Youth with congenital heart disease (CHD) have been found to experience higher levels of health anxiety and associated constructs than typically developing peers. The association between youth and parent health anxiety has been explored in typically developing youth but this association remains unknown in youth with CHD. This association was explored using a prospective, cross-sectional study that included 36 school-age children and adolescents with CHD (median age =10.5 years, IQR = 4) and 35 parents (median age = 44 years, IQR = 10.5). Participants completed a demographic form and measures of health anxiety, anxiety sensitivity, intolerance of uncertainty, and anxiety disorder symptom categories (youth) or general anxiety (parent). Associations were observed between child and adolescent panic/agoraphobia symptoms and parent state anxiety ( r = .41), child and adolescent intolerance of uncertainty and parent state and trait anxiety ( r = .37; r = .46, respectively), and child and adolescent anxiety sensitivity and parent state anxiety ( r = .40). No association was observed between health anxiety in children and adolescents and parents nor between child and adolescent health anxiety and parent associated constructs. For parents, associations between health anxiety and all measures of associated constructs of interest were observed. Study findings will facilitate improved understanding of the psychological needs of school-age children and adolescents with CHD.

BackgroundAdults with congenital heart disease (CHD) are living longer with more complex disease. Maintaining lifelong care prevents morbidity and mortality, but many patients remain lost to follow-up or experience care gaps. We sought to assess barriers to care for patients with adult CHD (ACHD) in Saskatchewan, a Canadian province with no local congenital cardiac surgical support and no clear framework for ACHD care.MethodsWe performed a telephone survey of patients with CHD transferred from pediatric to adult cardiology from 2007 to 2014. Our primary outcome was loss to follow-up > 2 years from last recommended cardiology appointment and/or multiple missed cardiology appointments. Secondary outcomes were guideline-based care (specialist training, adherence to appropriate endocarditis prophylaxis, pre-pregnancy counselling for women), presence or absence of previously described barriers to care in ACHD, and health care autonomy using the Krantz Health Opinion Survey.ResultsWe interviewed 32 patients (30% response rate). One-quarter met the primary outcome: lost to follow-up > 2 years from last recommended cardiology appointment and/or self-report of missed cardiology appointments. Only 69% of young adults in Saskatchewan were receiving guideline-based care for their CHD (appropriate level of specialist expertise and frequency of follow-up). Only 72% of patients were adhering to endocarditis prophylaxis recommendations and 61% of women surveyed received counselling regarding pregnancy. Patients indicated a low preference for participating in decision making regarding their care on the Krantz Health Opinion Survey.ConclusionsWith our survey, we have created a novel snapshot of CHD care in Saskatchewan and have identified significant deficits.

Children with congenital heart disease (CHD) have an elevated risk of future cardiovascular disease but the underlying mechanisms are unclear. Abdominal obesity (measured as waist circumference) is a risk factor for adult onset of cardiovascular diseases and is correlated with low physical activity levels, commonly found in children with congenital heart disease. Elevated waist circumference may be a mechanism by which cardiovascular disease risk is elevated in children with CHD. The purpose of this study was to compare waist circumference between children with and without CHD, while considering potential confounders. We hypothesized that children with CHD would have higher measures of waist circumference when controlling for differences in birthweight, lean mass, and physical activity. Thirty-two children with CHD (10.9 ± 2.6 years; 12 female) from the Children’s Healthy-Heart Activity Monitoring Program in Saskatchewan, and 23 healthy controls (11.7 ± 2.5 years; 10 female) were studied. Waist circumference, physical activity (physical activity questionnaire), body composition (lean mass; dual x-ray absorptiometry), and birthweight were assessed. Analysis of covariance, Mann-Whitney U, and independent sample t-tests were used to assess group differences (p < 0.05). Children with CHD had greater waist circumference than controls, controlling for lean mass, physical activity, birthweight, and sex (F (1, 49) = 4.488, p = 0.039). Physical activity, lean mass, and birthweight were not significantly different between groups (p > 0.05). Our findings generate a novel hypothesis—higher waist circumferences in children with CHD compared to age-matched controls, may contribute to an elevated risk of cardiovascular disease.

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Individuals with the Fontan circulation and single ventricle physiology have elevated sympathetic nerve activity at rest and during muscle metaboreflex activation that is consistent with autonomic dysfunction. Adults with the Fontan circulation also show reduced baroreflex sensitivity (BRS); however, there is limited understanding of BRS in children or adolescents with the Fontan circulation. In healthy adults, BRS decreases with increased sympathetic nerve activity during isometric handgrip exercise, but not during isolated muscle metaboreflex activation. The effect of handgrip exercise and muscle metaboreflex activation on BRS in children and adolescents with the Fontan circulation is currently unknown.PURPOSEWe tested the hypothesis that BRS is lower at rest and less responsive during handgrip exercise and post‐exercise circulatory occlusion (PECO) in children/adolescents with the Fontan circulation compared to healthy controls.METHODSEight children/adolescents with the Fontan circulation (12 ± 2 yrs; 3 males) and 8 healthy controls (13 ± 4 yrs; 5 males) were studied. Continuous heart rate (ECG) and non‐invasive blood pressure (Finometer® MIDI) were recorded during 3‐min of resting baseline, 2‐min of isometric handgrip exercise at 30% of maximal voluntary contraction, and 3‐min of PECO. Continuous heart rate, systolic blood pressure, and diastolic blood pressure signals were analyzed using the BRS Analysis software (Nevrokard, Slovenia, 2018) to yield average BRS values during rest, handgrip, and PECO for each group. Differences between groups and across conditions were assessed using two‐way repeated measures (2 × 3, group × condition) ANOVA. P<0.05 was considered significant.RESULTSThere was a significant group × condition interaction for BRS (P<0.001). BRS was lower in children/adolescents with the Fontan circulation vs. healthy controls at rest (13 ± 8 vs. 38 ± 10 ms/mmHg; P<0.001) and during PECO (18 ± 17 vs. 37 ± 18 ms/mmHg; P=0.044), but not during handgrip (13 ± 10 vs. 14 ± 6 ms/mmHg; P=0.843). BRS in children/adolescents with the Fontan circulation did not change across conditions (P=0.188).CONCLUSIONOur findings suggest that BRS is lower at rest and has a blunted response during sympatho‐excitation in children/adolescents with the Fontan circulation compared to healthy controls. Collectively, our findings indicate potential autonomic dysfunction in children/adolescents with the Fontan circulation.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Children with congenital heart disease are at risk for developing increased arterial stiffness and this may be modulated by physical activity. OBJECTIVE To compare arterial stiffness in high- and low-physically active children with congenital heart disease and healthy age- and sex-matched controls. PATIENTS Seventeen children with congenital heart disease (12 ± 2 years; females = 9), grouped by low- and high-physical activity levels from accelerometry step count values, and 20 matched controls (11 ± 3 years; females = 9) were studied. OUTCOME MEASURES Carotid-radial pulse wave velocity was assessed with applanation tonometry to determine arterial stiffness. Body composition and 6-min walk test measures were performed. Data were analyzed using analysis of variance and multiple regression. Significance was P < .05. RESULTS Arterial stiffness was increased in low-physically active children with congenital heart disease (9.79 ± 0.97 m/s) compared to high-physically active children with congenital heart disease (7.88 ± 0.71 m/s; P = .002) and healthy-matched controls (8.67 ± 1.28 m/s; P = .015). There were no differences in body composition measures between groups (all P > .05), but 6-min walk test distance was less in both congenital heart disease groups (high-physically active: 514 ± 40 m; low-physically active: 539 ± 49 m) versus controls (605 ± 79 m; all P < .05). Average daily step count significantly predicted arterial stiffness in children with congenital heart disease (R2 = 0.358) with a negative correlation (R = -0.599, P = .011), while % fat mass (P = .519) and % lean mass (P = .290) did not predict arterial stiffness. CONCLUSIONS Low-physically active children with congenital heart disease have increased arterial stiffness compared to high-physically active children with congenital heart disease and healthy-matched controls. Regular physical activity in children with congenital heart disease may modulate arterial stiffness.

This study explored health anxiety and associated constructs in children and adolescents with congenital heart disease and typically developing children and adolescents. A total of 84 participants (7–16 years) completed measures of health anxiety, intolerance of uncertainty, anxiety sensitivity, and DSM-IV anxiety disorder symptom categories. Results demonstrated that children and adolescents with congenital heart disease experienced significantly higher levels of health anxiety and associated constructs compared to typically developing children and adolescents. Our findings highlight a specific chronic physical health population who may be at risk of clinical levels of health anxiety and related psychopathology and require appropriate intervention.

Children after the Fontan operation have reduced heart rate variability (HRV) and altered blood pressure control, consistent with autonomic dysfunction. We tested the hypothesis that increasing sympathetic nerve activity via the muscle metaboreflex may improve post exercise blood pressure responses in children after the Fontan operation. PURPOSE: To determine resting HRV and the mean arterial pressure (MAP) response to post-handgrip exercise muscle metaboreflex activation in children after the Fontan operation compared to age- and sex-matched healthy controls. METHODS: Five children after the Fontan operation and 10 controls (12 ± 2 yrs) underwent resting electrocardiography and continuous finger arterial plethysmography. Children then completed 2 min of isometric handgrip exercise at 30% of maximal voluntary contraction, followed in random order by either (1) 3 min of rest with no occlusion or (2) 3 min of brachial cuff occlusion to produce post exercise ischemia and increased sympathetic nerve activity via the muscle metaboreflex. Post-handgrip MAP changes were calculated as the 1 min average value after 3 min of recovery minus the pre-handgrip resting 1 min average value. Comparisons were made using unpaired t-tests. P < 0.05 was significant. RESULTS: Resting heart rate was higher in children after the Fontan operation vs. controls (78 ± 14 vs. 67 ± 5 beats/min; P = 0.041). HRV spectral analyses were similar in the low frequency domain (24 ± 10 vs. 22 ± 13%; P = 0.720), but increased in the high frequency domain (23 ± 15 vs. 52 ± 16%; P = 0.005) and low/high frequency domain ratio (1.5 ± 1.3 vs. 0.6 ± 0.4; P = 0.046) for children after the Fontan operation vs. controls, indicating autonomic dysfunction. Following isometric handgrip exercise with no occlusion, the change in heart rate (-2 ± 5 vs. -3 ± 5 beats/min; P = 0.646) was similar, but children after the Fontan operation had greater lowering in MAP (-5 ± 1 vs. 0 ± 5 mmHg; P = 0.024) vs. controls. With brachial occlusion, changes in heart rate (0 ± 5 vs. -1 ± 6 beats/min; P = 0.701) and MAP (6 ± 7 vs. 6 ± 7 mmHg; P = 0.980) were similar between children after the Fontan operation vs. controls. CONCLUSION: Our findings suggest that increasing sympathetic nerve activity via the muscle metaboreflex helps to improve post exercise blood pressure responses in children after the Fontan operation.

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Physical activity is a key modulator for arterial health and greater arterial stiffness increases mortality risk. Children with congenital heart disease (CHD) are often less physically active compared to healthy children and this may predispose them to greater arterial stiffness. PURPOSE: To explore the relationships of body composition, aerobic fitness and physical activity levels with arterial stiffness in children with CHD and healthy age- and sex-matched controls. METHODS: Nineteen children with CHD (m/f: 9/10; mean ± SD; age 11 ± 3 years) and 22 age-matched healthy controls (m/f: 12/10; age 11 ± 3 years) were studied. Carotid-radial pulse-wave velocity (PWV) was assessed with applanation tonometry (foot-to-foot method) to determine arterial stiffness. Average daily minutes of moderate-to-vigorous physical activity (MVPA) was assessed by 7-days of accelerometry. Total lean body mass (LBM) was measured via dual-energy x-ray absorptiometry. Aerobic fitness was determined by 6-minute walk test (6MWT). Data were analyzed with linear correlations and stepwise multiple regressions, with significance accepted at P < 0.05. Analyses were performed across all participants pooled, split into CHD and control groups only, and split into high MVPA (N = 21; 64 ± 19 minutes/day) and low MVPA (N = 20; 23 ± 11 minutes/day) groups. RESULTS: There was a significant correlation of LBM with PWV in all participants pooled (R = 0.536, P < 0.001) and in controls only (R = 0.668, P < 0.001), but not in CHD only. There was no significant correlation of 6MWT or MVPA with PWV in pooled analyses or when split into CHD and control groups. When split by physical activity level, in the high MVPA group, LBM significantly predicted PWV (R2 = 0.224, P = 0.03), and in the low MVPA group, LBM and 6MWT distance significantly predicted PWV (R2 = 0.571, P = 0.001). CONCLUSIONS: In children with CHD and healthy controls, body composition predicts arterial stiffness independent of physical activity levels. Aerobic fitness further predicts arterial stiffness only in children with low physical activity levels. Our findings suggest that interventions to improve body composition and aerobic fitness may be especially important for arterial health in less physically activity children, independent of health status.

Children with hypoplastic left heart syndrome after the Fontan operation (post-Fontan) have low exercise tolerance and impaired autonomic cardiovascular control. Given that mechano- and metaboreceptors play a major role in the exercise pressor reflex, the purpose of this study was to determine the cardiovascular response to sympathetic nervous system activation during exercise that engages mechano- and metaboreceptors (handgrip exercise) and metaboreceptors only (post-exercise circulatory occlusion, PECO) in post-Fontan versus healthy controls (CTL). Seven post-Fontan (f=3, m=4; 13 +/- 4 years) were compared with 9 CTL (f=3, m=6; 13 +/- 3 years). After 10 minutes of supine rest, participants performed 2 minutes of isometric handgrip exercise at 40% of maximal voluntary contraction to elicit both the mechano- and metaboreceptor responses, followed by 3 minutes of PECO to isolate just the muscle metaboreflex component of the exercise pressor reflex. Beat-by-beat MAP was recorded continuously by finger photoplethysmography, beat-by-beat HR by ECG, and breath-by-breath minute ventilation (VE) by pneumotach. Resting, handgrip, and PECO data were analyzed as average values over 30 sec. Data are reported in the table as mean +/- SD change from resting values (delta). Data was analyzed with a 2x3 repeated measures ANOVA (group: HLHS and CTL; condition: rest, handgrip, PECO) and Holm-Sidak post-hoc tests performed with P < 0.05 as the level of significance. As expected, CTL had increased MAP, HR, and VE during isometric handgrip exercise compared with rest. Then, during PECO in CTL, MAP remained elevated and HR and VE responses started to normalize. Post-Fontan had significantly lower MAP, HR, and VE responses during isometric handgrip exercise compared with CTL. During PECO, post-Fontan also had a significantly lower MAP response compared with CTL, whereas HR and VE responses were similar. We show, for the first time, that the exercise pressor reflex is blunted in children with hypoplastic left heart syndrome after the Fontan operation. This exercise pressor reflex may play a key role in the exercise intolerance encountered by children with HLHS after the Fontan operation.

BACKGROUND: Pulmonary vein stenosis is emerging as an important clinical problem in ex-premature infants.METHODS: We sought to describe the epidemiology of pulmonary vein stenosis affecting ex-premature infants by a multicenter retrospective cohort study of patients from seven children's hospitals diagnosed between 2000-2014.RESULTS: We identified 39 ex-premature patients (26 males, median gestational age 28 weeks range 22-36 weeks, birth weight 1.1 kg range 433-2645-g) with pulmonary vein stenosis. Median age at diagnosis was 6.5 months (1 month-6 years). Presentation with pulmonary hypertension occurred in 26/39 (67%) and 29/39 (74%) had bronchopulmonary dysplasia, 15 (39%) were born of twin pregnancies with unaffected twin siblings. A median of 5 (range 1-25) echocardiograms was performed prior to diagnosis. The diagnosis was made using echocardiography in 22/39 (56%), by multi-detector contrast computed tomography scan (CT) in 8/39 (21%), cardiac catheterization in 6/39 (15%) patients, magnetic resonance imaging in 3/39 (8%). Freedom from death or re-stenosis was 73% at 1-year, 55% at 2, 5, and 10 years. Factors associated with shorter survival or re-stenosis were stenosis of >= 3 pulmonary veins (P < 0.01), bilateral pulmonary vein stenosis (P< 0.01) small for gestational age (P = 0.05), aged < 6 months at diagnosis (P < 0.01).CONCLUSION: Pulmonary vein stenosis of ex-premature infants is a complex problem with poor survival, delayed diagnosis, and unsatisfactory treatment. The lack of concordance in twins suggests epigenetic or environmental factors may play a role in the development of pulmonary vein stenosis. In ex-premature infants with pulmonary hypertension and bronchopulmonary dysplasia a focused echocardiographic assessment of the pulmonary veins is required with further imaging if the echocardiogram is inconclusive.

Children with congenital heart disease (CHD) are often less physically active and have reduced aerobic fitness compared to healthy matched controls. Children with CHD are also at risk for developing greater arterial stiffness, and physical inactivity is known to potentiate this risk. The degree of arterial stiffness in physically active children with CHD is not known. PURPOSE: To determine arterial stiffness in self-reported physically active children with CHD and similarly active healthy age- and sex-matched children. METHODS: Twenty children with CHD (11 ± 3 years; m = 9; f = 11) and 24 age- and sex-matched controls (11 ± 3 years; m = 12; f = 12) were studied. Children had similar self-reported physical activity scores (CHD: 3.1 ± 0.7 vs. control: 3.3 ± 0.7; scale = 1-5 from lowest (1) to highest (5) physical activity level; Physical Activity Questionnaire for Children). CHD diagnoses included tetralogy of Fallot (n = 7), hypoplastic left or right heart syndrome (n = 3), Ebstien’s anomaly (n = 1), atrial or ventricular septal defect (n = 5), transposition of the great arteries (n=2), double inlet left ventricle (n = 1), tricuspid or pulmonary atresia (n = 2), coarctation of the aorta (n = 2), single ventricle (n = 1), dilated cardiomyopathy (n = 1), and heart transplantation (n = 1). Children performed a 6MWT. Arterial stiffness was determined from ECG-gated pulse wave velocity assessment with applanation tonometry at the carotid and radial artery sites. Data were analyzed with t-tests and simple linear regression. Data are mean ± SD and p < 0.05 was significant. RESULTS: Body mass index (CHD: 18 ± 4 kg/m2 vs. controls: 19 ± 4 kg/m2; p > 0.05) and waist circumference (CHD: 66 ± 10 cm vs. controls: 68 ± 10 cm; p > 0.05) were similar between groups. 6MWT distance was lower in children with CHD (514 ± 58 m) vs. healthy controls (604 ± 77 m, p < 0.05). Pulse wave velocity was similar between children with CHD (8.8 ± 1.2 m/s) and healthy controls (8.8 ± 1.3 m/s; p > 0.05). There was no significant relationship between pulse wave velocity and 6MWT distance in either group (both p > 0.05). CONCLUSION: Self-reported physically active children with CHD have normal arterial stiffness compared to similarly active healthy matched children. Regular physical activity in children with CHD may maintain arterial health but does not normalize aerobic fitness.

Introduction: A slow recovery in heart rate (HR) following exercise is due to autonomic dysfunction and is associated with increased cardiovascular event risk. Children with congenital heart defects (CHD) display autonomic dysfunction as shown by a reduction in HR variability (HRV). Whether children with CHD have impairment in post-exercise HR recovery is unknown. Hypothesis: We tested the hypothesis that children with CHD would have reduced HRV at rest and slower HR recovery kinetics following 6-minute walk testing (6MWT) compared to healthy controls. Methods: Twenty-five children with CHD (11±2 years; males=14; females=11) and 21 age- and sex-matched controls (11±3 years; males=10; females=11) were studied. CHD diagnoses included Tetralogy of Fallot (n=7), pulmonary or aortic stenosis (n=3), hypoplastic left or right heart syndrome (n=5), Ebstien’s anomaly (n=1), atrial or ventricular septal defect (n=3), transposition of the great arteries (n=1), double inlet left ventricle (n=1), tricuspid atresia (n=1), coarctation of the aorta (n=2), single ventricle (n=1), and dilated cardiomyopathy (n=1). HRV was determined following 10 min supine rest using a 5 min surface ECG recorded epoch. Post-exercise HR kinetics were determined over a 4-min period following the 6MWT using telemetry-based HR. Mono-exponential modeling was used to derive a HR recovery time constant, tau (time to reach 63% change). Analyses were completed using unpaired t -tests with P < 0.05 being significant. Data are mean ± SD. Results: Children with CHD had a lower 6MWT distance (513±75 vs. 599±81 m; P < 0.001) and lower average exercise HR (122±15 vs. 139±18 beats/min; P = 0.001) compared to controls. Time domain HRV parameters revealed a reduction in the standard deviation of normal R-R intervals (55.9±40.4 vs. 92.1±24.5 ms), the root mean square of successive R-R interval differences (57.4±53.0 vs. 101.1±40.0 ms), and the percentage of consecutive normal R-R intervals that differ by more than 50 ms (24.6±28.7 vs. 53.2±14.0 %) in children with CHD vs. controls, respectively (all P < 0.01). Power spectral HRV analyses revealed no difference in low frequency (LF) power (30±16 vs. 25±16 %; P > 0.05), but significant differences in high frequency (HF) power (34±19 vs. 49±14 %) and the LF/HF ratio (1.4±1.5 vs. 0.6±0.3 %) in children with CHD vs. controls, respectively (all P < 0.05). Post-exercise HR kinetics were slower in children with CHD (tau = 34±15 s) compared to controls (tau = 24±8 s; P = 0.01), indicating a longer recovery time for HR. Conclusions: Children with CHD have autonomic dysfunction as measured by a reduction in HRV and greater LF/HF ratio. Slower HR kinetics in children with CHD may be due to a reduction in parasympathetic activation during the post-exercise recovery period. Our findings suggest that autonomic dysfunction in children with CHD functionally alters HR control during or immediately following exercise.

Children with congenital heart disease (CHD) have previously been shown to be less physically active, have greater fatness, have less lean muscle mass, and lower aerobic fitness compared to healthy matched controls. The relationship between body composition measurements and aerobic fitness in physically active children with CHD compared to similarly active healthy age- and sex-matched children is unclear. PURPOSE: To determine body composition and it’s relationship with 6MWT distance in children with CHD and similarly physically active healthy age- and sex-matched children. METHODS: Twenty-five children with CHD (11 ± 2 years; m = 15; f = 10) and 15 age- and sex-matched controls (11 ± 2 years; m = 8; f = 7) were studied. Children had similar self-reported physical activity scores (CHD: 3.0 ± 0.8 vs. control: 3.3 ± 0.6; scale = 1-5 from lowest (1) to highest (5) physical activity level; Physical Activity Questionnaire for Children). CHD diagnoses included tetralogy of Fallot (n = 6), pulmonary or aortic stenosis (n = 3), hypoplastic left or right heart syndrome (n = 4), Ebstien’s anomaly (n = 1), atrial or ventricular septal defect (n = 5), transposition of the great arteries (n = 2), double inlet left ventricle (n = 1), tricuspid or pulmonary atresia (n = 2), coarctation of the aorta (n = 2), dilated cardiomyopathy (n = 1), and heart transplantation (n = 1). Children performed a 6MWT. Total body lean mass and total body fat was determined using dual-energy X-ray absorptiometry. Comparisons were made with t-tests or Mann-Whitney tests. The relationship between body composition and 6MWT distance was determined using multiple linear regression. Data are mean ± SD and p < 0.05 was significant. RESULTS: 6MWT distance was lower in children with CHD (501 ± 80 m) vs. healthy controls (592 ± 77 m, p < 0.05). Total body lean mass (CHD: 26.2 ± 12.2 kg vs. control: 27.6 ± 12.1 kg), and total body fat (CHD: 24 ± 7 % vs. control: 23 ± 9%) were not different between groups (all p > 0.05). Body composition was not related to 6MWT distance in children with CHD (p > 0.05), whereas total body lean mass and body fat significantly predicted 6MWT in controls (R2 = 0.471, p < 0.05). CONCLUSION: Self-reported physically active children with CHD have a reduction in aerobic fitness compared to similarly active healthy matched children, independent of similar body composition.

Introduction: Metabolically sensitive afferent fibers in skeletal muscle can signal an increase the sympathetic control of arterial blood pressure during exercise. This process, called the muscle metaboreflex, is augmented in adults with cardiovascular disease and contributes to exercise intolerance. The role of the muscle metaboreflex on blood pressure control in children with congenital heart defects (CHD) is not known. Hypothesis: We tested the hypothesis that the mean arterial pressure (MAP) response to the muscle metaboreflex would be augmented in children with CHD compared to healthy controls. Methods: Twenty-six children with CHD (11±2 years; males=14; females=12) and 21 age- and sex-matched controls (11±3 years; males=10; females=11) were studied. CHD diagnoses included Tetralogy of Fallot (n=7), pulmonary or aortic stenosis (n=3), hypoplastic left or right heart syndrome (n=5), Ebstien’s anomaly (n=1), atrial or ventricular septal defect (n=5), transposition of the great arteries (n=2), double inlet left ventricle (n=1), heart transplantation (n=2), tricuspid or pulmonary atresia (n=2), coarctation of the aorta (n=2), and dilated cardiomyopathy (n=1). Testing included a 3 min rest period followed by isometric handgrip exercise at 30% of maximal voluntary contraction for 2 min. Exercise was followed by 3 min of either a free flow control condition or circulatory occlusion to isolate the muscle metaboreflex. Beat-by-beat MAP was recorded using finger plethysmography. Analyses were completed using mixed designs factorial ANOVA with P < 0.05 as the level of significance. Data are mean ± SD. Results: During the free flow control condition, there was no significant difference in resting MAP (75±9 mmHg vs. 78±9 mmHg), exercise MAP (86±14 mmHg vs. 87±12 mmHg), or free flow MAP (72±10 mmHg vs. 78±9 mmHg) between children with CHD vs. controls, respectively ( P > 0.05). MAP significantly increased from rest to exercise and returned to resting levels during the free flow control condition for both groups. For the circulatory occlusion condition, there was no significant difference in resting MAP (73±11 mmHg vs. 74±8 mmHg), exercise MAP (84±15 mmHg vs. 81±11 mmHg), or circulatory occlusion MAP (79±13 mmHg vs. 79±13 mmHg) between children with CHD vs. controls, respectively ( P > 0.05). MAP significantly increased from rest to exercise and MAP remained elevated above resting levels during circulatory occlusion for both children with CHD and controls ( P < 0.001 for all). Conclusions: Post-exercise circulatory occlusion significantly increases MAP in children with CHD and healthy children, with no significant difference in the magnitude of the MAP response between groups. We conclude that children with CHD demonstrate a normal muscle metaboreflex during post-exercise circulatory occlusion.

PAH is a severe disease, in which pulmonary arterial remodeling leads to an increase in pulmonary vascular resistance and pulmonary arterial pressure, eventually resulting in right ventricular failure and death. Epidemiology and understanding of PAH in pediatric patients remains poorly understood. In an effort to expand knowledge of pediatric PAH in Canada, a prospective, observational registry of pediatric patients with PAH was established in May 2010 including all eleven academic pediatric cardiac centers across Canada. The main objective is to describe demographics and disease characteristics, incidence and prevalence and outcomes. Criteria for enrollment: age between 3 months and 17 years, PAH WHO Group 1 confirmed by right heart catheterization with following hemodynamics: Mean pulmonary artery pressure ≥ 25mm Hg at rest and pulmonary arterial wedge pressure ≤ 15 mm Hg. Both incident patients (PAH diagnosed within 4 months of enrollment in the study) and prevalent patients (diagnosis more than 4 months prior to enrollment in the study) were screened. Patients with persistent pulmonary hypertension of the newborn were not eligible. A total of 80 patients have been enrolled between May 1 2010 and April 30 2015. The median age was 2 years range from (<1 to 17 years), 54 female and 26 male. Mean pulmonary artery pressure at presentation ranged from 12 to 89 mm Hg (mean 46.4 mm Hg, median 44 mm Hg). Pulmonary vascular resistance (indexed for body surface area) ranged from 2.6 to 45 WUxm2 (mean 11.7, median 8.0 WUxm2). Documented follow-up visits were established for 11 patients (1 visit), 16 patients (2 visits), 19 patients (3 visits), 2 patients (4 visits) and 1 patient (5 visits). Predominantly female patients were enrolled in the Canadian Pediatric PAH registry; patients are relatively young in age and present with higher mean pulmonary artery pressures and pulmonary vascular resistance compared to adults. Future follow-up data will provide insight into survival.

Congenital diaphragmatic hernia (CDH) occurs in 1 of 4,000–5,000 live births. Despite advances in the care of these infants, pulmonary hypoplasia and resulting pulmonary hypertension (PH) carry significant morbidity and mortality. Thus, additional therapeutic strategies are needed. The use of continuous treprostinil for chronic pediatric pulmonary hypertensive disorders is increasing. However, its use for acute therapy is limited. We describe two 6-week-old infants with CDH and severe pulmonary hypertension treated with treprostinil. Rapid and dramatic clinical and hemodynamic improvement occurred in both cases. Both infants were weaned off the drug, representing the first reports of successful short-term treprostinil use in neonates with CDH. Case 1 was a female infant born at 37 weeks’ gestation, after a pregnancy complicated by late prenatal care, with left-sided, liver-up CDH. Patient underwent an uncomplicated hernia repair of DOL 3. Cardiac echo demonstrated suprasystemic RVp, requiring intubation with iNO. Patient was treated with PGE1 to maintain ductal patency with improvement in respiratory function and echo estimate of RVp. However, at 4 weeks of age, the child’s status deteriorated with a PH crises. At 6 weeks of age, cardiac catheterization measured suprasystemic PAp with severely elevated PVR of 13.5 Wood units; minimal PVR was 9.9 with vasodilators. Continuous IV epoprostenol was started, with transition to IV treprostinil after 48 hours. The dose was titrated over the next 4 weeks to a peak dose of 48 ng/kg/min, with minimal side effects. This resulted in significant clinical improvement and a decrease in BNP from 4,080 to 25 pg/mL. At 10 weeks, the patient was weaned off treprostinil, and treprostinil therapy was discontinued 30 days later. The infant was discharged at 5 months of age on bosentan and 0.5 LPM NC oxygen. Repeat cardiac catheterization at 7 months demonstrated a PVR of 3.7 Wood units. At 1-year follow-up, the infant was weaned off both oxygen and bosentan and continues to grow and develop well, with normal pulmonary pressures estimated by echo. Case 2 was a full-term female infant with prenatally diagnosed severe, left-sided, liver-up CDH. Echo on DOL 1 demonstrated suprasystemic RVp and decreased function. Patient underwent hernia repair with internal oblique muscle flap on DOL 2. Infant was supported on HFOV, FiO2 of 100%, 20-ppm iNO, and PGE. Patient was extubated to NCPAP at 2 weeks but continued on iNO, PGE, and milrinone. Repeat echo at 6 weeks was unchanged, with suprasystemic RVp and decreased function. At 6.5 weeks of age, cardiac catheterization measured systemic pulmonary pressures at baseline, with elevated PVR of 7.1 Wood units; minimal PVR was 5.8 with vasodilators. Continuous SC treprostinil was initiated and titrated up over the next 5 weeks to a peak dose of 52 ng/kg/min. This resulted in significant clinical improvement, including a successful weaning off PGE, milrinone, and iNO within 2 weeks. BNP decreased from 143 to 5 pg/mL. Patient was discharged home at 3.5 months of age on 0.5 L/min O2 and SC treprostinil. Bosentan was initiated at 6 months in anticipation of treprostinil weaning, and repeat cardiac catheterization at 8 months of age on room air demonstrated normal pulmonary pressures and a PVR of 4.3 Wood units. Patient was successfully weaned off treprostinil over the next 4 weeks and is maintained on bosentan, with excellent growth and development and normal pulmonary pressures estimated by echo. In conclusion, these 2 cases demonstrate the benefit of short-term treprostinil use initiated at 6–8 weeks of age in neonates with severe PH following CDH repair. These cases are consistent with our prior report demonstrating pulmonary vascular reactivity in infants with CDH at 2–3 months of age. Further, the successful use of SC treprostinil improves the safety of administration of prostacyclins in this vulnerable population, eliminating the need for a central line and its associated risks and allowing for outpatient therapy in a young infant.

Different surgical techniques for complete atrioventricular septal defect (CAVSD) repair have been described, with the double-patch technique being most frequently employed. More recently a newer technique using a modified single-patch repair has been advocated. We hypothesized that the modified single-patch technique would result in an increased incidence of the two major post-repair comorbidities, namely, distortion of the left AV valve (LAVV) leaflets and narrowing of the left-ventricular outflow tract (LVOT). We studied 14 patients with CAVSD who underwent either traditional double-patch technique [group 1 (n = 7)] or modified single-patch technique [group 2 (n = 7)]. Preoperative and immediate postoperative two-dimensional (2D) echocardiograms, as well as follow-up 2D and three-dimensional (3D) studies, were reviewed. For group 1, the median age at repair was 4.1 months with a median duration from surgical repair and last echocardiogram of 44 months. For group 2, the median age at repair was 3 months with a median duration from surgical repair and last echocardiogram of 28 months. The two groups had similar demographics and ventricular septal defect size before surgery. For the LAVV, no significant difference was observed with respect to LAVV annulus size, tenting height, and the size of the vena contracta. Furthermore, there was no significant difference in the 2D echocardiographic areas and volumes of the LVOT between pre-repair and immediate post-repair studies for both groups. At the last evaluation, although there had been growth of the LVOT in both groups, no significant difference between areas and volumes were observed. Areas of the LVOT measured by 3D echocardiography on the final study showed no significant statistical difference between both groups. There was good correlation of the areas measured by 2D and 3D echocardiography within each group. In this small group, modified single-patch technique does not appear to tether the LAVV or promote an increase in regurgitation. In the short term, LVOT growth is unaffected, and the repair does not promote LVOT obstruction. 3D echocardiography is useful for area measurements of the LVOT and showed good correlation with areas measured by assumption of the LVOT shape as determined using 2D techniques.