Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults: Suspected Myocarditis After COVID-19 Vaccination.

BACKGROUND: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. METHODS: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions. RESULTS: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1-20.3; interquartile range [IQR], 14.5-17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0-22; IQR, 1-3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0-10; IQR, 2-3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50-15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25-1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0-88; IQR, 3-17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25). CONCLUSIONS: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes.

Results of the FUEL Trial.

BACKGROUND: The Fontan operation creates a total cavopulmonary connection, a circulation in which the importance of pulmonary vascular resistance is magnified. Over time, this circulation leads to deterioration of cardiovascular efficiency associated with a decline in exercise performance. Rigorous clinical trials aimed at improving physiology and guiding pharmacotherapy are lacking. METHODS: The FUEL trial (Fontan Udenafil Exercise Longitudinal) was a phase III clinical trial conducted at 30 centers. Participants were randomly assigned udenafil, 87.5 mg twice daily, or placebo in a 1:1 ratio. The primary outcome was the between-group difference in change in oxygen consumption at peak exercise. Secondary outcomes included between-group differences in changes in submaximal exercise at the ventilatory anaerobic threshold, the myocardial performance index, the natural log of the reactive hyperemia index, and serum brain-type natriuretic peptide. RESULTS: Between 2017 and 2019, 30 clinical sites in North America and the Republic of Korea randomly assigned 400 participants with Fontan physiology. The mean age at randomization was 15.5±2 years; 60% of participants were male, and 81% were white. All 400 participants were included in the primary analysis with imputation of the 26-week end point for 21 participants with missing data (11 randomly assigned to udenafil and 10 to placebo). Among randomly assigned participants, peak oxygen consumption increased by 44±245 mL/min (2.8%) in the udenafil group and declined by 3.7±228 mL/min (-0.2%) in the placebo group (P=0.071). Analysis at ventilatory anaerobic threshold demonstrated improvements in the udenafil group versus the placebo group in oxygen consumption (+33±185 [3.2%] versus -9±193 [-0.9%] mL/min, P=0.012), ventilatory equivalents of carbon dioxide (-0.8 versus -0.06, P=0.014), and work rate (+3.8 versus +0.34 W, P=0.021). There was no difference in change of myocardial performance index, the natural log of the reactive hyperemia index, or serum brain-type natriuretic peptide level. CONCLUSIONS: In the FUEL trial, treatment with udenafil (87.5 mg twice daily) was not associated with an improvement in oxygen consumption at peak exercise but was associated with improvements in multiple measures of exercise performance at the ventilatory anaerobic threshold. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02741115.

Kawasaki Disease in the Time of COVID-19 and MIS-C: The International Kawasaki Disease Registry.

BACKGROUND: Patients with multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) have overlapping clinical features. We compared demographics, clinical presentation, management, and outcomes of patients according to evidence of previous SARS-CoV-2 infection. METHODS: The International Kawasaki Disease Registry (IKDR) enrolled KD and MIS-C patients from sites in North, Central, and South America, Europe, Asia, and the Middle East. Evidence of previous infection was defined as: Positive (household contact or positive polymerase chain reaction [PCR]/serology), Possible (suggestive clinical features of MIS-C and/or KD with negative PCR or serology but not both), Negative (negative PCR and serology and no known exposure), and Unknown (incomplete testing and no known exposure). RESULTS: Of 2345 enrolled patients SARS-CoV-2 status was Positive for 1541 (66%) patients, Possible for 89 (4%), Negative for 404 (17%) and Unknown for 311 (13%). Clinical outcomes varied significantly among the groups, with more patients in the Positive/Possible groups presenting with shock, having admission to intensive care, receiving inotropic support, and having longer hospital stays. Regarding cardiac abnormalities, patients in the Positive/Possible groups had a higher prevalence of left ventricular dysfunction, and patients in the Negative and Unknown groups had more severe coronary artery abnormalities. CONCLUSIONS: There appears to be a spectrum of clinical features from MIS-C to KD with a great deal of heterogeneity, and one primary differentiating factor is evidence for previous acute SARS-CoV-2 infection/exposure. SARS-CoV-2 Positive/Possible patients had more severe presentations and required more intensive management, with a greater likelihood of ventricular dysfunction but less severe coronary artery adverse outcomes, in keeping with MIS-C.

Impact of overweight and obesity on epicardial adipose tissue in children with type 1 diabetes.

OBJECTIVES: Epicardial adipose tissue (EAT) thickness, a novel marker of cardiovascular disease (CVD), is increased in children with a healthy weight and type 1 diabetes (T1D). The prevalence of obesity has increased in children with T1D and may confer additional CVD risk. The purpose of this study was to examine EAT thickness in youth with and without T1D in the setting of overweight/obesity. METHODS: Youth with overweight/obesity and T1D (n=38) or without T1D (n=34) between the ages of 6-18 years were included in this study. Echocardiogram using spectral and color flow Doppler was used to measure EAT and cardiac function. Waist circumference, blood pressure, and HbA1c, were used to calculate estimated glucose disposal rate (eGDR) to estimate insulin resistance in children with T1D. RESULTS: EAT thickness was not significantly different in youth with T1D compared to controls (2.10 ± 0.67 mm vs. 1.90 ± 0.59 mm, p=0.19). When groups were combined, EAT significantly correlated with age (r=0.449, p≤0.001), BMI (r=0.538, p≤0.001), waist circumference (r=0.552, p≤0.001), systolic BP (r=0.247, p=0.036), myocardial performance index (r=-0.287, p=0.015), ejection fraction (r=-0.442, p≤0.001), and cardiac output index (r=-0.306, p=0.009). In the group with T1D, diastolic BP (r=0.39, p=0.02) and eGDR (r=-0.48, p=0.002) correlated with EAT. CONCLUSIONS: EAT was associated with measures of adiposity and insulin resistance but does not differ by diabetes status among youth with overweight/obesity. These findings suggest that adiposity rather than glycemia is the main driver of EAT thickness among youth with T1D.

Absent aortic valve associated with double outlet right ventricle and aortopulmonary window: physiologic implications of a rare malformation in both the fetus and neonate.

Absence of the aortic valve is a rare congenital heart defect that is detectable in the prenatal period. In this condition, functional aortic valve leaflets are absent; in their place are rudimentary, immobile noncoapting plate-like structures at the level of the annulus resulting in severe aortic regurgitation. We report the fetal diagnosis and subsequent postnatal course of an infant with the novel association of absent aortic valve, double outlet right ventricle, and aortopulmonary window. This unique combination of defects resulted in an unusual pattern of circular shunting that produced evidence of fetal heart failure. Shortly after birth, the abnormal physiology led to compromised systemic perfusion, intestinal perforation and subsequent rapid demise of the patient. Abrupt postnatal deterioration typifies the vast majority of the absent aortic valve cases found in the literature. Our patient is unique in that it is the first female reported with absent aortic valve and the first reported with an aortopulmonary window. This report demonstrates that absent aortic valve is a condition that can be diagnosed prenatally by fetal echocardiogram; the highly abnormal physiology places these patients at risk for fetal heart failure. Given the potential for clinical instability and rapid deterioration after birth, such patients should undergo rapid postnatal assessment and immediate surgical intervention when deemed appropriate.

Characteristics of gastroesophageal reflux in adults with cystic fibrosis.

BACKGROUND: Gastroesophageal reflux (GER) in adults with cystic fibrosis (CF) is poorly characterized. This study examines the frequency and predictors of GER symptoms and their relationship to lung function in adults with CF. METHODS: Cross-sectional study of adults at the University of Minnesota CF Clinic using two validated self report surveys: The Mayo GER questionnaire and the GERD Symptom Assessment Scale (GSAS). RESULTS: Of 274 invited patients, 201 (73%) completed the surveys and 173 performed spirometry at the same visit. Frequent symptoms (at least weekly) were reported by 24% of the patients and an additional 39% experienced occasional symptoms. Heartburn, acid regurgitation and dysphagia were the most common symptoms and 18% reported that GER symptoms worsened their respiratory condition. Females and patients reporting weight loss had more symptoms (mean GSAS symptom score 4.9 vs. 4.0, p=0.025 and 5.3 vs. 4.2, p=0.04) and more severe symptoms (mean GSAS distress score 5.6 vs. 3.8, p=0.005 and 6.8 vs. 4.0, p=0.01) compared to males and those who did not report weight loss. Patients on acid suppression (n=122, 61%) continued to report heartburn (n=80, 66%) and acid regurgitation (n=47, 23%). GER symptoms and severity of symptoms were not predictive of FEV(1) or FVC. CONCLUSIONS: GER symptoms were present in a majority of patients. Females and patients with weight loss require special attention to their GER symptoms. Many patients on acid suppression continued to be report symptoms.

Achievement of feeding milestones after primary repair of long-gap esophageal atresia.

OBJECTIVES: To determine the pattern of feeding milestones following primary repair of long-gap esophageal atresia (EA). METHOD: A questionnaire based upon well established feeding milestones was used. Children after long-gap EA repair, n=40, were compared from after primary repair to healthy children from birth, n=102. RESULTS: The age when surveyed of the EA group and controls was different: 6.2+/-4.7 (mean+/-standard deviation) years, range 1.1-20.9, versus 2.5+/-2.4 years, range 0.0-12.1, p=0.00. The esophageal gap length in the EA group was 5.1+/-1.2 cm and age at repair was 5.5+/-5.0 months. There was no statistically significant difference between the atresia group and controls for feeding milestones; Self feeding finger foods approached significance. There was, however, greater variability in the timing of milestones in the atresia group compared to controls. Feeding milestones were negatively correlated with age at primary repair: drinking with a covered sippy cup, rho=-0.51, p=0.01 and self feeding finger foods, rho=-0.36, p=0.04 were statistically significant. Drinking from a cup correlated with gestational age, rho=0.38, p=0.04, and negatively correlated to esophageal gap length, rho=-0.45, p=0.01. CONCLUSIONS: Despite delayed onset of feeding, major milestones after EA repair occurred in similar pattern to normal infants. An early referral for primary repair is beneficial for earlier acquisition of milestones for infants with long-gap EA.

The effect of traction on esophageal structure in children with long-gap esophageal atresia.

We examined the esophageal structure in children who underwent traction to achieve primary repair of long-gap esophageal atresia. High-resolution ultrasound was used to compare thickness of the proximal and distal esophagus in children who had traction to achieve primary repair (n=15) to cases of esophageal atresia with shorter gaps that did not require traction (n=8). The muscularis propria of the upper esophagus was thicker in the traction compared to the non-traction group, though not statistically significant (respectively, 0.79 (0.18) mm vs. 0.71 (0.16) mm; p=0.29), measurements were similar for the lower esophagus (respectively, 0.79 (0.21) mm vs. 0.75 (0.13) mm; p=0.64). Combined mucosa and submucosa was very similar in both groups for the upper (respectively, 1.03 (0.15) mm vs. 1.04 (0.16) mm; p=0.95) and lower esophagus (respectively, 1.09 (0.23) mm vs. 1.01 (0.13) mm; p=0.37). The thickness of individual mural layers is maintained after increasing esophageal length with traction.