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Researchers Detect Subtle Changes in Cardiac Function in Young Patients With MIS-C
Editor’s Note: Multisystem Inflammatory Syndrome in Children (MIS-C) has emerged as a new disease, mostly affecting children four to six weeks after asymptomatic exposure to SARS-CoV-2 virus. Because MIS-C shares some external similarities with Kawasaki disease (KD), deductions arose about possible coronary artery involvement. Initially, this was a cause for consternation for both physicians and parents alike, due to a paucity of published research about the cardiac manifestations of MIS-C. Anirban Banerjee, MD, FACC, an attending cardiologist at Children’s Hospital of Philadelphia, and colleagues in the Division of Cardiology, including first author Daisuke Matsubara, MD, PhD, analyzed echocardiographic manifestations of this illness and reported their findings online ahead of print in the Journal of the American College of Cardiology. Dr. Banerjee, who is also a professor of Clinical Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, shared the study team’s insights in this Q&A.
Why was it important to tackle this research question?
Most of the scientific papers published since the first patient reports of MIS-C focus on conventional echocardiographic parameters; however, it was our opinion that conventional echocardiographic parameters would not detect subtle, subclinical changes in cardiac function. For evaluating subtle changes in cardiac function in MIS-C patients, we decided to use newer parameters known as strain that can reveal abnormalities, when conventional parameters are normal. This approach was novel and had not been reported previously in children from anywhere else in the world.
Moreover, our opinion was that the cardiac manifestations of MIS-C were different than those of KD, and a picture of myocardial injury was more common in MIS-C. The latter was the focus of our research.
How is CHOP ideally situated to conduct this research?
MIS-C is a relatively rare disease affecting only 0.6% in children infected by COVID-19. The high volume of patients is one of the strong points of CHOP. Our study enrolled perhaps the maximal achievable number of patients (n=28) for a single, tertiary care center collected within a short time frame of two months, which was comparable even with multicenter U.S. and European studies. Moreover, CHOP has an established infrastructure that fosters novel research projects such as this.
What are the clinical/therapeutic implications of these findings?
Since cardiac involvement is common in MIS-C, physicians may have to treat them in a manner as we would treat other viral myocarditis cases. We noted cardiogenic shock in 85% of our MIS-C patients. In contrast, the incidence of cardiogenic shock is quite rare in classic KD. Physicians should remember that along with conventional echocardiography, evaluation of strain parameters are quite useful in evaluating subtle changes in heart function in MIS-C patients. Long-term effects of myocardial injury will need to be studied, as this may have implications on sports participation in these children.
What are the main messages you hope physicians will take away from this report?
We have several take-home messages for physicians in the front line. First, coronary arteries are relatively spared (4%) in the acute stage of this disease. Second, cardiac injury/dysfunction is common (60%), with subtle myocardial changes detected by echocardiographic strain parameters. Third, systolic dysfunction recovered quickly within several days; however, diastolic dysfunction persisted. Lastly, not only the left ventricle, but the two “forgotten chambers” of the heart (left atrium and right ventricle), were significantly affected. In fact, strain measurements in the latter two chambers correlated strongly with biomarkers of myocardial injury in MIS-C.
What should future investigations of coronary function in MIS-C look at?
Although one of our MIS-C patients showed a dilated coronary artery, it normalized rapidly. In our study, no other progressive coronary lesions were detected in the MIS-C group. Larger studies will be needed to fully characterize coronary involvement in MIS-C.
In addition, long-term follow-up is essential to fully understand this new disease. Cardiac MRI should be performed in the future to evaluate for myocardial scarring. This is especially true when considering the possible lingering effects of myocardial injury and consequent need for caution in sports participation. In a manner similar to KD, a follow-up period of a year may be needed, even if the child is clinically well outwardly.
What other points, if any, would you like to make?
First, in the absence of biopsy and cardiac MRI in our MIS-C patients, we used the term “cardiac injury” for those with positive Troponin I (> 0.3 ng/mL) and/or elevated BNP(>500 pg/mL) levels, although other studies in children have used the term myocarditis. In a study of adults appearing in JACC, the authors studied the impact of elevated troponin levels in more than 2,700 hospitalized patients in New York with COVID- 19 infections. They used the term myocardial injury to describe elevations in Troponin I level. They showed that even mild increases in Troponin I levels (0.03-0.09 ng/ml) were associated with increased mortality in adults during hospitalization.
In contrast, most of MIS-C patients in our study, even with higher Troponin I levels, recovered their systolic function quickly. In the largest study in hospitalized children published in NEJM, the diagnosis of SARS-CoV-2 infection was confirmed in 95 children. Out of these 95 children, fortunately only 2 died (2.1%). This is far less than the death rate in hospitalized adults with COVID-19 with troponin elevation (about 18.5%). Therefore, we speculate that the elevation in cardiac troponins may have less dire implications in children, likely due to a more transient and reversible type of cardiac injury and fewer co-morbidities. Clearly, further studies are needed before a definitive statement can be made; nonetheless, close longitudinal follow-up of these children is essential.
For more details, please see the CHOP press release.