IMPORTANCE: Vaccination against COVID-19 provides clear public health benefits, but vaccination also carries potential risks. The risks and outcomes of myocarditis after COVID-19 vaccination are ...unclear. OBJECTIVE: To describe reports of myocarditis and the reporting rates after mRNA-based COVID-19 vaccination in the US. DESIGN, SETTING, AND PARTICIPANTS: Descriptive study of reports of myocarditis to the Vaccine Adverse Event Reporting System (VAERS) that occurred after mRNA-based COVID-19 vaccine administration between December 2020 and August 2021 in 192 405 448 individuals older than 12 years of age in the US; data were processed by VAERS as of September 30, 2021. EXPOSURES: Vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna). MAIN OUTCOMES AND MEASURES: Reports of myocarditis to VAERS were adjudicated and summarized for all age groups. Crude reporting rates were calculated across age and sex strata. Expected rates of myocarditis by age and sex were calculated using 2017-2019 claims data. For persons younger than 30 years of age, medical record reviews and clinician interviews were conducted to describe clinical presentation, diagnostic test results, treatment, and early outcomes. RESULTS: Among 192 405 448 persons receiving a total of 354 100 845 mRNA-based COVID-19 vaccines during the study period, there were 1991 reports of myocarditis to VAERS and 1626 of these reports met the case definition of myocarditis. Of those with myocarditis, the median age was 21 years (IQR, 16-31 years) and the median time to symptom onset was 2 days (IQR, 1-3 days). Males comprised 82% of the myocarditis cases for whom sex was reported. The crude reporting rates for cases of myocarditis within 7 days after COVID-19 vaccination exceeded the expected rates of myocarditis across multiple age and sex strata. The rates of myocarditis were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively). There were 826 cases of myocarditis among those younger than 30 years of age who had detailed clinical information available; of these cases, 792 of 809 (98%) had elevated troponin levels, 569 of 794 (72%) had abnormal electrocardiogram results, and 223 of 312 (72%) had abnormal cardiac magnetic resonance imaging results. Approximately 96% of persons (784/813) were hospitalized and 87% (577/661) of these had resolution of presenting symptoms by hospital discharge. The most common treatment was nonsteroidal anti-inflammatory drugs (589/676; 87%). CONCLUSIONS AND RELEVANCE: Based on passive surveillance reporting in the US, the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata and was highest after the second vaccination dose in adolescent males and young men. This risk should be considered in the context of the benefits of COVID-19 vaccination.
Recent evidence shows an association between coronavirus disease 2019 (COVID-19) infection and a severe inflammatory syndrome in children. Cardiovascular magnetic resonance (CMR) data about ...myocardial injury in children are limited to small cohorts. The aim of this multicenter, international registry is to describe clinical and cardiac characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 using CMR so as to better understand the real extent of myocardial damage in this vulnerable cohort.
Hundred-eleven patients meeting the World Health Organization criteria for MIS-C associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), having clinical cardiac involvement and having received CMR imaging scan were included from 17 centers. Median age at disease onset was 10.0 years (IQR 7.0-13.8). The majority of children had COVID-19 serology positive (98%) with 27% of children still having both, positive serology and polymerase chain reaction (PCR). CMR was performed at a median of 28 days (19-47) after onset of symptoms. Twenty out of 111 (18%) patients had CMR criteria for acute myocarditis (as defined by the Lake Louise Criteria) with 18/20 showing subepicardial late gadolinium enhancement (LGE). CMR myocarditis was significantly associated with New York Heart Association class IV (p = 0.005, OR 6.56 (95%-CI 1.87-23.00)) and the need for mechanical support (p = 0.039, OR 4.98 (95%-CI 1.18-21.02)). At discharge, 11/111 (10%) patients still had left ventricular systolic dysfunction.
No CMR evidence of myocardial damage was found in most of our MIS-C cohort. Nevertheless, acute myocarditis is a possible manifestation of MIS-C associated with SARS-CoV-2 with CMR evidence of myocardial necrosis in 18% of our cohort. CMR may be an important diagnostic tool to identify a subset of patients at risk for cardiac sequelae and more prone to myocardial damage.
The study has been registered on ClinicalTrials.gov, Identifier NCT04455347, registered on 01/07/2020, retrospectively registered.
Myocarditis is a potential complication after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a known cause of sudden cardiac death. Given the athletic demands of soldiers, ...identification of myocarditis and characterization of post-acute sequelae of SARS-CoV-2 infection with cardiovascular symptoms (CV PASC) may be critical to guide return-to-service. This study sought to evaluate the spectrum of cardiac involvement among soldiers with cardiopulmonary symptoms in the late convalescent phase of recovery from SARS-CoV-2 compared to a healthy soldier control group, and to determine the rate of progression to CV PASC.
All soldiers referred for cardiovascular magnetic resonance (CMR) imaging for cardiopulmonary symptoms following COVID-19 were enrolled and matched by age, gender, and athletic phenotype 1:1 to soldiers undergoing CMR in the year prior to the first case of COVID-19 at our institution. Demographic, clinical, laboratory, and imaging parameters were compared between groups. The diagnosis of acute myocarditis was made using modified Lake Louise criteria. Wilcoxon rank sum and chi-squared tests were used for comparison of continuous and categorical variables, respectively.
Fifty soldier cases and 50 healthy soldier controls were included. The median time from SARS-CoV-2 detection to CMR was 71 days. The majority of cases experienced moderate symptoms (N = 43, 86%), while only 10% required hospitalization. The right ventricular (RV) ejection fraction (RVEF) was reduced in soldier cases compared to controls (51.0% vs. 53.2%, p = 0.012). Four cases were diagnosed with myocarditis (8%), 1 (2%) was diagnosed with Takotsubo cardiomyopathy, and 1 (2%) had new biventricular systolic dysfunction of unclear etiology. Isolated inferior RV septal insertion late gadolinium enhancement (LGE) was present in 8 cases and 8 controls (16% vs. 24%, p = 0.09). Seven of the 19 (37%) cases that completed an intermediate-term follow-up survey reported CV PASC at a median of 139 days of follow-up. Two of the 7 soldiers (29%) with CV PASC had a pathological clinical diagnosis (myocarditis) on CMR.
Cardiovascular pathology was diagnosed in 6 symptomatic soldiers (12%) after recovery from SARS-CoV-2, with myocarditis found in 4 (8%). RVEF was reduced in soldier cases compared to controls. CV PASC occurred in over one-third of soldiers surveyed, but did not occur in any soldiers with asymptomatic acute SARS-CoV-2 infection.
Background
Duchenne muscular dystrophy (DMD) is associated with progressive muscle weakness and respiratory decline. To date, studies have focused on respiratory decline and loss of ambulation as a ...metric of loss of skeletal muscle strength. However, new functional measures can assess skeletal muscle disease regardless of ambulatory status. The relationship between these tests and concurrent lung function is currently unexplored.
Objective
To assess the correlation between spirometry measurements and functional muscle assessments such as accelerometry and quantitative muscle testing (QMT).
Methods
Enrolled patients with DMD underwent accelerometry and QMT at study clinic visits. Any pulmonary function testing within 6 months of visit was obtained from the electronic medical record. The Spearman correlation coefficient was used to assess the relationship between spirometry and functional muscle testing.
Results
Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) demonstrated the strongest correlation with accelerometry. Both FVC and FEV1 showed a similar relationship to accelerometry when activity was divided into intensity categories, with low intensity and moderate‐to‐vigorous activity categories showing the strongest correlation. Maximal expiratory pressure (MEP) and FVC showed the most robust correlations with total QMT (p < 0.001 and p < 0.01, respectively).
Conclusion
Lung function, specifically FVC percent predicted and FEV1%p, shows a good correlation with upper and lower extremity skeletal muscle functional testing such as accelerometry and QMT.
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.
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.
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.
Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD), but studies suggest heart failure biomarkers correlate poorly with cardiomyopathy severity. DMD clinical trials have ...used troponin I (cTnI) as a biomarker of toxicity, but it is unclear if asymptomatic DMD patients have elevated cTnI. We longitudinally evaluated cTnI, brain natriuretic peptide (BNP), and N-terminal pro-BNP (NT-proBNP) in a DMD cohort.
DMD patients were prospectively enrolled and followed for 3 years. Serum was drawn at the time of cardiac magnetic resonance (CMR). Normal biomarker values were derived from healthy subjects. Biomarkers were correlated with CMR markers.
All subjects were asymptomatic at the time of enrollment. Several DMD subjects had transiently elevated cTnI. Those with elevated cTnI were more likely to have late gadolinium enhancement on baseline CMR. NT-proBNP correlated with indexed left ventricular end diastolic and maximum left atrial volumes. Otherwise, standard cardiac biomarkers did not correlate with CMR markers of cardiomyopathy.
CTnI, BNP, and NT-proBNP do not correlate with CMR assessment of cardiomyopathy progression. A subset of DMD patients have asymptomatic cTnI leak of uncertain clinical significance, though of critical importance if cTnI is used to assess for cardiac toxicity in future drug trials.
Asymptomatic patients with Duchenne muscular dystrophy (DMD) exhibit transient troponin I leak. NT-proBNP correlated with indexed left ventricular end diastolic volume and indexed maximum left atrial volume. Other cardiac biomarkers did not correlate with cardiac magnetic resonance (CMR) markers of cardiomyopathy.
Patients with repaired Tetralogy of Fallot (rTOF) experience a high burden of long-term morbidity, particularly arrhythmias. Cardiovascular magnetic resonance (CMR) is routinely used to assess ...ventricular characteristics but the relationship between CMR diastolic function and arrhythmia has not been evaluated. We hypothesized in rTOF, left ventricular (LV) diastolic dysfunction on CMR would correlate with arrhythmias and mortality.
Adolescents and adults with rTOF who underwent CMR were compared to healthy controls (n = 58). Standard ventricular parameters were assessed and manual planimetry was performed to generate filling curves and indices of diastolic function. Chart review was performed to collect outcomes. Univariate and multivariable logistic regression was performed to identify outcome associations.
One-hundred sixty-seven subjects with rTOF (mean age 32 years) and 58 healthy control subjects underwent CMR. Patients with rTOF had decreased LV volumes and increased right ventricular (RV) volumes, lower RV ejection fraction (RVEF), lower peak ejection rate (PER), peak filling rate (PFR) and PFR indexed to end-diastolic volume (PFR/EDV) compared to healthy controls. Eighty-three subjects with rTOF had arrhythmia (63 atrial, 47 ventricular) and 11 died. Left atrial (LA) volumes, time to peak filling rate (tPFR), and PFR/EDV were associated with arrhythmia on univariate analysis. PER/EDV was associated with ventricular (Odds ratio, OR 0.43 0.24–0.80, p = 0.007) and total arrhythmia (OR 0.56 0.37–0.92, p = 0.021) burden. A multivariable predictive model including diastolic covariates showed improved prediction for arrhythmia compared to clinical and conventional CMR measures (area under curve (AUC) 0.749 v. 0.685 for overall arrhythmia). PFR/EDV was decreased and tPFR was increased in rTOF subjects with mortality as compared to those without mortality.
Subjects with rTOF have abnormal LV diastolic function compared to healthy controls. Indices of LV diastolic function were associated with arrhythmia and mortality. CMR diastolic indices may be helpful in risk stratification for arrhythmia.
Patients with Duchenne muscular dystrophy (DMD) require frequent imaging to assess left ventricular (LV) function. Poor imaging windows can limit the diagnostic utility of echocardiography. Cardiac ...magnetic resonance imaging (CMR) is the gold standard for the assessment of LV function but has not been universally adopted in patients with DMD. The study objectives were (1) to evaluate the reproducibility of echocardiographic measures of LV function, (2) to evaluate which echocardiographic methods correlate best with CMR LV ejection fraction (LVEF), and (3) to evaluate whether CMR provides additional value compared with echocardiography.
Twenty-eight participants with DMD prospectively underwent echocardiography and CMR. Two blinded readers measured fractional shortening from M-mode and two-dimensional images and LVEF using four-chamber, biplane Simpson, 5/6 area-length, and three-dimensional methods. Speckle-tracking echocardiography was used to analyze circumferential strain. Readers subjectively rated function and segmental wall motion. Agreement was assessed using intraclass correlation coefficients, Bland-Altman plots, Spearman correlation, and weighted κ.
Two-dimensional fractional shortening and 5/6 area-length LVEF had the best combination of reproducibility and correlation with CMR LVEF, though both misclassified approximately 20% as either normal or abnormal function. Other measures of LV function were less reproducible, with worse correlations with CMR LVEF. Thirty-seven percent of segments not visible on echocardiography were believed to have wall motion abnormalities by CMR.
Two-dimensional fractional shortening and 5/6 area-length LVEF represent the most accurate and reproducible echocardiographic measures of LV function in patients with DMD. CMR should be considered when neither of these techniques is measurable or when it is necessary to detect more subtle cardiovascular changes.
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