Cardiovascular Assessment 5 Years After MIS-C

Official title

Cardiovascular Evaluation 5 Years After Multisystem Inflammatory Syndrome in Children (MIS-C)

Overview

Multisystem inflammatory syndrome in children (MIS-C) is a severe complication associated with SARS-CoV-2 infection that frequently affects the cardiovascular system. Although acute cardiac abnormalities usually resolve, the long-term cardiovascular consequences of MIS-C remain uncertain. Previous follow-up of this cohort 2 years after MIS-C identified signs of subclinical cardiovascular abnormalities compared with healthy controls. This cross-sectional study aims to evaluate cardiovascular health in individuals 5 years after MIS-C. Participants with a history of MIS-C will be compared with age- and sex-matched healthy controls using cardiovascular imaging, vascular assessments, cardiopulmonary exercise testing, and biomarkers of endothelial injury.

Detailed description

Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe hyperinflammatory condition associated with SARS-CoV-2 infection. Cardiovascular involvement is common during the acute phase of the disease and may include myocardial dysfunction, arrhythmias, hypotension, and coronary artery abnormalities. Although most patients experience rapid clinical recovery following immunomodulatory treatment, the long-term cardiovascular consequences of MIS-C remain incompletely understood.

The investigators previously evaluated cardiovascular health approximately 2 years after MIS-C and found evidence of subclinical cardiovascular abnormalities, including higher blood pressure values, increased concentrations of biomarkers associated with endothelial injury, and increased carotid intima-media thickness compared with healthy controls. These findings suggested that vascular changes may persist beyond the acute phase of the disease.

The aim of the present study is to assess cardiovascular health 5 years after MIS-C and to determine whether cardiovascular abnormalities remain detectable in long-term follow-up.

This is a cross-sectional study with a healthy control group. The MIS-C group will consist of individuals who were hospitalized with MIS-C at the Department of Pediatrics of the Medical University of Warsaw Children's Clinical Hospital between October 2020 and February 2021. Healthy controls will be recruited from primary care clinics and matched to the MIS-C group by age and sex.

All participants will undergo a comprehensive cardiovascular evaluation including:

* laboratory testing (complete blood count, fasting glucose, HbA1c, lipid profile); * assessment of endothelial injury biomarkers, including galectin-3, soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble intercellular adhesion molecule-1 (sICAM-1); * arterial stiffness assessment using pulse wave analysis and pulse wave velocity measurements; * carotid intima-media thickness (cIMT) ultrasound; * transthoracic echocardiography; * cardiopulmonary exercise testing on a cycle ergometer.

The primary outcome is aortic (central) systolic blood pressure. Secondary outcomes include peripheral blood pressure, vascular stiffness parameters, carotid intima-media thickness, echocardiographic parameters, cardiopulmonary exercise test results, and concentrations of galectin-3, sICAM-1, and sVCAM-1. Outcomes will be compared between participants with a history of MIS-C and healthy controls to determine whether subclinical cardiovascular abnormalities persist 5 years after MIS-C.

The study is expected to provide important information regarding the long-term cardiovascular health of post-MIS-C patients and may help identify individuals who could benefit from ongoing cardiovascular surveillance.

Primary outcome measures

• Aortic (central) systolic blood pressure [Time frame: At the study visit, approximately 5 years after MIS-C diagnosis]

Secondary outcome measures (7)

• Peripheral blood pressure [Time frame: At the study visit, approximately 5 years after MIS-C diagnosis]
• Arterial stiffness [Time frame: At the study visit, approximately 5 years after MIS-C diagnosis]
• Carotid intima-media thickness [Time frame: At the study visit, approximately 5 years after MIS-C diagnosis]
• Endothelial injury biomarker concentrations [Time frame: At the study visit, approximately 5 years after MIS-C diagnosis]
• Echocardiographic parameters [Time frame: At the study visit, approximately 5 years after MIS-C diagnosis]
• Cardiopulmonary exercise capacity [Time frame: At the study visit, approximately 5 years after MIS-C diagnosis]
• Comparison of cardiovascular outcomes between MIS-C participants and healthy controls [Time frame: At the study visit, approximately 5 years after MIS-C diagnosis]

Eligibility criteria

Inclusion criteria

• For the MIS-C group: History of MIS-C diagnosed according to World Health Organization (WHO) criteria
• For all participants: Written informed consent from a parent or legal guardian and, where applicable, assent/consent from participants aged 16 years or older /

Exclusion criteria

MIS-C group:

• Known heart disease, including congenital heart disease.
• Significant chronic disease affecting growth, development, or daily functioning.

Control group:

• Elimination diet.
• Competitive athletic training.
• Known heart disease, including congenital heart disease.
• Significant chronic disease affecting growth, development, or daily functioning.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Case-control

Study locations

Poland · 1 center

• Medical University of Warsaw Children's Clinical Hospital — Warsaw

Publications

• Belhadjer Z, Meot M, Bajolle F, Khraiche D, Legendre A, Abakka S, Auriau J, Grimaud M, Oualha M, Beghetti M, Wacker J, Ovaert C, Hascoet S, Selegny M, Malekzadeh-Milani S, Maltret A, Bosser G, Giroux N, Bonnemains L, Bordet J, Di Filippo S, Mauran P, Falcon-Eicher S, Thambo JB, Lefort B, Moceri P, Houyel L, Renolleau S, Bonnet D. Acute Heart Failure in Multisystem Inflammatory Syndrome in Children PMID 32418446
• Abrams JY, Oster ME, Godfred-Cato SE, Bryant B, Datta SD, Campbell AP, Leung JW, Tsang CA, Pierce TJ, Kennedy JL, Hammett TA, Belay ED. Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study. Lancet Child Adolesc Health. 2021 May;5(5):323-331. doi: 10.1016/S2352-4642(21)00050-X. Epub 2021 Mar 10. PMID 33711293
• Clark BC, Sanchez-de-Toledo J, Bautista-Rodriguez C, Choueiter N, Lara D, Kang H, Mohsin S, Fraisse A, Cesar S, Sattar Shaikh A, Escobar-Diaz MC, Hsu DT, Randanne PC, Aslam N, Kleinmahon J, Lamour JM, Johnson JN, Sarquella-Brugada G, Chowdhury D. Cardiac Abnormalities Seen in Pediatric Patients During the SARS-CoV2 Pandemic: An International Experience. J Am Heart Assoc. 2020 Nov 3;9(21):e018007. PMID 32957826
• Krupickova S, Bautista-Rodriguez C, Hatipoglu S, Kang H, Fraisse A, Di Salvo G, Piccinelli E, Rowlinson G, Lane M, Altamar Bermejo I, Moscatelli S, Wage R, Mohiaddin R, Pennell DJ, Voges I. Myocardial deformation assessed by CMR in children after multisystem inflammatory syndrome (MIS-C). Int J Cardiol. 2022 Jan 1;346:105-106. doi: 10.1016/j.ijcard.2021.11.036. Epub 2021 Nov 16. PMID 34798209
• Feldstein LR, Tenforde MW, Friedman KG, Newhams M, Rose EB, Dapul H, Soma VL, Maddux AB, Mourani PM, Bowens C, Maamari M, Hall MW, Riggs BJ, Giuliano JS Jr, Singh AR, Li S, Kong M, Schuster JE, McLaughlin GE, Schwartz SP, Walker TC, Loftis LL, Hobbs CV, Halasa NB, Doymaz S, Babbitt CJ, Hume JR, Gertz SJ, Irby K, Clouser KN, Cvijanovich NZ, Bradford TT, Smith LS, Heidemann SM, Zackai SP, Wellnitz K PMID 33625505
• Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, Ramnarayan P, Fraisse A, Miller O, Davies P, Kucera F, Brierley J, McDougall M, Carter M, Tremoulet A, Shimizu C, Herberg J, Burns JC, Lyall H, Levin M; PIMS-TS Study Group and EUCLIDS and PERFORM Consortia. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. PMID 32511692
• Flood J, Shingleton J, Bennett E, Walker B, Amin-Chowdhury Z, Oligbu G, Avis J, Lynn RM, Davis P, Bharucha T, Pain CE, Jyothish D, Whittaker E, Dwarakanathan B, Wood R, Williams C, Swann O, Semple MG, Ramsay ME, Jones CE, Ramanan AV, Gent N, Ladhani SN. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): Prospective, national surveillance, United Kingdom a PMID 34027512

Identifiers

NCT: NCT07659847 · KB/86/2025 · 2W9/1/M/MGN25

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗