Myocarditis as a Complication of Enterovirus Infection in Infants

Background: Enterovirus infection is frequent in the pediatric population and can be complicated by severe multi-organ failure, including myocarditis, especially in young infants. Early identification of cardiac involvement is critical to guide treatment and prevent morbidity and mortality; however definitive diagnosis is based on biopsy, a procedure that carries significant risk for the affected infant. The first aim of this study was to identify patterns of clinical presentation and evaluate the non-invasive measures of laboratory values, EKG, and echocardiogram to differentiate infants with and without myocardial involvement complicating a confirmed enterovirus infection. The secondary objective was to assess the kinetic of cardiac troponin I (cTnI) values in our population.

Methods: We identified all infants less than 6 weeks of age hospitalized in our institution between January 2017 and January 2020 with a confirmed diagnosis of enterovirus. Cases were confirmed based on a positive enterovirus polymerase chain reaction (PCR) assay on cerebral spinal fluid (CSF), or a positive nucleic acid amplification test (NAAT) on nasopharyngeal swab plus positive viral culture. Clinical myocarditis was defined as presence of a cTnI value ≥ 5 times the upper limit of an adult normal value. Characteristics were compared between patients with and without myocardial involvement. Data collected included clinical and laboratory data, electrocardiography, and echocardiography.

Results: A total of 125 charts were reviewed, 86 patients met the inclusion criteria of definitive enteroviral infection. Only 44 patients had troponin level measured and constituted the study population. 16 of 44 patients (36.4%) presented with clinical myocarditis. Findings favoring a diagnosis of myocarditis included history of maternal illness (75% vs. 23% p=0.001), respiratory distress (50% vs. 11% p=0.010), thrombopenia (31% vs. 3% p=0.020) and ST-T segment anomalies on EKG (56% vs. 9% p=0.002). Peak cTnI values were measured between 4 and 6 days from symptoms onset. Predictive positive value for EKG was 71.4% and negative predictive value for echocardiography was 50.0%. 3 patients with myocarditis were treated with vasopressors and 7 patients received intravenous immunoglobulins, all of which had ≥ 20 times the upper limit of normal cTnI value. There was no mortality. Only 3 patients (6.8%) remained with echocardiography abnormalities and medication at 1 year.

Conclusion: The results suggest that infants with vertical transmission of the infection are at greater risk to develop myocardial involvement. History of maternal infection should be evaluated at initial presentation. The peak of myocardial damage occurs after 4 to 6 days of symptoms onset and can be detected by cTnI. Thereby, patients with cardiac involvement should be followed minimally for that period. The overall outcome in our cohort was better than reported in the previous literature.