Fetal diagnosis and management of pulmonary artery sling: A case series.

OBJECTIVE: Pulmonary artery sling is a rare congenital anomaly accounting for 2% of all patients with vascular anomalies that cause airway obstruction. In the normal heart, the left (LPA) and right (RPA) pulmonary arteries arise in the intrapericardial space. However, in the pulmonary artery sling, the LPA trunk arises in the extrapericardial space from the posterior aspect of the mid RPA and courses posterior to the trachea causing tracheal compression and, at times, bronchial compression. While a full spectrum of congenital cardiac pathology can be identified before birth, only a few case reports document the prenatal diagnosis of an Left pulmonary artery sling (LPAS). METHOD: We retrospectively identified all cases of prenatal LPAS from three Canadian fetal cardiology centers (2015-2022). RESULTS: Using the 3-vessel-tracheal view via fetal echocardiography (FE), four fetuses from three pregnancies demonstrated abnormal origin of the LPA from RPA and echogenic trachea. In one of two affected monochorionic twins coronal imaging demonstrated a significant narrowing of the large airways consistent with significant airway obstruction. CONCLUSION: Prenatal detection of LPAS by FE is possible and should prompt an evaluation for airway obstruction in the coronal view. Investigating associated lesions and genetic testing are recommended for informed shared decision making.

Building Bridges from Genome to Physiology Using Machine Learning and Drosophila Experimental Evolution.

Drosophila experimental evolution, with its well-defined selection protocols, has long supplied useful genetic material for the analysis of functional physiology. While there is a long tradition of interpreting the effects of large-effect mutants physiologically, identifying and interpreting gene-to-phenotype relationships has been challenging in the genomic era, with many labs not resolving how physiological traits are affected by multiple genes throughout the genome. Drosophila experimental evolution has demonstrated that multiple phenotypes change because of the evolution of many loci across the genome, creating the scientific challenge of sifting out differentiated but noncausal loci for individual characters. The fused lasso additive model method allows us to infer some of the differentiated loci that have relatively greater causal effects on the differentiation of specific phenotypes. The experimental material that we use in the present study comes from 50 populations that have been selected for different life histories and levels of stress resistance. Differentiation of cardiac robustness, starvation resistance, desiccation resistance, lipid content, glycogen content, water content, and body masses was assayed among 40-50 of these experimentally evolved populations. Through the fused lasso additive model, we combined physiological analyses from eight parameters with whole-body pooled-seq genomic data to identify potentially causally linked genomic regions. We have identified approximately 2,176 significantly differentiated 50-kb genomic windows among our 50 populations, with 142 of those identified genomic regions that are highly likely to have a causal effect connecting specific genome sites to specific physiological characters.

Health anxiety and associated constructs in school-age children and adolescents with congenital heart disease and their parents: A children's healthy-heart activity monitoring program in Saskatchewan cohort study.

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.

Effects of 12-Week Home-based Resistance Training on Peripheral Muscle Oxygenation in Children With Congenital Heart Disease: A CHAMPS Study.

Background: A hallmark feature of children with congenital heart disease (CHD) is exercise intolerance. Whether a home-based resistance training intervention improves muscle oxygenation (as measured by tissue oxygenation index, TOI) and exercise tolerance (V˙O2 reserve) during aerobic exercise in children with CHD compared with healthy children is unknown. Methods: We report findings for 10 children with CHD (female/male: 4/6; mean ± standard deviation age: 13 ± 1 years) and 9 healthy controls (female/male: 5/4; age: 12 ± 3 years). Children with CHD completed a 12-week home-based exercise programme in addition to 6 in-person sessions. Exercise tolerance was assessed with a peak exercise test. Vastus lateralis TOI was continuously sampled during the peak V˙O2 test via near-infrared spectroscopy. Results: There was a medium effect (Cohen's d = 0.67) of exercise training on lowering TOI at peak exercise (pre: 30 ± 16 %total labile signal vs post: 20 ± 13 % total labile signal; P = 0.099). Exercise training had a small effect (Cohen's d = 0.23) on increasing V˙O2 reserve by 1.6 mL/kg/min (pre: 27.2 ± 5.7 mL/kg/min vs post: 29.4 ± 8.8 mL/kg/min; P = 0.382). There was also a small effect (Cohen's d = 0.27) of exercise on peak heart rate (pre: 175 ± 23 beats/min vs post: 169 ± 21 beats/min; P = 0.18). TOI, V˙O2 reserve, and heart rate were generally lower than healthy control participants. Conclusions: Our findings indicate that home-based resistance training may enhance skeletal muscle oxygen extraction (lower TOI) and subsequently V˙O2 reserve in children with CHD.

Contexte: L'une des manifestations caractéristiques de la cardiopathie congénitale chez les enfants est l'intolérance à l'effort. Il n'est pas clair si un entraînement musculaire à la maison permet d'améliorer l'oxygénation musculaire (selon l'indice d'oxygénation tissulaire, ou TOI pour tissue oxygenation index) et la tolérance à l'effort (réserve de consommation d'oxygène [V˙O2]) lors d'un exercice aérobique chez les enfants atteints d'une cardiopathie congénitale, comparativement aux enfants en bonne santé. Méthodologie: Les résultats présentés concernent 10 enfants atteints d'une cardiopathie congénitale (filles/garçons : 4/6; âge moyen ± écart-type : 13 ans ± 1 an) et neuf enfants témoins en bonne santé (filles/garçons : 5/4; âge : 12 ans ± 3 ans). Les enfants atteints d'une cardiopathie congénitale ont participé à un programme d'exercices à la maison de 12 semaines, en plus d'assister en personne à six séances. La tolérance à l'effort a été évaluée au moyen de l'épreuve d'effort maximal. Le TOI du muscle vaste externe a été mesuré de façon continue pendant le test du V˙O2 max par spectroscopie proche infrarouge. Résultats: Le programme d'exercices a entraîné un effet modéré (valeur d de Cohen = 0,67) sur la réduction du TOI au moment de l'effort maximal (pré-entraînement : signal labile total de 30 ± 16 % vs post-entraînement : signal labile total de 20 ± 13 % ; p = 0,099). Le programme d'exercices a eu un effet léger (valeur d de Cohen = 0,23) sur l'augmentation de la réserve de V˙O2, soit de 1,6 ml/kg/min (pré-entraînement : 27,2 ± 5,7 ml/kg/min vs post-entraînement : 29,4 ± 8,8 ml/kg/min; p = 0,382). On a également observé un effet léger (valeur d de Cohen = 0,27) sur la fréquence cardiaque maximale (pré-entraînement : 175 ± 23 battements/minute vs post-entraînement : 169 ± 21 battements/minute; p = 0,18). Le TOI, la réserve de V˙O2 et la fréquence cardiaque étaient généralement inférieurs comparativement aux témoins en bonne santé. Conclusions: Nos résultats montrent qu'un entraînement musculaire à la maison pourrait améliorer la capacité d'extraction de l'oxygène par les muscles squelettiques (TOI inférieur) et ultimement la réserve de V˙O2 chez les enfants atteints d'une cardiopathie congénitale.

Alternative to Body Surface Area as a Solution to Correct Systematic Bias in Pediatric Echocardiography z Scores.

BACKGROUND: Z scores are the method of choice to report dimensions in pediatric echocardiography. Z scores based on body surface area (BSA) have been shown to cause systematic biases in overweight and obese children. Using aortic valve (AoV) diameters as a paradigm, the aims of this study were to assess the magnitude of z score underestimation in children with increased body mass index z score (BMI-z) and to determine if a predicting model with height and weight as independent predictors would minimise this bias. METHODS: In this multicentre, retrospective, cross-sectional study, 15,006 normal echocardiograms in healthy children 1-18 years old were analyzed. Residual associations with body size were assessed for previously published z score. BSA-based and alternate prediction models based on height and weight were developed and validated in separate training and validation samples. RESULTS: Existing BSA-based z scores incompletely adjusted for weight, BSA, and BMI-z and led to an underestimation of > 0.8 z score units in subjects with higher BMI-z compared with lean subjects. BSA-based models led to overestimation of predicted AoV diameters with increasing weight or BMI-z. Models using height and weight as independent predictors improved adjustment with body size, including in children with higher BMI-z. CONCLUSIONS: BSA-based models result in underestimation of z scores in patients with high BMI-z. Prediction models using height and weight as independent predictors minimise residual associations with body size and generate well fitted predicted values that could apply to all children, including those with low or high BMI-z.

Barriers to Care in ACHD: A Study of Young Adults in Saskatchewan.

BACKGROUND: Adults 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: With our survey, we have created a novel snapshot of CHD care in Saskatchewan and have identified significant deficits.

CONTEXTE: Les adultes souffrant d'une cardiopathie congénitale vivent de plus en plus longtemps avec une maladie complexe. Les soins qui leur sont prodigués toute leur vie aident à prévenir la morbidité et la mortalité, mais nombreux sont les patients qui sont perdus de vue en cours de route ou qui vivent des périodes sans recevoir de soins. Nous avons tenté d'évaluer les obstacles aux soins des patients adultes atteints d'une cardiopathie congénitale en Saskatchewan, une province canadienne où il n'existe aucun programme local de soutien en matière de chirurgie cardiaque pour les troubles congénitaux ni de cadre définissant clairement les soins à prodiguer aux adultes atteints d'une cardiopathie congénitale. MÉTHODOLOGIE: Nous avons interviewé par téléphone des patients atteints d'une cardiopathie congénitale qui sont passés d'un suivi en cardiologie en soins pédiatriques aux soins aux adultes entre 2007 et 2014. Le critère d'évaluation principal était la perte de vue pendant plus de 2 ans après le dernier rendez-vous de suivi en cardiologie recommandé et/ou plusieurs rendez-vous en cardiologie manqués. Les critères d'évaluation secondaires étaient les soins recommandés dans les lignes directrices (formation spécialisée, observance d'une prophylaxie endocardite appropriée, counseling préalable à la grossesse chez les femmes), la présence ou l'absence d'obstacles aux soins relatifs à la cardiopathie congénitale chez l'adulte cités antérieurement et l'autonomie en matière de soins de santé selon le sondage d'opinion sur la santé de Krantz. RÉSULTATS: Nous avons interviewé 32 patients (taux de réponse de 30 %). Le quart des patients interrogés répondaient au critère d'évaluation principal, soit la perte de vue pendant plus de 2 ans après le dernier rendez-vous de suivi en cardiologie recommandé et/ou plusieurs rendez-vous en cardiologie manqués autodéclarés. Seulement 69 % des jeunes patients adultes de la Saskatchewan recevaient les soins recommandés dans les lignes directrices en matière de cardiopathie congénitale (degré approprié d'expertise spécialisée du médecin et fréquence des consultations de suivi). Seulement 72 % des patients observaient les recommandations en matière de prophylaxie endocardite, et 61 % des femmes interrogées avaient reçu des services de counseling concernant la grossesse. Selon les résultats au sondage d'opinion sur la santé de Krantz, les patients étaient généralement peu disposés à participer aux décisions concernant leur programme de soins. CONCLUSIONS: Grâce à notre enquête, nous disposons maintenant d'un portrait à jour des soins aux patients atteints de cardiopathie congénitale en Saskatchewan; l'exercice nous a par ailleurs permis de cerner d'importantes lacunes à cet égard.

A cardiovascular disease risk factor in children with congenital heart disease: unmasking elevated waist circumference - a CHAMPS* study *CHAMPS: Children's Healthy-Heart Activity Monitoring Program in Saskatchewan.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSION: 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.

New Comprehensive Reference Values for Arterial Vascular Parameters in Children.

BACKGROUND: Noninvasive measurements of vascular parameters can be used for the detection and risk stratification of cardiovascular diseases. Most vascular parameters are influenced by age and body size, but pediatric reference values are scarce and limited to a few parameters. The aim of this study was to develop pediatric reference values and Z score equations for a comprehensive set of vascular parameters. METHODS: A total of 292 healthy subjects aged 0 to 18 years were prospectively recruited. Stiffness index ß, pressure-strain elastic modulus, common carotid intima-media thickness, brachial flow-mediated dilation, radial augmentation index, central and right arm peripheral artery pulse-wave velocities, and pulse-wave velocity ratio were assessed. Normalization for age and anthropometric variables was performed using parametric multivariate regression modeling. Z scores were assessed for heteroscedasticity, residual association with age and body size, and distribution. RESULTS: Multivariate regression models with various combinations of height, weight, and age were used to obtain Z scores that were independent of age and body size. There was no residual association between Z scores and body size, age, or body mass index. There was no significant departure from the normal distribution. CONCLUSIONS: The authors present reference values and Z score equations for a comprehensive set of vascular parameters during childhood. Further studies are necessary to assess their usefulness in detecting the vascular signs of subclinical atherosclerosis and chronic diseases, including congenital heart disease.

Health anxiety and associated constructs in children and adolescents with congenital heart disease: A CHAMPS cohort study.

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.

Genomics of Early Cardiac Dysfunction and Mortality in Obese Drosophila melanogaster.

In experimental evolution, we impose functional demands on laboratory populations of model organisms using selection. After enough generations of such selection, the resulting populations constitute excellent material for physiological research. An intense selection regime for increased starvation resistance was imposed on 10 large outbred Drosophila populations. We observed the selection responses of starvation and desiccation resistance, metabolic reserves, and heart robustness via electrical pacing. Furthermore, we sequenced the pooled genomes of these populations. As expected, significant increases in starvation resistance and lipid content were found in our 10 intensely selected SCO populations. The selection regime also improved desiccation resistance, water content, and glycogen content among these populations. Additionally, the average rate of cardiac arrests in our 10 obese SCO populations was double the rate of the 10 ancestral CO populations. Age-specific mortality rates were increased at early adult ages by selection. Genomic analysis revealed a large number of single nucleotide polymorphisms across the genome that changed in frequency as a result of selection. These genomic results were similar to those obtained in our laboratory from less direct selection procedures. The combination of extensive genomic and phenotypic differentiation between these 10 populations and their ancestors makes them a powerful system for the analysis of the physiological underpinnings of starvation resistance.

Non-invasive assessment of aortic stiffness and blood pressure in young Turner syndrome patients.

Background Females 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. Methods This 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. Results Of 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. Conclusions Young patients with TS had dilated proximal aortas when scaled for height2.7 and 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.

Cardiovascular Magnetic Resonance Provides Evidence of Abnormal Myocardial Strain and Primary Cardiomyopathy in Marfan syndrome.

OBJECTIVE: Marfan syndrome is an autosomal-dominant genetic disorder caused by mutations in the fibrillin-1 gene. The condition is a connective tissue disease that frequently involves the cardiovascular system. The existence of a primary cardiomyopathy in Marfan syndrome, however, is controversial. The aims of this study were to investigate the prevalence of left ventricular dysfunction with both transthoracic echocardiography and cardiovascular magnetic resonance (CMR) in a cohort of Marfan syndrome patients and to investigate patterns of myocardial strain across the cohort. METHODS: We used an institutional database to identify all patients with a firm diagnosis of Marfan syndrome based on Ghent criteria. Inclusion required left ventricular ejection fraction (LVEF) to have been measured by both CMR and transthoracic echocardiography within 12 months of each other. Normal LVEF was defined as a value of >55% when measured by CMR. Velocity vector imaging was used to measure left ventricular longitudinal strain patterns by application of feature tracking to cine magnetic resonance images. Results were compared with data from 20 age-matched control subjects. RESULTS: Sixty-nine Marfan syndrome patients met the inclusion criteria. The mean age was 35.4 ± 15.0 years, and 56.5% were male. The mean LVEF was 59.0% ± 7.0% by CMR and 59.1% ± 5.8% by echo. One-fifth of Marfan syndrome patients (15/69; 21.7%) had reduced function with LVEF ≤55% by CMR, but only 5 of these were identified by echo. Furthermore, echo identified 5 Marfan syndrome patients as having reduced LVEF in the presence of a normal LVEF by CMR. Some Marfan syndrome patients had abnormal longitudinal strain patterns even with LVEF within the reference range. CONCLUSIONS: These data provide support for a primary cardiomyopathy in some Marfan syndrome patients. Cardiovascular magnetic resonance is more sensitive than echo for identifying cases with mild systolic dysfunction. Strain analysis may be more sensitive than simple LVEF assessment for identifying at-risk individuals.

Increased Arterial Stiffness Adversely Affects Left Ventricular Mechanics in Patients With Pediatric Takayasu Arteritis From a Toronto Cohort.

BACKGROUND/OBJECTIVE: Takayasu arteritis (TA) is characterized by extensive aortic, large and midsize arterial wall inflammation. The aim of this study was to assess the morphological and elastic properties of the aorta and large arteries and the impact on left ventricular (LV) mechanics in children with TA. METHODS: Seven pediatric TA patients (6 female patients, 13.8 ± 3.2 years) were assessed with magnetic resonance imaging, vascular ultrasound, applanation tonometry, and echocardiography from February 2015 until July 2017 and compared with 7 age- and sex-matched controls. Takayasu arteritis disease activity was assessed clinically by the Pediatric Vasculitis Activity Score (PVAS). RESULTS: Pediatric TA patients showed increased carotid-to-radial artery pulse wave velocity (8.1 ± 1.8 vs. 6.4 ± 0.6 m/s, p = 0.03) and increased carotid-to-femoral artery pulse wave velocity (8.3 ± 1.9 vs. 5.1 ± 0.8 m/s, p < 0.01) when compared with controls. Patients demonstrated increased LV mass index (74.3 ± 18.8 vs. 56.3 ± 10.9 g/m, p = 0.04), altered myocardial deformation with increased basal rotation (-9.8 ± 4.5 vs. -4.0 ± 2.0 degrees, p = 0.01) and torsion (19.9 ± 8.1 vs. 9.1 ± 3.1 degrees, p = 0.01), and impaired LV diastolic function with decreased mitral valve E/A ratio (1.45 ± 0.17 vs. 2.40 ± 0.84, p = 0.01), increased mitral valve E/E' ratio (6.8 ± 1.4 vs. 4.9 ± 0.7, p < 0.01), and increased pulmonary vein A-wave velocity (26.7 ± 5.7 vs. 16.8 ± 3.3 cm/s, p = 0.03). Carotid-to-radial artery pulse wave velocity was associated with systolic (R = 0.94, p < 0.01), diastolic (R = 0.85, p = 0.02), and mean blood pressure (R = 0.91, p < 0.01), as well as disease activity by PVAS (R = 0.75, p = 0.05). The PVAS was associated with carotid-to-radial artery pulse wave velocity (R = 0.75, p = 0.05), as well as systolic (R = 0.84, p = 0.02), diastolic (R = 0.82, p = 0.03), and mean blood pressure (R = 0.84, p = 0.02). CONCLUSIONS: Increased arterial stiffness is present in pediatric TA patients and associated with increased blood pressure and TA disease activity. Pediatric TA patients demonstrate altered LV mechanics, LV hypertrophy, and impaired diastolic function.

Health-Related Quality of Life in Children and Young Adults with Marfan Syndrome.

OBJECTIVE: To assess health-related quality of life (HRQOL) in a large multicenter cohort of children and young adults with Marfan syndrome participating in the Pediatric Heart Network Marfan Trial. STUDY DESIGN: The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales were administered to 321 subjects with Marfan syndrome (5-25 years). PedsQL scores were compared with healthy population norms. The impact of treatment arm (atenolol vs losartan), severity of clinical features, and number of patient-reported symptoms on HRQOL was assessed by general linear models. RESULTS: Mean PedsQL scores in children (5-18 years) with Marfan syndrome were lower than healthy population norms for physical (P ≤ .003) and psychosocial (P < .001) domains; mean psychosocial scores for adults (19-25 years) were greater than healthy norms (P < .001). HRQOL across multiple domains correlated inversely with frequency of patient-reported symptoms (r = 0.30-0.38, P < .0001). Those <18 years of age with neurodevelopmental disorders (mainly learning disability, attention-deficit/hyperactivity disorder) had lower mean PedsQL scores (5.5-7.4 lower, P < .04). A multivariable model found age, sex, patient-reported symptoms, and neurodevelopmental disorder to be independent predictors of HRQOL. There were no differences in HRQOL scores by treatment arm, aortic root z score, number of skeletal features, or presence of ectopia lentis. CONCLUSIONS: Children and adolescents with Marfan syndrome were at high risk for impaired HRQOL. Patient-reported symptoms and neurodevelopmental disorder, but not treatment arm or severity of Marfan syndrome-related physical findings, were associated with lower HRQOL.

Physical activity modulates arterial stiffness in children with congenital heart disease: A CHAMPS cohort study.

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.

Predictors of Rapid Aortic Root Dilation and Referral for Aortic Surgery in Marfan Syndrome.

Few data exist regarding predictors of rapid aortic root dilation and referral for aortic surgery in Marfan syndrome (MFS). To identify independent predictors of the rate of aortic root (AoR) dilation and referral for aortic surgery, we investigated the data from the Pediatric Heart Network randomized trial of atenolol versus losartan in young patients with MFS. Data were analyzed from the echocardiograms at 0, 12, 24, and 36 months read in the core laboratory of 608 trial subjects, aged 6 months to 25 years, who met original Ghent criteria and had an AoR z-score (AoRz) > 3. Repeated measures linear and logistic regressions were used to determine multivariable predictors of AoR dilation. Receiver operator characteristic curves were used to determine cut-points in AoR dilation predicting referral for aortic surgery. Multivariable analysis showed rapid AoR dilation as defined by change in AoRz/year > 90th percentile was associated with older age, higher sinotubular junction z-score, and atenolol use (R2 = 0.01) or by change in AoR diameter (AoRd)/year > 90th percentile with higher sinotubular junction z-score and non-white race (R2 = 0.02). Referral for aortic root surgery was associated with higher AoRd, higher ascending aorta z-score, and higher sinotubular junction diameter:ascending aorta diameter ratio (R2 = 0.17). Change in AoRz of 0.72 SD units/year had 42% sensitivity and 92% specificity and change in AoRd of 0.34 cm/year had 38% sensitivity and 95% specificity for predicting referral for aortic surgery. In this cohort of young patients with MFS, no new robust predictors of rapid AoR dilation or referral for aortic root surgery were identified. Further investigation may determine whether generalized proximal aortic dilation and effacement of the sinotubular junction will allow for better risk stratification. Rate of AoR dilation cut-points had high specificity, but low sensitivity for predicting referral for aortic surgery, limiting their clinical use. Clinical Trial Number ClinicalTrials.gov number, NCT00429364.

Influence of Aortic Stiffness on Aortic-Root Growth Rate and Outcome in Patients With the Marfan Syndrome.

The Pediatric Heart Network randomized trial of atenolol versus losartan in the Marfan syndrome showed no treatment differences in the rates of aortic-root growth or clinical outcomes. In this report we present treatment effects on aortic stiffness and determine whether baseline aortic stiffness predicts aortic-root growth and clinical outcomes. Echocardiograms at 0, 6, 12, 24, and 36 months from 608 subjects (6 months to 25 years) who met original Ghent criteria and had a maximum aortic-root z-score (ARz) >3 were centrally reviewed. Stiffness index (SI) and elastic modulus (EM) were calculated for aortic root and ascending aorta. Data were analyzed using multivariable mixed effects modeling and Cox regression. Heart rate-corrected aortic-root SI over 3 years decreased with atenolol but did not change with losartan (-0.298 ± 0.139 vs 0.141 ± 0.139/year, p = 0.01). In the entire cohort, above-median aortic-root SI (>9.1) and EM (>618 mm Hg) predicted a smaller annual decrease in ARz (p ≤0.001). Upper-quartile aortic-root EM (>914 mm Hg) predicted the composite outcome of aortic-root surgery, dissection, or death (hazard ratio 2.17, 95% confidence interval 1.02 to 4.63, p = 0.04). Crude 3-year event rates were 10.4% versus 3.2% for higher versus lower EM groups. In conclusion, atenolol was associated with a decrease in aortic-root SI, whereas losartan was not. Higher baseline aortic-root SI and EM were associated with a smaller decrease in ARz and increased risk for clinical outcomes. These data suggest that noninvasive aortic stiffness measures may identify patients at higher risk of progressive aortic enlargement and adverse clinical outcomes, potentially allowing for closer monitoring and more aggressive therapy.