The emergence of SARS-CoV-2 has resulted in significant morbidity and mortality across the globe. We are only just starting to ascertain the long-term impact that this new virus will have on human health. Acute cardiac dysfunction is a prominent and critical manifestation for children who develop MIS-C following infection with SARS-CoV-2. Whether acute cardiac dysfunction during MIS-C ultimately results in permanent cardiac dysfunction or persistent inflammation as seen in other viral induced myocarditis syndromes remains undefined. Determining the presence of cardiac inflammation and myocardial damage has significant implications towards counseling, as the presence of residual inflammation may necessitate restrictions from sports participation until such inflammation has resolved.Improving our understanding of the potential lifelong impact that MIS-C will have on children’s cardiac health is therefore essential to our ability to guide families and determine treatment plans.
We report on the mid-term CMR findings in children 6-9 months following hospitalization for MIS-C. Subjects overall have normal ventricular size and systolic function, with LV dysfunction present in only one subject. There is no evidence of edema and parametric mapping values were normal as compared to controls. LGE was present in only one subject with no evidence of perfusion defects and overall normal T1 times in this subject. Importantly, we show near-complete recovery in ejection fraction among subjects with a history of ventricular dysfunction.
Our group previously reported on six-month echocardiographic findings in this population and demonstrated excellent recovery in almost all patients.(3) While echocardiography is a valuable tool to assess global ventricular function, CMR remains the gold standard measure to assess myocardial tissue characterization.(9) Furthermore, LVEF by echocardiography requires numerous assumptions on LV geometry, and assessment of RV function is predominantly qualitative; CMR allows for a more granular calculation of EF.
Early CMR data among patients hospitalized with MIS-C has previously been reported, with variable degrees of edema and LGE, as well as diminished LV strain in those with LV dysfunction.(17, 20, 22) These findings are consistent with our prior data demonstrating significant functional impairment in many children with MIS-C.(1, 3) Our CMR cohort demonstrated a similar degree of dysfunction during hospitalization, with almost half of our subjects having had LV dysfunction by echocardiography.
Webster et al. previously reported on early term outcomes among children with a history of symptomatic COVID 1-3 months following presentation, including 6 subjects with MIS-C.(18) They demonstrated globally normal ventricular function and parametric mapping values by CMR among the 6 MIS-C patients, though prior cardiac dysfunction in their cohort was isolated to two subjects with history MIS-C. Similarly, Capone et al. demonstrated normal LV systolic function and no evidence of edema or fibrosis among 11 subjects 4-6 weeks following initial hospitalization for MIS-C.(19) Our findings are consistent with theirs, with a larger MIS-C sample size further from hospitalization. Our data further reinforces the narrative that recovery is overall excellent.
Beyond presenting prospective data further from hospitalization, our study is novel in that we incorporated the use of a parametric mapping for myocardial tissue characterization in a cohort exclusively comprised of a MIS-C population. Parametric mapping is quickly becoming a standard of care method in the evaluation of myocardial edema and diffuse fibrosis in patients, and has recently been incorporated as part of revised Lake Louise criteria in the evaluation of myocarditis.(7) Webster et al. evaluated native T1 and T2 values in pediatric patients with symptomatic COVID; however, they did not administer contrast in their cohort, and therefore were unable to assess for LGE. While Barris et al report on mid-term CMR findings in patients hospitalized with MIS-C, they did not perform parametric mapping; evaluation of edema and fibrosis was therefore limited to a qualitative analysis. Furthermore, while LGE can identify focal or replacement fibrosis, it is unable to identify diffuse fibrosis. .(11, 18, 21)
There are several limitations to this study. Our sample size is limited, due to an a priori decision to only obtain clinical CMR to patients who had evidence of cardiac dysfunction during initial presentation and few subjects willing to consent to a research CMR with contrast administration. Therefore, we may have been underpowered to detect differences in functional and myocardial tissue characterization parameters. Furthermore, younger subjects were excluded from research CMR; as a result, we may not be able to extrapolate our findings to those hospitalized at a younger age. That said, our sample is biased to those with initial cardiac dysfunction, and therefore would be biased to those most at risk. Finally, control data were available for native T1 and T2 values as part of recommendations by SCMR to obtain local references;(11) as control data were based on subjects referred for clinical CMR, it is possible that myocardial tissue abnormalities were present. However, we ensured that all subjects used as controls had normal biventricular size and systolic function with no evidence of identifiable congenital heart disease or systemic diseases. Therefore, the likelihood of myocardial abnormalities is minimal. As availability of normal control myocardial T1 data were limited, we could not age match in this study, and therefore it is possible that lack of differences between controls and subjects was due to age dependent phenomenon. Furthermore, normal controls were not available for ECV due to the need for contrast administration. While comparisons to published reference values have been deemed acceptable, the availability of published data in children are limited to small single center cohorts.(11)