Letter to the Editor: Coronavirus disease 2019, multisystem inflammatory syndrome, and children’s hearts: Finding answers with cardiac magnetic resonance imaging

Abstract

The article refers to “Persistent long-term subclinical myocardial changes in multisystem inflammatory syndrome in children revealed by cardiac magnetic resonance and galectin-3” by OV et al published in the World Journal of Clinical Pediatrics, multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) and its cardiovascular complications. MIS-C frequently causes cardiovascular complications, including coronary artery dilatation, low left ventricular (LV) ejection fraction, diastolic dysfunction, myocarditis, and pericardial effusion, decreases over time, usually resolving within 6-9 months after the disease onset. Echocardiographic evaluations reveal mild to moderate LV dysfunction, resolving within two weeks. Severe dysfunction normalizes after approximately 1.5 months. Global longitudinal strain proves valuable for detecting subclinical myocardial damage. Long-term effects based on cardiac magnetic resonance imaging (CMRI) data indicate the persistent myocardial edema and/or fibrosisupto12 months after the initialevent. Signs of interstitial fibrosis were found in 7.7% of patients during a one-year follow-up period. CMRI is an important additional method in the assessment of children who have experienced multisystem inflammatory syndrome in COVID-19, especially in patients with persistent symptoms or abnormal data from other cardiac findings.

Key Words: Multisystem inflammatory syndrome in children; Myocarditis; Myocardial dysfunction; Cardiac magnetic resonance imaging; Coronavirus disease 2019

Core Tip: Multisystem inflammatory syndrome in children related to coronavirus disease 2019 (COVID-19), concentrating on cardiovascular complications, including myocardial dysfunction, primarily due to myocarditis. While coronary artery dilation is usually moderate and resolves quickly, myocarditis can be severe but typically improves over time. Cardiovascular abnormalities such as dilated coronary arteries, reduced left ventricular ejection fraction, diastolic dysfunction, myocarditis, and pericardial effusions generally subside within 6 to 9 months. Global longitudinal strain is effective for detecting subtle myocardial damage. Long-term cardiac magnetic resonance imaging reveals persistent myocardial edema or fibrosis for up to a year, with interstitial fibrosis and could be recommended as the primary or follow-up imaging technique for COVID-19 patients.

TO THE EDITOR

This article refers to “Persistent long-term subclinical myocardial changes in multisystem inflammatory syndrome in children revealed by cardiac magnetic resonance and galectin-3” by OV et al[1] published in the World Journal of Clinical Pediatrics.

The multisystem inflammatory syndrome associated with coronavirus disease 2019 (COVID-19) in children is often accompanied by cardiovascular complications, most notably myocardial dysfunction, typically resulting from myocarditis. Coronary artery dilatation is generally moderate in severity and tends to resolve rapidly, usually in six weeks. Myocarditis can be severe and occasionally fatal, but in the majority of cases, it resolves favorably, with subsequent assessments usually showing normalization. The incidence of cardiovascular complications, including coronary artery dilatation (Z-score ≥ 2), low left ventricular ejection fraction (LVEF) < 55%, diastolic dysfunction, myocarditis, and pericardial effusion, diminishes over time, with most of these abnormalities resolving by 6-9 months post-onset of the disease. In certain patients, arrhythmias may persist or recur over an extended period, and levels of cardiospecific biomarkers may increase, despite normal electrocardiographic and echocardiographic findings[2].

The increased incidence of sudden cardiac deaths, not exclusively attributable to coronary artery disease, among young adults following the COVID-19 pandemic underscores the critical need for the development and validation of robust methods for assessing myocardial status in individuals who have experienced COVID-19, including multisystem inflammatory syndrome in children (MIS-C).

According to standard echocardiographic evaluations, mild to moderate left ventricular (LV) dysfunction typically resolves within two weeks, while severe dysfunction typically normalizes after approximately 1.5 months. The prevalence of systolic dysfunction is more frequently observed in adolescents[3]. A comprehensive meta-analysis of 11 studies, search in PubMed and EMBASE databases, including the literature for cardiac magnetic resonance imaging (CMRI) in children after MIS-C based on the comparable duration of observations and the significance of the detected changes as indicators of myocardial damage-edema and/or fibrosis and covering the period from the onset of the COVID-19 pandemic through 2022, utilizing echocardiographic assessments, revealed that the incidence of minimal to moderate LV dysfunction in the acute phase of MIS-C was 46.8%, decreased to 2.1% after six months[4]. However, even in the absence of abnormal LVEF values, a significant proportion of patients who have experienced MIS-C exhibit abnormal values of global longitudinal strain (GLS), which measures myocardial deformation[5]. It detects subclinical LV damage, such as myocardial fibrosis or ischemia. LV-GLS is expressed as a negative percentage. A normal, healthy left ventricle typically demonstrates a GLS value between (-18%) and (-22%), whereas values less negative than (-16%) are highly indicative of dysfunction[6].

At present, only a limited number of publications examine CMRI data collected between six months and two years following MIS-C. The findings from these studies are inconclusive and necessitate further investigation. No enduring alterations were observed on CMRI three months post-hospital admission in children diagnosed with MIS-C and myocardial involvement. The authors propose that myocardial damage in MIS-C is attributable to a transient inflammatory response rather than direct and potentially enduring damage induced by the virus[7].

According to another study, 29% of patients exhibited high signal intensity in T2-weighted imaging during CMRI, and 61.3% displayed at least one of the following conditions: Pericardial effusion, LV dysfunction, or right ventricular dysfunction within six months post-MIS-C diagnosis[8]. High signal intensity on T2-weighted CMRI imaging is typically a sign of myocardial edema (fluid accumulation) caused by active tissue injury, inflammation, or ischemia[9]. Serial CMRI performed on children with MIS-C revealed the persistence of myocardial edema and/or fibrosis up to 12 months after the initial event[10]. Additionally, CMRI identified signs of interstitial fibrosis in 7.7% of patients during a one-year follow-up period[11].

The present study reveals subclinical myocardial alterations in CMRI data, encompassing a reduction in LVEF, stroke volume, and elevated signal intensity on T1-weighted sequences, among children who have experienced MIS-C for an average duration of two years[12]. These findings are correlated with increased levels of galectin-3. An increased level of the Galectin-3 marker in blood is primarily recognized as an indicator of ongoing inflammation and tissue scarring (fibrosis) in the body. It is most frequently used to assess the risk and progression of heart failure and cardiovascular disease[13]. These observations indicate the ongoing myocardial remodeling or low-grade inflammation and underscore the necessity for further research into the long-term cardiovascular consequences of critical COVID-19 in pediatric populations. Additionally, the importance of CMRI as a significant assessment modality for these patients is emphasized. Further studies of myocardial damage after a multisystem inflammatory syndrome using CMRI with simultaneous assessment of fibrosis biomarkers appear to be the most promising for determining therapeutic strategies.