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The existence of a "weekend effect" in heart transplantation (HTx) is understudied. The present study sought to determine whether the odds of (HTx) offer acceptance differed for adult and pediatric candidates depending upon the day on which the offer occurred.United Network for Organ Sharing data were used to identify all HTx offers to adult (listing age ≥18) and pediatric candidates from 2000-2019. Odds of offer acceptance were studied, comparing weekends, holidays, and conferences (Society of Thoracic Surgeons [STS], American Association for Thoracic Surgery [AATS], International Society for Heart and Lung Transplantation [ISHLT]) to "baseline" (all other days). Multivariable binary logistic regression analyses were performed to determine independent predictors of offer nonacceptance, controlling for the impacts of program transplant volume, region, and candidate characteristics.A total of 323,953 offers occurred - 298,405 to adults and 25,548 to pediatric candidates. Clinically significant differences did not exist in donor or candidate characteristics between baseline or other events. The number of offers per day was stable throughout the year for both adults (p = 0.191) and pediatrics (p = 0.976). In adults, independently lower odds of acceptance existed on weekends (OR 0.88 [95% CI 0.84-0.92]), conferences in aggregate (0.86 [0.77-0.95]), and holidays in aggregate (0.81 [0.72-0.91]). In children, independently lower odds of acceptance were seen on weekends (0.88 [0.79-0.98]), during STS (0.46 [0.25-0.83], and during Christmas (0.32 [0.14-0.76]).The day on which a HTx offer occurs significantly impacts its likelihood of acceptance. Further work can determine the impacts of human behavior or resource distribution, but knowledge of this phenomenon can inform efforts to ensure ideal organ allocation throughout the year.

BackgroundCardiac rehabilitation (CR) is an important tool for improving fitness and quality of life in those with heart disease (HD). Few pediatric centers use CR to care for these patients, and virtual CR is rarely used. Additionally, it is unclear how the COVID-19 era has changed CR outcomes.ObjectivesThis study assessed fitness improvements in young HD patients participating in both facility-based and virtual CR during the COVID-19 pandemic.MethodsThis retrospective single-center cohort study included new patients who completed CR from March 2020 through July 2022. CR outcomes included physical, performance, and psychosocial measures. Comparison between serial testing was performed with a paired t-test with PResultsThere were 47 patients (19±7.3 years-old; 49% male) who completed CR. Improvements were seen in peak oxygen consumption (VO2, 62.3±16.1 v 71±18.2% of predicted, p=0.0007), 6-minute walk (6MW) distance (401±163.8 v 480.7±119.2 meters, p=2(60±15.3 v 70.2±17.8 % of predicted; p=0.002) were seen among those that completed facility-based CR; this was not observed in the virtual group. Both groups demonstrated improvement in 6MW distance, sit-to-stand repetitions, and sit-and-reach distance.ConclusionsCompletion of a CR program resulted in fitness improvements during the COVID-19 era regardless of location.

Aims Risk stratification algorithms for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) and regional differences in clinical practice have evolved over time. We sought to compare primary prevention implantable cardioverter defibrillator (ICD) implantation rates and associated clinical outcomes in US vs. non-US tertiary HCM centres within the international Sarcomeric Human Cardiomyopathy Registry. Methods and results We included patients with HCM enrolled from eight US sites (n = 2650) and five non-US (n = 2660) sites and used multivariable Cox-proportional hazards models to compare outcomes between sites. Primary prevention ICD implantation rates in US sites were two-fold higher than non-US sites (hazard ratio (HR) 2.27 [1.89–2.74]), including in individuals deemed at high 5-year SCD risk (≥6%) based on the HCM risk-SCD score (HR 3.27 [1.76–6.05]). US ICD recipients also had fewer traditional SCD risk factors. Among ICD recipients, rates of appropriate ICD therapy were significantly lower in US vs. non-US sites (HR 0.52 [0.28–0.97]). No significant difference was identified in the incidence of SCD/resuscitated cardiac arrest among non-recipients of ICDs in US vs. non-US sites (HR 1.21 [0.74–1.97]). Conclusion Primary prevention ICDs are implanted more frequently in patients with HCM in US vs. non-US sites across the spectrum of SCD risk. There was a lower rate of appropriate ICD therapy in US sites, consistent with a lower-risk population, and no significant difference in SCD in US vs. non-US patients who did not receive an ICD. Further studies are needed to understand what drives malignant arrhythmias, optimize ICD allocation, and examine the impact of different ICD utilization strategies on long-term outcomes in HCM.

Patients with Anderson-Fabry disease (AFD) have an elevated incidence of resting arrhythmias and ischemic heart disease, but their exercise arrhythmia burden and ischemic changes are not well understood. In addition, little research has been done on heart rate recovery in these patients. We retrospectively reviewed charts of patients with AFD who underwent maximal effort cardiopulmonary exercise testing (CPET) (n=44; 38.2 ± 13.8 yr; 23 men) from 2012 through 2018. Electrocardiographic, Holter monitoring, echocardiographic, cardiac magnetic resonance imaging, and patient demographic data were collected. No patient had adverse events that necessitated CPET termination, whereas 25 (57%) had ectopy during CPET, including 3 (7%) with frequent premature atrial contractions and 5 (11%) with frequent premature ventricular contractions. The ectopic burden was higher during resting electrocardiographic monitoring before exercise. In addition, 7 patients (16%) had pathologic ST-segment or T-wave changes on CPET, defined as ST-segment changes ≥2 mm. Among the patients who had concurrent cardiac magnetic resonance findings with their CPET (n=27), ST-segment or T-wave changes were associated with left ventricular myocardial mass (r=0.43, P=0.02). Chronotropic incompetence was seen during CPET in 28 patients (64%); however, only 2 patients (4%) had abnormal heart rate recovery at 1 minute. This study shows that patients with AFD can safely undergo exercise testing but have a high incidence of exercise-induced arrhythmias and ischemic changes. Ischemic electrocardiographic changes during exercise testing are associated with myocardial mass. Despite the chronotropic incompetence associated with AFD, heart rate recovery appears to be generally preserved in these patients.

The aim of this study was to improve understanding of exercise medicine training needs for pediatric cardiology fellows. A survey was sent via email to all (N = 63) pediatric cardiology training program directors in the United States to evaluate the perceived exercise training needs of pediatric cardiology fellows. The survey consisted of multiple-choice responses as well as a few open-ended responses. A 60% response rate was achieved. 74% of programs did not have a pre-existing exercise core program. This type of training was felt to be important or very important in 84%. A wide variability of time allotted for exercise training exists amongst programs from 4 weeks, with 2 weeks being most common. There was no consensus on a target number of total exercise tests nor types of tests in which fellows should participate. Preferred methods in training consisted of lectures and online media. Less preferred methods of teaching methods included dedicated reading of a handbook, a dedicated rotation, or live webinars. There was general support to develop exercise training competencies as well as the associated online learning materials with a focus on competency rather than target numbers. There is a need for educational recommendations for exercise training in pediatric cardiology fellowships as well as a unified method of achieving competencies.

Aims Childhood-onset hypertrophic cardiomyopathy (HCM) is far less common than adult-onset disease, thus natural history is not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM. Methods and results We performed an observational cohort study of 7677 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Hypertrophic cardiomyopathy patients were stratified by age at diagnosis [18 years (adulthood)] and assessed for composite endpoints reflecting heart failure (HF), life-threatening ventricular arrhythmias, atrial fibrillation (AF), and an overall composite that also included stroke and death. Stratifying by age of diagnosis, 184 (2.4%) patients were diagnosed in infancy; 1128 (14.7%) in childhood; and 6365 (82.9%) in adulthood. Childhood-onset HCM patients had an ∼2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the 1st decade following baseline visit, but HF and AF becoming more common by the end of the 2nd decade. Sarcomeric variants were more common in childhood-onset HCM (63%) and carried a worse prognosis than non-sarcomeric disease, including a greater than two-fold increased risk of HF [HRadj 2.39 (1.36–4.20), P = 0.003] and 67% increased risk of the overall composite outcome [HRadj 1.67 (1.16–2.41), P = 0.006]. When compared with adult-onset HCM, childhood-onset was 36% more likely to develop life-threatening ventricular arrhythmias [HRadj 1.36 (1.03–1.80)] and twice as likely to require transplant or ventricular assist device [HRadj 1.99 (1.23–3.23)]. Conclusion Patients with childhood-onset HCM are more likely to have sarcomeric disease, carry a higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. These findings provide insight into the natural history of disease and can help inform clinical risk stratification.

There have been significant improvements in the skeletal muscle and respiratory care for patients with Duchenne muscular dystrophy (DMD) over the last two decades. This has resulted in longer expected survival as many patients will live into their 20s and 30s. This timeline has resulted in a greater proportion of patients experiencing heart failure and cardiac-related mortality. Herein, we describe the current indications for medical therapy for patients with DMD.

Visual Abstract, Highlights • Mentees are more satisfied with their mentorship experience when they have had more than 3 mentors or a mentor from outside of their practice/institution. • Satisfaction with the mentoring relationship is significantly associated with perceived satisfaction in achieving professional goals. • Sex and race/ethnicity concordance in mentoring relationships is associated with positive outcomes. • Characteristics that mentees desire in a mentor tend to change with time/career stage., Summary The effects of mentorship on measurable outcomes of success and the aspects of mentorship that are most valuable in promoting the careers of cardiologists are unclear. To address this, we conducted a large-scale survey of cardiologists in a real-world setting. We identified factors that enhance the mentorship experience, and found that mentee needs change with career stage. Importantly, satisfaction with the mentoring relationship is significantly associated with perceived satisfaction in achieving professional goals. Furthermore, we found that gender and race concordance in mentoring relationships is an important variable with the potential to increase diversity in the field of cardiology.

Patients with Duchenne muscular dystrophy have multiple risk factors for lower extremity oedema. This study sought to define the frequency and predictors of oedema. Patients aged 15 years and older were screened by patient questionnaire, and the presence of oedema was confirmed by subsequent physical exam. Twenty-four of 52 patients (46%) had oedema, 12 of whom had swelling extending above the foot and two with sores/skin breakdown. There was no significant difference in age, frequency, or duration of glucocorticoid use, non-invasive respiratory support use, forced vital capacity, cardiac medication use, or ejection fraction between patients with and without oedema (all p > 0.2). Those with oedema had a greater time since the loss of ambulation (8.4 years versus 3.5 years; p = 0.004), higher body mass index (28.3 versus 24.8; p = 0.014), and lower frequency of deflazacort use (67% versus 89%; p = 0.008). Multivariate analysis revealed a longer duration of loss of ambulation (p = 0.02) and higher body mass index (p = 0.009) as predictors of oedema. Lower extremity oedema is common in Duchenne muscular dystrophy but independent of cardiac function. Interventions focused on minimising body mass index increases over time may be a therapeutic target.

Aims Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM). The newly developed HCM Risk-Kids model provides clinicians with individualized estimates of risk. The aim of this study was to externally validate the model in a large independent, multi-centre patient cohort. Methods and results A retrospective, longitudinal cohort of 421 patients diagnosed with HCM aged 1–16 years independent of the HCM Risk-Kids development and internal validation cohort was studied. Data on HCM Risk-Kids predictor variables (unexplained syncope, non-sustained ventricular tachycardia, maximal left ventricular wall thickness, left atrial diameter, and left ventricular outflow tract gradient) were collected from the time of baseline clinical evaluation. The performance of the HCM Risk-Kids model in predicting risk at 5 years was assessed. Twenty-three patients (5.4%) met the SCD end-point within 5 years, with an overall incidence rate of 2.03 per 100 patient-years [95% confidence interval (CI) 1.48–2.78]. Model validation showed a Harrell’s C-index of 0.745 (95% CI 0.52–0.97) and Uno’s C-index 0.714 (95% 0.58–0.85) with a calibration slope of 1.15 (95% 0.51–1.80). A 5-year predicted risk threshold of ≥6% identified 17 (73.9%) SCD events with a corresponding C-statistic of 0.702 (95% CI 0.60–0.81). Conclusions This study reports the first external validation of the HCM Risk-Kids model in a large and geographically diverse patient population. A 5-year predicted risk of ≥6% identified over 70% of events, confirming that HCM Risk-Kids provides a method for individualized risk predictions and shared decision-making in children with HCM.

Cardiovascular disease (CVD) is a major competing cause of morbidity and mortality in patients with cancer. Cancer treatment can have detrimental short- and long-term cardiovascular effects. Moreover, cancer patients may have a significant loss in cardiorespiratory fitness, a key CVD risk factor, during and after cancer treatment. Exercise training has emerged as a potential intervention to improve fitness and reduce the risk of CVD in cancer. In this review, we discuss the role of cardiorespiratory fitness to predict cancer and CVD outcomes, as well as explore the impact of exercise training to improve fitness and other key outcomes in patients with cancer. The role of cardio-oncology rehabilitation will also be highlighted.

Exercise limitation is almost universal among Fontan patients. Identifying unique clinical features in the small fraction of Fontan patients with normal exercise capacity (high-capacity Fontan [HCF]) provides potential to inform clinical strategies for those with low exercise capacity (usual Fontan).We performed a retrospective chart review of all patients with single-ventricle physiology palliated with a Fontan operation who underwent incremental cardiopulmonary exercise testing at Cincinnati Children's Hospital Medical Center from 2013 to 2018. Comparison was between patients with peak oxygen uptakevs ≥ 80% predicted.A total of 22 of 112 patients were classified as HCF (68% were female; aged 18 ± 7 years). During incremental exercise, peak oxygen uptake (86.1% ± 6.1% vs 62% ± 12.2% predicted; P0.001) was greater in HCF vs usual Fontan despite similar chronotropic impairment, resulting in a greater oxygen pulse in HCF. Pulmonary function, breathing reserve, and ventilatory equivalent for COApproximately 1 in 5 Fontan patients who undergo cardiopulmonary exercise testing have normal exercise capacity despite chronotropic impairment. This implies a better preserved stroke volume, perhaps due to greater muscle pump-mediated preload. Additionally, a complicated perioperative Fontan course is associated with eventual impaired functional capacity.

Pediatric chest pain is common and though usually benign often leads to unnecessary diagnostic testing. There is limited evidence as to whether a local consensus guideline can decrease testing frequency without negatively affecting the overall yield. In addition, it is unknown whether the addition of pulmonary function testing to a cardiopulmonary exercise test increases the diagnostic yield in pediatric patients with chest pain. A retrospective chart review was performed on all new pediatric patients who presented with chest pain at our academic center’s pediatric cardiology clinic 18 months before and after the implementation of a standard management guideline. Data from the encounter-associated echocardiogram, cardiopulmonary exercise test, and pulmonary function test, when available, were analyzed. There were no significant differences in patient volume or demographic characteristics in the 18 months before (n = 768) and after (n = 778) guideline implementation. There were significant reductions in the number of ordered echocardiograms (n = 131; 17% vs. n = 75; 9.6%, p

INTRODUCTION Cardiorespiratory fitness (CRF) measured by oxygen consumption (V˙O2) during exercise is an important marker of health. The traditional method of indexing V˙O2 to total body mass is suboptimal because skeletal muscle mass (SMM), rather than fat and extracellular fluid, is the main contributor to CRF. The traditional estimating equations for peak V˙O2 in youth do not account for this. Bioelectric impedance analysis (BIA) is a noninvasive method to accurately measure body composition. The objectives of this study were to 1) examine the relationship of body composition indices and peak V˙O2 in healthy children, adolescents, and young adults, and 2) derive an optimized estimating equation incorporating BIA and compare its performance with traditional estimating equations. METHODS A retrospective, cross-sectional, single-center study of patients

Background: The term “end stage” has been used to describe hypertrophic cardiomyopathy (HCM) with left ventricular systolic dysfunction (LVSD), defined as occurring when left ventricular ejection fraction is Methods: Data from 11 high-volume HCM specialty centers making up the international SHaRe Registry (Sarcomeric Human Cardiomyopathy Registry) were used to describe the natural history of patients with HCM-LVSD. Cox proportional hazards models were used to identify predictors of prognosis and incident development. Results: From a cohort of 6793 patients with HCM, 553 (8%) met the criteria for HCM-LVSD. Overall, 75% of patients with HCM-LVSD experienced clinically relevant events, and 35% met the composite outcome (all-cause death [n=128], cardiac transplantation [n=55], or left ventricular assist device implantation [n=9]). After recognition of HCM-LVSD, the median time to composite outcome was 8.4 years. However, there was substantial individual variation in natural history. Significant predictors of the composite outcome included the presence of multiple pathogenic/likely pathogenic sarcomeric variants (hazard ratio [HR], 5.6 [95% CI, 2.3–13.5]), atrial fibrillation (HR, 2.6 [95% CI, 1.7–3.5]), and left ventricular ejection fraction Conclusions: HCM-LVSD affects ≈8% of patients with HCM. Although the natural history of HCM-LVSD was variable, 75% of patients experienced adverse events, including 35% experiencing a death equivalent an estimated median time of 8.4 years after developing systolic dysfunction. In addition to clinical features, genetic substrate appears to play a role in both prognosis (multiple sarcomeric variants) and the risk for incident development of HCM-LVSD (thin filament variants).

Background: Pathogenic variants in MYBPC3 , encoding cardiac MyBP-C (myosin binding protein C), are the most common cause of familial hypertrophic cardiomyopathy. A large number of unique MYBPC3 variants and relatively small genotyped hypertrophic cardiomyopathy cohorts have precluded detailed genotype-phenotype correlations. Methods: Patients with hypertrophic cardiomyopathy and MYBPC3 variants were identified from the Sarcomeric Human Cardiomyopathy Registry. Variant types and locations were analyzed, morphological severity was assessed, and time-event analysis was performed (composite clinical outcome of sudden death, class III/IV heart failure, left ventricular assist device/transplant, atrial fibrillation). For selected missense variants falling in enriched domains, myofilament localization and degradation rates were measured in vitro. Results: Among 4756 genotyped patients with hypertrophic cardiomyopathy in Sarcomeric Human Cardiomyopathy Registry, 1316 patients were identified with adjudicated pathogenic truncating (N=234 unique variants, 1047 patients) or nontruncating (N=22 unique variants, 191 patients) variants in MYBPC3 . Truncating variants were evenly dispersed throughout the gene, and hypertrophy severity and outcomes were not associated with variant location (grouped by 5′–3′ quartiles or by founder variant subgroup). Nontruncating pathogenic variants clustered in the C3, C6, and C10 domains (18 of 22, 82%, P Conclusions: Truncating variants account for 91% of MYBPC3 pathogenic variants and cause similar clinical severity and outcomes regardless of location, consistent with locus-independent loss-of-function. Nontruncating MYBPC3 pathogenic variants are regionally clustered, and a subset also cause loss of function through failure of myofilament incorporation and rapid degradation. Cardiac morphology and clinical outcomes are similar in patients with truncating versus nontruncating variants.

Supplemental Digital Content is available in the text., Background: Hypertrophic cardiomyopathy is the leading cause of sudden cardiac death (SCD) in children and young adults. Our objective was to develop and validate a SCD risk prediction model in pediatric hypertrophic cardiomyopathy to guide SCD prevention strategies. Methods: In an international multicenter observational cohort study, phenotype-positive patients with isolated hypertrophic cardiomyopathy 70% prediction accuracy and incorporates risk factors that are unique to pediatric hypertrophic cardiomyopathy. An individualized risk prediction model has the potential to improve the application of clinical practice guidelines and shared decision making for implantable cardioverter defibrillator insertion. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT0403679.

Despite increasing utilization of continuous-flow pediatric ventricular assist devices (VAD) in children, data on exercise testing and cardiac rehabilitation (CR) are unknown. We described variation in CR practices and identified barriers to exercise testing and CR. A survey was performed through the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) representing pediatric VAD centers across North America. Descriptive statistics were performed. A multidisciplinary cohort of 52 respondents from 28 pediatric VAD centers responded. Although 38% reported performing exercise testing, most (65%) used 6 minute walk tests rather than formal cycle or treadmill exercise testing. While all respondents refer to physical therapy during the initial inpatient stay for VAD placement, only 52% refer to a CR program. When performed, CR was performed at an ACTION center (84%), a local specialized center (21%), or a home-based CR program (26%). Commonly cited barriers to either CR or exercise testing were inadequate resources, inadequate implementation logistics knowledge, concerns about safety, inability of patients to travel to a CR facility, and concern about utility of exercise testing or CR. Over 90% of centers were interested in implementing a standardized pediatric VAD CR program. Utilization of exercise testing and CR after VAD placement is variable. Despite perceived barriers, most pediatric VAD centers are interested in implementing a standardized CR program for recipients. In response to this interest, we plan to implement a standardized CR protocol to all ACTION pediatric VAD centers in an effort to improve pretransplant waitlist rehabilitation and post-transplant outcomes.

Background Emergency care planning is an important component of healthcare transition, particularly for patients with medical complexity. Duchenne muscular dystrophy (DMD) is a complex, progressive pediatric-onset disease affecting multiple organ systems including impairment of cardiac and pulmonary function, high risk for fractures, fat embolism, adrenal crisis and malignant hyperthermia. Appropriate interdisciplinary emergency management is critical for survival for these patients. The purpose of this quality improvement project was to develop a process to reliably share an individualized emergency care plan (ECP) with patients and their families as part of a larger plan to develop an integrated transition program. Methods An interdisciplinary team of nurses and clinicians used the principles of quality improvement to develop a reliable process to assure patients with DMD received an individualized, multidisciplinary ECP at routine interdisciplinary clinic visits. Additionally, the project used surveys to assess patient and family satisfaction with the letter and whether it improved their knowledge of emergency care. Results Sixty-two patients were seen during the study timeframe. All received an ECP. Sixty-two surveys were sent and twenty-three surveys were returned. Of those that responded, the majority stated the ECP increased their knowledge of emergency care. Conclusion ECPs can be developed and disseminated to patients with DMD and their caregivers. This tool can potentially promote timely and appropriate emergency care for these patients with unique and complex medical needs.

PurposeVariants inMYBPC3causing loss-of-function are the most common cause of HCM. However, a substantial number of patients carry missense variants of uncertain significance (VUS) inMYBPC3.We hypothesize that a structural-based algorithm, STRUM, which estimates the effect of missense variants on protein folding, will improve clinical risk stratification of patients with HCM and aMYBPC3VUS.MethodsAmong 7,963 patients in the multi-center Sarcomeric Human Cardiomyopathy Registry, 120 unique missense VUSs inMYBPC3were identified. Variants were evaluated for their effect on subdomain folding and a stratified time-to-event analysis for an overall composite endpoint (first occurrence of ventricular arrhythmia, heart failure, all-cause mortality, atrial fibrillation, and stroke) was performed for patients with HCM and aMYBPC3missense VUS.ResultsWe demonstrated that patients carrying aMYBPC3VUS predicted to cause subdomain misfolding (STRUM +, ΔΔG ≤-1.2 kcal/mol) exhibited a higher rate of adverse events compared to those with a STRUM-VUS (Hazard Ratio=2.29, P=0.0282).In silicosaturation mutagenesis ofMYBPC3identified 4,943/23,427 (21%) missense variants that were predicted to cause subdomain misfolding.ConclusionsSTRUM enables clinical risk stratification of patients with HCM and aMYBPC3VUS and has the capacity to improve prognostic predictions and clinical decision making.

Introduction: The prevalence of childhood-onset hypertrophic cardiomyopathy (HCM) is lower than adult-onset disease, thus natural history is not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM. Methods: We performed an observational cohort study of 6345 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe) and Toronto's SickKids hospital. HCM patients were stratified by age at diagnosis (18 years (adulthood)) and assessed for composite endpoints reflecting heart failure (HF), life-threatening ventricular arrhythmias, atrial fibrillation (AF), and an overall composite that also included stroke and death. Results: Based on defined age of diagnosis stratification, 173 (3%) patients were diagnosed in infancy, 909 (14%) in childhood, and 5263 (83%) in adulthood. Childhood-onset HCM patients had a 2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the 1st decade following diagnosis, and HF and AF more common by the end of the 2nd decade ( Fig, a ). Sarcomeric HCM was more common in childhood-onset HCM (62%) and carried a worse prognosis than non-sarcomeric disease, including a >2-fold increased risk of HF (HR adj 2.39 [1.36-4.20], p=0.003) and 67% increased risk of overall composite events (HR adj 1.67 [1.16-2.41], p=0.006). When compared to adult-onset HCM, childhood-onset was 36% more likely to develop life-threatening ventricular arrhythmias (HR adj 1.36 [1.03-1.80]) and twice as likely to require transplant or ventricular assist device (HR adj 1.99 [1.23-3.23]) ( Fig, b ). Conclusion: Patients with childhood-onset HCM are more likely to have sarcomeric disease, carry higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. These findings provide insight into disease biology and can help improve the precision of risk prediction.

Introduction: Risk stratification for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) has evolved with notable differences in international practice trends and US vs European guidelines. Hypothesis: Utilization of primary prevention implantable cardioverter defibrillators (ICD) is higher in the US. Methods: We examined rates of primary prevention ICD implantation in 5,063 HCM patients in the international SHaRe registry from 2000 - 2020 (NUS=2,390; Nnon-US=2,673). Using multiple logistic regression we compared probability of ICD implantation for US vs non-US sites adjusting for standard SCD risk factors (Figure 1A). Interaction tests were performed to identify risk factors differentially associated with ICD implantation in US vs non-US sites after 2014 when the European Society of Cardiology (ESC) risk score was introduced. Results: The odds of ICD implantation were 3-fold higher in US sites [ORUS/non-US=3.11 (2.54 -3.81)] (Figure 1A). Odds remained similar after adjustment for ESC risk score [OR =3.17 (2.57 -3.91)]. Implantation rates were higher in the US throughout the study period with a notable drop in rates in both US and non-US sites after 2014 and a reduction in the magnitude of the difference in ICD utilization between US and non-US sites (ORUS/non-US ( 40 mm) was a stronger predictor in non-US sites [ORNon-US=2.9 (2.1-4.0) vs ORUS=1.3 (1-1.6); pinteraction Conclusions: ICD utilization rates vary globally. In this study, primary prevention ICD utilization rates were 3-fold higher in the US despite adjustment for standard SCD risk factors. Further studies are needed to evaluate outcomes of these practice differences.

Introduction: Obesity is associated with comorbidities that may be detrimental to single-ventricle patients who have had a Fontan procedure. We assessed the prevalence of obesity in adults with a Fontan circulation and evaluated the hypothesis that higher body mass index (BMI) in early childhood is associated with obesity in adulthood. Methods: Retrospective cohort study of patients with a Fontan circulation aged 18-32 years, seen 2011-2019. Those with an atriopulmonary Fontan or chromosomal abnormality known to affect growth were excluded. Historical height and weight measurements, results of recent cardiac testing, and body mass index (BMI) over time were recorded. Obesity was defined as BMI ≥30 kg/m 2 . The associations between childhood anthropometrics, adult BMI, and most recent cardiac testing were assessed. Results: The cohort included 113 adults with a Fontan circulation (median age 22.7 [IQR 20.2-26.4] years; 44% female). There were no significant differences in age, age at Fontan, Fontan type, or ventricular morphology between obese (n=21, 19%; 52% female) and non-obese (n=92, 81%; 41% female) patients. Compared to non-obese adults, obese patients had higher BMI percentiles at age 2 years (80 th [33-95] vs 43 rd [13-82] percentile, p=0.02), at age 4 years (90 th [73-93] vs 57 th [22-81] percentile, p=0.002), and at the time of the Fontan procedure (85 th [51-98] vs 20 th [5-57] percentile, p=0.002). Being overweight at time of Fontan (BMI percentile >85%) strongly predicted later obesity (OR=18.3, 95% CI 3.7-90.3, p2 (19.1±5.2 vs 25.5±6.6 mL/kg/min, p2 (59±13 vs 65±14% predicted, p=0.06), higher systolic blood pressure (121±17 vs 112±12 mmHg, p=0.007) and higher ventricular end-diastolic pressure (11±4 vs 9±3 mmHg, p= 0.03). Adult BMI weakly correlated with ventricular end-diastolic pressure (r=0.24, p=0.048). Conclusions: Higher BMI in early childhood is associated with obesity in adults with a Fontan circulation. Adult obesity is associated with worse exercise capacity, higher blood pressure, and higher ventricular end-diastolic pressure. Weight interventions in children with a Fontan circulation may help prevent later obesity and its adverse consequences.

Background: Early detection of left ventricular (LV) dysfunction before the onset of overt Duchenne muscular dystrophy–associated cardiomyopathy (DMDAC) may direct clinical management to slow onset of dysfunction. We aimed to assess whether LV strain will predict those who develop DMDAC. Methods: We performed a single center retrospective case control study of patients with Duchenne muscular dystrophy who underwent serial cardiac magnetic resonance between 2006 and 2019. Patients with Duchenne muscular dystrophy with an LV ejection fraction ≥55% on ≥1 cardiac magnetic resonance were identified and grouped into age-matched +DMDAC and –DMDAC. Within 3 years, +DMDAC had a subsequent cardiac magnetic resonance with a decline in LV ejection fraction ≥10% and absolute LV ejection fraction ≤50%. −DMDAC maintained an LV ejection fraction ≥55% on serial cardiac magnetic resonances. Two-dimensional and 3-dimensional global radial strain, global circumferential strain (GCS), and global longitudinal strain were measured using tissue tracking software and their ability to predict DMDAC onset was assessed. Multivariable analysis adjusted for late gadolinium enhancement. Results: Thirty +DMDAC and 30 age-matched −DMDAC patients were included with a total of 164 studies analyzed. Before DMDAC onset, 2-dimensional global radial strain and GCS were significantly worse in +DMDAC compared with −DMDAC (25.1±6.0 versus 29.0±6.3, P =0.011; −15.4%±2.4 versus −17.3%±2.6, P =0.003). Three-dimensional GCS and global radial strain had similar findings. Among strain measures, 3-dimensional GCS had the highest area under the curve to predict DMDAC in our cohort. These findings persisted after adjusting for the presence of late gadolinium enhancement. Conclusions: Reduced global radial strain and GCS may predict those at risk for developing DMDAC before onset of LV dysfunction and its clinical utility warrants further exploration.

BACKGROUND Antithymocyte globulin (ATG) consists of polyclonal antibodies directed primarily against human T lymphocytes but may contain antibodies with affinity for other tissues in the transplanted organ, resulting in complement (C4d) deposition. This phenomenon has been demonstrated in endomyocardial biopsies (EMBs) of adult cardiac transplants. We examined the relationship of induction immunosuppression with ATG and C4d deposition in EMB of pediatric cardiac transplants. METHODS Results of C4d immunohistochemistry were available from all EMB of patients transplanted at our center between June 2012 and April 2018 (n = 48) who received induction immunosuppression with either ATG (n = 20) or basiliximab (n = 28) as the standard of care. RESULTS C4d deposition in the first year post-heart transplant was more commonly seen among patients who received ATG induction (20% of EMBs in ATG group vs 1% of EMBs in basiliximab group; p

Supplemental Digital Content is available in the text., Background: Pathogenic variants in MYBPC3, encoding cardiac MyBP-C (myosin binding protein C), are the most common cause of familial hypertrophic cardiomyopathy. A large number of unique MYBPC3 variants and relatively small genotyped hypertrophic cardiomyopathy cohorts have precluded detailed genotype-phenotype correlations. Methods: Patients with hypertrophic cardiomyopathy and MYBPC3 variants were identified from the Sarcomeric Human Cardiomyopathy Registry. Variant types and locations were analyzed, morphological severity was assessed, and time-event analysis was performed (composite clinical outcome of sudden death, class III/IV heart failure, left ventricular assist device/transplant, atrial fibrillation). For selected missense variants falling in enriched domains, myofilament localization and degradation rates were measured in vitro. Results: Among 4756 genotyped patients with hypertrophic cardiomyopathy in Sarcomeric Human Cardiomyopathy Registry, 1316 patients were identified with adjudicated pathogenic truncating (N=234 unique variants, 1047 patients) or nontruncating (N=22 unique variants, 191 patients) variants in MYBPC3. Truncating variants were evenly dispersed throughout the gene, and hypertrophy severity and outcomes were not associated with variant location (grouped by 5′–3′ quartiles or by founder variant subgroup). Nontruncating pathogenic variants clustered in the C3, C6, and C10 domains (18 of 22, 82%, P

With the new era of increasing use of mechanical circulatory support (MCS) in children, seemingly more patients with elevated pulmonary vascular resistance (PVR) are having positive outcomes. The purpose of this study was to define the effect of MCS on pediatric patients listed for heart transplant with an elevated PVR. The United Network for Organ Sharing (UNOS) database was used to identify patients aged 0-18 at the time of listing for heart transplant between 2010 and 2019 who had PVR documented (n = 2081). Patients were divided into MCS (LVAD, RVAD, BiVAD, and TAH) and No MCS groups, then divided by PVR (PVR) at the time of listing:3, 3-6, and6 Wood units (WU). MCS was used in 20% overall (n = 426); 57% of those with PVR3, 27% with PVR 3-6, and 16% with PVR6. MCS, PVR3 patients had a higher chance of positive waitlist outcome than all No MCS groups (vs. PVR3, P = .049; vs. PVR 3-6, P = .004; vs. PVR6, P.001). MCS, PVR 3-6 patients had a higher chance of positive waitlist outcome than all No MCS groups (vs. PVR3, P = .048; vs. PVR 3-6, P = .009; vs. PVR6, P.001). MCS, PVR6 patients had a higher chance of positive waitlist outcome than No MCS, PVR6 patients (P = .012). Within the No MCS group, patients with a PVR6 had a higher incidence of negative waitlist outcome compared to PVR3 (17% vs. 10%, P = .002); this was not the case in the MCS group (5% vs. 6%, P = .693). More patients in the MCS group were ventilator dependent (15% vs. 9%, P.001) at the time of listing and less likely to have a functional status50% (43% vs. 73%, P.001). No significant differences in post-transplant survival were found in pairwise comparisons of MCS and No MCS PVR subgroups. Patients supported with MCS had a significantly higher chance of a positive waitlist outcome than those without such support regardless of PVR status. This was most pronounced with a PVR greater than 6 WU. MCS compared to No MCS patients had better waitlist survival and equivalent post-transplant survival. MCS patients, despite being more ill, had better overall survival regardless of PVR.

Pediatric chest pain is common and though usually benign often leads to unnecessary diagnostic testing. There is limited evidence as to whether a local consensus guideline can decrease testing frequency without negatively affecting the overall yield. In addition, it is unknown whether the addition of pulmonary function testing to a cardiopulmonary exercise test increases the diagnostic yield in pediatric patients with chest pain. A retrospective chart review was performed on all new pediatric patients who presented with chest pain at our academic center's pediatric cardiology clinic 18 months before and after the implementation of a standard management guideline. Data from the encounter-associated echocardiogram, cardiopulmonary exercise test, and pulmonary function test, when available, were analyzed. There were no significant differences in patient volume or demographic characteristics in the 18 months before (n = 768) and after (n = 778) guideline implementation. There were significant reductions in the number of ordered echocardiograms (n = 131; 17% vs. n = 75; 9.6%, p 0.001) and cardiopulmonary exercise tests (n = 46; 6% vs. n = 29; 4%, p = 0.04) with no concerning pathology discovered in either group. Associated pulmonary function testing performed prior to with exercise testing discovered abnormalities in 19% of the total patients tested. The implementation of a local consensus guideline for pediatric chest pain results in fewer unnecessary tests ordered. There was no concerning pathology before or after guideline implementation, therefore conclusions regarding the diagnostic yield of these guidelines are unfeasible. The addition of pulmonary function testing to cardiopulmonary exercise tests increases the potential diagnostic yield in these patients.

Nonischemic dilated cardiomyopathy is deadly and costly, and treatment options are limited. Cardiac rehabilitation has proved safe and beneficial for adults with various types of heart failure. Therefore, we retrospectively evaluated the hypothesis that rehabilitation is safe and improves cardiometabolic health in young patients with nonischemic dilated cardiomypathy. From 2011 through 2015, 8 patients (4 males) (mean age, 20.6 ± 6.6 yr; range, 10–31 yr) underwent rehabilitation at our institution. They were in American Heart Association class C or D heart failure and were on maximal medical therapy. Their mean left ventricular ejection fraction at baseline was 0.26 ± 0.15. Two patients had a left ventricular assist device, and 2 were inpatients. To evaluate safety, we documented adverse events during rehabilitation sessions. Clinical endpoints were measured at baseline, immediately after completing rehabilitation, and after one year. Patients attended 120 of 141 possible sessions (85%), with no adverse events. There were no marked changes in mean left ventricular ejection fraction or body mass index. The patients' mean waist circumference decreased by 1.37 ± 0.6 in (n=5; 95% CI, −2.1 to −0.63). Their 6-minute walk distance increased by a mean of 111 ± 75 m (n=5; 95% CI, 18–205). In our small sample of young patients with nonischemic dilated cardiomyopathy, cardiac rehabilitation was feasible and was associated with minimal risk. Our findings suggest that prospective studies in this population are warranted.

Although medium-term survival following Fontan operations in the modern era has improved dramatically, late cardiovascular and extracardiac morbidity are common and are associated with impaired quality of life and premature late mortality. This serves as a reminder of the extraordinary adaptations required of the cardiovascular system when the systemic arterial, systemic venous and pulmonary circulations are placed in series coupled to a single ventricular pump. This article reviews the key features and principles that govern interactions between the ventricle, systemic arterial circulation, the systemic venous and pulmonary circulatory compartments, the microcirculation, and lymphatic circulations. The overarching aim is to provide insight into the integrative pathophysiology that governs the Fontan circulation and stimulate thoughtful approaches to advance research.

Iron deficiency anemia has been associated with a secondary and potentially reversible cardiomyopathy. The pathophysiologic paradigm has been that the hematologic disease begets cardiac dysfunction. There may be, however, a point at which myocardial injury is irreversible in susceptible individuals. We present the case of a 4-year-old, developmentally normal, child who presented with iron deficiency anemia and a dilated cardiomyopathy with congestive heart failure. Despite appropriate correction of the anemia, the patient developed decompensated heart failure requiring milrinone therapy and eventual heart transplantation. This report will alert clinicians to the potential for irreversible adverse cardiac remodeling and the importance of close pediatric cardiology consultation and serial assessment in order to implement appropriate heart failure therapy.

OBJECTIVE The initial costs of a CF-VAD exceed those of a PF-VAD. However, the safety profile of CF-VAD is superior and the possibility of outpatient device support may justify the additional initial costs. This study analyzed the cost-utility of CF-VAD use in the pediatric population. METHODS A Markov-state transition model was constructed for the clinical course of the two VAD subtypes from implantation until death with variables extracted from internal financial records and the published literature. The modeled population consisted of pediatric heart failure patients who met indications for VAD implant (INTERMACS profile 1 or 2) and were size-eligible for either a PF-VAD or CF-VAD. RESULTS The cost-utility analysis illustrated that CF-VAD is both more effective and less costly compared to PF-VAD at base-case conditions. Sensitivity analyses demonstrated that only in extreme conditions did a CF-VAD strategy not meet criteria for cost-effectiveness (if readmission rate >20% weekly, neurologic event rate >8% weekly, or CF-VAD discharge rates

Purpose Functional status at listing predicts waitlist survival in adult heart transplant candidates including those on mechanical circulatory support. This has not been studied in pediatric heart transplantation although it is an independent predictor of outcomes in pediatric liver transplantation. We aimed to determine the association of: 1) functional status at listing with waitlist and post-transplant outcomes, and 2) functional status at transplant with post-transplant outcomes in pediatric heart transplant candidates. Methods Retrospective registry study of 5754 patients ≤18 years old listed for heart transplant between 1995 and 2019 with Lansky/Karnofsky Play Performance Scale (LPPS) scores in the UNOS database. Standard statistical methods were used to assess relationships of LPPS scores at listing and transplant with waitlist and post-transplant outcomes. A positive waitlist outcome was defined as transplantation, removal from waitlist due to clinical improvement, or remaining on waitlist. Results At listing, 1463 patients had the ability to carry out normal activities (LPPS 80-100), 2338 had mild-moderate restriction in functional status (LPPS 50-70), and 1953 had moderate-severe restriction (LPPS 10-40). Normal activity and mild-moderate restriction at listing were associated with a higher positive waitlist outcome rate compared with moderate-severe restriction (90% vs 80%, p Conclusion Candidate functional status is associated with waitlist as well as post-transplant outcomes. Improvement in functional status between listing and transplant is associated with better outcomes 1-year post-transplant. These data suggest that interventions targeting functional impairment (e.g. physical rehabilitation) have the potential to improve pediatric heart transplant outcomes.

Purpose With the new era of more effective medicines and increasing use of mechanical circulatory support (MCS) in children, seemingly more patients with elevated pulmonary vascular resistance (PVR) are having positive outcomes. The purpose of this study is to define the effect of MCS on pediatric patients listed for heart transplant with an elevated PVR. Methods The United Network for Organ Sharing (UNOS) database was used to identify patients ages 0-18 at time of listing for heart transplant between 2010 and 2019 who had PVR documented. Patients were divided into MCS (LVAD, RVAD, BiVAD, and TAH) and No-MCS groups, then divided by indexed PVR (PVRi) at time of listing: 6 Wood units. Positive waitlist outcome was defined as reaching transplant or delisted because of clinical improvement. Negative waitlist outcome was defined as death or delisted because too sick to transplant. Results 2081 pediatric patients were listed for heart transplant between 2010 and 2019. MCS was used in 20% overall (n=426); 57% of those with PVRi 6. Median MCS duration was 68 days (IQR 30-142). In all three PVRi groups, MCS patients had a significantly higher incidence of positive waitlist outcome compared to No-MCS patients (Table 1). Within the No-MCS group, patients with a PVRi >6 had a higher incidence of negative waitlist outcome compared to PVRi Conclusion Patients supported with MCS had a significantly higher chance of a positive waitlist outcome than those without such support regardless of PVR status. With better waitlist survival and equivalent post-transplant survival compared to No-MCS patients, MCS patients had better overall survival from listing regardless of PVR.

Pediatric restrictive cardiomyopathy (RCM) has high mortality in historical cohorts, and traditional management often involves early referral for heart transplantation (HTx). This study sought to determine outcomes of pediatric RCM at a center that has favored medical management over early listing for HTx. All patients (N = 43) with pure RCM phenotype (RCM, N = 26) and hypertrophic cardiomyopathy with restrictive physiology (RCM/HCM, N = 17) managed at our center over a 15-year period were investigated. Outcomes of those listed for HTx (N = 18) were compared to a benchmark of contemporaneous pediatric RCM patients in the UNOS database (N = 377). Proportional hazards models were used to determine predictors of adverse outcomes. The mean age was 11 ± 9 years and 49% were male. 14 of 18 patients listed received HTx. Overall mortality (12%) was identical between the phenotypes; however, RCM patients were more likely to be listed (P = 0.001) and receive HTx (P = 0.02) compared to RCM/HCM. Prior to HTx, 60% had documented arrhythmia, 16% had cardiac arrest, and 7% required mechanical circulatory support. 4 of 17 patients with an ICD/PM received device therapies (four of five shocks appropriate for VT/VF, and two effective anti-tachycardia pacing interventions). Outcomes of those listed for HTx at our center were similar to the UNOS benchmark. In multivariate analysis, markers of congestive heart failure were associated with adverse outcomes. Heart failure and arrhythmia treatments can delay or possibly prevent the need for HTx in some cases of pediatric RCM. Survival post-HTx is not compromised using this approach.

We aimed to (1) compare a subjective and objective measure of habitual physical activity (PA), (2) determine the association of PA and cardiovascular risk factors, and (3) test the hypothesis that PA is an independent determinant of target organ damage in youth.Cross-sectional analysis of youth with and without type 2 diabetes [mean age = 22 (3.9) y]. PA was measured with International Physical Activity Questionnaire and Actical accelerometer. Target organ damage was assessed with echocardiography and peripheral arterial testing. Subjects were stratified into tertiles of total PA, and differences were tested by analysis of variance and χThe correlation between International Physical Activity Questionnaire and accelerometry was weak (r = .23, P = .0003). Less active subjects had worse cardiovascular risk profiles and target organ damage, including stiffer arteries (P .01). These outcome differences did not reach statistical significance when adjusted for covariates, such as lipid levels and glycemic control.Survey assessment of PA is complicated by inaccurate reporting. There is a strong association of habitual PA with cardiovascular risk factor clustering. PA may exert its beneficial effect on arterial stiffness in obese youth through improved glycemic control.

Background Impaired quality of life (QOL) is associated with congenital heart disease (CHD) and country of residence; however, few studies have compared QOL in patients with differing complexities of CHD across regional populations. The current study examined regional variation in QOL outcomes in a large multinational sample of patients with a Fontan relative to patients with atrial septal defects (ASDs) and ventricular septal defects (VSDs). Methods From the Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease—International Study (APPROACH-IS), 405 patients (163 Fontan and 242 ASD/VSD) across Asia, Europe, and North America provided consent for access to their medical records and completed a survey evaluating QOL (0 to 100 linear analog scale). Primary CHD diagnosis, disease complexity, surgical history, and documented history of mood and anxiety disorders were recorded. Differences in QOL, medical complications, and mood and anxiety disorders between Fontan and ASD/VSD patients, and across geographic regions, were examined using analysis of covariance. Hierarchical regression analyses were conducted to identify variables associated with the QOL ratings. Results Patients with a Fontan reported significantly lower QOL, and greater medical complications and mood and anxiety disorders relative to patients with ASD/VSD. Inpatient cardiac admissions, mood disorders, and anxiety disorders were associated with lower QOL among patients with a Fontan, and mood disorders were associated with lower QOL among patients with ASD/VSD. Regional differences for QOL were not observed in patients with a Fontan; however, significant differences were identified in patients with ASD/VSD. Conclusions Regional variation of QOL is commonplace in adults with CHD; however, it appears affected by greater disease burden. Among patients with a Fontan, regional variation of QOL is lost. Specific attempts to screen for QOL and mood and anxiety disorders among CHD patients may improve the care of patients with the greatest disease burden.

Dystrophic myocardial calcification occurs in the setting of myocardial injury and normal serum calcium. We present a case of a neonate with prominent dystrophic calcification and severe left ventricular systolic dysfunction in the setting of enterovirus myocarditis. These findings are superbly illustrated by multiple imaging modalities. The patient was treated with the novel antiviral, pocapavir, in addition to a standard heart failure regimen. The dystrophic calcification persisted but the left ventricle remodeled significantly. To our knowledge, this is the first reported use of pocapavir for this indication. The literature regarding enterovirus myocarditis and pocapavir is briefly reviewed.