Elsevier

American Heart Journal

Volume 187, May 2017, Pages 133-144
American Heart Journal

Trial Design
Toward evidence-based diagnosis of myocarditis in children and adolescents: Rationale, design, and first baseline data of MYKKE, a multicenter registry and study platform

https://doi.org/10.1016/j.ahj.2017.02.027Get rights and content

Aims

The aim of this registry is to provide data on age-related clinical features of suspected myocarditis and to create a study platform allowing for deriving diagnostic criteria and, at a later stage, testing therapeutic interventions in patients with myocarditis.

Study design and results

After an initial 6-month pilot phase, MYKKE was opened in June 2014 as a prospective multicenter registry for patients from pediatric heart centers, university hospitals, and community hospitals with pediatric cardiology wards in Germany. Inclusion criteria consisted of age<18 years and hospitalization for suspected myocarditis as leading diagnosis at the discretion of the treating physician. By December 31, 2015, fifteen centers across Germany were actively participating and had enrolled 149 patients. Baseline data reveal 2 age peaks (<2 years, >12 years), show higher proportions of males, and document a high prevalence of severe disease courses in pediatric patients with suspected myocarditis. Severe clinical courses and early adverse events were more prevalent in younger patients and were related to severely impaired leftventricular ejection fraction at initial presentation.

Summary

MYKKE represents a multicenter registry and research platform for children and adolescents with suspected myocarditis that achieve steady recruitment and generate a wide range of real-world data on clinical course, diagnostic workup, and treatment of this group of patients. The baseline data reveal the presence of 2 age peaks and provide important insights into the severity of disease in children with suspected myocarditis. In the future, MYKKE might facilitate interventional substudies by providing an established collaborating network using common diagnostic approaches.

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

References (19)

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Trial registration: ClinicalTrials.govNCT02590341.

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