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Viadero MT, Caldeiro MJ, Fernández-Suarez N, Garde J, Cabero MJ, González-Lamuño D. Molecular Mechanisms and Pathophysiology of Myocardial Disease: Insights from Pediatric Inflammatory Multisystem Syndrome (PIMS) Associated with SARS-CoV-2. Int J Mol Sci 2025; 26:3580. [PMID: 40332089 PMCID: PMC12026855 DOI: 10.3390/ijms26083580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 04/05/2025] [Accepted: 04/06/2025] [Indexed: 05/08/2025] Open
Abstract
Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multisystem syndrome (PIMS), presents significant challenges in pediatric cardiology, due to its complex molecular pathophysiology. In this retrospective analysis of 15 cases that were managed at a single tertiary care center, we investigated the molecular contributors to myocardial dysfunction, including cytokine storms, hyperinflammation markers, and hypercoagulable states. Transient myocardial involvement was identified in 46.6% of patients, with complete recovery achieved within 2-4 weeks following treatment. Ferritin, NT-ProBNP, and troponin levels were significantly elevated in patients with ventricular dysfunction compared to those without. The neutrophil-to-lymphocyte ratio (NLR), which was previously identified as a severity marker in acute COVID-19, was also significantly higher in patients with ventricular dysfunction, suggesting its potential as a prognostic indicator in MIS-C. Notably, no coronary artery aneurysms were detected in the cohort. These findings underscore the importance of early, standardized therapeutic interventions in mitigating severe outcomes, and they provide valuable insights into the molecular mechanisms driving myocardial dysfunction in MIS-C. Incorporating NLR and ferritin into the initial diagnostic workup may improve the early triage and identification of high-risk MIS-C patients.
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Affiliation(s)
- María Teresa Viadero
- Pediatric Cardiology, Division of Pediatrics, University Hospital “Marqués de Valdecilla”, University of Cantabria, Avda. Valdecilla s/n, 39008 Santander, Spain; (M.T.V.); (N.F.-S.); (J.G.)
- Division of Pediatrics, University Hospital “Marqués de Valdecilla”, Avda. Valdecilla s/n, 39008 Santander, Spain;
| | - María Jesús Caldeiro
- Division of Pediatrics, University Hospital “Marqués de Valdecilla”, Avda. Valdecilla s/n, 39008 Santander, Spain;
| | - Natalia Fernández-Suarez
- Pediatric Cardiology, Division of Pediatrics, University Hospital “Marqués de Valdecilla”, University of Cantabria, Avda. Valdecilla s/n, 39008 Santander, Spain; (M.T.V.); (N.F.-S.); (J.G.)
- Division of Pediatrics, University Hospital “Marqués de Valdecilla”, Avda. Valdecilla s/n, 39008 Santander, Spain;
| | - Jesús Garde
- Pediatric Cardiology, Division of Pediatrics, University Hospital “Marqués de Valdecilla”, University of Cantabria, Avda. Valdecilla s/n, 39008 Santander, Spain; (M.T.V.); (N.F.-S.); (J.G.)
- Division of Pediatrics, University Hospital “Marqués de Valdecilla”, Avda. Valdecilla s/n, 39008 Santander, Spain;
| | - María Jesús Cabero
- Head of Pediatrics Division, University Hospital “Marqués de Valdecilla”, University of Cantabria, Avda. Valdecilla s/n, 39008 Santander, Spain
| | - Domingo González-Lamuño
- Consultant of Nefrology, Rare Diseases and Clinical Genetics Department, Division of Pediatrics University Hospital “Marqués de Valdecilla”, University of Cantabria, Avda. Valdecilla s/n, 39008 Santander, Spain
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Varadarajan P, Solomon RS, Subramani S, Subramanian R, Srividya G, Raghunathan E. Cardiovascular involvement in multisystem inflammatory syndrome in children and midterm follow-up from a pediatric tertiary center in India. World J Clin Pediatr 2025; 14:100453. [DOI: 10.5409/wjcp.v14.i1.100453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 10/02/2024] [Accepted: 10/30/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND In multisystem inflammatory syndrome in children (MIS-C) with coronavirus disease 2019, there was paucity of data from low-income and middle-income countries on cardiovascular involvement and its longitudinal outcomes. We planned to estimate the pattern of cardiovascular involvement among children with MIS-C and its mid-term outcomes.
AIM To determine association between cardiovascular abnormalities and clinical and laboratory parameters. To study the time-line for resolution of various abnormalities.
METHODS In this prospective study done in a tertiary care hospital, 270 were recruited from June 2020 to January 2022. Baseline demographic data and clinical presentation were recorded. Laboratory parameters and echocardiography were done at admission. Follow-up was done at 2 weeks, 3 months, 6 months and 1 year after diagnosis. Descriptive statistics were used for parametric and non-parametric data. Risk factors were identified by multivariate regression analysis.
RESULTS The 211 (78.2%) had cardiac involvement and 102 needed intensive care unit (ICU) admission. Cardiovascular abnormalities observed were shock 123 (45.6%), coronary dilatation 28 (10.4%), coronary aneurysm 77 (28.5%), left ventricular (LV) dysfunction 78 (29.3%), mitral regurgitation (MR) 77 (28.5%) and pericardial effusion 98 (36.3%). Coronary artery aneurysm/dilatation during follow-up at 2 weeks and 1 year were 25.7% and 0.9% respectively. Multivariate regression analysis revealed breathlessness [odds ratio (OR) = 3.91, 95%CI: 1.25-12.21, P = 0.019] and hi-flow nasal cannula (HFNC) support (OR = 8.5, 95%CI: 1.06-68.38, P = 0.044) as predictors of cardiovascular involvement. Higher mean age (OR = 1.16, 95%CI: 1.02-1.32, P = 0.026), breathlessness (OR = 4.99, 95%CI: 2.05-12.20, P < 0.001), gallop (OR = 4.45, 95%CI: 0.41-2.52, P = 0.016), MR (OR = 3.61, 95%CI: 1.53-8.53, P = 0.004) and invasive ventilation (OR = 4.01, 95%CI: 1.28-12.58, P = 0.017) were predictive of LV dysfunction. Altered sensorium (OR = 4.96, 95%CI: 2.23-11.02, P < 0.001), headache (OR = 6.61, 95%CI: 1.46-29.92, P = 0.014), HFNC (OR = 7.03, 95%CI: 2.04-24.29, P = 0.002), non-rebreathing mask usage (OR = 21.13, 95%CI: 9.00-49.61, P < 0.001) and invasive ventilation (OR = 5.64, 95%CI: 1.42-22.45, P = 0.014) were risk factors for shock. Anemia was a risk factor for coronary involvement (OR = 3.09, 95%CI: 1.79- 5.34, P < 0.001).
CONCLUSION Significant number of children with MIS-C had cardiovascular involvement contributing to higher ICU management. Although shock resolved quickly, resolution of ventricular function and coronary abnormalities were slower, and hence warrants a structured long-term follow-up protocol.
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Affiliation(s)
- Poovazhagi Varadarajan
- Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai 600003, Tamil Nādu, India
| | - Ritchie Sharon Solomon
- Department of Pediatric Cardiology, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai 600003, Tamil Nādu, India
| | - Seenivasan Subramani
- Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai 600003, Tamil Nādu, India
| | - Ramesh Subramanian
- Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai 600003, Tamil Nādu, India
| | - Gomathy Srividya
- Department of Pediatric Intensive Care, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai 600003, Tamil Nādu, India
| | - Elilarasi Raghunathan
- Department of Pediatrics, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai 600003, Tamil Nādu, India
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Mehdizadegan N, Omidbakhsh S, Shorafa E, Hosseini H, Amoozgar H, Mohammadi H, Naghshzan A, Edraki M, Hozhabri K, Abootalebi N, Mohammadi MH. Speckle-tracking and conventional echocardiography in MIS-C: tracking cardiac involvement and recovery. BMC Pediatr 2025; 25:137. [PMID: 40001107 PMCID: PMC11853775 DOI: 10.1186/s12887-025-05509-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 02/12/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Multisystem inflammatory syndrome in children (MIS-C), a complication of COVID-19, is frequently associated with cardiac involvement. Although most affected children recover, the extent and duration of myocardial abnormalities remain uncertain. This study evaluates mid-term cardiac function in MIS-C patients, with and without cardiac involvement, using transthoracic echocardiography (TTE) and speckle-tracking echocardiography (STE). METHODS This case-control study (2022-2023) included 90 children: 30 with MIS-C and cardiac involvement, 30 with MIS-C without cardiac involvement, and 30 healthy controls. TTE and STE were used to assess left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) at diagnosis and at three months, comparing outcomes across groups. RESULTS The cardiac involvement group exhibited significantly elevated ferritin and C-reactive protein levels (P = 0.006 and P = 0.017, respectively) and a higher prevalence of troponin positivity (56.67% vs. 20%, P = 0.009). At baseline, these patients had markedly reduced LVEF (56.5 ± 4.3) and GLS (-21.6 ± 3.21) compared to healthy controls (LVEF: 68.2 ± 5.21; GLS: -24.8 ± 1.48; both P < 0.001). Notably, the basal segment showed significant longitudinal strain reduction (-18.75 ± 3.89 vs. -23.58 ± 0.27, P = 0.027), while differences in the apical and mid segments were not significant. By three months, LVEF (69 ± 4.21, P = 0.53) and GLS (-24.13 ± 2.39, P = 0.17) normalized. Heart failure and coronary artery brightness resolved in all affected patients, and most structural abnormalities improved; only two cases exhibited persistent mild left ventricular dilation. Regional strain analysis at follow-up revealed values comparable to those of healthy controls across all segments. CONCLUSION Cardiac dysfunction in MIS-C largely resolves within three months, with LVEF and GLS returning to normal. However, persistent myocardial abnormalities in a few cases highlight the need for long-term cardiac monitoring to detect and manage potential sequelae.
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Affiliation(s)
- Nima Mehdizadegan
- Department of Pediatrics, Division of Pediatric Cardiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Cardiovascular Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sajedeh Omidbakhsh
- Clinical Department of Pediatrics, Amol Campus of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Eslam Shorafa
- Department of Pediatrics, Division of Intensive Care Unit, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Hossein Hosseini
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamid Amoozgar
- Department of Pediatrics, Division of Pediatric Cardiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Cardiovascular Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamid Mohammadi
- Department of Pediatrics, Division of Pediatric Cardiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Cardiovascular Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amir Naghshzan
- Department of Pediatrics, Division of Pediatric Cardiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Cardiovascular Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammadreza Edraki
- Department of Pediatrics, Division of Pediatric Cardiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
- Cardiovascular Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Katayoon Hozhabri
- Clinical Department of Pediatrics, Amol Campus of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
| | - Narjes Abootalebi
- Clinical Department of Pediatrics, Amol Campus of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
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Stasiak A, Kędziora P, Smolewska E. Complications of Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 Infection-Many Facets of One Disease-A Literature Review Based on a Case Report. J Clin Med 2024; 13:4146. [PMID: 39064185 PMCID: PMC11278001 DOI: 10.3390/jcm13144146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/10/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024] Open
Abstract
Multisystem inflammatory syndrome in children (MIS-C) is a disease that made its mark in the early days of the COVID-19 pandemic due to the diverse course and symptoms affecting multiple body systems. It is a condition that develops in pediatric patients about 2-6 weeks after contact with a person infected with the SARS-CoV-2 virus. In many instances, MIS-C has caused multiple organ failure, with particularly severe complications involving the cardiovascular system and manifesting as hypotension, various cardiac arrhythmias, myocarditis or coronary artery lesions resembling those seen in Kawasaki disease. Currently, the incidence of MIS-C is about 1-3 per 1000 children, with a decreasing trend in recent years due to the introduction of immunization against the SARS-CoV-2 virus for children as young as 6 months. In our paper, we present the case of a patient with a severe course of MIS-C with numerous cardiovascular and neurological complications, in whom the symptoms of the disease were managed by administering biological treatment. We also present a review of the literature on the subject, which shows how many different facets this disease can have and that physicians still need to remain alert, as there are cases of severe MIS-C, especially in unvaccinated patients.
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Affiliation(s)
- Aleksandra Stasiak
- Department of Pediatric Cardiology and Rheumatology, Medical University of Lodz, Sporna 36/50 Street, 91-738 Lodz, Poland; (P.K.); (E.S.)
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Ptak K, Olszewska M, Szymońska I, Olchawa-Czech A, Mól N, Rudek-Budzyńska A, Kukla K, Cisowska M, Sabat O, Grzyb A, Kwinta P. Should we be afraid of long-term cardiac consequences in children with multisystem inflammatory syndrome? Experience from subsequent waves of COVID-19. Eur J Pediatr 2024; 183:2683-2692. [PMID: 38517518 DOI: 10.1007/s00431-024-05528-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 03/12/2024] [Accepted: 03/14/2024] [Indexed: 03/24/2024]
Abstract
The purpose of the study was to assess and compare short- and long-term cardiac complications of the multisystem inflammatory syndrome in children (MIS-C) by predominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants throughout the pandemic. The analysis of prospectively collected data comparing cardiac complications of MIS-C during and after hospitalization across the original/alpha, delta, and omicron waves. Cardiac complications were defined as cardiac failure with systolic function impairment or hypotension or abnormalities in echocardiographic findings (decrease in LVEF, FS, valvular insufficiency, pericardial effusion, or coronary artery abnormalities). A total of 120 patients with MIS-C admitted to the Children's Hospital of Krakow between November 1, 2020, and May 5, 2023, were included in the study (74 during original/alpha dominance, 31 delta, and 15 omicron). Patients in the omicron group were found to be younger than those in the alpha and delta groups (37 vs. 75 vs. 80 months, p = 0.03). The frequency of cardiac failure with systolic function impairment or hypotension was diagnosed more frequently in the original/alpha and delta groups than in the omicron group (44.59% vs. 41.94% vs. 13.33%, p = 0.08) also echocardiographic abnormalities changed, with rates of 60.8%, 35.5%, and 13.3% (p < 0.001) accordingly. The multivariable regression revealed an older age (OR = 1.19, 95% CI = 1.07-1.33, p = 0.002) as the only independent factors of cardiac failure with systolic function impairment or hypotension. In all patients, signs of cardiac failure resolved during the hospitalization. Moreover, in 98.3% of patients, all echocardiagraphic abnormalities resolved completely during the observation period. Conclusion: The cardiac complications of MIS-C appeared to advance less severely in younger children during the Omicron outbreak. In long-term observation, symptoms of cardiac failure resolve completely. Similarly, also echocardiographic abnormalities normalize in the vast majority of patients. What is Known: • Knowledge about the long-term cardiac complications of MIS-C is still evolving and uncertain. • The greatest concern of MIS-C is cardiac complications, including cardiac failure and coronary artery dilatation. What is New: • Long-term observations revealed complete resolution of cardiac complications in the vast majority of patients with MIS-C, irrespective of the dominant variant. • Cardiac complications of MIS-C were less common in younger children during subsequent pandemic waves in our patient population.
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Affiliation(s)
- Katarzyna Ptak
- Department of Pediatrics, Jagiellonian University Medical College, Krakow, Poland.
| | - Marta Olszewska
- Department of Pediatrics, Jagiellonian University Medical College, Krakow, Poland
| | - Izabela Szymońska
- Department of Pediatrics, Jagiellonian University Medical College, Krakow, Poland
| | - Anna Olchawa-Czech
- Department of Pediatrics, Jagiellonian University Medical College, Krakow, Poland
| | - Nina Mól
- Department of Pediatrics, Jagiellonian University Medical College, Krakow, Poland
| | | | - Kornelia Kukla
- Department of Pediatrics, University Children's Hospital, Krakow, Poland
| | - Marta Cisowska
- Department of Pediatrics, University Children's Hospital, Krakow, Poland
| | - Oliwia Sabat
- Department of Pediatrics, Jagiellonian University Medical College, Students' Scientific Group, Krakow, Poland
| | - Aleksandra Grzyb
- Department of Pediatrics, Jagiellonian University Medical College, Students' Scientific Group, Krakow, Poland
| | - Przemko Kwinta
- Department of Pediatrics, Jagiellonian University Medical College, Krakow, Poland
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Patel MA, Fraser DD, Daley M, Cepinskas G, Veraldi N, Grazioli S. The plasma proteome differentiates the multisystem inflammatory syndrome in children (MIS-C) from children with SARS-CoV-2 negative sepsis. Mol Med 2024; 30:51. [PMID: 38632526 PMCID: PMC11022403 DOI: 10.1186/s10020-024-00806-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 03/09/2024] [Indexed: 04/19/2024] Open
Abstract
BACKGROUND The Multi-System Inflammatory Syndrome in Children (MIS-C) can develop several weeks after SARS-CoV-2 infection and requires a distinct treatment protocol. Distinguishing MIS-C from SARS-CoV-2 negative sepsis (SCNS) patients is important to quickly institute the correct therapies. We performed targeted proteomics and machine learning analysis to identify novel plasma proteins of MIS-C for early disease recognition. METHODS A case-control study comparing the expression of 2,870 unique blood proteins in MIS-C versus SCNS patients, measured using proximity extension assays. The 2,870 proteins were reduced in number with either feature selection alone or with a prior COMBAT-Seq batch effect adjustment. The leading proteins were correlated with demographic and clinical variables. Organ system and cell type expression patterns were analyzed with Natural Language Processing (NLP). RESULTS The cohorts were well-balanced for age and sex. Of the 2,870 unique blood proteins, 58 proteins were identified with feature selection (FDR-adjusted P < 0.005, P < 0.0001; accuracy = 0.96, AUC = 1.00, F1 = 0.95), and 15 proteins were identified with a COMBAT-Seq batch effect adjusted feature selection (FDR-adjusted P < 0.05, P < 0.0001; accuracy = 0.92, AUC = 1.00, F1 = 0.89). All of the latter 15 proteins were present in the former 58-protein model. Several proteins were correlated with illness severity scores, length of stay, and interventions (LTA4H, PTN, PPBP, and EGF; P < 0.001). NLP analysis highlighted the multi-system nature of MIS-C, with the 58-protein set expressed in all organ systems; the highest levels of expression were found in the digestive system. The cell types most involved included leukocytes not yet determined, lymphocytes, macrophages, and platelets. CONCLUSIONS The plasma proteome of MIS-C patients was distinct from that of SCNS. The key proteins demonstrated expression in all organ systems and most cell types. The unique proteomic signature identified in MIS-C patients could aid future diagnostic and therapeutic advancements, as well as predict hospital length of stays, interventions, and mortality risks.
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Affiliation(s)
- Maitray A Patel
- Epidemiology and Biostatistics, Western University, N6A 3K7, London, ON, Canada
| | - Douglas D Fraser
- Lawson Health Research Institute, N6C 2R5, London, ON, Canada.
- Children's Health Research Institute, N6C 4V3, London, ON, Canada.
- Pediatrics, Western University, N6A 3K7, London, ON, Canada.
- Clinical Neurological Sciences, Western University, N6A 3K7, London, ON, Canada.
- Physiology & Pharmacology, Western University, N6A 3K7, London, ON, Canada.
- London Health Sciences Centre, Room C2-C82, 800 Commissioners Road East, N6A 5W9, London, ON, Canada.
| | - Mark Daley
- Epidemiology and Biostatistics, Western University, N6A 3K7, London, ON, Canada
- Computer Science, Western University, N6A 3K7, London, ON, Canada
| | - Gediminas Cepinskas
- Lawson Health Research Institute, N6C 2R5, London, ON, Canada
- Medical Biophysics, Western University, N6A 3K7, London, ON, Canada
| | - Noemi Veraldi
- Department of Pediatrics, Gynaecology and Obstetrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Serge Grazioli
- Department of Pediatrics, Gynaecology and Obstetrics, Faculty of Medicine, University of Geneva, Geneva, Switzerland
- Division of Neonatal and Pediatric Intensive Care, Department of Child, Woman, and Adolescent Medicine, Geneva University Hospitals, Geneva, Switzerland
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Baykan A, Kum YE, Yılmazer MM, Varan C, Yakut K, Sert A, Öztunç F, Öncül M, Uç D, Başpınar O, Pamukçu Ö, Murat M, Tanıdır İC, Alkan G, Murt NU, Akın A, Karakurt C, Şahin DA, Doğan A, Duman D, Öztürk E, Coşkun Yİ, Türe M, Temel MT, Elkıran Ö. One-Year Follow-Up Results of MIS-C Patients with Coronary Artery Involvement: A Multi-center Study. Pediatr Cardiol 2024; 45:282-291. [PMID: 38159144 DOI: 10.1007/s00246-023-03364-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 11/26/2023] [Indexed: 01/03/2024]
Abstract
Multisystem inflammatory syndrome (MIS-C) in children is a rare complication of SARS-CoV-2 infection. Knowing the course of the affected or unaffected coronary arteries in the patients under follow-up is important in terms of defining the long-term prognosis of the disease and determining the follow-up plan. This is a multicenter and retrospective study. The data were obtained from nine different centers. Between May 2020 and August 2022, 68 of 790 patients had coronary artery involvement. One-year echocardiographic data of 67 of 789 MIS-C patients with coronary artery involvement were analyzed. Existing pathologies of the coronary arteries were grouped as increased echogenicity, dilatation and aneurysm according to Z scores, and their changes over a 1-year period were determined. The data of all three groups are defined as frequency. SPSS Statistics version 22 was used to evaluate the data. In our study, aneurysm was observed in 16.4%, dilatation in 68.7% and increased echogenicity in 13.4% of the patients. All of the patients with involvement in the form of increased echogenicity recovered without sequelae by the end of the first month. No progression to aneurysm was observed in any of the patients with dilatation. No new-onset involvement was observed in patients with previously healthy coronary arteries during the convalescent period. In addition, from the sixth month follow-up period, there was no worsening in the amount of dilatation in any of the patients. At least 94% of the patients who completed the 12th month control period returned to normal.
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Affiliation(s)
- Ali Baykan
- Department of Pediatric Cardiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Yunus Emre Kum
- Department of Pediatric Cardiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey.
| | - Murat Muhtar Yılmazer
- Department of Pediatric Cardiology, Dr. Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital, University of Health Sciences, İzmir, Turkey
| | - Celal Varan
- Department of Pediatric Cardiology, Adıyaman Training and Research Hospital, Adıyaman, Turkey
| | - Kahraman Yakut
- Department of Pediatric Cardiology, Istanbul Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey
| | - Ahmet Sert
- Department of Pediatric Cardiology, Faculty of Medicine, Selçuk University, Konya, Turkey
| | - Funda Öztunç
- Department of Pediatric Cardiology, Faculty of Medicine, Istanbul University Cerrahpaşa, Istanbul, Turkey
| | - Mehmet Öncül
- Department of Pediatric Cardiology, Faculty of Medicine, İnönü University, Malatya, Turkey
| | - Duygu Uç
- Department of Pediatric Cardiology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey
| | - Osman Başpınar
- Department of Pediatric Cardiology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Özge Pamukçu
- Department of Pediatric Cardiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
| | - Mehmet Murat
- Department of Pediatric Cardiology, Dr. Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital, University of Health Sciences, İzmir, Turkey
| | - İbrahim Cansaran Tanıdır
- Department of Pediatric Cardiology, Istanbul Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey
| | - Gülsüm Alkan
- Department of Pediatric Infectious Disease, Faculty of Medicine, Selçuk University, Konya, Turkey
| | - Nujin Uluğ Murt
- Department of Pediatric Cardiology, Faculty of Medicine, Istanbul University Cerrahpaşa, Istanbul, Turkey
| | - Alper Akın
- Department of Pediatric Cardiology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey
| | - Cemşit Karakurt
- Department of Pediatric Cardiology, Faculty of Medicine, İnönü University, Malatya, Turkey
| | - Derya Aydın Şahin
- Department of Pediatric Cardiology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Alper Doğan
- Department of Pediatric Cardiology, Batman Training and Research Hospital, Batman, Turkey
| | - Derya Duman
- Department of Pediatric Cardiology, Faculty of Medicine, Mersin University, Mersin, Turkey
| | - Erkut Öztürk
- Department of Pediatric Cardiology, Istanbul Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey
| | - Yusuf İskender Coşkun
- Department of Pediatric Cardiology, Faculty of Medicine, Istanbul University Cerrahpaşa, Istanbul, Turkey
| | - Mehmet Türe
- Department of Pediatric Cardiology, Faculty of Medicine, Dicle University, Diyarbakır, Turkey
| | - Münevver Tuğba Temel
- Department of Pediatric Cardiology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Özlem Elkıran
- Department of Pediatric Cardiology, Faculty of Medicine, İnönü University, Malatya, Turkey
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Campu A, Muresan I, Potara M, Lazar DR, Lazar FL, Cainap S, Olinic DM, Maniu D, Astilean S, Focsan M. Portable microfluidic plasmonic chip for fast real-time cardiac troponin I biomarker thermoplasmonic detection. J Mater Chem B 2024; 12:962-972. [PMID: 38044663 DOI: 10.1039/d3tb02190d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2023]
Abstract
Acute myocardial infarction is one of the most serious cardiovascular pathologies, impacting patients' long-term outcomes and health systems worldwide. Significant effort is directed toward the development of biosensing technologies, which are able to efficiently and accurately detect an early rise of cardiac troponin levels, the gold standard in detecting myocardial injury. In this context, this work aims to develop a microfluidic plasmonic chip for the fast and accurate real-time detection of the cardiac troponin I biomarker (cTnI) via three complementary detection techniques using portable equipment. Furthermore, the study focuses on providing a better understanding of the thermoplasmonic biosensing mechanism taking advantage of the intrinsic photothermal properties of gold nanoparticles. Specifically, a plasmonic nanoplatform based on immobilized gold nanobipyramids was fabricated, exhibiting optical and thermoplasmonic properties that promote, based on a sandwich-like immunoassay, the "proof-of-concept" multimodal detection of cTnI via localized surface plasmon resonance, surface enhanced Raman spectroscopy and thermoplasmonic effects under simulated conditions. Furthermore, after the integration of the plasmonic nanoplatform in a microfluidic channel, the determination of cTnI in 16 real plasma samples was successfully realized via thermoplasmonic detection. The results are compared with a conventional high-sensitivity enzyme-linked immunosorbent clinical assay (ELISA), showing high sensitivity (75%) and specificity (100%) as well as fast response features (5 minutes). Thus, the proposed portable and miniaturized microfluidic plasmonic chip is successfully validated for clinical applications and transferred to clinical settings for the early diagnosis of cardiac diseases, leading towards the progress of personalized medicine.
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Affiliation(s)
- Andreea Campu
- Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes-Bolyai University, Treboniu Laurian No. 42, 400271 Cluj-Napoca, Romania.
| | - Ilinca Muresan
- Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes-Bolyai University, Treboniu Laurian No. 42, 400271 Cluj-Napoca, Romania.
| | - Monica Potara
- Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes-Bolyai University, Treboniu Laurian No. 42, 400271 Cluj-Napoca, Romania.
| | - Diana Raluca Lazar
- Department of Pediatric Cardiology, Pediatric Clinic No. 2, Emergency County Hospital for Children, Crisan No. 3 - 5, 400124 Cluj-Napoca, Romania
- 11th Department of Medical Oncology, University of Medicine and Pharmacology "Iuliu Hatieganu", Republicii No. 34 - 36, 400171 Cluj-Napoca, Romania
| | - Florin-Leontin Lazar
- Department of Interventional Cardiology, Medical Clinic No. 1, Emergency County Hospital, Clinicilor No. 3 - 5, 400006 Cluj-Napoca, Romania
| | - Simona Cainap
- Department of Pediatric Cardiology, Pediatric Clinic No. 2, Emergency County Hospital for Children, Crisan No. 3 - 5, 400124 Cluj-Napoca, Romania
- Department of Mother & Child, University of Medicine and Pharmacology "Iuliu Hatieganu", Louis Pasteur No. 4, 400349 Cluj-Napoca, Romania
| | - Dan Mircea Olinic
- Department of Interventional Cardiology, Medical Clinic No. 1, Emergency County Hospital, Clinicilor No. 3 - 5, 400006 Cluj-Napoca, Romania
- Cardiology Discipline, University of Medicine and Pharmacology "Iuliu Hatieganu", Louis Pasteur No. 4, 400349 Cluj-Napoca, Romania
| | - Dana Maniu
- Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes-Bolyai University, Treboniu Laurian No. 42, 400271 Cluj-Napoca, Romania.
- Biomolecular Physics Department, Faculty of Physics, Babes-Bolyai University, Mihail Kogalniceanu No. 1, 400084 Cluj-Napoca, Romania
| | - Simion Astilean
- Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes-Bolyai University, Treboniu Laurian No. 42, 400271 Cluj-Napoca, Romania.
- Biomolecular Physics Department, Faculty of Physics, Babes-Bolyai University, Mihail Kogalniceanu No. 1, 400084 Cluj-Napoca, Romania
| | - Monica Focsan
- Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes-Bolyai University, Treboniu Laurian No. 42, 400271 Cluj-Napoca, Romania.
- Biomolecular Physics Department, Faculty of Physics, Babes-Bolyai University, Mihail Kogalniceanu No. 1, 400084 Cluj-Napoca, Romania
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De Wolf R, Zaqout M, Tanaka K, Muiño-Mosquera L, van Berlaer G, Vandekerckhove K, Dewals W, De Wolf D. Evaluation of late cardiac effects after multisystem inflammatory syndrome in children. Front Pediatr 2023; 11:1253608. [PMID: 37691776 PMCID: PMC10484557 DOI: 10.3389/fped.2023.1253608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 08/01/2023] [Indexed: 09/12/2023] Open
Abstract
Introduction Multisystem inflammatory syndrome in children (MIS-C) is associated with important cardiovascular morbidity during the acute phase. Follow-up shows a swift recovery of cardiac abnormalities in most patients. However, a small portion of patients has persistent cardiac sequelae at mid-term. The goal of our study was to assess late cardiac outcomes of MIS-C. Methods A prospective observational multicenter study was performed in children admitted with MIS-C and cardiac involvement between April 2020 and March 2022. A follow-up by NT-proBNP measurement, echocardiography, 24-h Holter monitoring, and cardiac MRI (CMR) was performed at least 6 months after MIS-C diagnosis. Results We included 36 children with a median age of 10 (8.0-11.0) years, and among them, 21 (58%) were girls. At diagnosis, all patients had an elevated NT-proBNP, and 39% had a decreased left ventricular ejection fraction (LVEF) (<55%). ECG abnormalities were present in 13 (36%) patients, but none presented with arrhythmia. Almost two-thirds of patients (58%) had echocardiographic abnormalities such as coronary artery dilation (20%), pericardial effusion (17%), and mitral valve insufficiency (14%). A decreased echocardiographic systolic left ventricular (LV) function was detected in 14 (39%) patients. A follow-up visit was done at a mean time of 12.1 (±5.8) months (range 6-28 months). The ECG normalized in all except one, and no arrhythmias were detected on 24-h Holter monitoring. None had persistent coronary artery dilation or pericardial effusion. The NT-proBNP level and echocardiographic systolic LV function normalized in all patients, except for one, who had a severely reduced EF. The LV global longitudinal strain (GLS), as a marker of subclinical myocardial dysfunction, decreased (z < -2) in 35%. CMR identified one patient with severely reduced EF and extensive myocardial fibrosis requiring heart transplantation. None of the other patients had signs of myocardial scarring on CMR. Conclusion Late cardiac outcomes after MIS-C, if treated according to the current guidelines, are excellent. CMR does not show any myocardial scarring in children with normal systolic LV function. However, a subgroup had a decreased GLS at follow-up, possibly as a reflection of persistent subclinical myocardial dysfunction.
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Affiliation(s)
- Rik De Wolf
- Department of Pediatric Cardiology, University Hospital Brussels, Brussels, Belgium
| | - Mahmoud Zaqout
- Department of Pediatric Cardiology, Antwerp University Hospital, Antwerp, Belgium
- Department of Pediatric Cardiology, ZNA Queen Paola Children’s Hospital, Antwerp, Belgium
| | - Kaoru Tanaka
- Department of Radiology, University Hospital Brussels, Brussels, Belgium
| | | | - Gerlant van Berlaer
- Department of Pediatric Intensive Care, University Hospital Brussels, Brussels, Belgium
| | | | - Wendy Dewals
- Department of Pediatric Cardiology, Antwerp University Hospital, Antwerp, Belgium
| | - Daniël De Wolf
- Department of Pediatric Cardiology, University Hospital Brussels, Brussels, Belgium
- Department of Pediatric Cardiology, Ghent University Hospital, Ghent, Belgium
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10
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Gentili F, Calcagni G, Cantarutti N, Manno EC, Cafiero G, Tranchita E, Salvati A, Palma P, Giordano U, Drago F, Turchetta A. Cardiopulmonary Exercise Testing in Children and Young Adolescents after a Multisystem Inflammatory Syndrome: Physical Deconditioning or Residual Pathology? J Clin Med 2023; 12:jcm12062375. [PMID: 36983374 PMCID: PMC10057515 DOI: 10.3390/jcm12062375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 03/02/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023] Open
Abstract
Multisystem inflammatory syndrome in children (MIS-C) is a serious health condition that imposes a long-term follow-up. The purpose of our pilot study is to evaluate the usefulness of the cardiopulmonary stress test (CPET) in the follow-up after MIS-C. All patients admitted for MIS-C in our hospital in the 12 months preceding the date of observation were considered for inclusion in the study. Pre-existing cardio-respiratory diseases and/or the lack of collaboration were the exclusion criteria. At enrolment, each subject passed a cardiological examination, rest ECG, echocardiogram, 24 h Holter-ECG, blood tests, and a CPET complete of spirometry. A total of 20 patients met the inclusion criteria (11.76 ± 3.29 years, 13 male). In contrast to the normality of all second-level investigations, CPET showed lower-than-expected peakVO2 and peak-oxygen-pulse values (50% of cases) and higher-than-expected VE/VCO2-slope values (95% of cases). A statistically significant inverse correlation was observed between P-reactive-protein values at admission and peakVO2/kg values (p = 0.034), uric acid values at admission, and peakVO2 (p = 0.011) or peak-oxygen-pulse expressed as a percentage of predicted (p = 0.021), NT-proBNP values at admission and peakVO2 expressed as a percentage of predicted (p = 0.046). After MIS-C (4-12 months) relevant anomalies can be observed at CPET, which can be a valuable tool in the follow-up after this condition.
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Affiliation(s)
- Federica Gentili
- Complex Unit of Cardiology S. Paolo, Palidoro, Santa Marinella and Arrhythmology, Clinical Area of Fetal, Neonatal and Cardiological Sciences, Bambino Gesù Children's Hospital, IRCCS, L.go S. Onofrio 4, 00165 Rome, Italy
| | - Giulio Calcagni
- Complex Unit of Cardiology S. Paolo, Palidoro, Santa Marinella and Arrhythmology, Clinical Area of Fetal, Neonatal and Cardiological Sciences, Bambino Gesù Children's Hospital, IRCCS, L.go S. Onofrio 4, 00165 Rome, Italy
| | - Nicoletta Cantarutti
- Complex Unit of Cardiology S. Paolo, Palidoro, Santa Marinella and Arrhythmology, Clinical Area of Fetal, Neonatal and Cardiological Sciences, Bambino Gesù Children's Hospital, IRCCS, L.go S. Onofrio 4, 00165 Rome, Italy
| | - Emma Concetta Manno
- Complex Unit of Clinical Immunology and Vaccinology, Clinical Area of University Hospital Pediatrics, Bambino Gesù Children's Hospital, IRCCS, L.go S. Onofrio 4, 00165 Rome, Italy
| | - Giulia Cafiero
- Complex Unit of Cardiology S. Paolo, Palidoro, Santa Marinella and Arrhythmology, Clinical Area of Fetal, Neonatal and Cardiological Sciences, Bambino Gesù Children's Hospital, IRCCS, L.go S. Onofrio 4, 00165 Rome, Italy
| | - Eliana Tranchita
- Complex Unit of Cardiology S. Paolo, Palidoro, Santa Marinella and Arrhythmology, Clinical Area of Fetal, Neonatal and Cardiological Sciences, Bambino Gesù Children's Hospital, IRCCS, L.go S. Onofrio 4, 00165 Rome, Italy
| | - Annamaria Salvati
- Complex Unit of Cardiology S. Paolo, Palidoro, Santa Marinella and Arrhythmology, Clinical Area of Fetal, Neonatal and Cardiological Sciences, Bambino Gesù Children's Hospital, IRCCS, L.go S. Onofrio 4, 00165 Rome, Italy
| | - Paolo Palma
- Complex Unit of Clinical Immunology and Vaccinology, Clinical Area of University Hospital Pediatrics, Bambino Gesù Children's Hospital, IRCCS, L.go S. Onofrio 4, 00165 Rome, Italy
| | - Ugo Giordano
- Complex Unit of Cardiology S. Paolo, Palidoro, Santa Marinella and Arrhythmology, Clinical Area of Fetal, Neonatal and Cardiological Sciences, Bambino Gesù Children's Hospital, IRCCS, L.go S. Onofrio 4, 00165 Rome, Italy
| | - Fabrizio Drago
- Complex Unit of Cardiology S. Paolo, Palidoro, Santa Marinella and Arrhythmology, Clinical Area of Fetal, Neonatal and Cardiological Sciences, Bambino Gesù Children's Hospital, IRCCS, L.go S. Onofrio 4, 00165 Rome, Italy
| | - Attilio Turchetta
- Complex Unit of Cardiology S. Paolo, Palidoro, Santa Marinella and Arrhythmology, Clinical Area of Fetal, Neonatal and Cardiological Sciences, Bambino Gesù Children's Hospital, IRCCS, L.go S. Onofrio 4, 00165 Rome, Italy
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11
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Differentiating abdominal pain due to COVID-19 associated multisystem inflammatory syndrome from children with acute appendicitis: a score system. Pediatr Surg Int 2023; 39:151. [PMID: 36897476 PMCID: PMC9999317 DOI: 10.1007/s00383-023-05432-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/20/2023] [Indexed: 03/11/2023]
Abstract
PURPOSE Differentiating abdominal pain due to coronavirus disease (COVID-19)-associated multisystem inflammatory syndrome (MIS-C) in children with acute appendicitis (AA) can cause diagnostic dilemmas. This study aimed to evaluate the efficacy of a previously described scoring system and improve its diagnostic ability in differentiating between these diseases. METHODS This study was conducted between March 2020 and January 2022. Patients who had MIS-C with gastrointestinal system (GIS) involvement and patients who underwent surgery for appendicitis were included. First, all patients were evaluated using the new scoring system (NSS). The groups were compared by adding new MISC-specific parameters to NSS. The scoring system was evaluated using propensity score matching (PSM). RESULTS A total of 35 patients with abdominal pain due to GIS involvement in MIS-C (group A) and 37 patients with AA who had ALT, PRC, and D-dimer results at their first admission (group B) were included in the study. The mean age of patients in group A was lower than that of patients in group B (p < 0.001). False NSS positivity was found in 45.7% of the patients with MIS-C. Lymphocyte (p = 0.021) and platelet counts (p = 0.036) were significantly lower in the blood count and serum D-dimer (p = 0.034), C-reactive protein (CRP) (p < 0.001), and procalcitonin (p < 0.001) were significantly higher in the MIS-C group. We created a scoring system called the Appendicitis-MISC Score (AMS) using the NSS and new parameters. The sensitivity and specificity of AMS diagnostic scores were 91.9% and 80%, respectively. CONCLUSION MIS-C with GIS involvement may present as acute abdomen. It is difficult to differentiate this condition from acute appendicitis. AMS has been shown to be useful for this differentiation.
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