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

Condition(s) studied

Investigational drug(s) / intervention(s)

support treatment, cardiac medical treatment, aetiology-specific treatment, device implant, arrhythmia ablation: Treatment will be patient-tailored, integrating international guidelines recommendation and the experience of the center where enrollment takes place.

Study 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.

1. 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.
2. Biomarkers to identify myocarditis aetiology, predisposition, prognosis and response to treatment are still to be defined.
3. 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.
4. 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.
5. 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

Primary outcome measure(s)

• Occurrence of major cardiac events — By 12-month follow-up
  death; cardiac death; malignant ventricular arrhythmias ( = VT, VF, appropriate ICD therapy); heart transplantation; end-stage heart failure
• Occurrence of major cardiac events — By 24-month follow-up
  death; cardiac death; malignant ventricular arrhythmias ( = VT, VF, appropriate ICD therapy); heart transplantation; end-stage heart failure
• Occurrence of major cardiac events — By 3-year follow-up
  death; cardiac death; malignant ventricular arrhythmias ( = VT, VF, appropriate ICD therapy); heart transplantation; end-stage heart failure
• Occurrence of major cardiac events — By 5-year follow-up
  death; cardiac death; malignant ventricular arrhythmias ( = VT, VF, appropriate ICD therapy); heart transplantation; end-stage heart failure
• Occurrence of major cardiac events — By 7-year follow-up
  death; cardiac death; malignant ventricular arrhythmias ( = VT, VF, appropriate ICD therapy); heart transplantation; end-stage heart failure
• Occurrence of major cardiac events — By 10-year follow-up
  death; cardiac death; malignant ventricular arrhythmias ( = VT, VF, appropriate ICD therapy); heart transplantation; end-stage heart failure
• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary — At baseline assessment
  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value
• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary — By 6-month follow-up
  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value
• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary — By 12-month follow-up
  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value
• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary — By 24-month follow-up
  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value
• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary — By 3-year follow-up
  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value
• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary — By 5-year follow-up
  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value
• Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) between EMB and second level imaging findings - Primary — By 10-year follow-up
  Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value
• Comparison of troponin values in patients with different aetiologies — At baseline assessment
  Measurement of troponin blood concentration (ng/l) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Description of troponin values changes during follow-up — By 10-year follow-up
  Measurement of troponin blood concentration (ng/l) during follow-up, and description of its relative variation compared to baseline assessment.
• Comparison of creatine-phosphokinase values in patients with different aetiologies — At baseline assessment
  Measurement of creatine-phosphokinase (U/l) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Description of creatine-phosphokinase values changes during follow-up — By 10-year follow-up
  Measurement of creatine-phosphokinase (U/l) during follow-up, and description of its relative variation compared to baseline assessment.
• Comparison of natriuretic peptides values in patients with different aetiologies — At baseline assessment
  Measurement of natriuretic peptides (pg/ml) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Description of natriuretic peptides values changes during follow-up — By 10-year follow-up
  Measurement of natriuretic peptides (pg/ml) during follow-up, and description of its relative variation compared to baseline assessment.
• Comparison of C-reactive protein values in patients with different aetiologies — At baseline assessment
  Measurement of C-reactive protein (mg/l) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Description of C-reactive protein values changes during follow-up — By 10-year follow-up
  Measurement of C-reactive protein (mg/l) during follow-up, and description of its relative variation compared to baseline assessment.
• Comparison of erythrocyte sedimentation rate values in patients with different aetiologies — At baseline assessment
  Measurement of erythrocyte sedimentation rate (mm/h) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Description of erythrocyte sedimentation rate values changes during follow-up — By 10-year follow-up
  Measurement of erythrocyte sedimentation rate (mm/h) during follow-up, and description of its relative variation compared to baseline assessment.
• Comparison of procalcitonin values in patients with different aetiologies — At baseline assessment
  Measurement of procalcitonin (mcg/ml) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Comparison of procalcitonin values in patients with different aetiologies — By 10-year follow-up
  Measurement of procalcitonin (mcg/ml) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Comparison of serum uric acid values in patients with different aetiologies — At baseline assessment
  Measurement of serum uric acid (mg/dl) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Comparison of serum uric acid values in patients with different aetiologies — By 10-year follow-up
  Measurement of serum uric acid (mg/dl) and comparison of values found in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Comparison of leukocyte values in patients with different aetiologies — At baseline assessment
  Measurement of leukocytes (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Comparison of leukocyte values in patients with different aetiologies — By 10-year follow-up
  Measurement of leukocytes (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Comparison of hemoglobin values in patients with different aetiologies — At baseline assessment
  Measurement of hemoglobin (g/dl) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Comparison of hemoglobin values in patients with different aetiologies — By 10-year follow-up
  Measurement of hemoglobin (g/dl) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Comparison of platelet values in patients with different aetiologies — At baseline assessment
  Measurement of platelets (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Comparison of platelet values in patients with different aetiologies — By 10-year follow-up
  Measurement of platelets (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Comparison of thyroid function in patients with different aetiologies — At baseline assessment
  Measurement of thyroid stimulating hormone (mU/ml; total and fractions) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Comparison of thyroid function in patients with different aetiologies — By 10-year follow-up
  Measurement of thyroid stimulating hormone (mU/ml; total and fractions) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Comparison of organ damage in patients with different aetiologies — At baseline assessment
  Measurement of organ damage by application of the Sequential Organ Failure Assessment (SOFA) score in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Comparison of organ damage in patients with different aetiologies — By 10-year follow-up
  Measurement of organ damage by application of the Sequential Organ Failure Assessment (SOFA) score in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Reporting the results of autoimmunity screening — At baseline assessment
  Measurement of circulating autoantibodies (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Reporting the results of autoimmunity screening — By 10-year follow-up
  Measurement of circulating autoantibodies (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Reporting the results of infectious screening — At baseline assessment
  Measurement of viral antibodies (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Reporting the results of infectious screening — By 10-year follow-up
  Measurement of viral antibodies (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Reporting the results of toxicology screening — At baseline assessment
  Measurement of toxic urynalisis (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Reporting the results of toxicology screening — By 10-year follow-up
  Measurement of toxic urynalisis (U/ml) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Reporting the results of genetic test screening — At baseline assessment
  Reporting the results of next generation sequencing analysis (mutation type) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Reporting the results of genetic test screening — By 10-year follow-up
  Reporting the results of next generation sequencing analysis (mutation type) in patients with different aetiologies (viral; autoimmune; toxic; non-myocarditis).
• Validation of optimal management of arrhythmic myocarditis by comparing the occurrence of major cardiac events in patients undergoing different therapeutic strategies - Primary — By 10-year follow-up
  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.
• Validation of optimal management of arrhythmic myocarditis by comparing the occurrence of major cardiac events in patients undergoing different therapeutic strategies - Primary — By 12-month follow-up
  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.
• Validation of optimal management of arrhythmic myocarditis by comparing the occurrence of major cardiac events in patients undergoing different therapeutic strategies - Primary — By 24-month follow-up
  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.
• Validation of optimal management of arrhythmic myocarditis by comparing the occurrence of major cardiac events in patients undergoing different therapeutic strategies - Primary — By 3-year follow-up
  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.
• Validation of optimal management of arrhythmic myocarditis by comparing the occurrence of major cardiac events in patients undergoing different therapeutic strategies - Primary — By 5-year follow-up
  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.
• Validation of optimal management of arrhythmic myocarditis by comparing the occurrence of major cardiac events in patients undergoing different therapeutic strategies - Primary — By 7-year follow-up
  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.
• Evaluation of healing timing in myocarditis - Primary — By 1-month follow-up
  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.
• Evaluation of healing timing in myocarditis - Primary — By 3-month follow-up
  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.
• Evaluation of healing timing in myocarditis - Primary — By 6-month follow-up
  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.
• Evaluation of healing timing in myocarditis - Primary — By 9-month follow-up
  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.
• Evaluation of healing timing in myocarditis - Primary — By 12-month follow-up
  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.
• Evaluation of healing timing in myocarditis - Primary — By 18-month follow-up
  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.
• Evaluation of healing timing in myocarditis - Primary — By 24-month follow-up
  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.
• Evaluation of healing timing in myocarditis - Primary — By 3-year follow-up
  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.
• Evaluation of healing timing in myocarditis - Primary — By 5-year follow-up
  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.
• Evaluation of healing timing in myocarditis - Primary — By 7-year follow-up
  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.
• Evaluation of healing timing in myocarditis - Primary — By 10-year follow-up
  Any degree of recovery through analysis of CMR, other second level imaging, echocardiogram, cardiac and inflammatory biomarkers, symptoms, arrhythmia burden, and exercise tolerance.
• Comparison of the incidence of major cardiac events in different patient subgroups - Primary — At baseline assessment
  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.
• Comparison of the incidence of major cardiac events in different patient subgroups - Primary — By 12-month follow-up
  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.
• Comparison of the incidence of major cardiac events in different patient subgroups - Primary — By 24-month follow-up
  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.
• Comparison of the incidence of major cardiac events in different patient subgroups - Primary — By 3-year follow-up
  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.
• Comparison of the incidence of major cardiac events in different patient subgroups - Primary — By 5-year follow-up
  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.
• Comparison of the incidence of major cardiac events in different patient subgroups - Primary — By 7-year follow-up
  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.
• Comparison of the incidence of major cardiac events in different patient subgroups - Primary — By 10-year follow-up
  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.

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