Myocarditis in children 2024, new themes and continued questions.

PURPOSE OF REVIEW: While pediatric myocarditis incidence has increased since the coronavirus disease 2019 (COVID-19) pandemic, there remain questions regarding diagnosis, risk stratification, and optimal therapy. This review highlights recent publications and continued unanswered questions related to myocarditis in children. RECENT FINDINGS: Emergence from the COVID-19 era has allowed more accurate description of the incidence and prognosis of myocarditis adjacent to COVID-19 infection and vaccine administration as well that of multi-system inflammatory disease in children (MIS-C). As cardiac magnetic resonance technology has shown increased availability and evidence in pediatric myocarditis, it is important to understand conclusions from adult imaging studies and define the use of this imaging biomarker in children. Precision medicine has begun to allow real-time molecular evaluations to help diagnose and risk-stratify cardiovascular diseases, with emerging evidence of these modalities in myocarditis. SUMMARY: Recent information regarding COVID-19 associated myocarditis, cardiac magnetic resonance, and molecular biomarkers may help clinicians caring for children with myocarditis and identify needs for future investigations.

Design and implementation of multicenter pediatric and congenital studies with cardiovascular magnetic resonance: Big data in smaller bodies.

Cardiovascular magnetic resonance (CMR) has become the reference standard for quantitative and qualitative assessment of ventricular function, blood flow, and myocardial tissue characterization. There is a preponderance of large CMR studies and registries in adults; However, similarly powered studies are lacking for the pediatric and congenital heart disease (PCHD) population. To date, most CMR studies in children are limited to small single or multicenter studies, thereby limiting the conclusions that can be drawn. Within the PCHD CMR community, a collaborative effort has been successfully employed to recognize knowledge gaps with the aim to embolden the development and initiation of high-quality, large-scale multicenter research. In this publication, we highlight the underlying challenges and provide a practical guide toward the development of larger, multicenter initiatives focusing on PCHD populations, which can serve as a model for future multicenter efforts.

Vitamin D Status and Cardiovascular Disease in College Athletes After SARS-CoV-2 Infection.

OBJECTIVE: To evaluate the association between vitamin D status and CV disease after COVID-19 in college athletes. DESIGN: Retrospective cohort study. SETTING: National College Athletic Association Division-I college athletes from a single academic institution. PATIENTS: A total of 157 athletes (60 female; median age: 20 years) from 9 sports with a positive SARS-CoV-2 test, cardiac magnetic resonance imaging (CMR), and vitamin D level. INDEPENDENT VARIABLES: Serum 25-hydroxyvitamin D level (primary); age, sex (regression models). MAIN OUTCOMES MEASURES: Differences in age, sex, race, ethnicity, myocarditis, pericarditis, and CMR metrics by vitamin D status were analyzed. Regression models were used to assess the relationship between vitamin D status and CMR metrics accounting for age and sex. RESULTS: Low vitamin D (LVD) was found in 33 (21.0%) of athletes, particularly Black males (P < 0.001). Athletes with LVD had higher biventricular and lower mid-ventricular extracellular volumes, but these differences were not significant when corrected for age and sex. Athletes with LVD had higher left ventricle (LV) mass (P < 0.001) and LV mass index (P = 0.001) independent of age and sex. Differences in global circumferential strain were noted but are likely clinically insignificant. Vitamin D status did not associate with myocarditis and pericarditis (P = 0.544). CONCLUSIONS: LVD is common in athletes, particularly in Black males. Although athletes with LVD had higher LV mass, cardiac function and tissue characterization did not differ by vitamin D status. Future studies are needed to determine if the differences in LV mass and LV mass index by vitamin D status are clinically significant. This study suggests that vitamin D status does not impact the development of myocarditis or pericarditis after COVID-19 infection.

Quantifying the impact of post-acute sequelae of coronavirus on the cardiopulmonary endurance of athletes.

Post-acute sequelae of Coronavirus (PASC), or Long COVID, has emerged as a critical health concern. The clinical manifestations of PASC have been described, but studies have not quantified the cardiopulmonary effects. The goal of this study was to quantify PASC cardiopulmonary changes among endurance athletes. Endurance athletes were recruited via social media; 45 met inclusion criteria, 32 had PASC and 13 were asymptomatic at 3 months (control). Comprehensive interviews were conducted to assess: cardiopulmonary symptoms at 3 months; quantitative and qualitative changes in cardiovascular endurance; exercise hours per week at baseline and 3 months; and Modified Oslo, Dyspnea, and EQ-5D-5L scales. All collected data was based on self-reported symptoms. Wilcoxon rank sum compared PASC with control to distinguish the effects of PASC vs effects of COVID infection/lockdown. PASC subjects were more likely to be female (Table). The most common 3-month symptoms in PASC were fatigue and shortness of breath. Based on self-reported data, subjects endorsed a median decrease of 27% in cardiopulmonary endurance levels compared with 0% in controls (p = 0.0019). PASC subjects exercised less hours and had worse self-reported health as compared with controls. PASC subjects also had significantly worse Modified Oslo, Dyspnea, and EQ-5D-5L scores. Of the 32 PASC patients, 10 (31%) reported a complete inability to engage in any cardiovascular endurance exercise at 3 months. PASC leads to a significant, quantifiable decrease in cardiopulmonary health and endurance.

Cardiac magnetic resonance assessment of acute rejection and cardiac allograft vasculopathy in pediatric heart transplant.

BACKGROUND: In pediatric heart transplant (PHT), cardiac catheterization with endomyocardial biopsy (EMB) is standard for diagnosing acute rejection (AR) and cardiac allograft vasculopathy (CAV) but is costly and invasive. OBJECTIVES: To evaluate the ability of cardiac magnetic resonance (CMR) to noninvasively identify differences in PHT patients with AR and CAV. METHODS: Patients were enrolled at three children's hospitals. Data were collected from surveillance EMB or EMB for-cause AR. Patients were excluded if they had concurrent diagnoses of AR and CAV, CMR obtained >7days from AR diagnosis, they had EMB negative AR, or could not undergo contrasted, unsedated CMR. Kruskal-Wallis test was used to compare groups: (1) No AR or CAV (Healthy), (2) AR, (3) CAV. Wilcoxon rank-sum test was used for pairwise comparisons. RESULTS: Fifty-nine patients met inclusion criteria (median age 17years [IQR 15-19]) 10 (17%) with AR, and 11 (19%) with CAV. AR subjects had worse left ventricular ejection fraction compared to Healthy patients (p = 0.001). Global circumferential strain (GCS) was worse in AR (p = 0.054) and CAV (p = 0.019), compared to Healthy patients. ECV, native T1, and T2 z-scores were elevated in patients with AR. CONCLUSIONS: CMR was able to identify differences between CAV and AR. CAV subjects had normal global function but abnormal GCS which may suggest subclinical dysfunction. AR patients have abnormal function and tissue characteristics consistent with edema (elevated ECV, native T1 and T2 z-scores). Characterization of CMR patterns is critical for the development of noninvasive biomarkers for PHT and may decrease dependence on EMB.

Rate of Change in Cardiac Magnetic Resonance Imaging Measures Is Associated With Death in Duchenne Muscular Dystrophy.

BACKGROUND: Cardiovascular disease is the leading cause of death among patients with Duchenne muscular dystrophy (DMD). Identifying patients at risk of early death could allow for increased monitoring and more intensive therapy. Measures that associate with death could serve as surrogate outcomes in clinical trials. METHODS AND RESULTS: Duchenne muscular dystrophy subjects prospectively enrolled in observational studies were included. Models using generalized least squares were used to assess the difference of cardiac magnetic resonance measurements between deceased and alive subjects. A total of 63 participants underwent multiple cardiac magnetic resonance imaging and were included in the analyses. Twelve subjects (19.1%) died over a median follow-up of 5 years (interquartile range, 3.1-7.0). Rate of decline in left ventricular ejection fraction was faster in deceased than alive subjects (P<0.0001). Rate of increase in indexed left ventricular end-diastolic (P=0.0132) and systolic (P<0.0001) volumes were higher in deceased subjects. Faster worsening in midcircumferential strain was seen in deceased subjects (P=0.049) while no difference in global circumferential strain was seen. The rate of increase in late gadolinium enhancement, base T1, and mid T1 did not differ between groups. CONCLUSIONS: Duchenne muscular dystrophy death is associated with the rate of change in left ventricular ejection fraction, midcircumferential strain, and ventricular volumes. Aggressive medical therapy to decrease the rate of progression may improve the mortality rate in this population. A decrease in the rate of progression may serve as a valid surrogate outcome for therapeutic trials.

Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial.

BACKGROUND: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being. METHODS: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied. Metrics correlating with baseline HRQOL and CPET performance were identified. The impact of valsartan treatment on these measures was analyzed in the early stage cohort. RESULTS: Two hundred participants were included: 166 with early stage HCM (mean age, 23±10 years; 40% female; 97% White; and 92% New York Heart Association class I) and 34 subclinical sarcomere variant carriers (mean age, 16±5 years; 50% female; and 100% White). Baseline HRQOL was good in both cohorts, although slightly better in subclinical HCM (composite pediatric quality of life score 84.6±10.6 versus 90.2±9.8; P=0.005). Both cohorts demonstrated mildly reduced functional status (mean percent predicted peak oxygen uptake 73±16 versus 78±12 mL/kg per minute; P=0.18). Percent predicted peak oxygen uptake and peak oxygen pulse correlated with HRQOL. Valsartan improved physical HRQOL in early stage HCM (adjusted mean change in pediatric quality of life score +4.1 versus placebo; P=0.01) but did not significantly impact CPET performance. CONCLUSIONS: Functional capacity can be impaired in young, healthy people with early stage HCM, despite New York Heart Association class I status and good HRQOL. Peak oxygen uptake was similarly decreased in subclinical HCM despite normal left ventricular wall thickness and excellent HRQOL. Valsartan improved physical pediatric quality of life scores but did not significantly impact CPET performance. Further studies are needed for validation and to understand how to improve patient experience. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01912534.