Age-adjusted NT-proBNP could help in the early identification and follow-up of children at risk for severe multisystem inflammatory syndrome associated with COVID-19 (MIS-C)

ARTICLE HIGHLIGHTS

Research background

Multisystem inflammatory syndrome in children (MIS-C) emerged as a severe new disease associated with coronavirus disease 2019. One of the most critical issues is the high prevalence of cardiovascular involvement in these children, leading to a high percentage of cardiogenic shock, myocardial dysfunction secondary to the inflammatory response, and the need for inotropic support and extracorporeal membrane oxygenation (ECMO).

Research motivation

MIS-C is a severe new entity, and we still know very little about it. Therefore, it is necessary to communicate the experience in the management of these patients as well as to generate scientific evidence on all aspects of MIS-C that allow the best management of these patients.

Research objectives

This study was designed to identify clinical and laboratory markers of severity in this new disease. MIS-C is a condition with cardiac involvement in almost all cases. Therefore, we decided to analyze whether NT-proBNP, one of the most widely used cardiac biomarkers in routine clinical practice, was capable of identifying the most severe cases that required admission to the pediatric intensive care unit (PICU) and administration of inotropic support. We also aimed to determine whether NT-proBNP was an adequate follow-up parameter in this setting.

Research methods

A retrospective study was conducted which included children with MIS-C managed at our institution between April 1, 2020, and February 28, 2022. We divided the population into groups of severity based on PICU admission. We compared Z-log-NT-proBNP values adjusted for age in days across these groups and analyzed Z-log-NT-proBNP dynamics throughout the one-month follow-up.

Research results

We included 17 participants (median age 3 (2-9) years) and seven (41%) required PICU admission. All (100%) of these cases presented very high (Z-log > 4) levels of NT-proBNP at the time of admission compared to only 5 (50%) patients with non-severe MIS-C (P = 0.025). NT-proBNP was significantly correlated with high-sensitivity Troponin I levels (P = 0.045), Ross modified score (P = 0.003) and left ventricle ejection fraction (P = 0.021). NT-proBNP was raised in all of our patients at admission, and we observed a significant rapid, gradual, and continuous decrease in our patients following immunomodulatory therapy administration. In the follow-up visit at the pediatric cardiologist outpatient clinic one month after of the hospitalization, we documented complete normalization of the cardiac state, without cardiac sequelae in any of the patients.

Research conclusions

Raised NT-proBNP, specifically very high values (Z-log-NT-proBNP > 4), could help identify MIS-C patients with myocardial dysfunction requiring inotropic support and PICU admission. NT-proBNP could also have a role in the post-hospitalization follow-up of these patients to monitor their cardiovascular recovery.

Research perspectives

NT-proBNP is a promising biomarker for the initial screening and monitoring of myocardial dysfunction during the acute phase of MIS-C. However, its use in pediatrics is limited by its strong age dependency. Using Z-log-NT-proBNP values could provide constant reference values of NT-proBNP in children with MIS-C and would lead to consistency in data analysis across centers worldwide. NT-proBNP could also be used as a laboratory marker of subclinical myocardial dysfunction, aiding in the appropriate monitoring of cardiovascular complications in these patients during their post-hospitalization follow-up, especially in centers where speckle tracking echocardiography is not available. Therefore, this study could be an appropriate starting point to explore in future prospective studies with larger sample sizes and to confirm our results.