Trial DesignToward evidence-based diagnosis of myocarditis in children and adolescents: Rationale, design, and first baseline data of MYKKE, a multicenter registry and study platform
Section snippets
Rationale of the MYKKE registry
The aim of this project is to overcome the lack of prospectively collected multicenter data on epidemiology, clinical presentation, and diagnostic value of currently available diagnostic tools in children and adolescents with myocarditis to define age-specific properties and to establish clinically meaningful criteria for the diagnosis of myocarditis. To this end, MYKKE is designed to include patients with suspected myocarditis rather than patients with definitive myocarditis only, as the
Study design
MYKKE is a long-term prospective registry providing a research platform for clinical studies that are attached in a modular fashion. After a 1-year pilot phase including 8 centers, the registry was opened in June 2014 to all hospitals in Germany treating pediatric patients with heart disease. Although the scientific lead is with 2 study coordinators (D.M. and S.S.) and a study group consisting of principal investigators from the collaborating centers (“MYKKE Investigators”), MYKKE is hosted and
Funding
The pilot phase and scientific planning of the study were funded through 2 project grants by the Deutsche Herzstiftung (Frankfurt am Main, Germany) granted to Dr Schubert and Dr Messroghli.
Logistic support and management of the research database are provided by the Competence Network for Congenital Heart Defects (Berlin, Germany), which received funding from the Federal Ministry of Education and Research, grant number 01GI0601 (until 2014), and the DZHK (as of 2015).
Baseline data
By December 31, 2015, fifteen centers across Germany (4 heart centers, 10 university hospitals, 1 community hospital) were actively participating in MYKKE and had enrolled 149 patients. Figure 1 illustrates the increase in recruitment sites and patients enrolled since the beginning of the study.
Table I, Table II provide the baseline data of the patients enrolled so far.
Two age groups are dominating at presentation: the first year of life and adolescence (Figure 2). In the age group 0-<2 years,
Severity of disease as a function of age and gender
Out of 149 patients, 57 patients (38%) met at least 1 of the following criteria: death, survived sudden cardiac death, assist device, decompensated heart failure, heart transplantation, catecholamine therapy, or malignant arrhythmia. Taking this combined endpoint as a marker for a severe course of disease, the influence of age and gender on this combined end point was examined. The odds for a severe disease course decreased statistically significantly with age by 14% per year (95% CI,8%-19%;P <
Discussion
In the past, clinical research on myocarditis has primarily been performed by single centers and provided only limited insight into the epidemiology, clinical course, and impact of diagnostic and therapeutic actions for 2 reasons. Firstly, single centers do not see large numbers of pediatric patients with myocarditis. Although there are no systematic data on the prevalence or incidence of myocarditis in children and adolescents, information, for example, from analyses of admission rates and
Conclusions
MYKKE is the first multicenter prospective registry for children and adolescents with suspected myocarditis that is designed to collect evidence on epidemiology, diagnosis, and therapy in this disease. The baseline data from 149 patients enrolled at 15 centers reveal 2 age peaks and a high proportion of patients with severe courses of disease and early adverse events including the need for mechanical circulatory support, heart transplantation, and death. Severe courses of disease are related to
Acknowledgements
The following researchers (“MYKKE Consortium") significantly contributed to the development and implementation of MYKKE: Felix Berger, MD (Deutsches Herzzentrum Berlin/Charité–Universitätsmedizin Berlin/DZHK Partner Site Berlin, Berlin); Guido Haverkämper, MD (Charité–Universitätsmedizin Berlin, Berlin); Edzard zu Knyphausen, MD, and Deniz Kececioglu, MD (Herz- und Diabetes-Zentrum Nordrhein-Westfahlen, Bad Oeynhausen); Trong Phi Lê, MD (Klinikum Links der Weser, Bremen); Sven Dittrich, MD, and
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Cited by (26)
Society for Cardiovascular Magnetic Resonance/European Society of Cardiovascular Imaging/American Society of Echocardiography/Society for Pediatric Radiology/North American Society for Cardiovascular Imaging Guidelines for the use of cardiovascular magnetic resonance in pediatric congenital and acquired heart disease: Endorsed by The American Heart Association
2022, Journal of Cardiovascular Magnetic ResonanceClinical characteristics and outcome of biopsy-proven myocarditis in children – Results of the German prospective multicentre registry “MYKKE”
2022, International Journal of CardiologyCitation Excerpt :Thus, it can direct and monitor treatment strategies, which has been proven in single-centre studies in adults but not yet in children with suspected myocarditis [13,18]. Therefore, the aim of this study was to investigate the current clinical practice of EMB, its diagnostic value, impact on therapeutic strategies, and relation to outcomes in paediatric patients with suspected myocarditis by analysing data from the prospective multicentre registry “MYKKE” [19]. MYKKE is a prospective multicentre registry for suspected myocarditis in children and adolescents, which aims to gain knowledge on incidence, pathogenesis, and outcome of paediatric myocarditis.
Clinical characteristics and predictive factors of outcomes in children with acute myocarditis: Focusing on vasoactive-inotropic score
2022, Progress in Pediatric CardiologyCitation Excerpt :In our study, there was a bimodal age distribution with peaks in age at less than 3 years and at 9–11 years. A similar age distribution was described in a retrospective review of a large administrative database from the United States [3] and a prospective multicenter registry and study platform from Germany [17]. It is possible that very young children are more typically susceptible to virus-induced pathogenesis and do not tolerate cardiac dysfunction well, thus requiring medical attention, whereas older children are able to communicate their symptoms to their caregivers and seek treatment.
Could the unfortunate outcome of pediatric acute myocarditis be predicted? Factors contributing to a poor outcome in myocarditis
2021, Revista Portuguesa de CardiologiaCitation Excerpt :An echocardiographic assessment of myocardial function showed that patients with systolic impairment were at increased risk of DCM, while EDD Z score >2+ increased the risk of a poor outcome by almost 12-fold. Rodriguez-Gonzalez et al. and researchers from the MYKKE study, established that EF<30% was an independent risk factor for DCM.1,9 Some studies conducted in a pediatric population have shown that 69% of children had spontaneous recovery of myocardial function at one-year follow-up.1
Diagnosis, Evaluation, and Treatment of Myocarditis in Children
2020, Pediatric Clinics of North AmericaCitation Excerpt :Multiple studies have shown a bimodal peak in incidence. Most cases occur in infancy and adolescents, with those in infancy having worse outcomes.3,9–12 There may be a higher prevalence among men.5,11
Trial registration: ClinicalTrials.govNCT02590341.