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)

NCT06591260 | Recruiting

• 1 other identifier: MYOPED
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myocarditis; Ventricular Arrhythmia; Inflammatory Cardiomyopathy; Genetic Predisposition; Autoimmunity; Arrhythmia; Cardiomyopathies; Immunosuppresion; Catheter Ablation

Keywords

Myocarditis; Ventricular arrhythmias; Arrhythmias; Arrhythmogenic inflammatory cardiomyopathy; Endomyocardial biopsy; Cardiac magnetic resonance; Ablation; Positron emission tomography; Electroanatomical mapping; Immunosuppressive therapy; Arrhythmic risk stratification; Genetic predisposition; Environment; Implantable cardioverter defibrillator; Implantable loop recorder; Multicenter

Outcome Measures

Primary Outcomes (69)

• Occurrence of major cardiac events

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

  By 12-month follow-up

• Occurrence of major cardiac events

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

  By 24-month follow-up

• Occurrence of major cardiac events

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

  By 3-year follow-up

• Occurrence of major cardiac events

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

  By 5-year follow-up

• Occurrence of major cardiac events

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

  By 7-year follow-up

• Occurrence of major cardiac events

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

  By 10-year follow-up

• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary

  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value

  At baseline assessment

• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary

  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value

  By 6-month follow-up

• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary

  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value

  By 12-month follow-up

• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary

  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value

  By 24-month follow-up

• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary

  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value

  By 3-year follow-up

• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary

  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value

  By 5-year follow-up

• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary

  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value

  By 10-year follow-up

• Comparison of troponin values in patients with different aetiologies

  Measurement of troponin blood concentration (ng/l) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Description of troponin values changes during follow-up

  Measurement of troponin blood concentration (ng/l) during follow-up, and description of its relative variation compared to baseline assessment.

  By 10-year follow-up

• Comparison of creatine-phosphokinase values in patients with different aetiologies

  Measurement of creatine-phosphokinase (U/l) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Description of creatine-phosphokinase values changes during follow-up

  Measurement of creatine-phosphokinase (U/l) during follow-up, and description of its relative variation compared to baseline assessment.

  By 10-year follow-up

• Comparison of natriuretic peptides values in patients with different aetiologies

  Measurement of natriuretic peptides (pg/ml) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Description of natriuretic peptides values changes during follow-up

  Measurement of natriuretic peptides (pg/ml) during follow-up, and description of its relative variation compared to baseline assessment.

  By 10-year follow-up

• Comparison of C-reactive protein values in patients with different aetiologies

  Measurement of C-reactive protein (mg/l) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Description of C-reactive protein values changes during follow-up

  Measurement of C-reactive protein (mg/l) during follow-up, and description of its relative variation compared to baseline assessment.

  By 10-year follow-up

• Comparison of erythrocyte sedimentation rate values in patients with different aetiologies

  Measurement of erythrocyte sedimentation rate (mm/h) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Description of erythrocyte sedimentation rate values changes during follow-up

  Measurement of erythrocyte sedimentation rate (mm/h) during follow-up, and description of its relative variation compared to baseline assessment.

  By 10-year follow-up

• Comparison of procalcitonin values in patients with different aetiologies

  Measurement of procalcitonin (mcg/ml) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Comparison of procalcitonin values in patients with different aetiologies

  Measurement of procalcitonin (mcg/ml) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  By 10-year follow-up

• Comparison of serum uric acid values in patients with different aetiologies

  Measurement of serum uric acid (mg/dl) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Comparison of serum uric acid values in patients with different aetiologies

  Measurement of serum uric acid (mg/dl) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  By 10-year follow-up

• Comparison of leukocyte values in patients with different aetiologies

  Measurement of leukocytes (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Comparison of leukocyte values in patients with different aetiologies

  Measurement of leukocytes (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  By 10-year follow-up

• Comparison of hemoglobin values in patients with different aetiologies

  Measurement of hemoglobin (g/dl) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Comparison of hemoglobin values in patients with different aetiologies

  Measurement of hemoglobin (g/dl) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  By 10-year follow-up

• Comparison of platelet values in patients with different aetiologies

  Measurement of platelets (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Comparison of platelet values in patients with different aetiologies

  Measurement of platelets (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  By 10-year follow-up

• Comparison of thyroid function in patients with different aetiologies

  Measurement of thyroid stimulating hormone (mU/ml; total and fractions) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Comparison of thyroid function in patients with different aetiologies

  Measurement of thyroid stimulating hormone (mU/ml; total and fractions) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  By 10-year follow-up

• Comparison of organ damage in patients with different aetiologies

  Measurement of organ damage by application of the Sequential Organ Failure Assessment (SOFA) score in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Comparison of organ damage in patients with different aetiologies

  Measurement of organ damage by application of the Sequential Organ Failure Assessment (SOFA) score in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  By 10-year follow-up

• Reporting the results of autoimmunity screening

  Measurement of circulating autoantibodies (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Reporting the results of autoimmunity screening

  Measurement of circulating autoantibodies (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  By 10-year follow-up

• Reporting the results of infectious screening

  Measurement of viral antibodies (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Reporting the results of infectious screening

  Measurement of viral antibodies (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  By 10-year follow-up

• Reporting the results of toxicology screening

  Measurement of toxic urynalisis (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Reporting the results of toxicology screening

  Measurement of toxic urynalisis (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  By 10-year follow-up

• Reporting the results of genetic test screening

  Reporting the results of next generation sequencing analysis (mutation type) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  At baseline assessment

• Reporting the results of genetic test screening

  Reporting the results of next generation sequencing analysis (mutation type) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).

  By 10-year follow-up

• Validation of optimal management of arrhythmic myocarditis by comparing the occurrence of major cardiac events in patients undergoing different therapeutic strategies - Primary

  Evaluation of the occurrence of major cardiac events (death; cardiac death; malignant ventricular arrhythmias= VT, VF, appropriate ICD therapy; heart transplantation; end-stage heart failure) in patient groups differing for: 1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.

  By 12-month follow-up

• Validation of optimal management of arrhythmic myocarditis by comparing the occurrence of major cardiac events in patients undergoing different therapeutic strategies - Primary

  Evaluation of the occurrence of major cardiac events (death; cardiac death; malignant ventricular arrhythmias= VT, VF, appropriate ICD therapy; heart transplantation; end-stage heart failure) in patient groups differing for: 1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.

  By 24-month follow-up

• Validation of optimal management of arrhythmic myocarditis by comparing the occurrence of major cardiac events in patients undergoing different therapeutic strategies - Primary

  Evaluation of the occurrence of major cardiac events (death; cardiac death; malignant ventricular arrhythmias= VT, VF, appropriate ICD therapy; heart transplantation; end-stage heart failure) in patient groups differing for: 1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.

  By 3-year follow-up

• Validation of optimal management of arrhythmic myocarditis by comparing the occurrence of major cardiac events in patients undergoing different therapeutic strategies - Primary

  Evaluation of the occurrence of major cardiac events (death; cardiac death; malignant ventricular arrhythmias= VT, VF, appropriate ICD therapy; heart transplantation; end-stage heart failure) in patient groups differing for: 1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.

  By 5-year follow-up

• Validation of optimal management of arrhythmic myocarditis by comparing the occurrence of major cardiac events in patients undergoing different therapeutic strategies - Primary

  Evaluation of the occurrence of major cardiac events (death; cardiac death; malignant ventricular arrhythmias= VT, VF, appropriate ICD therapy; heart transplantation; end-stage heart failure) in patient groups differing for: 1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.

  By 7-year follow-up

• Validation of optimal management of arrhythmic myocarditis by comparing the occurrence of major cardiac events in patients undergoing different therapeutic strategies - Primary

  Evaluation of the occurrence of major cardiac events (death; cardiac death; malignant ventricular arrhythmias= VT, VF, appropriate ICD therapy; heart transplantation; end-stage heart failure) in patient groups differing for: 1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.

  By 10-year follow-up

• Evaluation of healing timing in myocarditis - Primary

  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.

  By 1-month follow-up

• Evaluation of healing timing in myocarditis - Primary

  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.

  By 3-month follow-up

• Evaluation of healing timing in myocarditis - Primary

  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.

  By 6-month follow-up

• Evaluation of healing timing in myocarditis - Primary

  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.

  By 9-month follow-up

• Evaluation of healing timing in myocarditis - Primary

  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.

  By 12-month follow-up

• Evaluation of healing timing in myocarditis - Primary

  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.

  By 18-month follow-up

• Evaluation of healing timing in myocarditis - Primary

  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.

  By 24-month follow-up

• Evaluation of healing timing in myocarditis - Primary

  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.

  By 3-year follow-up

• Evaluation of healing timing in myocarditis - Primary

  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.

  By 5-year follow-up

• Evaluation of healing timing in myocarditis - Primary

  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.

  By 7-year follow-up

• Evaluation of healing timing in myocarditis - Primary

  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.

  By 10-year follow-up

• Comparison of the incidence of major cardiac events in different patient

  Evaluation of the occurrence of major cardiac events (death; cardiac death; malignant ventricular arrhythmias= VT, VF, appropriate ICD therapy; heart transplantation; end-stage heart failure) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups (i.e.: fulminant, acute coronary syndrome-like, pericarditis-like, heart failure, nonischaemic dilated /hypokinetic cardiomyopathies of unknown aetiology…). C.Infectious vs. autoimmune vs. toxic myocarditis. D.Myocarditis treated by aetiology-based treatment vs. isolated cardiac medical treatment. E.Myocarditis at different disease stages: acute, hyperacute, fulminant, chronic active, post-inflammatory, or active vs. previous vs. non-myocarditis. F. Myocarditis presenting as organ-specific diseases vs. in the context of a genetic disorder or systemic disease. G.Myocarditis vs. peri-myocarditis/myo-pericarditis. H.Other subgroups.

  At baseline assessment

• Comparison of the incidence of major cardiac events in different patient subgroups - Primary

  Evaluation of the occurrence of major cardiac events (death; cardiac death; malignant ventricular arrhythmias= VT, VF, appropriate ICD therapy; heart transplantation; end-stage heart failure) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups (i.e.: fulminant, acute coronary syndrome-like, pericarditis-like, heart failure, nonischaemic dilated /hypokinetic cardiomyopathies of unknown aetiology…). C.Infectious vs. autoimmune vs. toxic myocarditis. D.Myocarditis treated by aetiology-based treatment vs. isolated cardiac medical treatment. E.Myocarditis at different disease stages: acute, hyperacute, fulminant, chronic active, post-inflammatory, or active vs. previous vs. non-myocarditis. F. Myocarditis presenting as organ-specific diseases vs. in the context of a genetic disorder or systemic disease. G.Myocarditis vs. peri-myocarditis/myo-pericarditis. H.Other subgroups.

  By 12-month follow-up

• Comparison of the incidence of major cardiac events in different patient subgroups - Primary

  Evaluation of the occurrence of major cardiac events (death; cardiac death; malignant ventricular arrhythmias= VT, VF, appropriate ICD therapy; heart transplantation; end-stage heart failure) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups (i.e.: fulminant, acute coronary syndrome-like, pericarditis-like, heart failure, nonischaemic dilated /hypokinetic cardiomyopathies of unknown aetiology…). C.Infectious vs. autoimmune vs. toxic myocarditis. D.Myocarditis treated by aetiology-based treatment vs. isolated cardiac medical treatment. E.Myocarditis at different disease stages: acute, hyperacute, fulminant, chronic active, post-inflammatory, or active vs. previous vs. non-myocarditis. F. Myocarditis presenting as organ-specific diseases vs. in the context of a genetic disorder or systemic disease. G.Myocarditis vs. peri-myocarditis/myo-pericarditis. H.Other subgroups.

  By 24-month follow-up

• Comparison of the incidence of major cardiac events in different patient subgroups - Primary

  Evaluation of the occurrence of major cardiac events (death; cardiac death; malignant ventricular arrhythmias= VT, VF, appropriate ICD therapy; heart transplantation; end-stage heart failure) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups (i.e.: fulminant, acute coronary syndrome-like, pericarditis-like, heart failure, nonischaemic dilated /hypokinetic cardiomyopathies of unknown aetiology…). C.Infectious vs. autoimmune vs. toxic myocarditis. D.Myocarditis treated by aetiology-based treatment vs. isolated cardiac medical treatment. E.Myocarditis at different disease stages: acute, hyperacute, fulminant, chronic active, post-inflammatory, or active vs. previous vs. non-myocarditis. F. Myocarditis presenting as organ-specific diseases vs. in the context of a genetic disorder or systemic disease. G.Myocarditis vs. peri-myocarditis/myo-pericarditis. H.Other subgroups.

  By 3-year follow-up

• Comparison of the incidence of major cardiac events in different patient subgroups - Primary

  Evaluation of the occurrence of major cardiac events (death; cardiac death; malignant ventricular arrhythmias= VT, VF, appropriate ICD therapy; heart transplantation; end-stage heart failure) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups (i.e.: fulminant, acute coronary syndrome-like, pericarditis-like, heart failure, nonischaemic dilated /hypokinetic cardiomyopathies of unknown aetiology…). C.Infectious vs. autoimmune vs. toxic myocarditis. D.Myocarditis treated by aetiology-based treatment vs. isolated cardiac medical treatment. E.Myocarditis at different disease stages: acute, hyperacute, fulminant, chronic active, post-inflammatory, or active vs. previous vs. non-myocarditis. F. Myocarditis presenting as organ-specific diseases vs. in the context of a genetic disorder or systemic disease. G.Myocarditis vs. peri-myocarditis/myo-pericarditis. H.Other subgroups.

  By 5-year follow-up

• Comparison of the incidence of major cardiac events in different patient subgroups - Primary

  Evaluation of the occurrence of major cardiac events (death; cardiac death; malignant ventricular arrhythmias= VT, VF, appropriate ICD therapy; heart transplantation; end-stage heart failure) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups (i.e.: fulminant, acute coronary syndrome-like, pericarditis-like, heart failure, nonischaemic dilated /hypokinetic cardiomyopathies of unknown aetiology…). C.Infectious vs. autoimmune vs. toxic myocarditis. D.Myocarditis treated by aetiology-based treatment vs. isolated cardiac medical treatment. E.Myocarditis at different disease stages: acute, hyperacute, fulminant, chronic active, post-inflammatory, or active vs. previous vs. non-myocarditis. F. Myocarditis presenting as organ-specific diseases vs. in the context of a genetic disorder or systemic disease. G.Myocarditis vs. peri-myocarditis/myo-pericarditis. H.Other subgroups.

  By 7-year follow-up

• Comparison of the incidence of major cardiac events in different patient subgroups - Primary

  Evaluation of the occurrence of major cardiac events (death; cardiac death; malignant ventricular arrhythmias= VT, VF, appropriate ICD therapy; heart transplantation; end-stage heart failure) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups (i.e.: fulminant, acute coronary syndrome-like, pericarditis-like, heart failure, nonischaemic dilated /hypokinetic cardiomyopathies of unknown aetiology…). C.Infectious vs. autoimmune vs. toxic myocarditis. D.Myocarditis treated by aetiology-based treatment vs. isolated cardiac medical treatment. E.Myocarditis at different disease stages: acute, hyperacute, fulminant, chronic active, post-inflammatory, or active vs. previous vs. non-myocarditis. F. Myocarditis presenting as organ-specific diseases vs. in the context of a genetic disorder or systemic disease. G.Myocarditis vs. peri-myocarditis/myo-pericarditis. H.Other subgroups.

  By 10-year follow-up

Secondary Outcomes (105)

• Occurrence of minor arrhythmic events

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

• Any modification in imaging parameters

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

• Any modification in clinical parameters

  By 10-year follow-up

• Any modification in New York Heart Association class

  By 10-year follow-up

• Any modification in exercise peak heart rate

  By 10-year follow-up

Study Arms (3)

Arrhythmic (A)

Arrhythmic Group. To oversimplify, specific subgroups of patients will be considered. Group 1: major ventricular arrhythmias (haemodynamically unstable VT, hu-VT; ventricular fibrillation, VF). Group 2: other ventricular arrhythmias (high-burden premature ventricular complexes = hb-PVC; nonsustained VT = NSVT; haemodynamically stable VT = hs-VT). Group 3: bradyarrhythmias (2nd type II or 3rd degree atrioventricular block = advanced AVB; critical sinus pauses = SND). Group 4: supraventricular arrhythmias (atrial fibrillation = AF; atrial flutter = AFlu; atrial tachycardia = AT).

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

Nonarrhythmic (NA)

Nonarrhythmic Group. To oversimplify, specific subgroups of patients will be considered. 1. Heart failure presentation (and subtypes) 2. Chest pain presentation (and subtypes) 3. Asymptomatic presentation/screening (and subtypes)

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

Subgroups

For specific study aims, different patient subgroups will be compared. The main groups are hereby reported: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups (i.e.: fulminant, acute coronary syndrome-like, pericarditis-like, heart failure, nonischaemic dilated /hypokinetic cardiomyopathies of unknown aetiology…). C. Infectious vs. autoimmune vs. toxic myocarditis. D. Myocarditis treated by aetiology-based treatment vs. isolated cardiac medical treatment. E. Myocarditis at different disease stages: acute, hyperacute, fulminant, chronic active, post-inflammatory, or active vs. previous vs. non-myocarditis. F. Myocarditis presenting as organ-specific diseases vs. in the context of a genetic disorder or systemic disease. G. Myocarditis vs. peri-myocarditis/myo-pericarditis. H. Other subgroups

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

Interventions

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

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

Arrhythmic (A); Nonarrhythmic (NA); Subgroups

Eligibility Criteria

• Age: 0 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study 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.

You may qualify if:

• Written informed consent.
• Age \< 18 years.
• Clinically suspected myocarditis.
• Enrollment performed by one of the participating Centers.

You may not qualify if:

• Absence of written informed consent.
• Age \> 18 years (adults)

Sponsors & Collaborators

• Scientific Institute San Raffaele: lead

Study Sites (1)

IRCCS San Raffaele Scientific Institute

Milan, Milano, 20132, Italy

RECRUITING

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Biospecimen

Retention: SAMPLES WITH DNA

Undefined a-priori. Will be considered in clinically-indicated.

MeSH Terms

Conditions

Myocarditis; Genetic Predisposition to Disease; Autoimmune Diseases; Arrhythmias, Cardiac; Cardiomyopathies

Interventions

Equipment and Supplies

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Immune System Diseases

Study Officials

• Paolo Della Bella, MD

  San Raffaele Scientific Institute, Milan, Italy

  STUDY CHAIR

Central Study Contacts

Giovanni Peretto, MD

CONTACT

+39 0226437482; peretto.giovanni@hsr.it

Simone Sala, MD

CONTACT

+39 0226437483; sala.simone@hsr.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Target Duration: 30 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Principal Investigator

Study Record Dates

• First Submitted: September 7, 2024
• First Posted: September 19, 2024
• Study Start: January 1, 2013
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2030
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

IT (1)