the clinical outcomes associated with an early extubation strategy for all children undergoing congenital heart surgery, including neonates (age, 24 hours).ResultsWe operated on 613 children, including 97 neonates. Intraoperative extubation was achieved in 71% of the cases and early extubation (≤24 hours) was achieved in 89% of the cases. The overall mortality was 1.5% (9 of 613 patients). Early extubation was associated with lower mortality (1% vs 9%, P

Background Patients with anorexia nervosa (AN) have altered physiologic responses to exercise. The aim of this study was to investigate exercise capacity and ventricular function during exercise in adolescent patients with AN. Methods Sixty-six adolescent female patients with AN and 21 adolescent female control subjects who exercised to volitional fatigue on a semisupine ergometer, using an incremental step protocol of 20 W every 3 min, were retrospectively studied. Heart rate, blood pressure, and echocardiographic Doppler indices were measured at rest and during each stage of exercise. Fractional shortening, rate-corrected mean velocity of circumferential fiber shortening, stress at peak systole, cardiac output, and cardiac index were calculated. Minute ventilation, oxygen consumption, carbon dioxide production, and respiratory exchange ratio were measured using open-circuit spirometry. Results Patients with AN had significantly lower body mass index (16.7 vs 19.7 kg/m2, P Conclusions Adolescent patients with AN have reduced exercise capacity and peak cardiovascular indices compared with control subjects but normal patterns of cardiovascular response during progressive exercise. Systolic ventricular function is maintained during exercise in adolescents with AN.

Background Invasive studies have shown that children with Fontan palliation have abnormal arterial stiffness, impedance, and hydraulic power and efficiency. The aim of this study was to assess these indexes noninvasively in a cohort of children with Fontan circulation using Doppler echocardiography and compare their results with those of healthy peers. Methods This was a case-control study of 22 Fontan patients and 31 healthy control children. Using standard two-dimensional, M-mode, and Doppler echocardiographic imaging and carotid artery applanation tonometry, aortic flows, dimensions, and pulse-wave velocity were measured, and vascular impedance and arterial stiffness were calculated. Hydraulic power and efficiency were calculated from standard fluid dynamics formulae. Results The median age was similar between groups. Stroke volume index (39 vs 39 mL/min/m 2 ) and cardiac index (2.6 vs 2.5 L/min/m 2 ) were similar. Aortic cross-sectional area (3.3 vs 2.8 cm 2 ), peak aortic flow (302 vs 261 cm 3 /sec), and myocardial performance index (0.47 vs 0.25) were higher and ejection fraction (50% vs 66%) was lower in Fontan patients. Input impedance (61 vs 83 dyne · sec/cm 5 /m 2 ) was lower in Fontan patients. Pulse-wave velocity (488 vs 364 cm/sec), elastic pressure-strain modulus (305 vs 263 torr), and stiffness index (4.15 vs 3.04) were higher in Fontan patients. Total arterial compliance (1.29 vs 1.32 mL/torr/m 2 ) and mean power (606 vs 527 mW/m 2 ) were similar and total hydraulic power (716 vs 627 mW/m 2 ) was higher in Fontan patients. Efficiency and the power cost per unit of forward flow were similar. Conclusions Despite stiffer aortas, Fontan patients generate more hydraulic power associated with decreased ventricular function to achieve a similar hydraulic efficiency. In Fontan patients, therapy that is given to improve ventricular function may need to target vascular stiffness as well. This technique may be used to monitor the efficacy of therapeutic interventions.

Background— There is virtually no information assessing the insurability of families affected with Sudden Arrhythmia Death Syndromes (SADS) for the determination of the nonclinical implications of genetic screening. It is important to identify the barriers and challenges faced by families as a result of genetic screening for SADS to enable equitable access to insurance coverage. Methods and Results— To explore the insurance coverage experiences of SADS-affected families, we administered a cross-sectional online survey across North America from April 28, 2012 to November 13, 2013. Participants included individuals with a SADS diagnosis and their relatives who have applied for insurance (health, life, travel, and disability) or have existing insurance coverage. Of 202 participants, 92% had a SADS diagnosis (92%) as either a proband (50%) or an affected relative (42%); 8% of participants were unaffected family members of a proband; and genetic confirmation was reported by 73%. Of the 54% of SADS respondents who applied for insurance, 60% were rejected by insurers. The preexisting SADS diagnosis was the major reason reported for rejection (57%). Most respondents (80%) had insurance coverage through a spouse/parent plan at the time of diagnosis; 14% experienced a subsequent negative effect on coverage. Thirty-nine percent of affected SADS respondents reported an increase in insurance premium rates. Conclusions— Increased genetic testing has negatively impacted insurability for SADS patients and affected family members. The challenges in obtaining life and health insurance are mainly because of the preexisting condition, even in the presence of protective laws in the United States.

Determining safe levels of physical activity for children and adolescents with electrophysiologic and structural congenital heart disease is a challenging clinical problem. The body of evidence for making these recommendations is limited and likely based on expert opinion, medicolegal concerns, and perceived risks of sudden cardiac death (SCD) with activity. The Bethesda Conference has established consensus guidelines for determining the eligibility of athletes with cardiovascular abnormalities for competitive sports and their disqualification from them. However, literature on guidelines for noncompetitive physical activity is not available. A survey was designed to determine practice patterns for patients with electrophysiologic and structural congenital heart disease. Between July 2011 and December 2011, approximately 350 health care providers working with this group of patients were recruited by email or while attending professional meetings. The survey received 81 responses, primarily from pediatric cardiologists (70 %). The findings indicate that the majority of Canadian cardiac care providers surveyed are only partially implementing current recommendations. Areas of variance included physical activity recommendations for hypertrophic cardiomyopathy, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and heart transplantation, among others. The development of comprehensive consensus guidelines for activity recommendations was supported by 96 % of the respondents. The heterogeneity of responses may be attributable to conflicting and poorly evidenced information in the literature, a lack of emphasis on recreational activity, an entrenched tendency toward bed rest in the cardiology community, and a lack of awareness by cardiac care providers regarding the actual risk associated with physical activity in electrophysiologic and structural congenital heart disease. A balanced discussion is required in considering both the significant benefit of physical activity in reducing cardiovascular risk factors and the small possibility of SCD in children and young adults with electrophysiologic and structural congenital heart disease.

Background Stress echocardiography has been advocated for the detection of abnormal myocardial function and unmasking diminished myocardial reserve in pediatric patients. The aim of this study was to create a simplified index of myocardial reserve, derived from the myocardial inotropic response to peak semisupine exercise in healthy children, and illustrate its applicability in a sample of pediatric oncology patients. Methods In this prospective analysis, children (7–18 years of age) with normal cardiac structure and function performed semisupine stress echocardiography to volitional fatigue. The quotient of wall stress at peak systole and heart rate–corrected velocity of circumferential fiber shortening were calculated at baseline and at peak exercise, the difference of which was termed the index of myocardial reserve (IMR). The IMR was also calculated in a retrospective sample of pediatric oncology patients with normal resting left ventricular function who had received anthracycline treatment and had performed the same exercise protocol to illustrate utility. Results Fifty healthy subjects (mean age, 13.2 ± 2.6 years) and 33 oncology patients (mean age, 12.7 ± 4.0 years) were assessed. In the healthy children at peak exercise, heart rate–corrected velocity of circumferential fiber shortening significantly increased (from 1.17 ± 0.17 to 1.58 ± 0.24 circ · sec −1 , P −2 , P Conclusions The authors have developed a novel IMR. Relative to the normal distribution of this IMR in healthy subjects, it is possible to identify patients with abnormal myocardial reserve. Thus, this study demonstrates the application of the IMR to aid in clinical decision making in individual patients.

Background— Supraventricular tachycardia (SVT) is one of the most common conditions requiring emergent cardiac care in children, yet its management has never been subjected to a randomized controlled clinical trial. The purpose of this study was to compare the efficacy and safety of the 2 most commonly used medications for antiarrhythmic prophylaxis of SVT in infants: digoxin and propranolol. Methods and Results— This was a randomized, double-blind, multicenter study of infants P =0.25). No first recurrence occurred after 110 days of treatment. The 6-month recurrence-free status was 79% for patients on digoxin and 67% for patients on propranolol ( P =0.34), and there were no first recurrences in either group between 6 and 12 months. There were no deaths and no serious adverse events related to study medication. Conclusions— There was no difference in SVT recurrence in infants treated with digoxin versus propranolol. The current standard practice may be treating infants longer than required and indicates the need for a placebo-controlled trial. Clinical Trial Registration Information— http://clinicaltrials.gov ; NCT-00390546.

We sought to determine whether childhood obesity is associated with increased aortic stiffness by measuring the biophysical properties of the aorta in obese children using a noninvasive echocardiographic Doppler method. Increased aortic stiffness is a strong predictor of future cardiovascular events and mortality in adults. Obesity is known to be associated with increased aortic stiffness and arterial disease in adults. We prospectively evaluated a cohort of obese children (n = 61) and compared them to normal-weight controls (n = 55). The anthropometric data were recorded. The pulsewave velocity (PWV), aortic input impedance (Zi), characteristic impedance (Zc), arterial pressure-strain elastic modulus (Ep), arterial wall stiffness index (B index), and peak aortic velocity were calculated. We correlated our echocardiographic Doppler findings with the lipid levels. We assessed the left ventricular (LV) dimensions and standard measures of cardiac function. Cardiopulmonary exercise testing was performed on all obese children. Compared to normal-weight children, obese children had a greater PWV, Zc, B index, Ep, and peak aortic velocity. Obese children had greater systolic blood pressure than normal-weight children but no difference in diastolic blood pressure. The LV dimensions and standard measures of cardiac systolic function were similar in the 2 groups, but the obese children had altered diastolic properties. The LV mass was greater in the obese children. No association was found between the lipid levels and the biophysical properties of the aorta. The relative oxygen consumption was 68% predicted in obese children. In conclusion, measures of the biophysical properties of the aorta are already abnormal in obese children, reflecting increased aortic stiffness at this early stage of disease. Obese children also had an increased LV mass, altered diastolic properties, and an abnormal exercise capacity. PWV might be useful in monitoring the progression of arterial disease or the effect of therapeutic interventions.

The diagnosis and management of prenatal tachyarrhythmias is well established; however, the postnatal course and outcomes are not. The purpose of our study was to review the natural history of patients with fetal tachycardia, determine the incidence of postnatal arrhythmias, and determine whether there are factors to predict which fetuses will develop postnatal arrhythmias. A retrospective chart review of patients with fetal tachyarrhythmias investigated at British Columbia Children's and Women's Hospitals between 1983 and 2010 was conducted. Sixty-nine mother-fetus pairs were eligible for the study. Fifty-two had fetal supraventricular tachycardia, and 17 had fetal atrial flutter. Conversion to sinus rhythm occurred prenatally in 52 % of patients. Postnatal arrhythmia occurred in two thirds of patients, with 82 % of those cases occurring within the first 48 h of life. Hydrops fetalis, female sex, and lack of conversion to sinus rhythm was predictive of postnatal arrhythmia (P = 0.01, P = 0.01, and P = 0.001, respectively). Conversion to sinus rhythm prenatally did not predict postnatal arrhythmia. Median duration of treatment was 9 months. Two postnatal deaths of unknown etiology occurred. Two thirds of all patients with prenatal tachycardia will develop postnatal arrhythmia. Prenatal factors that predict postnatal arrhythmia include hydrops, sex, and whether or not conversion to sinus rhythm occurred prenatally. The majority of patients with postnatal arrhythmia present within 48 h of life, which has clinical implications for monitoring. Postnatal outcome is generally very good with most patients being weaned off medication in 6-12 months.

The purpose of this study was to determine if healthy young women of various aerobic fitness levels are vulnerable to intrapulmonary arteriovenous shunts (IPAVS) at sub maximal work rates. Female volunteers (n=24) performed semi-recumbent cycling exercise to exhaustion and agitated saline contrast echocardiography was used to determine the presence of IPAVS at rest, during exercise, and post exercise. Subjects were classified as untrained (UT, n=8), moderately trained (MT, n=6) and highly trained (HT, n=10) based on their respective (V(O(2,peak)) (UT=35±5; MT=43±1 and HT = 50 ± 3 ml kg(-1) min(-1)). We found that the % (V(O(2,peak)) at IPAVS onset was not significantly different between women of varying fitness (P>0.05). The majority of individuals exhibited IPAVS during modest levels of exercise intensity. In conclusion, there is no association between aerobic capacity or exercise intensity at IPAVS onset in women performing semi-recumbent cycle exercise.

Yeung JP, Human DG, Sandor GGS, De Souza AM, Potts JE. Serial measurements of exercise performance in pediatric heart transplant patients using stress echocardiography. Pediatr Transplantation 2011: 15: 265–271. © 2011 John Wiley & Sons A/S. Abstract: Heart transplantation is an increasingly acceptable therapeutic option for children with end-stage and complex congenital heart disease. With advances in surgery, immunosuppression, and follow-up care, functional outcomes need to be evaluated. We report the results of serial exercise testing performed using stress echocardiography in a cohort of pediatric HTP. HTP (n = 7) exercised on a semi-recumbent ergometer to volitional fatigue. Echocardiography-Doppler measurements, HR, and blood pressure were taken at rest and during staged exercise. Results were compared with healthy CON (n = 12). HTP did significantly less work during exercise (940 vs. 1218 J/kg, p

Author(s): Roston, Thomas M; Haji-Ghassemi, Omid; LaPage, Martin J; Batra, Anjan S; Bar-Cohen, Yaniv; Anderson, Chris; Lau, Yung R; Maginot, Kathleen; Gebauer, Roman A; Etheridge, Susan P; Potts, James E; Van Petegem, Filip; Sanatani, Shubhayan | Abstract: BackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) is often a life-threatening arrhythmia disorder with variable penetrance and expressivity. Little is known about the incidence or outcomes of CPVT patients with ≥2 variants.MethodsThe phenotypes, genotypes and outcomes of patients in the Pediatric and Congenital Electrophysiology Society CPVT Registry with ≥2 variants in genes linked to CPVT were ascertained. The American College of Medical Genetics a Genomics (ACMG) criteria and structural mapping were used to predict the pathogenicity of variants (3D model of pig RyR2 in open-state).ResultsAmong 237 CPVT subjects, 193 (81%) had genetic testing. Fifteen patients (8%) with a median age of 9 years (IQR 5-12) had ≥2 variants. Sudden cardiac arrest occurred in 11 children (73%), although none died during a median follow-up of 4.3 years (IQR 2.5-6.1). Thirteen patients (80%) had at least two RYR2 variants, while the remaining two patients had RYR2 variants plus variants in other CPVT-linked genes. Among all variants identified, re-classification of the commercial laboratory interpretation using ACMG criteria led to the upgrade from variant of unknown significance (VUS) to pathogenic/likely pathogenic (P/LP) for 5 variants, and downgrade from P/LP to VUS for 6 variants. For RYR2 variants, 3D mapping using the RyR2 model suggested that 2 VUS by ACMG criteria were P/LP, while 2 variants were downgraded to likely benign.ConclusionsThis severely affected cohort demonstrates that a minority of CPVT cases are related to ≥2 variants, which may have implications on family-based genetic counselling. While multi-variant CPVT patients were at high-risk for sudden cardiac arrest, there are insufficient data to conclude that this genetic phenomenon has prognostic implications at present. Further research is needed to determine the significance and generalizability of this observation. This study also shows that a rigorous approach to variant re-classification using the ACMG criteria and 3D mapping is important in reaching an accurate diagnosis, especially in the multi-variant population.

Objective To measure aerobic fitness (maximum oxygen consumption [VO2peak]), fatigue, quality of life (QOL), and disease activity in young persons with systemic lupus erythematosus (SLE), and to determine an equation for predicting VO2peak from the distance walked in 6 minutes (6MW). Methods Fifteen young patients ages 12–19 years with SLE participated. VO2 was measured by a graded treadmill exercise test. Submaximal exercise intensity was determined from the ventilatory anaerobic threshold. Submaximal aerobic capacity was measured using the 6MW. Patient questionnaires included measures of fatigue, QOL, and physical activity. Physician questionnaires included the Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Results Compared with age-matched norms, our patients had moderate impairment in aerobic fitness, with a mean ± SD VO2peak of 31.1 ± 7.9 ml/minute/kg and a mean 6MW distance Z score of −2.4 ± 2.3. The regression equation to predict VO2peak (ml/minute/kg) from 6MW was as follows: 57.1 + [0.038 × distance (meters)] + (−0.35 × maximal heart rate) (R = 0.67, P = 0.027). Ten subjects (67%) reported significant fatigue. There was no significant correlation of fatigue with fitness measures. Neither fatigue nor fitness was significantly correlated with disease activity, disease damage, or QOL measures. Conclusion Young SLE patients have lower aerobic fitness than reference norms. The 6MW may be used as a marker of fitness, but it is preferable to determine VO2 with a graded exercise test. Fatigue is a significant symptom in young SLE patients. The application of fatigue measures in young persons is exploratory. The relationship between fatigue and aerobic fitness is not clear.

Background. Hepatic fibrosis is a potential complication following Fontan surgery and heralds long-term risk for cirrhosis. Transient elastography (TE) is a rapid, noninvasive method to assess liver fibrosis by measuring liver stiffness.Objectives. To compare liver stiffness and liver biochemistries in pediatric Fontan patients with age- and sex-matched controls and to determine patients’ acceptance of TE.Methods. Patients were recruited from British Columbia Children’s Hospital. Twenty-two Fontan patients (15 males) were identified. Demographic information and cardiac data were collected. TE was measured using size-appropriate probes.Results. The median age of the Fontan cohort was 13.7 (5.9–16.8) years. Time from Fontan surgery to TE was 9.6 (1.0–12.9) years. The median Fontan circuit pressure was 13 (11–14) mmHg. TE values were higher in Fontan patients versus controls (18.6 versus 4.7 kPa,p<0.001). There was no association between TE values and patient age (r=0.41,p=0.058), time since Fontan surgery (r=0.40,p=0.062), or median Fontan circuit pressure (CVP) (r=0.35,p=0.111). Patients found TE to be nonpainful, convenient, and safe.Conclusions. TE is feasible to assess liver stiffness in children following Fontan surgery. Pediatric Fontan patients have markedly elevated liver stiffness values. TE may have important utility in liver care follow-up of pediatric Fontan patients.

A male infant presented at birth with severe coarctation of the aorta and marginal left ventricular and mitral valve dimensions associated with a large secundum atrial septal defect. Following successful arch repair, the left ventricle remained small with preferential left-to-right atrial shunting and a dilated right ventricle. Clinically, the infant continued with tachypnea, poor feeding, and failure to thrive. At 4 months of age, the defect was closed with an Amplatzer Atrial Septal Occluder which resulted in immediate left ventricular cavity enlargement and clinical improvement.

Background Anthracycline-treated patients (AP) are at risk for cardiac dysfunction years after treatment. Cardiac function has not been evaluated during exercise in AP. The purpose of this study was to assess exercise tolerance, left ventricular (LV) function, and hemodynamics during progressive exercise. Procedure We studied 47 AP (cumulative dose: 36–504 mg/m2) who were in complete remission and 12 healthy controls (CON). AP were further grouped by cumulative dose (LOW ≤ 260 mg/m2; HIGH ≥ 260 mg/m2) and resting echocardiographic function. All subjects performed 3-min incremental stages on a semi-recumbent cycle ergometer until volitional fatigue. Using echocardiography and Doppler, LV dimensions, posterior wall thickness (LVPWs), peak aortic velocity (PAoV), shortening fraction (SF), rate-corrected mean velocity of fiber shortening (MVCFc), wall stress at peak systole (σPS), stroke volume index (SVI), and cardiac index (CI) were determined. Measurements were performed at rest, during each stage of exercise, and in recovery. Results AP did less work than CON (P

Background Anorexia nervosa (AN) is associated with abnormalities in biomarkers of cardiovascular risk. Arterial stiffness, as measured by pulse-wave velocity (PWV), is also a risk factor for cardiovascular disease. The aims of this study were to determine the stiffness of the aorta in female adolescents with AN and to determine if either the severity or the type of AN was associated with PWV. Methods This was a retrospective case-control study. Adolescent patients with a clinical diagnosis of AN were included. Aortic diameter and pulse-wave transit time over a portion of the thoracic aorta were measured using Doppler echocardiography, and PWV was calculated. Results There were 94 female patients with AN and 60 adolescent female control subjects. There was no significant difference in age between patients with AN and control subjects (15.5 ± 1.7 vs 15.1 ± 2.6 years, P = .220). Body mass index (16.0 ± 2.4 vs 19.7 ± 2.7 kg/m 2 , P P P Conclusions Female adolescents with AN have increased aortic stiffness compared with control subjects. This study suggests that patients with AN may be at increased risk for future cardiovascular disease. Future studies are required to determine the reversibility of these changes with weight restoration.

We present a case series of pediatric blunt cardiac trauma with a variety of cardiac abnormalities, occurring immediately and after the initial insult. The range of complications and importance of serial evaluations are emphasized.

This study was performed to: (1) assess the feasibility of measuring pulse wave velocity (PWV) from aortic (AO) Doppler flow and deriving AO input and characteristic impedances and the arterial pressure strain elastic modulus; and (2) compare these indices in pediatric patients with arterial disease to control (C) patients.There were 14 healthy children in the C group, 9 with inflammatory connective tissue diseases (ICTD), and 6 with Marfan syndrome (M). Using standard echocardiographic equipment, the AO annulus, AO root diameter in systole (AO(S)) and diastole (AO(D)), and AO length (L) were measured. The time taken for the Doppler signal to travel from the ascending to descending aorta was measured. AO peak flow was calculated from AO annulus cross-sectional area x peak aortic velocity (AoV); PWV = L/time taken for the Doppler signal to travel from the ascending to descending aorta; input impedance = (systolic - diastolic blood pressure)/(AO cross-sectional area x AoV); characteristic impedance = (PWV x rho)/Ao cross-sectional area (where rho = 1.06); and pressure strain elastic modulus = (systolic - diastolic blood pressure)/[(AO(S) - AO(D))/AO(D)]; beta index = ln (systolic/diastolic blood pressure)/[(AO(S) - AO(D))/AO(D)].Results for PWV were ICTD = MC (533, 496, 362 cm/s; P.02); for input impedance were ICTDM = C (245, 120, 116; P.03); for characteristic impedance were ICTDM = C (249, 107, 142; P.05); for pressure strain elastic modulus were MICTD = C (262, 447, 187; P.003); and for beta index were MICTDC (2.91, 2.51, 2.13; P.0006).This novel, relatively simple method of assessing the biophysical properties of the aorta shows abnormal function in patients with M and ICTD. This technique may be helpful in the long-term follow up of patients with arterial disease.

This retrospective case-control study investigated cardiac dimensions and ventricular function in female adolescents with anorexia nervosa (AN) compared with controls.Echocardiographic measurements of left ventricular (LV) dimensions, LV mass index, left atrial size and cardiac index were made. Detailed measures of systolic and diastolic ventricular function were made including tissue Doppler imaging. Patients were stratified by body mass index ≤10th percentile (AN ≤ 10th) and10th percentile (AN 10th).Ninety-five AN patients and 58 controls were included. AN and AN ≤ 10th groups had reduced LV dimensions, LV mass index, left atrial size and cardiac index compared with controls. There were no differences between groups in measures of systolic function. Measures of diastolic tissue Doppler imaging were decreased in AN and AN ≤ 10th. No differences in echocardiographic measurements existed between controls and AN 10th.Female adolescents with AN have preserved systolic function and abnormalities of diastolic ventricular function. AN ≤ 10th may be a higher risk group.

Objectives: To establish the prevalence of coronary arterial abnormalities in mid-trimester fetuses with pulmonary atresia with intact ventricular septum, and whether their presence correlates with right ventricular morphology. Background: The presence of coronary arterial fistulas significantly alters the surgical options and prognosis for patients with pulmonary atresia with intact ventricular septum. The lesion can reliably be diagnosed using fetal echocardiography, and further definition of the prognosis is important for counselling parents. Methods: We examined the hearts of 39 pathological specimens diagnosed during fetal life, 3 of whom died postnatally. Coronary arterial abnormalities were defined as non-connection of the left or right coronary arteries to the aorta, ostial stenosis, marked tortuosity, dilation, thickening or abnormal myocardial branching. Mild tortuosity, or myocardial bridging, were considered normal. We measured the dimensions of the tricuspid valve along with the inlet and outlet portions of the ventricles. Ebstein's malformation, tricuspid valvar dysplasia, and the presence or absence of the infundibulum, were especially noted. We examined also 12 normal hearts as controls. Results: Coronary arterial abnormalities were found in 14/39 (36%). The dimensions of the right ventricle and tricuspid valves, and the gestational ages of the fetuses, were compared for these 14 with the 25 having no abnormalities using independent t-tests. The gestational ages were similar, 21.9 vs 21.1 weeks. The mean dimensions of the tricuspid valve, median z-scores, and right ventricle were smaller, 2.9 vs 7.2 mm; p < 0.002; −4.46 vs 0.23; p < 0.03; and 6.9 vs 13.7 mm; p < 0.002, for those with coronary arterial abnormalities. Ebstein's malformation, or dysplasia of the tricuspid valve, was present in 4 of 14 with, vs 15 of 25 without, coronary arterial abnormalities. A patent infundibulum was noted in 34 of 39 specimens. Conclusions: Mid-trimester fetuses with pulmonary atresia with intact ventricular septum already exhibit coronary arterial abnormalities, with a prevalence of 36%. The presence of a patent infundibulum confirms that atresia of the pulmonary valve is an acquired process. Coronary arterial abnormalities are seen in 50% of those with hypoplastic right ventricles, but less frequently in the presence of well developed ventricles. This is important information for those involved in counselling parents.

The outcome of surgical repair of sinus venosus atrial septal defect was reviewed retrospectively. The operation was performed on 44 children aged 8 to 163 months, between April 1985 and November 1998. Median cardiopulmonary bypass and aortic crossclamp times were 58 minutes (range, 29 to 141 minutes) and 29 minutes (range, 4 to 67 minutes), respectively. Use of blood products decreased from 4.5 units per patient in the first period (1985 to 1989) to 0.6 units in the last period (1995 to 1998). Median intensive care and hospital stays were 2 days (range, 1 to 12 days) and 6 days (range, 4 to 16 days), respectively. There was 1 early death (2.3%). Complications included reexploration for bleeding in 2 patients (4.5%) and for superior vena cava obstruction in 1 (2.3%), and arrhythmias in 3 (6.8%), which required a pacemaker in one. During follow-up of 15 to 176 months, 83.8% of patients were in sinus rhythm. One required angioplasty for superior vena cava stenosis, hemodynamically insignificant residual shunt was found in 3, and mild superior vena cava stenosis in 3. Repair of sinus venosus atrial septal defect carries a low mortality and morbidity, but long-term follow-up is needed to monitor potential sinus node dysfunction and superior vena cava stenosis.