An 8-Week Virtual Exercise Training Program for Pediatric Solid Organ Transplant Recipients.

PURPOSE: Musculoskeletal strength can be impaired in pediatric solid organ transplant recipients. Exercise training programs can be beneficial but in-person delivery can be challenging; virtual exercise programs can alleviate some of these challenges. This feasibility study aimed to deliver an 8-week virtual exercise program in pediatric solid organ transplant recipients. METHOD: Program delivery occurred 3 times per week for 30 minutes. An exercise stress test was completed prior to program start. The Bruininks-Oseretsky Test of Motor Proficiency strength subtest and self-report surveys were used to assess musculoskeletal strength, quality of life, fatigue, and physical activity. Contact was maintained through a text messaging platform. Z scores were calculated using standardized normative data. Medians (interquartile range) are reported for all other data. RESULTS: Eleven participants completed the program (2 liver, 5 kidney, 4 heart; 58% females; median age = 11.5 [10.3-13.8] y). Six participants attended ≥60% of classes, 5 participants attended <50% of classes. After 8 weeks, strength scores improved (Z score, Pre: -1.0 [-1.65 to -0.60] to Post: -0.2 [-1.30 to 0.40]; P = .007) with no change in other outcome measures. CONCLUSION: The virtual exercise program was delivered without technical issues and received positive participant feedback. Engagement and costs need to be considered.

A text messaging intervention and quality of life in adolescents with solid organ transplants.

BACKGROUND: Facilitating communication between adolescents and HCP outside of appointments may enhance patient experience and outcomes. The purpose of this study was to determine whether SMS enhances the healthcare experience, QoL, and medication adherence in adolescent SOT patients. METHODS: This was a prospective observational study of an SMS platform (WelTel Inc) for SOT patients aged 12-19 years. QoL was assessed before and after using the PedsQL™ Transplant Module. Medication adherence was assessed with the frequency of therapeutic tacrolimus levels and variation based on control chart analysis. Patient experience and engagement was evaluated with surveys, response rate to messages, and number of clinical conversations (>2 messages). RESULTS: Twenty-three patients were included (median age 15.7 years (IQR 13.6-17.1)). Median intervention duration was 13.5 months (range 4.0-16.7 months). There was a 68% response rate (742/1095) with 375 clinical conversations. The majority of patients reported the intervention provided a positive outlook on their health (17/23), was useful (18/23), and improved their connection to HCPs (17/23). Following the intervention, there was no significant difference in the median scaled QoL scores (pre-intervention: 81 (IQR 76.5-93.3), post-intervention: 78 (IQR 76-93); p = .37), mean percentage of therapeutic tacrolimus levels (pre-intervention: 52 ± 25%, post-intervention: 65 ± 17%; p = .07), or variation on control chart analysis of tacrolimus levels. CONCLUSIONS: The WelTel messaging platform provided supplemental clinical care for a group of adolescent SOT patients that enhanced their healthcare experience. Patient QoL and adherence were unchanged following the intervention and remained at a high level.

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.

Adolescents with solid organ transplant: Using the BRIEF2 parent-report and self-report to measure parent-child agreement and everyday executive function.

Agreement between parent and adolescent ratings of executive function (EF) is not known in adolescents with solid organ transplant (SOT), even though pressing concerns about EF deficits are being raised in this population. The current study investigated EF in adolescents with SOT using parent and self report. Twenty-five adolescents (M = 15.51 years) with SOT and their parent completed a behavior rating scale assessing EF within everyday context using the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF2). Parents and their adolescents demonstrated moderate to excellent agreement across the BRIEF2 clinical and index scores, higher than previous research with a typical sample. Adolescent males had higher agreement with their parents than female adolescents. Both parents and adolescents reported significantly higher mean T scores on various BRIEF2 indices and domains, in addition to higher rates of clinically elevated executive dysfunction than their peers. Assessment of EF and targeting specific EF domains for intervention may be useful in this population.

Self-reported physical activity and lack of association with health-related quality of life in a pediatric solid-organ transplant population.

BACKGROUND: Physical activity (PA) has been shown to have benefits, including improving health-related quality of life (HRQOL). However, there are few and conflicting studies assessing PA and its relationship with HRQOL in a pediatric solid-organ transplant (SOT) population. The aim of this study was to assess whether overall HRQOL was associated with PA and to determine whether that association was independent of other baseline and contemporaneous clinical and demographic indicators. METHODS: A retrospective cross-sectional review was performed on 55 pediatric transplant patients (13 heart, 27 kidney, and 15 liver transplant). PA was measured by PAQ-C/PAQ-A, and HRQOL was measured using PedsQL. Demographics, baseline, and contemporaneous data were collected. RESULTS: There were no significant differences in baseline and contemporaneous characteristics between heart, kidney, and liver transplant recipients. SOT recipients were 15.0 (11.0-18.0) years old at completion of surveys. Median PAQ score was 2.3 (1.6-3.2), PedsQL total score was 77 (65-91), and PedsQL physical functioning score was 88 (72-97). The PedsQL total score was not significantly associated with PAQ score. The PAQ score was significantly associated with physical functioning subscore of the PedsQL (r = 0.37, p < 0.01). Higher physical functioning score was associated with time since transplant (r = 0.29, p = 0.031). CONCLUSION: Our SOT cohort has a HRQOL similar to other chronic conditions and higher than previous reported HRQOL in pediatric SOT populations. Higher levels of PA and longer time since transplant are associated with higher physical functioning scores.

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.

Burst Exercise Testing Can Unmask Arrhythmias in Patients With Incompletely Penetrant Catecholaminergic Polymorphic Ventricular Tachycardia.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by cardiac arrest during sudden exertion. However, standard exercise stress testing (EST) lacks sensitivity, leading to misdiagnosis and undertreatment. After a nondiagnostic standard gradual EST, we report 6 patients who underwent a novel burst exercise test characterized by sudden high workload at the outset of testing. In 5 of 6 patients, the burst EST induced new and more complex arrhythmias versus standard EST, which compelled medication initiation in 3 patients. We postulate that this simple EST modification better mimics a typical CPVT triggering event and could improve diagnostic sensitivity and therapeutic decision making.

Potential overdiagnosis of long QT syndrome using exercise stress and QT stand testing in children and adolescents with a low probability of disease.

BACKGROUND: Long QT syndrome (LQTS) is a dangerous arrhythmia disorder that often presents in childhood and adolescence. The exercise stress test (EST) and QT-stand test may unmask QT interval prolongation at key heart rate transition points in LQTS, but their utility in children is debated. OBJECTIVE: To determine if the QT-stand test or EST can differentiate children with a low probability of LQTS from those with confirmed LQTS. METHODS: This retrospective study compares the corrected QT intervals (QTc) of children (<19 years) during the QT-stand test and EST. Patients were divided into three groups for comparison: confirmed LQTS (n = 14), low probability of LQTS (n = 14), and a control population (n = 9). RESULTS: Using the Bazett formula, confirmed LQTS patients had longer QTc intervals than controls when supine, standing, and at 3-4 min of recovery (p ≤ .01). Patients with a low probability of LQTS had longer QTc duration upon standing (p = .018) and at 1 min of recovery (p = .016) versus controls. There were no significant QTc differences at any transition point between low probability and confirmed LQTS. Using the Fridericia formula, differences in QTc between low probability and confirmed LQTS were also absent at the transition points examined, except at 1 min into exercise, where low probability patients had shorter QTc intervals (437 vs. 460 ms, p = .029). CONCLUSION: The diagnostic utility of the QT stand test and EST remains unclear in pediatric LQTS. The formula used for heart rate correction may influence accuracy, and dynamic T-U wave morphology changes may confound interpretation in low probability situations.

Physical activity and its correlates in a pediatric solid-organ transplant population.

PA has been shown to have benefits in SOT patients. Studies assessing physical activity levels and its correlates in a pediatric solid-organ transplant population are limited. The aim of this study was to assess PA levels and identify baseline and contemporaneous factors that contribute to PA in a pediatric SOT population. A retrospective cross-sectional review was performed on 58 pediatric transplant patients (16 heart, 29 kidney, and 13 liver transplant). PA was measured by PAQ-C or PAQ-A. Demographics, baseline, and contemporaneous factors were collected. There were no significant differences in baseline and contemporaneous characteristics between heart, kidney, and liver transplant recipients. SOT recipients were 15.2 [12.3-17.3] years old at time of completing the PAQ. Median PAQ score was 2.2 [1.7-2.9]. There were no significant differences in PAQ scores between organ transplant type or between genders. Lower PAQ score was associated with sensory disability (9 vs 49 without disability; P = <.01) and age at time of completing the PAQ (r = -.50, P = <.01). These results suggest that older age at time of completing the PAQ and presence of sensory disability may influence PA levels in the pediatric SOT population.

Whole blood human transcriptome and virome analysis of ME/CFS patients experiencing post-exertional malaise following cardiopulmonary exercise testing.

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

Echocardiographic Assessment of Ventricular Function During Exercise in Adolescent Female Patients With Anorexia Nervosa.

BACKGROUND: Patients with anorexia nervosa (AN) have altered physiologic responses to exercise. The aim of this study was to investigate exercise capacity and ventricular function during exercise in adolescent patients with AN. METHODS: Sixty-six adolescent female patients with AN and 21 adolescent female control subjects who exercised to volitional fatigue on a semisupine ergometer, using an incremental step protocol of 20 W every 3 min, were retrospectively studied. Heart rate, blood pressure, and echocardiographic Doppler indices were measured at rest and during each stage of exercise. Fractional shortening, rate-corrected mean velocity of circumferential fiber shortening, stress at peak systole, cardiac output, and cardiac index were calculated. Minute ventilation, oxygen consumption, carbon dioxide production, and respiratory exchange ratio were measured using open-circuit spirometry. RESULTS: Patients with AN had significantly lower body mass index (16.7 vs 19.7 kg/m2, P < .001), total work (1,126 vs 1,914 J/kg, P < .001), and test duration (13.8 vs 20.8 min, P < .001) compared with control subjects. Peak minute ventilation, oxygen consumption, and carbon dioxide production were significantly decreased in patients with AN. Heart rate, systolic blood pressure, cardiac index, fractional shortening, and rate-corrected mean velocity of circumferential fiber shortening demonstrated similar patterns of increase with progressive exercise between groups but were decreased at peak exercise in patients with AN. Body mass index percentile, age, peak oxygen consumption, and peak cardiac output were independently associated with exercise duration. CONCLUSIONS: Adolescent patients with AN have reduced exercise capacity and peak cardiovascular indices compared with control subjects but normal patterns of cardiovascular response during progressive exercise. Systolic ventricular function is maintained during exercise in adolescents with AN.

Physiological Responses to Exercise in Pediatric Heart Transplant Recipients.

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

Assessment of cardiovascular risk and preparticipation screening protocols in masters athletes: the Masters Athlete Screening Study (MASS): a cross-sectional study.

BACKGROUND: Underlying coronary artery disease (CAD) is the primary cause of sudden cardiac death in masters athletes (>35 years). Preparticipation screening may detect cardiovascular disease; however, the optimal screening method is undefined in this population. The Physical Activity Readiness Questionnaire for Everyone (PAR-Q+) and the American Heart Association (AHA) Preparticipation Screening Questionnaire are often currently used; however, a more comprehensive risk assessment may be required. We sought to ascertain the cardiovascular risk and to assess the effectiveness of screening tools in masters athletes. METHODS: This cross-sectional study performed preparticipation screening on masters athletes, which included an ECG, the AHA 14-element recommendations and Framingham Risk Score (FRS). If the preparticipation screening was abnormal, further evaluations were performed. The effectiveness of the screening tools was determined by their positive predictive value (PPV). RESULTS: 798 athletes were included in the preparticipation screening analysis (62.7% male, 54.6±9.5 years, range 35-81). The metabolic equivalent task hours per week was 80.8±44.0, and the average physical activity experience was 35.1±14.8 years. Sixty-four per cent underwent additional evaluations. Cardiovascular disease was detected in 11.4%, with CAD (7.9%) being the most common diagnosis. High FRS (>20%) was seen in 8.5% of the study population. Ten athletes were diagnosed with significant CAD; 90% were asymptomatic. A high FRS was most indicative of underlying CAD (PPV 38.2%). CONCLUSION: Masters athletes are not immune to elevated cardiovascular risk and cardiovascular disease. Comprehensive preparticipation screening including an ECG and FRS can detect cardiovascular disease. An exercise stress test should be considered in those with risk factors, regardless of fitness level.

Doppler Echocardiography Assessment of Aortic Stiffness in Female Adolescents with Anorexia Nervosa.

BACKGROUND: Anorexia nervosa (AN) is associated with abnormalities in biomarkers of cardiovascular risk. Arterial stiffness, as measured by pulse-wave velocity (PWV), is also a risk factor for cardiovascular disease. The aims of this study were to determine the stiffness of the aorta in female adolescents with AN and to determine if either the severity or the type of AN was associated with PWV. METHODS: This was a retrospective case-control study. Adolescent patients with a clinical diagnosis of AN were included. Aortic diameter and pulse-wave transit time over a portion of the thoracic aorta were measured using Doppler echocardiography, and PWV was calculated. RESULTS: There were 94 female patients with AN and 60 adolescent female control subjects. There was no significant difference in age between patients with AN and control subjects (15.5 ± 1.7 vs 15.1 ± 2.6 years, P = .220). Body mass index (16.0 ± 2.4 vs 19.7 ± 2.7 kg/m2, P < .001) and body mass index percentile (9.4 ± 15.6 vs 45.5 ± 26.2, P < .001) were significantly lower for patients with AN than control subjects. PWV (443 ± 106 vs 383 ± 77 cm/sec, P < .001) was significantly higher in patients with AN than control subjects. Similar differences from control subjects were found in patients with AN with both lower and higher body mass index percentiles and also in patients with AN with the restrictive or the binge-purge subtype. CONCLUSIONS: Female adolescents with AN have increased aortic stiffness compared with control subjects. This study suggests that patients with AN may be at increased risk for future cardiovascular disease. Future studies are required to determine the reversibility of these changes with weight restoration.

A novel treadmill protocol for exercise testing in children: the British Columbia Children's Hospital protocol.

BACKGROUND: Exercise testing in children is widely recommended for a number of clinical and prescriptive reasons. Many institutions continue to use the Bruce protocol for treadmill testing; however, with its incremental changes in speed and grade, it has challenges for practical application in children. We have developed a novel institutional protocol (British Columbia Children's Hospital (BCCH)), which may have better utility in paediatric populations. AIM: To determine if our institutional protocol yields similar peak responses in minute ventilation (VE), oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER), metabolic equivalents (METS) and heart rate (HR) when compared with the traditional Bruce protocol. METHODS: On two different occasions, 70 children (boys=33; girls=37) aged 10-18 years completed an exercise test on a treadmill using each of the protocols. During each test, metabolic gas exchange parameters were measured. HR was monitored continuously during exercise using an HR monitor. RESULTS: Physiological variables were similar between the two protocols (median (IQR); rs): VE (L/min) (BCCH=96.7 (72.0-110.2); Bruce=99.2 (75.6-120.0); rs=0.95), peak VO2 (mL/min) (BCCH=2897 (2342-3807); Bruce=2901 (2427-3654); rs=0.94) and METS (BCCH=16.2 (14.8-17.7); Bruce=16.4 (14.7-17.9); rs=0.89). RERs were similar (BCCH=1.00 (0.96-1.02); Bruce=1.03 (0.99-1.07); rs=0.48). Total exercise time (in seconds) was longer for the BCCH protocol: BCCH=915 (829-1005); Bruce=810 (750-919); rs=0.67. CONCLUSION: The BCCH protocol produces similar peak exercise responses to the Bruce protocol and provides an alternative for clinical exercise testing in children.

A Doppler Echocardiographic Study of the Myocardial Inotropic Response to Peak Semisupine Exercise in Healthy Children: Development of a Simplified Index of Myocardial Reserve.

BACKGROUND: Stress echocardiography has been advocated for the detection of abnormal myocardial function and unmasking diminished myocardial reserve in pediatric patients. The aim of this study was to create a simplified index of myocardial reserve, derived from the myocardial inotropic response to peak semisupine exercise in healthy children, and illustrate its applicability in a sample of pediatric oncology patients. METHODS: In this prospective analysis, children (7-18 years of age) with normal cardiac structure and function performed semisupine stress echocardiography to volitional fatigue. The quotient of wall stress at peak systole and heart rate-corrected velocity of circumferential fiber shortening were calculated at baseline and at peak exercise, the difference of which was termed the index of myocardial reserve (IMR). The IMR was also calculated in a retrospective sample of pediatric oncology patients with normal resting left ventricular function who had received anthracycline treatment and had performed the same exercise protocol to illustrate utility. RESULTS: Fifty healthy subjects (mean age, 13.2 ± 2.6 years) and 33 oncology patients (mean age, 12.7 ± 4.0 years) were assessed. In the healthy children at peak exercise, heart rate-corrected velocity of circumferential fiber shortening significantly increased (from 1.17 ± 0.17 to 1.58 ± 0.24 circ · sec-1, P < .001), while the quotient of wall stress at peak systole significantly decreased (from 75.3 ± 17.1 to 55.3 ± 13.8 g · cm-2, P < .001), shifting the plot of the relationship between the two parameters upward and to the left. The mean IMR was -30.8 ± 17.8, and the normal distribution ranged from -4.7 (fifth percentile) to -67.3 (95th percentile). The IMR was abnormal in 10 oncology patients who were treated with anthracyclines. CONCLUSIONS: The authors have developed a novel IMR. Relative to the normal distribution of this IMR in healthy subjects, it is possible to identify patients with abnormal myocardial reserve. Thus, this study demonstrates the application of the IMR to aid in clinical decision making in individual patients.

Aspirin Dose and Prevention of Coronary Abnormalities in Kawasaki Disease.

BACKGROUND: Acetylsalicylic acid (ASA) is part of the recommended treatment of Kawasaki disease (KD). Controversies remain regarding the optimal dose of ASA to be used. We aimed to evaluate the noninferiority of ASA at an antiplatelet dose in acute KD in preventing coronary artery (CA) abnormalities. METHODS: This is a multicenter, retrospective, nonrandomized cohort study including children 0 to 10 years of age with acute KD between 2004 and 2015 from 5 institutions, of which 2 routinely use low-dose ASA (3-5 mg/kg per day) and 3 use high-dose ASA (80 mg/kg per day). Outcomes were CA abnormalities defined as a CA diameter with a z score ≥2.5. We assessed the risk difference of CA abnormalities according to ASA dose. All subjects received ASA and intravenous immunoglobulin within 10 days of fever onset. RESULTS: There were 1213 subjects included, 848 in the high-dose and 365 in the low-dose ASA group. There was no difference in the risk of CA abnormalities in the low-dose compared with the high-dose ASA group (22.2% vs 20.5%). The risk difference adjusted for potential confounders was 0.3% (95% confidence interval [CI]: -4.5% to 5.0%). The adjusted risk difference for CA abnormalities persisting at the 6-week follow-up was -1.9% (95% CI: -5.3% to 1.5%). The 95% CI of the risk difference of CA abnormalities adjusted for confounders was within the prespecified 5% margin considered to be noninferior. CONCLUSIONS: In conjunction with intravenous immunoglobulin, low-dose ASA in acute KD is not inferior to high-dose ASA for reducing the risk of CA abnormalities.

Physical Activity and Sedentary Behavior in Children With Congenital Heart Disease.

BACKGROUND: Children with congenital heart disease (CHD) are thought to have low levels of physical activity (PA), but few studies have used objective measures of PA in this population. METHODS AND RESULTS: We recruited patients with mild, moderate, and severe CHD and cardiac transplant recipients, aged 8 to 19 years, from pediatric cardiology clinics throughout British Columbia and Yukon, Canada. Participants were fitted with an ActiGraph accelerometer to be worn over the right hip for 7 days. Daily means were estimated for a variety of accelerometry-derived metrics, including moderate-to-vigorous PA and percentage of sedentary time if they had at least 3 valid days of accelerometry data. Participants also completed a PA questionnaire. We included 90 participants (aged 13.6±2.7 years; 54% male), of which 26 had mild CHD, 26 had moderate CHD, 29 had severe CHD, and 9 were cardiac transplant recipients. Median daily moderate-to-vigorous PA was 43 min/day (interquartile range: 28.9-56.9 min/day), and 8% met PA guidelines of 60 minutes of moderate-to-vigorous PA at least 6 days a week. There were no significant differences in any accelerometry-derived metric according to CHD severity. Boys were significantly more active and less sedentary than girls. Activity declined and sedentary behaviors increased with age in both sexes. Sports participation was common, including competitive out-of-school clubs (57%). PA restrictions from cardiologists were rare (15%). CONCLUSIONS: We found normal age-sex patterns of PA in children with CHD. There were no differences in PA by CHD severity, suggesting that sociocultural factors are likely important determinants of PA in these children.

Stress Echocardiographic Evaluation for D-Transposition of the Great Arteries after Atrial Redirection: Unmasking Early Signs of Myocardial Dysfunction and Baffle Stenosis.

BACKGROUND: The authors used semisupine cycle ergometry stress echocardiography to assess cardiac function and unmask baffle stenosis in patients with d-transposition of the great arteries after atrial redirection surgery. METHODS: This was a retrospective review of semisupine cycle ergometry stress echocardiography performed in 53 patients (64% male; mean age, 24.0 years; 90% Mustard procedure) and 56 healthy control subjects. Incremental exercise to volitional fatigue was performed. Hemodynamic data, echocardiographic cardiac dimensions, area change, tissue Doppler velocities, strain, ventricular synchronization, and superior vena cava flow velocities before and immediately after exercise are reported. RESULTS: Patients had lower exercise capacity (870 vs 1,854 J/kg, P < .001) and peak heart rates (132 vs 167 beats/min, P < .001). Stroke volume index did not increase with exercise (45 vs 47 mL/m2, P = .400). Cardiac index increased in both groups with exercise (3.0 vs 6.1 and 2.9 vs 7.0 L/min/m2, P < .001) and was higher in control subjects (P = .006). Right ventricular diastolic and systolic areas decreased significantly with exercise in both the short-axis and four-chamber views. Right and left ventricular contraction time shortened with exercise (405 vs 247 and 338 vs 217 msec, P < .001) and remained synchronous (ratio of right ventricular to left ventricular contraction time = 0.080). Doppler velocities in patients with baffle obstruction were higher in the lower superior vena cava with exercise compared with nonobstructed patients (1.87 vs 1.46 m/sec, P = .020) and normalized after catheter intervention (1.49 vs 1.46 m/sec, P = .800). CONCLUSIONS: Patients with d-transposition of the great arteries have lower exercise capacity and peak heart rates. The systemic right ventricle presents a lesser but qualitatively normal systolic response and decreased diastolic filling. Semisupine cycle ergometry stress echocardiography unmasked SVC obstruction.