Role of Endomyocardial Biopsy and Aetiology-based Treatment in Pediatric Patients with Inflammatory Heart Disease in Arrhythmic and Non-arrhythmic Clinical Presentations: an Integrated Approach for the Optimal Diagnostic and Therapeutic Management (MYOPED)

Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age0-17
SponsorScientific Institute San Raffaele

About this trial

Myocarditis is a complex inflammatory disease, usually occurring secondary to viral infections, autoimmune processes or toxic agents. Clinical presentations are multiple, including chest-pain, heart failure and a broad spectrum of arrhythmias. In turn, outcome is largely unpredictable, ranging from mild self-limiting disease, to chronic stage and progressive evolution towards dilated cardiomyopathy, to rapid adverse outcome in fulminant forms. Subsequently, myocarditis is often underdiagnosed and undertreated, and optimal diagnostic and therapeutic strategies are still to be defined. This study, both retrospective and prospective, originally single-center and subsequently upgraded to multicenter, aims at answering multiple questions about myocarditis, with special attention to its arrhythmic manifestations.

Optimal diagnostic workflow is still to be defined. In fact, although endomyocardial biopsy (EMB) is still the diagnostic gold standard, especially for aetiology identification, it is an invasive technique. Furthermore, it may lack sensitivity because of sampling errors. By converse, modern imaging techniques - cardiac magnetic resonance (CMR) in particular - have been proposed as alternative or complementary diagnostic tool in inflammatory heart disease. Other noninvasive diagnostic techniques, like delayed-enhanced CT (DECT) scan or position emission tomography (PET) scan, are under investigation.

Biomarkers to identify myocarditis aetiology, predisposition, prognosis and response to treatment are still to be defined.

Arrhythmic myocarditis is largely underdiagnosed and uninvestigated. Importantly, myocarditis presenting with arrhythmias requires specific diagnostic, prognostic and therapeutic considerations. At the group leader hospital, which is an international referral center for ventricular arrhythmias management and ablation, a relevant number of patients with unexplained arrhythmias had myocarditis as underlying aetiology. The experience of a dedicated third-level center is going to be shared with other centers, to considerably improve knowledge and management of arrhythmic myocarditis.

The role of CMR, as well as alternative noninvasive imaging techniques, in defining myocarditis healing is a relevant issue. In particular, optimal timing for follow-up diagnostic reassessment is still to be defined, in patients with myocarditis at different inflammatory stages, either with or without aetiology-dependent treatment.

Uniformly-designed studies are lacking, to compare myocarditis among different patient subgroups, differing by variables like: clinical presentations, myocarditis stage, associated cardiac or extra-cardiac diseases, aetiology-based treatment, associated arrhythmic manifestations, diagnostic workup, and devices or ablation treatment.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Written informed consent.

Age < 18 years.

Clinically suspected myocarditis.

Enrollment performed by one of the participating Centers.

Disqualifiers

Absence of written informed consent.

Age > 18 years (adults)

Trial population

We will enroll pediatric patients (age \< 18 y), of any gender or ethnic group, evaulated for clinically suspected myocarditis. Patients can be enrolled from any medical environment or department, including inpatients, outpatients, and patients transferred from other hospitals. The same inclusion criteria of the original single-center protocol will apply to the entire multicenter study.

Trial design

Design model

Case-control

Time perspective

Other

Treatments tested in this trial

  • support treatment, cardiac medical treatment, aetiology-specific treatment, device implant, arrhythmia ablation

    Other intervention

    Treatment will be patient-tailored, integrating international guidelines recommendation and the experience of the center where enrollment takes place.

Treatment groups

20 Participants
are divided into 3 treatment groups
Group A: Arrhythmic (A)1 intervention
Group B: Nonarrhythmic (NA)1 intervention
Group C: Subgroups1 intervention

Trial outcomes

Primary outcomes

1

Occurrence of major cardiac events

death; cardiac death; malignant ventricular arrhythmias ( = VT, VF, appropriate ICD therapy); heart transplantation; end-stage heart failure

Time frame
By 12-month follow-up
2

Occurrence of major cardiac events

death; cardiac death; malignant ventricular arrhythmias ( = VT, VF, appropriate ICD therapy); heart transplantation; end-stage heart failure

Time frame
By 24-month follow-up
3

Occurrence of major cardiac events

death; cardiac death; malignant ventricular arrhythmias ( = VT, VF, appropriate ICD therapy); heart transplantation; end-stage heart failure

Time frame
By 3-year follow-up
4

Occurrence of major cardiac events

death; cardiac death; malignant ventricular arrhythmias ( = VT, VF, appropriate ICD therapy); heart transplantation; end-stage heart failure

Time frame
By 5-year follow-up

Secondary outcomes

1

Occurrence of minor arrhythmic events

NSVT; PVC burden; supraventricular arrhythmias; bradyarrhythmias

Time frame
At baseline assessment and through study completion (up to 10 years)
2

Any modification in imaging parameters

Structural or functional myocardial abnormalities at echocardiogram or second level imaging (any chamber dilation, systolic or diastolic dysfunction, including strain analysis, pericardial, vascular or valvular involvement, any other detectable abnormalities; qualitative and quantitative evaluation); signal abnormalities detectable by advanced imaging techniques (Lake Louise criteria and T-mapping techniques at CMR; any qualitative or quantitative imaging abnormality detectable by CMR, DECT or PET scan, or other imaging techniques, alone or in association).

Time frame
At baseline assessment and through study completion (up to 10 years)
3

Any modification in clinical parameters

Signs and symptoms related to cardiac or multisystemic disease, as assessed by dedicated questionnaires.

Time frame
By 10-year follow-up
4

Any modification in New York Heart Association class

Change in New York Heart Association class (range I-IV; significant change for improvement by at least one class).

Time frame
By 10-year follow-up

Other outcomes

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