Advancing Wearable Biosensors for Congenital Heart Disease: Patient and Clinician Perspectives: A Science Advisory From the American Heart Association.

Wearable biosensors (wearables) enable continual, noninvasive physiologic and behavioral monitoring at home for those with pediatric or congenital heart disease. Wearables allow patients to access their personal data and monitor their health. Despite substantial technologic advances in recent years, issues with hardware design, data analysis, and integration into the clinical workflow prevent wearables from reaching their potential in high-risk congenital heart disease populations. This science advisory reviews the use of wearables in patients with congenital heart disease, how to improve these technologies for clinicians and patients, and ethical and regulatory considerations. Challenges related to the use of wearables are common to every clinical setting, but specific topics for consideration in congenital heart disease are highlighted.

Variation in paediatric 24-h ambulatory blood pressure monitoring interpretation by Canadian and UK physicians.

Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is widely accepted as a more accurate method for measurement of blood pressure (BP) compared to a single office-based measurement of BP. However, it is unclear how physicians interpret ABPM and make management decisions. This study's goal is to investigate variation in ABPM interpretation among paediatric nephrologists (Canada and UK) and paediatric cardiologists (Canada only) via an online survey. The survey content included baseline demographics, questions on the use and indications for ABPM, interpretation of results, and subsequent management decisions in various clinical scenarios. The survey was sent to 196 Canadian physicians, with 69 (35.2%) total responses. Thirty-five UK clinicians also completed the survey. Most respondents were >44 years old, were in practice for at least 11 years, and were university-based. There were substantial differences among clinicians in ABPM interpretation for isolated systolic, diastolic, and night-time hypertension. For example, only 53.1% of physicians would initiate or modify treatment in those with diastolic HTN in CKD. Further, even for the same abnormal ABPM parameter, the decision to start or alter treatment was influenced by the underlying medical condition. There is significant variation in clinical practice among physicians for interpretation and management of hypertension when using ABPM. Differences in guidelines among various jurisdictions, as well as knowledge gaps in the research on which guidelines are based, create ambiguity regarding ABPM interpretation and management decisions. A more protocolized approach and further insight into the reasoning behind the variation in physicians' interpretation may help to standardise practice.

The Detection, Evaluation, and Management of Dyslipidemia in Children and Adolescents: A Canadian Cardiovascular Society/Canadian Pediatric Cardiology Association Clinical Practice Update.

Atherosclerosis begins in youth and is directly linked with the presence and severity of cardiovascular risk factors, including dyslipidemia. Thus, the timely identification and management of dyslipidemia in childhood might slow atherosclerotic progression and decrease the risk of cardiovascular disease in adulthood. This is particularly true for children with genetic disorders resulting in marked dyslipidemia, including familial hypercholesterolemia, which remains frequently undiagnosed. Universal and cascade screening strategies can effectively identify cases of pediatric dyslipidemia. In the clinical evaluation of children with dyslipidemia, evaluating for secondary causes of dyslipidemia, including medications and systemic disorders is essential. The first line therapy generally centres around lifestyle modifications, with dietary changes specific to the dyslipidemia phenotype. Indications for medication depend on the severity of dyslipidemia and an individualized assessment of cardiovascular risk. Despite an expanding evidence base supporting the detection and timely management of pediatric dyslipidemia, numerous knowledge gaps remain, including a sufficient evidence base to support more widespread screening, thresholds for initiation of pharmacotherapy, and treatment targets. Further studies on the most appropriate age for statin initiation and long-term safety studies of statin use in youth are also required. The most pressing matter, however, is the development of knowledge translation strategies to improve the screening and detection of lipid disorders in Canadian youth.

Hepatic and Renal Consequences of Single-Ventricle Physiology Palliated With the Fontan Operation.

Over time, long-term survival has dramatically increased for patients with complex congenital heart disease who undergo the Fontan operation. With this increased survival, it has become apparent that such a circulation has important consequences for other organ systems, particularly the liver and kidney. The adverse milieu created by chronic venous hypertension, low cardiac output, and an inflammatory state contribute to the pathologic changes observed in the liver and kidneys over the long term in Fontan patients. The clinical importance of these hepatic and renal comorbidities have only recently begun to be recognized in the context of increasing life expectancy in this population. The objectives of this review are to provide an overview of the pathophysiology of the Fontan circulation and how liver and kidney disease evolve in this setting; to summarize the current evidence base as it relates to the diagnostic approach to liver and kidney disease in Fontan patients; and to discuss the therapeutic approaches to Fontan- associated liver and kidney disease. Given that this is a very active area of research in congenital heart disease, we have identified knowledge gaps and priority research areas to improve the care of Fontan patients. These include establishing the optimal diagnostic tests to detect and track liver and kidney disease change over time, determining which treatable risk factors contribute to the development of liver and kidney disease, and evaluating therapies to prevent or slow progression of liver and kidney disease.

Patterns of Early Coronary Artery Changes in Pediatric Heart Transplant Recipients Detected Using Optical Coherence Tomography.

BACKGROUND: Cardiac allograft vasculopathy, the leading cause of graft failure in pediatric heart transplant recipients, is characterized by diffuse and concentric coronary intimal thickening. Early treatment yields better outcomes. While coronary angiography is the standard for cardiac allograft vasculopathy screening and diagnosis, it only identifies luminal narrowing, which occurs in more severe disease. Coronary optical coherence tomography (OCT) is a high-definition intravascular imaging modality that may offer earlier diagnosis. We used OCT to investigate coronary intimal thickening in pediatric transplant recipients and examined its (1) location (ie, vessel type and location) and (2) nature (ie, characteristics of cross-sectional and longitudinal thickening). METHODS: Sites collected coronary angiography and OCT data from participants (N=258 vessel segments from 73 individuals; median age: 11.5 years [8.4-15.3]; 55% male). Images were collected from the left anterior descending, left circumflex, and right coronary arteries, and location (ie, proximal, middle, and distal) were classified using coronary angiography. RESULTS: OCT identified 32 vessel segments meeting criteria for significant thickening, 88% of which were angiographically silent. Longitudinal thickening was segmental rather than global in 88%, and cross-sectional thickening was 48% eccentric and 52% concentric. Intimal thickening prevalence and severity measures did not consistently differ between coronary artery type (P=1.000) or location (P=0.248) but increased with time since transplant and age at transplant and OCT procedure. CONCLUSIONS: In pediatric transplant recipients, we observed a surprisingly high prevalence of segmental and eccentric intimal thickening. Insights from intravascular imaging suggest these patterns of coronary vascular changes may precede overt cardiac allograft vasculopathy. Identifying early changes may offer opportunity for enhanced surveillance and earlier intervention.

A Survey of Immunization Practices in Patients With Congenital Heart Disease.

Background: Congenital heart disease, the most common congenital anomaly, often presents in neonates. Because of perceived risks, health care providers may consider deferring immunizations in this population. We sought to understand the perceived risk of immunizations in those providing health care to children with particular heart conditions. Methods: A survey, which included 6 hypothetical scenarios assessing immunization recommendations, was distributed internationally to relevant health care providers, and responses were compared between the different scenarios. Results: Majority of responses (n = 142) were from paediatric cardiologists (n = 98; 69%) and nurse practitioners (n = 27; 19%) located in the United States (n = 77; 54%) or Canada (n = 53; 37%) working in academic teaching hospitals (n = 133; 93.7%). Most favoured vaccinations (n = 107; 75.4%) and less likely to proceed with the first immunization in infants with structural heart disease compared with channelopathy (risk ratio: 0.80, confidence interval: 0.73-0.87; P < 0.001). Only 40% would proceed with immunization as normal in an infant with manifest Brugada type I electrocardiogram. Special precautions after the immunization included longer duration of observation (19%) and administering prophylactic antipyretic medication (92%). Conclusions: Respondents were 20% more likely to defer immunizations in the presence of treatable structural heart disease as compared with channelopathy despite the lack of evidence supporting deferring immunizations in children with structural heart disease. Most were cautious in their response to the scenario involving Brugada syndrome, indicating awareness of the risk of haemodynamic instability in the event of a fever. The majority of respondents still strongly recommend immunizations in this population as the benefits outweigh the potential for adverse events.

Contexte: La cardiopathie congénitale ­ l'anomalie congénitale la plus courante ­ est souvent observée chez les nouveau-nés. En raison des risques perçus, les dispensateurs de soins de santé peuvent parfois envisager de reporter la vaccination chez ces patients. Notre but était de comprendre le risque perçu à l'égard de la vaccination par les dispensateurs de soins de santé traitant des enfants atteints de certaines cardiopathies. Méthodologie: Un sondage comprenant six scénarios hypothétiques visant à évaluer les recommandations de vaccination a été distribué à des dispensateurs de soins de santé pertinents dans différents pays, et leurs réponses pour les différents scénarios ont été comparées. Résultats: La majorité des répondants (n = 142) étaient des cardiologues pédiatriques (n = 98; 69 %) ou des infirmières praticiennes (n = 27; 19 %) des États-Unis (n = 77; 54 %) ou du Canada (n = 53; 37 %) travaillant dans des hôpitaux universitaires (n = 133; 93,7 %). La plupart d'entre eux étaient en faveur de la vaccination (n = 107; 75,4 %), bien que moins enclins à administrer un premier vaccin à des nourrissons présentant une cardiopathie structurelle comparativement à une canalopathie (rapport des risques : 0,80, intervalle de confiance : 0,73-0,87; p < 0,001). Or, seulement 40 % d'entre eux vaccineraient de façon normale un nourrisson présentant un syndrome de Brugada de type 1 à l'ECG. Les précautions particulières prises après la vaccination comprenaient une période d'observation plus longue (19 %) et l'administration d'un antipyrétique à des fins prophylactiques (92 %). Conclusions: À la lumière des réponses obtenues, la probabilité de report de la vaccination était 20 % plus élevée en présence d'une cardiopathie structurelle traitable comparativement à une canalopathie, malgré le manque de données probantes justifiant ce report chez les enfants atteints d'une cardiopathie structurelle. La plupart des répondants ont répondu de façon prudente au scénario du syndrome de Brugada en évoquant un risque d'instabilité hémodynamique en cas de fièvre. La majorité d'entre eux recommandent quand même fortement la vaccination chez ces patients, car les bienfaits escomptés l'emportent sur les risques d'effets indésirables.

Reduced Physical Activity During COVID-19 in Children With Congenital Heart Disease: A Longitudinal Analysis.

Background: Coronavirus disease 2019 (COVID-19) was associated with a reduction in physical activity in children with congenital heart disease (CHD) in early 2020. Given the increased cardiovascular risk of this population, optimizing cardiovascular health behaviour is important. The aim of the study is to determine how the ongoing COVID-19 pandemic has impacted longitudinal physical activity measures in children with CHD. Methods: As part of a prospective cohort study, children and adolescents aged 9-16 years old with moderate-to-complex CHD were recruited from British Columbia Children's Hospital and partnership clinics across British Columbia and the Yukon territory. Daily step counts were measured continuously over 3 years (2018-2021) with Fitbit Charge 2. School status during the COVID-19 pandemic was assessed with parent- or self-report survey. Results: A total of 102, 114, and 93 participants had valid Fitbit data during 2018, 2019, and 2020, respectively. There was a significant reduction in the annual mean step count for 2020 (8225 ± 4328 steps) compared with both 2018 (9416 ± 3770 steps) and 2019 (9533 ± 4114 steps) (P < 0.001). There was a loss of seasonal variation in physical activity, and reduced levels of physical activity persisted when most children resumed in-person schooling in September 2020. Conclusions: We demonstrated a significant decrease in physical activity and loss of seasonal patterns in children with CHD during 2020. These findings represent a worsening of the cardiovascular risk profile in children with CHD, who are already at an increased risk of adverse cardiovascular outcomes. Mitigation strategies are needed to optimize the cardiovascular health status of children with CHD as the pandemic persists.

Contexte: Au début de l'année 2020, la maladie à coronavirus 2019 (COVID-19) a été associée à une diminution de l'activité physique chez les enfants présentant une cardiopathie congénitale. Compte tenu du risque cardiovasculaire accru chez ces patients, il importe d'optimiser les comportements en matière de santé cardiovasculaire. Cette étude visait à évaluer les répercussions de la pandémie actuelle de COVID-19 sur les mesures longitudinales de l'activité physique auprès d'enfants présentant une cardiopathie congénitale. Méthodologie: Pour cette étude de cohorte prospective, des enfants et des adolescents de 9 à 16 ans atteints de cardiopathie congénitale modérée ou complexe ont été recrutés au British Columbia Children's Hospital ainsi que dans les cliniques partenaires de la Colombie-Britannique et du Yukon. Le nombre de pas quotidiens a été compté en continu pendant trois ans (2018-2021) à l'aide d'un appareil Fitbit Charge 2. Les enfants ou leurs parents ont indiqué, à l'aide d'un sondage, s'ils allaient à l'école ou non pendant la pandémie de COVID-19. Résultats: Des données de l'appareil Fitbit ont été obtenues chez un total de 102, 114 et 93 participants en 2018, 2019 et 2020, respectivement. Une nette réduction du nombre de pas annuel moyen en 2020 (8225 ± 4328 pas) a été constatée par rapport à 2018 (9416 ± 3770 pas) et à 2019 (9533 ± 4114 pas) (p < 0,001). Les variations saisonnières de l'activité physique se sont amoindries, et le faible volume d'activité physique a perduré même lorsque la majorité des enfants avaient repris l'école en présentiel, en septembre 2020. Conclusions: Une nette diminution de l'activité physique et un affaiblissement des variations saisonnières de l'activité physique ont été observés chez les enfants présentant une cardiopathie congénitale en 2020. Ces résultats signifient une aggravation du risque cardiovasculaire que courent ces patients, déjà exposés à un risque accru d'événements cardiovasculaires. Comme la pandémie persiste, des stratégies d'atténuation des risques sont nécessaires pour optimiser la santé cardiovasculaire des enfants présentant une cardiopathie congénitale.

Physical Activity in Paediatric Long QT Syndrome Patients.

Background: Physical activity (PA) is important for cardiovascular health as well as social and emotional well-being of children. Patients with long QT syndrome (LQTS) often face PA restrictions and are often prescribed beta-blockers for disease management. The aim of this study was to determine if PA levels were lower in patients with LQTS compared with healthy controls. Methods: Participants with LQTS from an inherited arrhythmia clinic completed the Physical Activity Questionnaire for Children and Adolescents (PAQ-C/A) and an exercise stress test. PAQ score (a general measure of PA for youth, unitless) and endurance time were compared with healthy controls. Results: Twenty-three patients with LQTS completed the PAQ and had an exercise stress test within a year of having completed the PAQ. No difference was observed in PAQ scores between LQTS and control groups (LQTS: 2.3 ± 0.15 vs controls: 2.3 ± 0.18; P = 0.78). There was no effect of age on PA in patients with LQTS (P > 0.05), whereas PA significantly decreased in controls with age (eg, 11-12 vs 17-20 years: 3.2 ± 0.07 vs 1.5 ± 0.08, P = 0.005). Endurance time and heart rate at peak exercise were significantly lower in patients with LQTS compared with controls (11 ± 0.5 vs 15 ± 0.5 minutes, P < 0.0001; 169 ± 5 vs 198 ± 2 beats per minute, P < 0.0001). Conclusions: Despite guideline recommendations restricting PA, risk of sudden cardiac death, and use of beta-blockers, our cohort of patients with LQTS reported similar PA levels as healthy controls.

Contexte: L'activité physique est importante pour la santé cardiovasculaire ainsi que le bien-être social et émotionnel des enfants. Chez les patients qui présentent un syndrome du QT long (SQTL), l'activité physique est souvent restreinte, et des bêta-bloquants sont fréquemment prescrits pour la maîtrise de la maladie. L'objectif de cette étude était de déterminer si le degré d'activité physique était inférieur chez les patients atteints du SQTL à celui de témoins en bonne santé. Méthodologie: Des patients atteints du SQTL d'une clinique d'arythmie héréditaire ont rempli le questionnaire sur l'activité physique pour les enfants et les adolescents (PAQ-C/A, pour Physical Activity Questionnaire for Children and Adolescents) et subi une épreuve d'effort. Le score du PAQ (mesure générale de l'activité physique pour les jeunes, sans unité) et le temps d'endurance ont été comparés à ceux obtenus chez des témoins en bonne santé. Résultats: Vingt-trois patients atteints du SQTL ont rempli le PAQ et, dans l'année suivante, subi une épreuve d'effort. Pour ce qui est du score du PAQ, aucune différence n'a été observée entre le groupe atteint du SQTL et le groupe témoin (2,3 ± 0,15 chez les patients atteints du SQTL vs 2,3 ± 0,18 chez les témoins; p = 0,78). L'âge était sans effet sur l'activité physique chez les patients atteints du SQTL (p > 0,05), tandis que le degré d'activité physique diminuait significativement avec l'âge chez les témoins (p. ex. 3,2 ± 0,07 chez les témoins de 11 à 12 ans vs 1,5 ± 0,08 chez les témoins de 17 à 20 ans, p = 0,005). Pendant l'effort maximal, le temps d'endurance était significativement plus court et la fréquence cardiaque, significativement plus basse chez les patients atteints du SQTL que chez les témoins (11 ± 0,5 vs 15 ± 0,5 minutes, p < 0,0001; 169 ± 5 vs 198 ± 2 battements par minute, p < 0,0001). Conclusions: Malgré la restriction de l'activité physique recommandée par les lignes directrices, le risque de mort subite d'origine cardiaque et l'utilisation de bêta-bloquants, dans notre cohorte de patients atteints du SQTL, le degré d'activité physique a été semblable à celui des témoins en bonne santé.

Dosing Regimen Prediction and Confirmation With Rivaroxaban for Thromboprophylaxis in Children After the Fontan Procedure: Insights From the Phase III UNIVERSE Study.

Thrombosis remains an important complication for children with single-ventricle physiology following the Fontan procedure, and effective thromboprophylaxis is an important unmet medical need. To obviate conventional dose-finding studies and expedite clinical development, a rivaroxaban dose regimen for this indication was determined using a model-informed drug development approach. A physiologically based pharmacokinetic rivaroxaban model was used to predict a pediatric dosing regimen that would produce drug exposures similar to that of 10 mg once daily in adults. This regimen was used in an open-label, multicenter phase III study, which investigated the use of rivaroxaban for thromboprophylaxis in post-Fontan patients 2 to 8 years of age. The pharmacokinetics (PK) of rivaroxaban was assessed in part A (n = 12) and in part B (n = 64) of the UNIVERSE study. The safety and efficacy in the rivaroxaban group were compared to those in the acetylsalicylic acid group for 12 months. Pharmacodynamic end points were assessed in both parts of the study. Rivaroxaban exposures achieved in parts A and B were similar to the adult reference exposures. Prothrombin time also showed similarity to the adult reference. Exposure-response analysis did not identify a quantitative relationship between rivaroxaban exposures and efficacy/safety outcomes within the observed exposure ranges. A body weight-based dose regimen selected by physiologically based pharmacokinetic modeling was shown in the UNIVERSE study to be appropriate for thromboprophylaxis in the post-Fontan pediatric population. Model-based dose selection can support pediatric drug development and bridge adult dose data to pediatrics, thereby obviating the need for dose-finding studies in pediatric programs.

Association of Preoperative Diuretic Use With Early Acute Kidney Injury in Infants With Biventricular Hearts Following Cardiac Surgery.

Background Diuretics are used to manage congestive heart failure in infants with congenital heart disease. Adult data indicate that preoperative diuretic use increases the risk of cardiac surgery associated acute kidney injury (CS-AKI). We have sought to understand if preoperative diuretics in infants increases the risk of CS-AKI. Methods and Results This is a single-center retrospective study of infants (1-12 months) who had CS requiring cardiopulmonary bypass between 2013 and 2018. The diagnosis and severity of CS-AKI was defined according to the Kidney Disease Improving Global Outcomes guidelines. Three hundred patients were included (mean 6 months, SD 2.4, range 1.2-12.9 months). A total of 149 (49.7%) patients were diagnosed with CS-AKI (stage 1: 80 [54%], stage 2: 57 [38%], stage 3: 12 [8%]). Logistic regression analysis showed preoperative diuretics were not associated with CS-AKI (odds ratio [OR], 0.79; 95% CI, 0.43-1.44; P=0.45). A diagnosis of tetralogy of Fallot was an independent risk factor for CS-AKI (OR, 3.49; 95% CI, 1.33-9.1, P=0.01). A diagnosis of tetralogy of Fallot (OR, 3.6; 95% CI, 1.28-10.22; P=0.02) and longer cardiopulmonary bypass (OR, 1.01; 95% CI, 1.0-1.02; P=0.04) time are risk factors for moderate to severe CS-AKI. Conclusions Preoperative diuretic use does not contribute to the risk of CS-AKI in infants early after surgery. A diagnosis of tetralogy of Fallot was the only risk factor for CS-AKI identified using multivariate analysis in our cohort. Furthermore, a diagnosis of tetralogy of Fallot and longer cardiopulmonary bypass time are risk factors for moderate to severe CS-AKI.

Thromboprophylaxis for Children Post-Fontan Procedure: Insights From the UNIVERSE Study.

Background Patients with single-ventricle physiology who undergo the Fontan procedure are at risk for thrombotic events associated with significant morbidity and mortality. The UNIVERSE Study evaluated the efficacy and safety of a novel liquid rivaroxaban formulation, using a body weight-adjusted dosing regimen, versus acetylsalicylic acid (ASA) in children post-Fontan. Methods and Results The UNIVERSE Study was a randomized, multicenter, 2-part, open-label study of rivaroxaban, in children who had undergone a Fontan procedure, to evaluate its dosing regimen, safety, and efficacy. Part A was the single-arm part of the study that determined the pharmacokinetics/pharmacodynamics and safety of rivaroxaban in 12 participants before proceeding to part B, whereby 100 participants were randomized 2:1 to open-label rivaroxaban versus ASA. The study period was 12 months. A total of 112 participants were enrolled across 35 sites in 10 countries. In part B, for safety outcomes, major bleeding occurred in one participant on rivaroxaban (epistaxis that required transfusion). Clinically relevant nonmajor bleeding occurred in 6% of participants on rivaroxaban versus 9% on ASA. Trivial bleeding occurred in 33% of participants on rivaroxaban versus 35% on ASA. For efficacy outcomes, 1 participant on rivaroxaban in part B had a pulmonary embolism (2% overall event rate); and for ASA, 1 participant had ischemic stroke and 2 had venous thrombosis (9% overall event rate). Conclusions In this study, participants who received rivaroxaban for thromboprophylaxis had a similar safety profile and fewer thrombotic events, albeit not statistically significant, compared with those in the ASA group. Registration URL: https://www.clinicaltrials.gov. Identifier: NCT02846532.

Unique Challenges of Randomised Controlled Trials in Pediatric Cardiology.

Pediatric cardiology has evolved over time with reductions in childhood mortality due to congenital heart disease. Surgical innovation drove early changes in care. Increasingly, the need for more robust evidence provided by randomised controlled trials (RCTs) has been recognised. Although the number of RCTs has increased, there remains a relative paucity of truly impactful trials in the field. However, those trials that have changed practice have demonstrated the potential and importance of this work. Examples include the PRIMACORP trial, which established the safety and efficacy of milrinone after cardiac surgery, and the Single Ventricle Reconstruction trial, which was the first multicentre pediatric cardiac surgical RCT. The successful conduct and important findings emanating from these trials serve as beacons as clinicians strive to improve the evidence base in this field. The establishment of national and international networks such as the Pediatric Heart Network and the Canadian Pediatric Cardiology Research Network provide a strong foundation for future collaborative work. Despite this progress, there remain important challenges to designing and executing RCTs in pediatric cardiology. These include issues of greater disease and patient heterogeneity and increased costs. The use of innovative study designs and analytic methods and the establishment of core outcome measures have the potential to overcome some of the issues related to the smaller patient numbers compared with adult disciplines. As pediatric cardiologists look to the future, it is imperative that we work together to derive the maximum benefit from the considerable efforts directed toward conducting impactful clinical trials in pediatric cardiology.

Aortic Dimensions, Biophysical Properties, and Plasma Biomarkers in Children and Adults with Marfan or Loeys-Dietz Syndrome.

BACKGROUND: Aortic dilation, stiffening, and dissection are common and potentially lethal complications of Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS), which involve abnormal transforming growth factor beta (TGF-ß) signalling. The relation of aortic dimensions, stiffness, and biomarker levels is unknown. The objective of this study was to measure aortic dimensions, stiffness, TGF-ß and matrix metalloproteinase (MMP) levels, and endothelial function in patients with MFS, and to compare TGF-ß levels in patients with MFS receiving different therapeutic regimens. METHODS: This was a cohort study of 40 MFS and 4 LDS patients and 87 control participants. Aortic dimension and stiffness indexes, including pulse wave velocity (PWV), were measured using echocardiography and Doppler. Total and free TGF-ß and MMP blood levels were measured using Quantikine (R&D Systems, Inc, Minneapolis, MN) and Quanterix (Billerica, MA) kits. Endothelial function was measured using brachial artery flow-mediated dilation. RESULTS: PWV was increased in patients with MFS. There were increased MMP-2 levels in those with MFS but no increase in free or total TGF-ß or MMP-9 levels compared with control participants. There was no difference in TGF-ß levels between MFS patients receiving no medications, angiotensin receptor blockers, and ß-blockers. PWV correlated most strongly with age. Endothelial function showed premature gradual decline in patients with MFS. CONCLUSIONS: Despite the increased PWV, monitoring aortic stiffness or TGF-ß levels would not be helpful in patients with MFS. TGF-ß levels were not increased and the increased MMP-2 levels suggest consideration of a different therapeutic target.

CONTEXTE: La dilatation, la rigidification et la dissection de l'aorte sont des complications fréquentes et parfois mortelles du syndrome de Marfan (SM) et du syndrome de Loeys-Dietz (SLD), qui sont tous deux dûs à une anomalie de la voie de signalisation du facteur de croissance transformant bêta (TGF-ß). On ne connaît pas la relation entre les dimensions et la rigidité de l'aorte et la présence de biomarqueurs. Notre étude visait à mesurer les dimensions et la rigidité de l'aorte, les taux de TGF-ß et de métalloprotéases matricielles (MMP) et la fonction endothéliale chez des patients atteints du SM, et à les comparer aux taux de TGF-ß observés chez des patients également atteints de SM, mais recevant un autre traitement. MÉTHODOLOGIE: Il s'agissait d'une étude de cohorte menée auprès de 40 patients atteints du SM et de quatre patients atteints du SLD, ainsi que de 87 témoins. Les indices des dimensions et de la rigidité aortiques, y compris la vitesse d'onde de pouls (VOP), ont été mesurés par échocardiographie et par échographie Doppler. Les taux sanguins de TGF-ß et de MMP totaux et libres ont été mesurés à l'aide de trousses Quantikine (R&D Systems, Inc, Minneapolis, MN) et Quanterix (Billerica, MA). La fonction endothéliale a été mesurée par dilatation liée au flux dans l'artère brachiale. RÉSULTATS: La VOP était plus élevée chez les patients atteints du SM. On a aussi observé une hausse des taux de MMP-2 chez les patients atteints de SM, mais aucune augmentation des taux de TGF-ß ou de MMP-9 libres ou totaux comparativement aux témoins. Il n'y avait pas de différence entre les taux de TGF-ß chez les patients atteints de SM ne recevant aucun traitement, ceux qui prenaient un antagoniste des récepteurs de l'angiotensine et ceux qui prenaient un bêtabloquant. La VOP été plus fortement corrélée avec l'âge. La fonction endothéliale a affiché un déclin progressif prématuré chez les patients atteints du SM. CONCLUSIONS: Malgré l'augmentation de la VOP, il ne semble pas utile de surveiller la rigidité aortique ni les taux de TGF-ß en cas de SM. Les taux de TGF-ß n'étaient pas plus élevés chez les patients atteints du SM, et la hausse des taux de MMP-2 indique qu'il conviendrait de choisir une autre cible thérapeutique.

Evaluation of conventional troponin I testing for the detection of myocardial dysfunction in children.

Objectives: Troponin is a marker of myocardial injury but is not well studied in children. Our primary objective was to ascertain the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of conventional troponin I for the detection of acute myocardial dysfunction in previously healthy children. Our secondary objective was to identify clinical predictors of myocardial dysfunction in the setting of elevated troponin. Study Design: This was a retrospective chart review in a single, paediatric, tertiary care centre of troponin tests performed in all admitted children over a 4-year period. Demographics, symptoms, signs, chest x-ray, ECG, and echocardiogram abnormalities were documented. Myocardial dysfunction was presumed to be absent when the patient had a normal cardiac assessment, with or without echocardiography, and did not re-present. Results: From January 2014 through December 2017, 566 patients had troponin tested as a screen for myocardial injury. Troponin was positive in 38 of 566 cases (6.7%). Myocardial dysfunction was detected in 9 of 566 cases (1.6%). Troponin was elevated in six of nine cases of myocardial dysfunction. The sensitivity of conventional troponin I for detecting acute myocardial dysfunction was 66% (95% confidence interval [CI] 30 to 93%). The specificity was 94% (95% CI 92 to 96%). PPV was 16% (95% CI 6 to 31%) and NPV 99% (95% CI 98 to 100%). An abnormal ECG was more prevalent in patients with a true positive versus a false-positive troponin result (P=0.03). Conclusion: Troponin testing identified few cases of myocardial dysfunction. We found the test to have only 66% sensitivity. Troponin testing as a screen for myocardial injury in children has limited utility.

Children with congenital heart disease exhibit seasonal variation in physical activity.

OBJECTIVE: We sought to identify seasonal variation in physical activity that different physical activity measurement tools can capture in children with congenital heart disease. METHODS: Data were collected as part of a prospective cohort study at BC Children's Hospital, Vancouver, Canada. Daily step counts of children aged 9-16 years with moderate-to-severe CHD were assessed continuously for 1-year via a commercial activity tracker (Fitbit Charge 2™). Physical activity levels were also assessed conventionally at one time-point via accelerometers (ActiGraph) and physical activity questionnaires. RESULTS: 156 children (mean age 12.7±2.4 years; 42% female) participated in the study. Fitbit data (n = 96) over a 1-year period clearly illustrated seasonal peaks (late spring and autumn) and dips (winter and summer school holidays) in physical activity levels, with group mean values being below 12,000 steps per day throughout the year. According to conventional accelerometry data (n = 142), 26% met guidelines, which tended to differ according to season of measurement (spring: 39%, summer: 11%, fall: 20%, winter: 39%; p-value = 0.053). Questionnaire data (n = 134) identified that the most widely reported activities were walking (81%) and running (78%) with walking being the highest in summer and fall and running in winter and spring. Furthermore, regardless of overall activity levels the children exhibit similar seasonal variation. CONCLUSIONS: We demonstrated that physical activity level changes across seasons in children with CHD. It is important to be aware of these fluctuations when assessing and interpreting physical activity levels. Season specific counselling for physical activity may be beneficial in a clinical setting.