Long-Term Cardiovascular Sequelae in Multisystem Inflammatory Syndrome in Children (MIS-C): A Comprehensive Assessment


Multisystem inflammatory syndrome in children (MIS-C) has emerged as a distinct and critical postinfectious complication following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

This syndrome manifests several weeks after the acute infection, presenting a myriad of clinical challenges characterized by fever, elevated inflammatory markers, cytokine storm, and multisystem organ involvement. Among the myriad consequences, cardiovascular complications have been particularly prevalent, affecting up to 80% of MIS-C patients.

These complications range from abnormal laboratory markers to more severe manifestations such as systolic and diastolic dysfunction, abnormal strain, coronary artery aneurysms (CAAs), and conduction system abnormalities. Cardiogenic and vasodilatory shock are also common, with some cases necessitating inotropic support.

Clinical Recovery and Long-Term Implications:

While a majority of MIS-C patients show signs of clinical recovery, there exists a significant knowledge gap regarding the prevalence and severity of long-term cardiovascular sequelae. The lingering uncertainty surrounding the potential long-term impact on cardiovascular health raises important considerations for activity restrictions and the need for extended follow-up.

Midterm Cardiac MRI (CMR) Findings:

Several studies have attempted to shed light on the mid-term cardiac implications of MIS-C, typically ranging from 1 to 9 months postdischarge. These studies have employed cardiac MRI (CMR) to investigate potential abnormalities such as edema or fibrosis. However, findings have been inconsistent, with some studies indicating abnormalities in a minority of patients and others revealing no significant cardiac abnormalities. This diversity in results emphasizes the need for a more comprehensive understanding of residual cardiovascular pathology in MIS-C patients.

Addressing the Research Gap:

The primary objective of the study under discussion is to address this gap by conducting a thorough assessment of the prevalence of residual cardiovascular pathology in patients treated for MIS-C. The evaluation utilizes a multimodal approach, combining CMR, ambulatory rhythm monitoring, and cardiopulmonary exercise stress testing (CPET) at a median time of 7 to 8 months post-hospitalization.

Comparative Analysis:

A secondary aim of the study involves comparing the prevalence of cardiovascular findings in MIS-C patients with evidence of myocardial injury during their acute illness against those without such evidence. This comparative analysis aims to identify potential patterns and distinctions in long-term cardiovascular outcomes based on the severity of the initial cardiac involvement.

Implications for Clinical Practice:

The findings from this study could have significant implications for clinical practice, informing healthcare providers about the extent of cardiovascular sequelae in MIS-C patients and guiding decisions related to activity restrictions and long-term follow-up protocols. Understanding the prevalence of abnormal CMR findings, exercise capacity, and the risk for arrhythmias can contribute to the development of targeted interventions and therapeutic strategies.

Discussion: Unraveling the Residual Cardiovascular Pathology in MIS-C Patients

The emergence of Multisystem Inflammatory Syndrome in Children (MIS-C) as a consequence of the SARS-CoV-2 pandemic has raised numerous questions regarding the long-term outcomes associated with this novel disease entity. The present study represents a significant contribution to the understanding of MIS-C, as it delves into uncharted territory by examining the prevalence and persistence of residual cardiovascular pathology through the integration of cardiac MRI (CMR), ambulatory rhythm monitoring, and cardiopulmonary exercise stress testing (CPET).

Comparing Midterm Results: To our knowledge, this study is the first to comprehensively investigate these modalities in concert within the context of MIS-C, further distinguishing itself by comparing midterm results between patients with and without myocardial injury during acute illness. The findings reveal that both groups exhibit abnormal follow-up testing results, with no statistically significant difference in the prevalence of abnormalities. This suggests that regardless of the severity of the initial illness, all MIS-C patients warrant continued cardiology follow-up.

Cardiac MRI Abnormalities and Their Implications: The analysis of CMR data in MIS-C patients uncovered a spectrum of abnormalities, with elevated extracellular volume (ECV) being the most prevalent, followed by elevated native T1 and the presence of late gadolinium enhancement (LGE). These findings, commonly associated with diverse disease processes such as cardiomyopathy, myocardial ischemia/infarction, myocarditis, and systemic inflammatory conditions, pose challenges in discerning whether they reflect transient inflammatory processes or myocardial fibrosis.

Need for Longitudinal Studies: The study acknowledges the need for additional CMR studies at later time points to elucidate whether these changes resolve or persist. Interestingly, the study reports an overall higher prevalence of abnormal CMR findings compared to other studies, prompting speculation about potential variations in the virus or host factors within the studied population. While regional and temporal differences in circulating SARS-CoV-2 strains and MIS-C presentations are acknowledged, the study design precludes definitive confirmation of these hypotheses.

Ambulatory Rhythm Monitoring and CPET Findings: Ambulatory rhythm monitoring and CPET data further enrich the understanding of residual cardiovascular pathology in MIS-C patients. While limited studies have explored ambulatory rhythm monitoring post-MIS-C treatment, the present study notes a higher prevalence of arrhythmias than previously reported. CPET results indicate reduced functional capacity in a substantial number of patients, complicating interpretation due to confounding factors such as obesity and restrictions from strenuous exercise during recovery.

Co-Occurrence of Abnormalities: The study reveals that abnormalities on different testing modalities did not frequently cooccur, with a minority of patients exhibiting abnormalities on two or all three modalities. Interestingly, none of the patients with nonsustained ventricular tachycardia on ambulatory rhythm monitoring exhibited abnormal CMR findings. These observations underscore the complexity of the residual cardiovascular sequelae in MIS-C patients, requiring a nuanced and multifaceted approach to assessment and interpretation.

Implications for Clinical Practice: In conclusion, the study underscores the presence of residual subclinical cardiovascular pathology in a significant proportion of MIS-C patients, irrespective of the severity of the initial illness. This emphasizes the importance of maintaining a low threshold for referring patients reporting cardiovascular symptoms for further evaluation and workup. Moreover, considering the demographic characteristics of the study population, including racial/ethnic minorities and individuals with a higher risk profile for severe COVID-19, the discussion extends to the potential need for longer-term cardiology follow-up during childhood and adolescence.

Study Limitations and Generalizability: Acknowledging the retrospective nature and single-center design of the study, certain limitations are inherent, including variability in the timing of follow-up studies and potential type II errors. However, the study’s strength lies in its substantial cohort, representing approximately 2.3% of national MIS-C cases, and the demographic similarities to other published studies, suggesting reasonable generalizability.

Future Directions: As MIS-C continues to pose challenges in understanding its long-term implications, future research endeavors should focus on larger, multi-center studies with longitudinal follow-up to validate and expand upon the findings presented here. Such endeavors are vital for refining clinical guidelines, enhancing risk stratification, and ultimately improving the long-term care and outcomes for MIS-C patients.

reference link: https://publications.aap.org/pediatrics/article/doi/10.1542/peds.2023-063002/195462/Cardiovascular-Follow-up-of-Patients-Treated-for?autologincheck=redirected


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