European Journal of Cardiovascular Medicine

The emergence of Coronavirus Disease 2019 (COVID-19), caused by the novel SARS-CoV-2 virus first identified in Wuhan, China in late 2019, led to a global pandemic declared by the World Health Organization in March 2020 [1].  A relatively unseen and serious  condition, multi-system Inflammatory Syndrome in Children (MIS-C) began to be recognized from April 2020, mostly associated with COVID-19 infection . MIS-C is now understood as a post-infectious, immune-mediated hyperinflammatory condition that occurs typically 2–6 weeks following exposure, presenting with fever, systemic inflammation, and multi-organ dysfunction, particularly involving the cardiovascular system [2]. The syndrome shares overlapping clinical features with other inflammatory conditions such as Kawasaki disease, toxic shock syndrome, and viral myocarditis, making diagnosis challenging and necessitating a high index of suspicion .

A key concern in MIS-C is its significant cardiovascular involvement, which contributes substantially to morbidity and mortality. Children with MIS-C frequently present with shock, myocardial dysfunction, arrhythmias, coronary artery abnormalities, and elevated cardiac biomarkers such as troponin and brain natriuretic peptide (BNP) [3]. Studies have reported coronary artery involvement in approximately 6–24% of MIS-C cases, raising concerns about long-term cardiovascular sequelae similar to those seen in Kawasaki disease. Additionally, electrocardiographic changes such as ST-segment abnormalities, QT prolongation, and heart blocks further highlight the spectrum of cardiac involvement [5].

The diagnosis of MIS-C is guided by criteria established by The World Heath Organization (WHO) , which emphasize persistent fever, laboratory evidence of inflammation, multi system involvement, and evidence of recent COVID-19 infection or exposure[6].. Clinically, patients may present with a wide range of symptoms including rash, gastrointestinal disturbances, respiratory symptoms, and neurological manifestations, alongside cardiovascular compromise[7].

Management of MIS-C primarily focuses on controlling the hyperinflammatory state and providing supportive care. Current treatment strategies are largely based on expert consensus due to limited high-quality evidence and include the use of corticosteroids, intravenous immunoglobulin (IVIG), and, in severe cases, biologic agents such as anakinra or tocilizumab[8]. Hemodynamic support with fluids, inotropes, and mechanical ventilation is often required in critically ill patients. Furthermore, due to the prothrombotic state associated with MIS-C, antiplatelet and anticoagulant therapies are commonly recommended, particularly in patients with severe cardiac involvement or elevated D-dimer levels [9].

Despite the severity of presentation, short-term outcomes are generally favorable, with most children demonstrating recovery of cardiac function before discharge. However, the long-term prognosis remains uncertain. Some patients may develop persistent or late-onset coronary artery abnormalities, necessitating prolonged follow-up and monitoring. Current recommendations suggest regular cardiac evaluation, including echocardiography and electrocardiography, for at least one year following diagnosis to detect potential complications early [10]. Given the evolving nature of MIS-C and its potential for long-term cardiovascular consequences, there is a critical need for systematic studies to better understand its clinical spectrum, cardiac manifestations, and outcomes. Therefore, this study is undertaken to comprehensively evaluate the cardiovascular manifestations and short-term outcomes of MIS-C in children at a tertiary care center, aiming to contribute to improved clinical management and deeper understanding of this condition.

This study is conducted as a prospective cohort study aimed at evaluating cardiovascular manifestations and short-term outcomes in children diagnosed with Multi-system Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 infection, carried out in the Department of Pediatric Cardiology at JJM Medical College, Davangere, Karnataka, India over a period of six months, from May 2021 to November 2021. All patients between the age group of 0-18years diagnosed with MIS-C (as per WHO diagnostic criteria) and underwent cardiac evaluation by the Pediatric cardiologist were included to the study. Patients with alternative diagnoses such as tropical infections (malaria, dengue, rickettsial infections, enteric fever), bacterial sepsis, or toxic shock syndrome, patients with incomplete clinical evaluation or those lost to follow-up during the study period, and those whose parents or guardians did not provide informed consent were excluded from the study. A convenience sample size of 60 patients was considered for the study. A consecutive sampling technique was employed in the study. All eligible children admitted with suspected MIS-C during the study period were screened, and those fulfilling the inclusion criteria were enrolled sequentially. This method minimized selection bias and ensured representation of all cases presenting during the study duration. The study parameters included demographic, clinical, laboratory, and cardiac variables. Ethical committee approval was taken prior to start of the study. Written informed consent was obtained from parents or legal guardians of all participants. Patient confidentiality was strictly maintained by anonymising data. .Data were collected using a pre-structured proforma designed specifically for the study. Data were recorded as baseline at admission,  during hospital stay, and at follow-up visits. Laboratory values were interpreted based on standard reference ranges, and echocardiographic measurements were converted to z-scores for coronary artery assessment. Data were entered into Microsoft Excel and analyzed using SPSS version 22.0. Descriptive statistics were used to summarize baseline characteristics, expressed as frequencies, percentages, means, and standard deviations. Inferential statistical tests such as independent t-test and Chi-square test were applied to compare continuous and categorical variables, respectively. Correlation analysis was performed using Pearson’s or Spearman’s correlation coefficient based on data distribution to assess relationships between biomarkers and cardiac involvement. Multivariable regression analysis was conducted to identify risk factors associated with cardiovascular complications. A p-value of less than 0.05 was considered statistically significant

The study population predominantly consisted of younger children, with the highest proportion (38.9%) in the 0–6 years age group. There was a male predominance (61%). Most children (79.6%) had BMI within the normal percentile range, while a smaller proportion were undernourished (13.5%) or overweight (6.7%). On analysing the clinical features (Table-1), Fever was universally present among all patients (100%), confirming it as a hallmark feature of MIS-C. Gastrointestinal symptoms such as nausea/vomiting (54.2%) and abdominal pain (44%) were highly prevalent. Respiratory and neurological manifestations were also noted, though less frequently. The wide spectrum of symptoms highlights the multisystem involvement characteristic of MIS-C. The mean vital parameters indicated relative hemodynamic stability in most patients, although a notable proportion exhibited tachycardia (30.5%) and tachypnea (27%), suggestive of systemic inflammatory response and possible cardiovascular involvement. On analysing the cardiac parameters, most  patients had preserved left ventricular function (71.1%), though mild to moderate dysfunction was observed in a subset (28.9%) indicating cardiac involvement Right ventricular abnormalities and coronary wall changes were also noted, reflecting inflammatory cardiac pathology associated with MIS -C. Coronary artery involvement was relatively less frequent but clinically significant, with LMCA and LAD showing higher rates of abnormalities including aneurysms and ectasia. [Table-2] Valvular involvement [Table-3] was predominantly mild in severity, with tricuspid and pulmonary regurgitation being the most common findings. Pulmonary artery hypertension was observed in a significant proportion, indicating increased pulmonary vascular involvement.. These findings emphasize the need for careful cardiac monitoring in MIS-C patients. Trace pericardial effusion was common (52.4%), while moderate to severe effusion was rare (1.6%). Pleural effusion was present in a considerable number of patients (42.2%). Most children did not have underlying congenital heart disease (81.3%).  The mean PICU stay was 2.94days. Most patients (67.7%) required prolonged hospitalization (>14 days), indicating the severity of MIS-C. Despite this, the prognosis was favorable, with a high discharge rate (98.3%) and low mortality (1.6%), reflecting effective management and recovery in the majority of cases.

Table 1- Clinical features of MIS-C

Table 2- Cardiac functional parameters and coronary artery pinvolvement

This study provides a comprehensive evaluation of the demographic profile, clinical spectrum, cardiovascular manifestations, and outcomes of children diagnosed with Multisystem Inflammatory Syndrome in Children (MIS-C), and the findings are broadly consistent with previously published literature while also demonstrating some notable variations. In the current study, the mean age of affected children was 8.14 years, with the highest proportion in the 0–6 years age group (38.9%), followed by 6–12 years (32.3%) and >12 years (28.8%). This age distribution is comparable to earlier studies such as Balagurunathan et al., [11] who reported a mean age of 6.9 years, and Angurana et al., [12] observed a median age of 7 years, indicating that MIS-C predominantly affects younger pediatric populations . A male predominance was observed in the present study (61.0%), which aligns with findings from Balagurunathan et al.[11] (71.4% males) and Angurana et al. [12] (67% males), suggesting a consistent gender predisposition across studies . Regarding nutritional status, most children (79.6%) in the present study had normal BMI, with 13.5% undernourished and 6.7% overweight, whereas Balagurunathan et al. [11] identified overweight/obesity as a factor associated with prolonged hospital stay, indicating that nutritional status may influence disease severity and recovery .

Clinically, fever was present in 100% of cases in the present study, which is in agreement with multiple studies including Angurana et al. [11](99%), Bagri et al. [13] (100%), and Suresh et al. [14] (97.5%), reaffirming fever as a universal hallmark of MIS-C . Gastrointestinal manifestations were highly prevalent, with nausea/vomiting (54.2%) and abdominal pain (44.0%) in the present study, comparable to Angurana et al. [11] (81%) and Bagri et al. [13] (70.9%), where gastrointestinal involvement was one of the most common presentations . Neurological manifestations including convulsions (10.1%) and neurological deficits (13.5%) were also observed, supporting the multisystem involvement described in earlier studies.

Vital parameters in the present study revealed tachycardia in 30.5% and tachypnea in 27% of patients, reflecting systemic inflammation and possible cardiovascular compromise. These findings are consistent with the high rates of shock reported in other studies, such as Suresh et al. [14]

Cardiovascular involvement was a key finding in this study. Left ventricular (LV) dysfunction was observed in 16.8% of patients (13.5% mild and 3.3% moderate). 11.8% patients exhibited hyperdynamic function, which may reflect compensatory mechanisms during systemic inflammation. Right ventricular dysfunction was observed in 10.1% of cases, with 20.3% showing RV dilation, indicating involvement of both ventricles, although less severe than reported in some previous studies. Coronary artery abnormalities, a hallmark of MIS-C, were observed in a smaller proportion of patients in the present study, with LMCA showing mild aneurysm in 6.7% and moderate aneurysm in 3.3%, and LAD showing mild aneurysm in 6.7%.. Coronary wall hyperechogenicity was noted in 42.4% of cases, indicating subclinical inflammation even in the absence of overt aneurysm. Valvular involvement was predominantly mild in the present study, with tricuspid regurgitation (74.5%), pulmonary regurgitation (76.2%), and mitral regurgitation (61.0%) being common. Pulmonary artery hypertension (PAH) was observed in 55.9% (mild) and 13.5% (moderate), indicating significant pulmonary vascular involvement. These findings are in line with the inflammatory cardiac involvement described in MIS-C, Pericardial effusion was present in more than half of the patients (52.5% trace), and pleural effusion was noted in 42.2% of cases, reflecting systemic inflammation and capillary leak, which have also been described in previous studies.

In terms of outcomes, the present study demonstrated a favorable prognosis, with 98.3% of patients discharged and a mortality rate of 1.6%. This prolonged hospital stay in the present study may be attributed to cautious monitoring, especially for cardiac involvement, or differences in institutional protocols. The findings of the present study reinforce that MIS-C is a multisystem inflammatory condition with predominant cardiovascular involvement.. The universal presence of fever, high prevalence of gastrointestinal symptoms, and significant though variable cardiac involvement are consistent across studies. Importantly, despite the severity of presentation, outcomes remain favorable with timely diagnosis and appropriate management, as reflected by the high discharge rate and low mortality in the present study. These observations re-emphasise the importance of early recognition, multidisciplinary management, and continued follow-up, particularly for cardiac sequelae, to optimize outcomes in children with MIS-C.

Multisystem inflammatory syndrome in children (MIS-C) is a complex and potentially life-threatening condition associated with COVID-19, characterized by multisystem involvement with prominent cardiovascular manifestations. The study highlights that children commonly present with fever and a wide range of systemic symptoms, with frequent involvement of the gastrointestinal and cardiovascular systems. Cardiac abnormalities, including ventricular dysfunction, coronary changes, and valvular involvement, are important features requiring careful evaluation and monitoring. Despite the severity of presentation, the overall prognosis is favorable with timely diagnosis, appropriate immunomodulatory therapy, and supportive care. However, the presence of cardiac involvement and the need for prolonged hospitalization emphasize the importance of early recognition and multidisciplinary management. Long-term follow-up remains essential to monitor potential late cardiovascular sequelae and to ensure optimal recovery in affected children.

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