Genome-wide enhancer-associated tandem repeats are expanded in cardiomyopathy.

BACKGROUND: Cardiomyopathy is a clinically and genetically heterogeneous heart condition that can lead to heart failure and sudden cardiac death in childhood. While it has a strong genetic basis, the genetic aetiology for over 50% of cardiomyopathy cases remains unknown. METHODS: In this study, we analyse the characteristics of tandem repeats from genome sequence data of unrelated individuals diagnosed with cardiomyopathy from Canada and the United Kingdom (n = 1216) and compare them to those found in the general population. We perform burden analysis to identify genomic and epigenomic features that are impacted by rare tandem repeat expansions (TREs), and enrichment analysis to identify functional pathways that are involved in the TRE-associated genes in cardiomyopathy. We use Oxford Nanopore targeted long-read sequencing to validate repeat size and methylation status of one of the most recurrent TREs. We also compare the TRE-associated genes to those that are dysregulated in the heart tissues of individuals with cardiomyopathy. FINDINGS: We demonstrate that tandem repeats that are rarely expanded in the general population are predominantly expanded in cardiomyopathy. We find that rare TREs are disproportionately present in constrained genes near transcriptional start sites, have high GC content, and frequently overlap active enhancer H3K27ac marks, where expansion-related DNA methylation may reduce gene expression. We demonstrate the gene silencing effect of expanded CGG tandem repeats in DIP2B through promoter hypermethylation. We show that the enhancer-associated loci are found in genes that are highly expressed in human cardiomyocytes and are differentially expressed in the left ventricle of the heart in individuals with cardiomyopathy. INTERPRETATION: Our findings highlight the underrecognized contribution of rare tandem repeat expansions to the risk of cardiomyopathy and suggest that rare TREs contribute to ∼4% of cardiomyopathy risk. FUNDING: Government of Ontario (RKCY), The Canadian Institutes of Health Research PJT 175329 (RKCY), The Azrieli Foundation (RKCY), SickKids Catalyst Scholar in Genetics (RKCY), The University of Toronto McLaughlin Centre (RKCY, SM), Ted Rogers Centre for Heart Research (SM), Data Sciences Institute at the University of Toronto (SM), The Canadian Institutes of Health Research PJT 175034 (SM), The Canadian Institutes of Health Research ENP 161429 under the frame of ERA PerMed (SM, RL), Heart and Stroke Foundation of Ontario & Robert M Freedom Chair in Cardiovascular Science (SM), Bitove Family Professorship of Adult Congenital Heart Disease (EO), Canada Foundation for Innovation (SWS, JR), Canada Research Chair (PS), Genome Canada (PS, JR), The Canadian Institutes of Health Research (PS).

Age and Sex Differences in the Genetics of Cardiomyopathy.

Cardiomyopathy has variable penetrance. We analyzed age and sex-related genetic differences in 1,397 cardiomyopathy patients (Ontario, UK) with whole genome sequencing. Pediatric cases (n = 471) harbored more deleterious protein-coding variants in Tier 1 cardiomyopathy genes compared to adults (n = 926) (34.6% vs 25.9% respectively, p = 0.0015), with variant enrichment in constrained coding regions. Pediatric patients had a higher burden of sarcomere and lower burden of channelopathy gene variants compared to adults. Specifically, pediatric patients had more MYH7 and MYL3 variants in hypertrophic cardiomyopathy, and fewer TTN truncating variants in dilated cardiomyopathy. MYH7 variants clustered in the myosin head and neck domains in children. OBSCN was a top mutated gene in adults, enriched for protein-truncating variants. In dilated cardiomyopathy, female patients had a higher burden of z-disc gene variants compared to males. Genetic differences may explain age and sex-related variability in cardiomyopathy penetrance. Genotype-guided predictions of age of onset can inform pre-test genetic counseling. Pediatric cardiomyopathy patients were more likely to be genotype-positive than adults with a higher burden of variants in MYH7, MYL3, TNNT2, VCL. Adults had a higher burden of OBSCN and TTN variants. Females with dilated cardiomyopathy (DCM) had a higher burden of z-disc gene variants compared to males.

Impact of the 2022 American Heart Association pediatric ambulatory blood pressure monitoring statement on the diagnosis of hypertension.

BACKGROUND: The diagnosis of hypertension and hypertension-induced target organ injury by the 2022 American Heart Association (AHA) ambulatory blood pressure threshold as compared with 2014 AHA and 2016 European Society of Hypertension (ESH) thresholds has not been evaluated. METHODS: In a cross-sectional study (n = 291, aged 5-18 years, at a tertiary care outpatient clinic), we compared 2022 AHA with 2014 AHA and ESH thresholds (revised with 2018 adult ESH thresholds where applicable) to diagnose ambulatory hypertension (AH), and detect ambulatory arterial stiffness index (AASI) and left ventricular target organ injury (LVTOI). RESULTS: The 2022 AHA threshold diagnosed significantly more AH (53%) than the 2014 AHA (42%, p < 0.01) and ESH (36%, p < 0.001) thresholds. The 2022 AHA threshold demonstrated only a moderate agreement with the 2014 AHA (kappa (k) = 0.77) and ESH (k = 0.66) thresholds to diagnose AH. Adjusted logistic regression analysis found that only the 2022 AHA threshold predicted elevated AASI significantly (odds ratio 2.40, 95% CI 1.09, 5.25, p = 0.02; AUC 0.61, p < 0.01). In those with elevated AASI, more participants had AH by the 2022 AHA threshold (72%) than the 2014 AHA (46%, p = 0.02) and ESH (48%, p = 0.03) thresholds. AH defined by the 2022 AHA threshold continued to maintain higher odds, larger AUC, and higher sensitivity to identify LVTOI than the 2014 AHA and ESH thresholds; however, the difference did not reach a statistically significant level. CONCLUSIONS: AH defined by the 2022 AHA threshold diagnoses more children with hypertension and identifies more children with hypertension-induced target organ injury than the 2014 AHA and ESH thresholds. A higher resolution version of the Graphical abstract is available as Supplementary information.

Ambulatory hypertension diagnosed by 24-h mean ambulatory versus day and night ambulatory blood pressure thresholds in children: a cross-sectional study.

BACKGROUND: The agreement between the commonly used ambulatory blood pressure (ABP) thresholds to diagnose ambulatory hypertension in children (patient's 24-h mean ABP classified by 24-h 95th ABP percentile threshold, American Heart Association [AHA] threshold, or patient's day and night mean ABP classified by day-night 95th ABP percentile thresholds) is not known. We evaluated the agreement among 24-h ABP threshold, AHA threshold, and day-night ABP thresholds to diagnose ambulatory hypertension, white coat hypertension (WCH) and masked hypertension (MH). METHODS: In a cross-sectional study design, we analyzed ABP recordings from 450 participants with suspected hypertension from a tertiary care outpatient hypertension clinic. The American Academy of Pediatrics thresholds were used to diagnose office hypertension. RESULTS: The 24-h ABP threshold and day-night ABP thresholds classified 19% ABP (95% confidence interval [CI], 0.15-0.23) differently into ambulatory normotension/hypertension (kappa [κ], 0.58; 95% CI, 0.51-0.66). Ambulatory hypertension diagnosed by 24-h ABP threshold in 27% participants (95% CI, 0.22-0.32) was significantly lower than that by day-night ABP thresholds in 44% participants (95% CI, 0.37-0.50; P < 0.001). The AHA threshold had a stronger agreement with 24-h ABP threshold than with day-night ABP thresholds for classifying ABP into ambulatory normotension/hypertension (k 0.94, 95% CI 0.91-0.98 vs. k 0.59, 95% CI 0.52-0.66). The diagnosis of ambulatory hypertension by the AHA threshold (26%; 95% CI, 0.21-0.31) was closer to that by 24-h ABP threshold (27%, P = 0.73) than by day-night ABP thresholds (44%, P < 0.001). Similar agreement pattern persisted among these ABP thresholds for diagnosing WCH and MH. CONCLUSIONS: The 24-h ABP threshold classifies a lower proportion of ABP as ambulatory hypertension than day-night ABP thresholds. The AHA threshold exhibits a stronger agreement with 24-h ABP than with day-night ABP thresholds for diagnosing ambulatory hypertension, WCH and MH. Our findings are relevant for a consistent interpretation of hypertension by these ABP thresholds in clinical practice.

Diagnosis of hypertension: Ambulatory pediatric American Heart Association/European Society of Hypertension versus blood pressure load thresholds.

The agreement between the traditionally-used ambulatory blood pressure (ABP)-load thresholds in children and recently-recommended pediatric American Heart Association (AHA)/European Society of Hypertension (ESH) ABP thresholds for diagnosing ambulatory hypertension (AH), white coat hypertension (WCH), and masked hypertension (MH) has not been evaluated. In this cross-sectional study on 450 outpatient participants, the authors evaluated the agreement between previously used ABP-load 25%, 30%, 40%, 50% thresholds and the AHA/ESH thresholds for diagnosing AH, WCH, and MH. The American Academy of Pediatrics thresholds were used to diagnose office hypertension. The AHA threshold diagnosed ambulatory normotension/hypertension closest to ABP load 50% in 88% (95% CI 0.79, 0.96) participants (k 0.67, 95% CI 0.59, 0.75) and the ESH threshold diagnosed ambulatory normotension/hypertension closest to ABP load 40% in 86% (95% CI 0.77, 0.94) participants (k 0.66, 95% CI 0.59, 0.74). In contrast, the AHA/ESH thresholds had a relatively weaker agreement with ABP load 25%/30%. Therefore, the diagnosis of AH was closest between the AHA threshold and ABP load 50% (difference 3%, 95% CI -2.6%, 8.6%, p = .29) and between the ESH threshold and ABP load 40% (difference 4%, 95% CI -2.1%, 10.1%, p = .19) than between the AHA/ESH and ABP load 25%/30% thresholds. A similar agreement pattern persisted between the AHA/ESH and various ABP load thresholds for diagnosing WCH and MH. The AHA and ESH thresholds diagnosed AH, WCH, and MH closest to ABP load 40%/50% than ABP load 25%/30%. Future outcome-based studies are needed to guide the optimal use of these ABP thresholds in clinical practice.

Symptomatic mosaicism for a novel FBN1 splice site variant in a parent causing inherited neonatal Marfan syndrome.

Neonatal Marfan syndrome is a severe, early onset presentation of pathogenic variants in FBN1. Because of the significant cardiac involvement and early mortality, nearly all reported cases have been de novo, and the disorder has not been documented to be inherited from a symptomatic parent. Here, we present a female infant with neonatal Marfan syndrome who was born to a father with Marfan syndrome. Prior to the birth of his daughter, the father had been found to have an FBN1 missense variant of uncertain clinical significance. Initial familial variant testing of the infant did not reveal the same missense variant, but Sanger sequencing of FBN1 subsequently identified a pathogenic splice site variant. The father was then found to have 10%-20% mosaicism for the same splice site variant.

Diagnosis of Pediatric Hypertension: European Society of Hypertension-Recommended 24-Hour vs. 24-Hour-Day-Night Ambulatory Blood Pressure Thresholds.

BACKGROUND: The impact of diagnosing pediatric hypertension based on all three-24-hour, day and night ambulatory blood pressure (ABP) thresholds (combined ABP threshold) vs. conventionally used 24-hour ABP threshold is not known. METHODS: In this cross-sectional, retrospective study from a tertiary care outpatient clinic, we evaluated the diagnosis of hypertension based on the 24-hour European Society of Hypertension (ESH) and combined ESH ABP thresholds in untreated children with essential hypertension. The American Academy of Pediatrics (AAP) and Fourth Report thresholds were used to classify office blood pressure (OBP). RESULTS: In 159 children, aged 5-18 years, the 24-hour ESH and combined ESH thresholds classified 82% (95th confidence interval (CI) 0.68, 0.97) ABP similarly with the area under the curve (AUC) of 0.86 (95th CI 0.80, 0.91). However, the AUC of the 2 ABP thresholds was significantly higher in the participants with office hypertension than office normotension, with OBP classified by the AAP (AUC 0.93, 95th CI 0.84, 0.98 vs. 0.80, 95th CI 0.71, 0.88) or Fourth Report (AUC 0.93, 95th CI 0.83, 0.98 vs. 0.81, 95th CI 0.73, 0.88) threshold. With OBP classified by the either OBP threshold, the combined ESH threshold diagnosed significantly more masked hypertension (MH) (difference 15%, 95th CI 4.9, 24.7; P = 0.00); however, the diagnosis of white coat hypertension (WCH) by the 2 ABP thresholds did not differ significantly (difference 4%, 95th CI 1.8, 10; P = 0.16). CONCLUSIONS: In children with essential hypertension, the 24-hour and combined ESH thresholds have a stronger agreement for diagnosing WCH than MH.

Are Active Video Games Effective at Eliciting Moderate-Intensity Physical Activity in Children, and Do They Enjoy Playing Them?

BACKGROUND: Despite current physical activity (PA) guidelines, children spend an average of 1-3 hours/day playing video games. Some video games offer physically active components as part of gameplay. We sought to determine if these active video games (AVGs) can elicit at least moderate PA in children, identify game elements important for PA, and determine if they are fun to play. METHODS: Twenty children aged 8 to 16 years underwent cardiopulmonary exercise testing to determine their heart rate (HR) at ventilatory threshold. Participants played 2 different AVGs, and the gaming time that each participant's HR was above the HR thresholds for moderate and vigorous PA was determined. Gameplay elements that supported or inhibited active gameplay were also identified. Participants also completed questionnaires on physical activity, game engagement, and game experience. RESULTS: The Dance Central Spotlight and Kung-Fu for Kinect AVGs produced at least moderate PA, for a mean of 54.3% ± 29.5% and 87.8% ± 21.8% of gameplay time, respectively. Full-body movements, player autonomy, and self-efficacy were observed to be important elements of good AVG design. Although participants enjoyed these AVGs, they still preferred their favorite games (game engagement score of 1.82 ± 0.67 vs 0.95 ± 0.70 [Dance Central Spotlight] and 1.39 ± 0.37 [Kung Fu for Kinect]). CONCLUSIONS: AVGs can provide at least moderate PA and are enjoyable to play, but most popular video games do not incorporate active components. The implementation of government policies and a rating system concerning PA in video games may help address the widespread sedentary lifestyle of children.

CONTEXTE: Malgré les lignes directrices actuelles sur l'activité physique, les enfants passent en moyenne entre une et trois heures par jour à jouer à des jeux vidéo. Comme la jouabilité de certains jeux vidéo comporte des activités physiques, nous avons cherché à déterminer si les jeux vidéo dynamiques (JVD) pouvaient permettre aux enfants d'atteindre un degré d'activité physique au moins modéré, à cerner les éléments de jeu qui sont importants pour l'activité physique et à déterminer si ces jeux étaient amusants. MÉTHODOLOGIE: Nous avons soumis 20 enfants de 8 à 16 ans à des épreuves d'effort cardiopulmonaire pour déterminer leur fréquence cardiaque (FC) au seuil ventilatoire. Les participants ont joué à deux JVD différents et nous avons déterminé la durée pendant laquelle la FC de chaque participant était supérieure aux seuils de FC correspondant à une activité physique modérée et intense. Nous avons aussi cerné les éléments de la jouabilité qui favorisaient ou empêchaient la jouabilité dynamique. Les participants ont en outre rempli des questionnaires sur l'activité physique, l'intérêt des jeux et l'expérience de jeu. RÉSULTATS: Deux JVD, Dance Central Spotlight et Kung-Fu for Kinect, ont produit un degré d'activité physique au moins modéré pendant respectivement 54,3 % ± 29,5 % et 87,8 % ± 21,8 % de la durée de jouabilité. Nous avons constaté que les mouvements du corps entier, l'autonomie des joueurs et l'auto-efficacité étaient des éléments importants de la bonne conception d'un JVD. Les participants ont aimé ces JVD, mais ils préféraient toujours leurs jeux favoris (score d'intérêt à l'égard du jeu de 1,82 ± 0,67 vs 0,95 ± 0,70 [Dance Central Spotlight] et 1,39 ± 0,37 [Kung Fu for Kinect]). CONCLUSIONS: Les JVD semblent produire un degré d'activité physique au moins modéré et sont amusants, mais la plupart des jeux vidéo populaires ne font pas faire d'activité physique. La mise en œuvre de politiques gouvernementales et l'adoption d'un système de cotation concernant l'activité physique associée aux jeux vidéo pourraient permettre de s'attaquer au problème répandu que représente la sédentarité chez les enfants.

Comparative Analysis of American Heart Association and European Society of Hypertension Ambulatory Blood Pressure Thresholds for Diagnosing Hypertension in Children.

INTRODUCTION: The influence of using 24-hour ambulatory blood pressure (ABP) thresholds recommended by the American Heart Association (AHA) (24-hour mean ABP >95th percentile and ABP load >25%) or the European Society of Hypertension (ESH) (mean 24-hour ABP >95th percentile or >130/80 mm Hg if mean ABP 95th percentile exceeds 130/80 mm Hg) on the diagnosis of pediatric hypertension has been understudied. METHODS: In a cross-sectional, retrospective study of 159 children from a tertiary care outpatient clinic, we classified office blood pressure (OBP) as normotension or hypertension based on the OBP thresholds recommended by the American Academy of Pediatrics (AAP) and the fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents (herein referred to as the fourth report) by the National High Blood Pressure Educational Program Working Group on High Blood Pressure in Children and Adolescents separately. Thereafter, we evaluated the agreement between the ambulatory AHA and ESH thresholds for diagnosing normotension, white-coat hypertension (WCH), masked hypertension (MH), and hypertension based on the patient's ABP and OBP hypertension pattern. RESULTS: With office hypertension as per the AAP thresholds, the AHA and ESH thresholds classified 85% of subjects similarly into normotension, WCH, MH, and hypertension (κ = 0.78; 95% CI, 0.67-0.89). The agreement between the AHA and ESH thresholds did not change when OBP was reclassified by the fourth-report OBP thresholds (κ = 0.77; 95% CI, 0.65-0.88). With OBP classified by either AAP or fourth-report thresholds, the ESH thresholds diagnosed 6% to 7% more children as hypertensive, whereas the AHA threshold classified 11% more children as normotensive. CONCLUSION: The AHA and ESH thresholds have good agreement in classifying OBP. However, the ESH threshold classifies more OBP as hypertensive and the AHA threshold classifies more OBP as normotensive.

Improving remote lifestyle intervention studies in children: Participant and caregiver feedback of the smart heart study.

OBJECTIVES: We sought to describe and analyze the quantitative and qualitative feedback obtained from participants and their caregivers of the Smart Heart study, a successful 12-month lifestyle intervention for children with overweight or obesity and congenital heart disease that provided remote lifestyle counseling, to improve future lifestyle interventions in children. METHODS: Thirty-six participants and caregivers were polled using a standard program evaluation questionnaire at the end of the intervention. Feedback was compiled into themes, and facilitators and barriers to program success were identified. RESULTS: There was a high level of satisfaction with the intervention and staff interactions as well as a low perceived burden of participation. There were also specific concerns, including mixed impressions regarding technology usage and a less impressive indication of actual impactful behavior change. CONCLUSIONS: The study identified five themes, and corresponding facilitators and barriers to participant compliance, from the Smart Heart intervention feedback and offered suggestions for improving future lifestyle behavioral intervention study designs in children. PRACTICE IMPLICATIONS: Remote smartphone counseling is effective and efficient. It is recommended that the counseling messages are specific, the counseling schedule is patient-centric, patient burden is limited, methods with immediate patient feedback are used and family is included when feasible.

Return of genetic and genomic research findings: experience of a pediatric biorepository.

BACKGROUND: Assess process, uptake, validity and resource needs for return of actionable research findings to biobank participants. METHODS: Participants were prospectively enrolled in a multicenter biorepository of childhood onset heart disease. Clinically actionable research findings were reviewed by a Return of Research Results Committee (RRR) and returned to the physician or disclosed directly to the participant through a research genetic counselor. Action taken following receipt of this information was reviewed. RESULTS: Genetic data was generated in 1963 of 7408 participants. Fifty-nine new findings were presented to the RRR committee; 20 (34%) were deemed reportable. Twelve were returned to the physician, of which 7 were disclosed to participants (median time to disclosure, 192 days). Seven findings were returned to the research genetic counselor; all have been disclosed (median time to disclosure, 19 days). Twelve families (86%) opted for referral to clinical genetics after disclosure of findings; 7 results have been validated, 5 results are pending. Average cost of return and disclosure per reportable finding incurred by the research program was $750 when utilizing a research genetic counselor; clinical costs associated with return were not included. CONCLUSIONS: Return of actionable research findings was faster if disclosed directly to the participant by a research genetic counselor. There was a high acceptability amongst participants for receiving the findings, for referral to clinical genetics, and for clinical validation of research findings, with all referred cases being clinically confirmed.

Arterial Hypertension and Unusual Ascending Aortic Dilatation in a Neonate With Acute Kidney Injury: Mechanistic Computer Modeling.

BACKGROUND: Neonatal asphyxia caused kidney injury and severe hypertension in a newborn. An unusually dilatated ascending aorta developed. Dialysis and pharmacological treatment led to partial recovery of the ascending aortic diameters. It was hypothesized that the aortic dilatation may be associated with aortic stiffening, peripheral resistance, and cardiovascular changes. Mathematical modeling was used to better understand the potential causes of the hypertension, and to confirm our clinical treatment within the confines of the model's capabilities. METHODS: The patient's systolic arterial blood pressure showed hypertension. Echocardiographic exams showed ascending aorta dilatation during hypertension, which partially normalized upon antihypertensive treatment. To explore the underlying mechanisms of the aortic dilatation and hypertension, an existing lumped parameter hemodynamics model was deployed. Hypertension was simulated using realistic literature informed parameter values. It was also simulated using large parameter perturbations to demonstrate effects. Simulations were designed to permit examination of causal mechanisms. The hypertension inducing effects of aortic stiffnesses, vascular resistances, and cardiac hypertrophy on blood flow and pressure were simulated. Sensitivity analysis was used to stratify causes. RESULTS: In agreement with our clinical diagnosis, the model showed that an increase of aortic stiffness followed by augmentation of peripheral resistance are the prime causes of realistic hypertension. Increased left ventricular elastance may also cause hypertension. Ascending aortic pressure and flow increased in the simultaneous presence of left ventricle hypertrophy and augmented small vessel resistance, which indicate a plausible condition for ascending aorta dilatation. In case of realistic hypertension, sensitivity analysis showed that the treatment of both the large vessel stiffness and small vessel resistance are more important in comparison to cardiac hypertrophy. CONCLUSION AND DISCUSSION: Large vessel stiffness was found to be the prime factor in arterial hypertension, which confirmed the clinical treatment. Treatment of cardiac hypertrophy appears to provide significant benefit but may be secondary to treatment of large vessel stiffness. The quantitative grading of pathophysiological mechanisms provided by the modeling may contribute to treatment recommendations. The model was limited due to a lack of data suitable to permit model identification.

An unusual case of pericardial effusion.

We report a case of a 13-year-old male with trisomy 21 in Southwestern Ontario, Canada, who presented with bilateral pneumonia, pericardial effusion, and peripheral oedema. The pericardial effusion did not respond to standard treatment options. Evaluation revealed severe dietary restriction, consistent with kwashiorkor. Hospital course was complicated by severe hypoalbuminaemia, hypocalcaemia, hypomagnesaemia, and hypophosphataemia. The pericardial effusion and other findings resolved gradually upon slow introduction of a well-balanced diet and adequate caloric and protein intake. Kwashiorkor is an unusual cause of pericardial effusion and can be overlooked especially in developed countries. It is a type of protein-calorie malnutrition often seen in children of impoverished countries and famine. It is a result of insufficient protein intake in the context of adequate caloric intake. Pericardial effusion not responding to usual treatment is a challenge, and other aetiologies must be considered. Malnutrition is often underdiagnosed or misdiagnosed in developed countries with devastating outcomes if unrecognised. This makes it imperative to consider this diagnosis, recognise potential risk factors, and be prepared to accurately assess overall nutritional status.

Increased blood pressure is associated with increased carotid artery intima-media thickness in children with repaired coarctation of the aorta.

OBJECTIVES: The intima-media thickness of the common carotid artery (cIMT) is a good noninvasive surrogate marker for cardiovascular disease. Regular cIMT monitoring in children with congenital heart disease has great potential. We sought to determine which anthropomorphic and haemodynamic variables were significantly associated with the cIMT in paediatric patients with obesity and children with repaired coarctation of the aorta (CoA). METHODS: We measured the cIMT in 143 children aged 5 to less than 18 years including normal weight controls (n = 44), children with overweight/obesity (n = 73) and children with repaired CoA (n = 26). cIMT was compared and the association between the cIMT and patient characteristics, including obesity and blood pressure (BP), was investigated. RESULTS: BMI z score, sex and the presence of CoA were significant independent predictors of cIMT. The cIMT was significantly greater in children with overweight/obesity (0.53 ±â€Š0.06 mm) relative to normal weight controls (0.51 ±â€Š0.04 mm), as well as in CoA patients with abnormally high BP (0.57 ±â€Š0.08 mm) versus CoA patients with normal BP (0.52 ±â€Š0.05 mm) and controls (0.51 ±â€Š0.04 mm). CoA patients with normal BP did not have significantly increased cIMT. CONCLUSION: cIMT was positively associated with BMI z score, male sex and CoA repair in children. The increased cIMT in children with repaired CoA was because of those with abnormally high BP, which was masked in clinic for most of these patients. These findings warrant further investigations into the cIMT and other atherosclerotic risk factors to determine their potential clinical impact in these highly susceptible patients.

Lack of access to paediatric cardiology services in the public health system in four major urban centres in Perú.

For one-third of the Peruvian population living in large cities outside the capital city Lima, there is no access to paediatric cardiology services provided by the public health care system. Children with suspected CHD living in these areas are referred to the adult cardiologist working at the regional hospitals for care and treatment. This is a consequence of the universal health care system and the heavily skewed distribution of the health care workforce towards the capital city of Lima. This imbalance has resulted in a severe shortage of paediatric cardiologists practicing outside of Lima and the adult cardiologists that remain are left to make up for this deficit.To gain a better understanding of the current model of care for children with suspected CHD within the public health care system in Peru, we surveyed adult cardiologists from four major urban centres that serve one-third of the Peruvian population outside of Lima. We determined that adult cardiologists spend a significant amount of time treating children, but lack the specialised training and equipment to provide model care. The cardiologists indicated that receiving additional training and appropriate equipment would help enable them to provide proper care for these children.

Non-invasive measurement of cardiac output in children with repaired coarctation of the aorta using electrical cardiometry compared to transthoracic Doppler echocardiography.

OBJECTIVE: To evaluate the equivalence of the ICON® electrical cardiometry (EC) haemodynamic monitor to measure cardiac output (CO) relative to transthoracic Doppler echocardiography (TTE) in paediatric patients with repaired coarctation of the aorta (CoA). APPROACH: A group of n = 28 CoA patients and n = 27 matched controls were enrolled. EC and TTE were performed synchronously on each participant and CO measurements compared using linear regression and Bland-Altman analysis. The CoA group was further subdivided into two groups, with n = 10 and without n = 18 increased left ventricular outflow tract velocity (iLVOTv) for comparison. MAIN RESULTS: CO measurements from EC and TTE in controls showed a strong correlation (R = 0.80, p < 0.001) and an acceptable percentage error (PE) of 28.1%. However, combining CoA and control groups revealed a moderate correlation (R = 0.57, p < 0.001) and a poor PE (44.2%). We suspected that the CO in a subset of CoA participants with iLVOTv was overestimated by TTE. Excluding the iLVOTv CoA participants improved the correlation (R = 0.77, p < 0.001) and resulted in an acceptable PE of 31.2%. SIGNIFICANCE: CO measurements in paediatric CoA patients in the absence of iLVOTv are clinically equivalent between EC and TTE. The presence of iLVOTv may impact the accuracy of CO measurement by TTE, but not EC.

Does obesity affect the non-invasive measurement of cardiac output performed by electrical cardiometry in children and adolescents?

Electrical cardiometry (EC) is a non-invasive and inexpensive method for hemodynamic assessment and monitoring. However, its feasibility for widespread clinical use, especially for the obese population, has yet to be determined. In this study, we evaluated the agreement and reliability of EC compared to transthoracic Doppler echocardiography (TTE) in normal, overweight, and obese children and adolescents. We measured stroke volume (SV) and cardiac output (CO) of 131 participants using EC and TTE simultaneously. We further divided these participants according to BMI percentiles for subanalyses: <85% normal weight (n = 41), between 85 and 95% overweight (n = 7), and >95% obese (n = 83). Due to small sample size of the overweight group, we combined overweight and obese groups (OW+OB) with no significant change in results (SV and CO) before and after combining groups. There were strong correlations between EC and TTE measurements of SV (r = 0.869 and r = 0.846; p < 0.0001) and CO (r = 0.831 and r = 0.815; p < 0.0001) in normal and OW+OB groups, respectively. Bias and percentage error for CO measurements were 0.240 and 29.7%, and 0.042 and 29.5% in the normal and OW+OB groups, respectively. Indexed values for SV were lower in the OW+OB group than in the normal weight group when measured by EC (p < 0.0001) but no differences were seen when measured by TTE (p = 0.096). In all weight groups, there were strong correlations and good agreement between EC and TTE. However, EC may underestimate hemodynamic measurements in obese participants due to fat tissue.

The use of smartphones to influence lifestyle changes in overweight and obese youth with congenital heart disease: a single-arm study: Pilot and feasibility study protocol: Smart Heart Trial.

BACKGROUND: Both obesity and congenital heart disease (CHD) are risk factors for the long-term cardiovascular health of children and adolescents. The addition of smart mobile technology to conventional lifestyle counseling for weight management offers great potential to appeal to technologically literate youth and can address a large geographical area with minimal burden to participants. This pilot study seeks to examine the influence of a 1-year lifestyle intervention on nutrition and physical activity-related health outcomes in overweight or obese children and adolescents with CHD. METHODS: This is a pilot and feasibility study which utilizes a single-arm, prospective design with a goal to recruit 40 overweight and obese patients. The feasibility metrics will evaluate the integrity of the study protocol, data collection and questionnaires, recruitment and consent, and acceptability of the intervention protocol and primary outcome measures. The primary clinical outcome metrics are anthropometry, body composition, and cardiorespiratory exercise capacity. The secondary clinical metrics include quality of life, nutrition and physical activity behavior, lung and muscle function, and cardio-metabolic risk factors. Outcomes are assessed at baseline, 6 months, and 1 year. To date, a total of 36 children and youth (11 girls), aged 7-17 years (mean = 14.4 years), have commenced the intervention. Recruitment for the study was initiated in June 2012 and is currently ongoing. DISCUSSION: The information provided in this paper is intended to help researchers and health professionals with the development and evaluation of similar lifestyle intervention programs. Since the application of smartphones to pediatric cardiac health and obesity management is a novel approach, and continued research in this area is warranted, this paper may serve as a foundation for further exploration of this health frontier and inform the development of a broader strategy for obesity management in pediatric cardiology. TRIAL REGISTRATION: This pilot study was retrospectively registered at the www.ClinicalTrials.gov registry as NCT02980393 in November 2016, with the study commencing in May 2012. Study protocol version 15OCT2014.

Indomethacin induced and prostaglandin relieved coarctation of the aorta in right aortic arch with left arterial duct: a case report.

We describe the case of an infant with DiGeorge syndrome born with a right aortic arch and left arterial duct. Despite the remote location of the right aortic arch from the left arterial duct, he developed coarctation of the aorta during treatment with indomethacin. This was relieved by prostaglandin treatment. This case highlights the fact that, even in the absence of an arterial duct, ductal tissue can still be present in the aorta, and cause coarctation when exposed to indomethacin. We also demonstrate the utility of prostaglandin for relief of this type of obstruction.