Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study.

Background: We aimed to study the clinical characteristics, myocardial injury, and longitudinal outcomes of COVID-19 vaccine-associated myocarditis (C-VAM). Methods: In this longitudinal retrospective observational cohort multicenter study across 38 hospitals in the United States, 333 patients with C-VAM were compared with 100 patients with multisystem inflammatory syndrome in children (MIS-C). We included patients ≤30 years of age with a clinical diagnosis of acute myocarditis after COVID-19 vaccination based on clinical presentation, abnormal biomarkers and/or cardiovascular imaging findings. Demographics, past medical history, hospital course, biochemistry results, cardiovascular imaging, and follow-up information from April 2021 to November 2022 were collected. The primary outcome was presence of myocardial injury as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. Findings: Patients with C-VAM were predominantly white (67%) adolescent males (91%, 15.7 ± 2.8 years). Their initial clinical course was more likely to be mild (80% vs. 23%, p < 0.001) and cardiac dysfunction was less common (17% vs. 68%, p < 0.0001), compared to MIS-C. In contrast, LGE on CMR was more prevalent in C-VAM (82% vs. 16%, p < 0.001). The probability of LGE was higher in males (OR 3.28 [95% CI: 0.99, 10.6, p = 0.052]), in older patients (>15 years, OR 2.74 [95% CI: 1.28, 5.83, p = 0.009]) and when C-VAM occurred after the first or second dose as compared to the third dose of mRNA vaccine. Mid-term clinical outcomes of C-VAM at a median follow-up of 178 days (IQR 114-285 days) were reassuring. No cardiac deaths or heart transplantations were reported until the time of submission of this report. LGE persisted in 60% of the patients at follow up. Interpretation: Myocardial injury at initial presentation and its persistence at follow up, despite a mild initial course and favorable mid-term clinical outcome, warrants continued clinical surveillance and long-term studies in affected patients with C-VAM. Funding: The U.S. Food and Drug Administration.

Quantification of lymphatic burden in patients with Fontan circulation by T2 MR lymphangiography and associations with adverse Fontan status.

AIMS: To quantify thoracic lymphatic burden in paediatric Fontan patients using MRI and correlate with clinical status. METHODS AND RESULTS: Paediatric Fontan patients (<18-years-old) with clinical cardiac MRI that had routine lymphatic 3D T2 fast spin echo (FSE) imaging performed from May 2017 to October 2019 were included. 'Lymphatic burden' was quantified by thresholding-based segmentation of the 3D T2 FSE maximum intensity projection image and indexed to body surface area, performed by two independent readers blinded to patient status. There were 48 patients (27 males) with median age at MRI of 12.9 (9.4-14.7) years, time from Fontan surgery to MRI of 9.1 (5.9-10.4) years, and follow-up time post-Fontan surgery of 9.4 (6.6-11.0) years. Intraclass correlation coefficient between two observers for lymphatic burden was 0.96 (0.94-0.98). Greater lymphatic burden correlated with post-Fontan operation hospital length of stay and duration of chest tube drainage (rs = 0.416, P = 0.004 and rs = 0.439, P = 0.002). Median lymphatic burden was greater in patients with chylous effusions immediately post-Fontan (178 (118-393) vs. 113 (46-190) mL/m2, P = 0.028), and in patients with composite adverse Fontan status (n = 13) defined by heart failure (n = 3), transplant assessment (n = 2), recurrent effusions (n = 6), Fontan thrombus (n = 2), and/or PLE (n = 6) post-Fontan (435 (137-822) vs. 114 (51-178) mL/m2, P = 0.003). Lymphatic burden > 600 mL/m2 was associated with late adverse Fontan status with sensitivity of 57% and specificity of 95%. CONCLUSION: Quantification of MR lymphatic burden is a reliable tool to assess the lymphatics post-Fontan and is associated with clinical status.

Patients with repaired tetralogy of Fallot and the HIF1A1744C/T variant have increased imaging markers of diffuse myocardial fibrosis.

BACKGROUND: Right ventricular fibrotic remodeling has been identified pre- and postoperatively in patients with tetralogy of Fallot (ToF) and linked to adverse outcomes. Polymorphisms of hypoxia inducible factor-1-alpha (HIF1A) have been associated with the fibrotic burden by cardiac magnetic resonance (CMR) late gadolinium enhancement imaging. Their association with diffuse fibrotic myocardial remodeling is unknown. We sought to determine whether polymorphisms in HIF1A are related to CMR markers of diffuse myocardial fibrosis. METHODS: Patients with repaired ToF who had undergone CMR with T1 mapping as well as whole genome sequencing were included. Myocardial native T1 was quantified using a modified Look-Locker inversion recovery sequence and measured in the left ventricular free wall, the interventricular septum, and the right ventricular free wall. Patients who had at least one functioning allele of HIF1A were compared to those who did not using the Mann Whitney U test for continuous variables and chi-square or the Fischer test for discrete variables. RESULTS: 46 patients had both CMR and whole genome sequencing. Only one HIF1A variant was identified in the cohort and present in 13 patients. There were no significant differences in demographics, surgical variables, right or left ventricular volumes or function between patients with and without the variant. Despite a trend towards a lower age at the time of CMR (11.3 vs 13.7 years; p = 0.07), patients with HIF1A variants had higher native T1 values (1094 vs. 1050; p = 0.027) in the right ventricular outflow tract myocardium, reflecting increased diffuse interstitial ventricular fibrosis in them. CONCLUSION: Hypoxia-inducible factor is associated with imaging markers of increased diffuse right ventricular fibrosis late after repair of tetralogy of Fallot.