MyocarditisMYOPEDNCT06591260
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)
An observational study of Myocarditis and Ventricular Arrhythmia, run by Scientific Institute San Raffaele at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Myocarditis, Ventricular Arrhythmia, Inflammatory Cardiomyopathy
- What is being tested?
- support treatment, cardiac medical treatment, aetiology-specific treatment, device implant, arrhythmia ablation
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jan 2013to 31 Dec 2030
- How long will I take part?
- 30 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
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.
Who may be able to join
- Written informed consent.
- Age \< 18 years.
- Clinically suspected myocarditis.
- Enrollment performed by one of the participating Centers.
Who cannot join
- Absence of written informed consent.
- Age \> 18 years (adults)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
IRCCS San Raffaele Scientific Institute
Milan, Milano, 20132
Giovanni Peretto, MD, +39 0226437482, peretto.giovanni@hsr.it
Simone Sala, MD, +39 0226437483, sala.simone@hsr.it
About this study
Official title: 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
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.
Read more
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.
Read the detailed description
This study, previously designed as a single-center experience, is multicenter, observational and both retrospective and prospective.
Retrospective phase includes all clinical data occurring before the index event (hospitalization or clinically suspected myocarditis) and myocarditis diagnosis. Prospective phase includes all data following index event and myocarditis diagnosis.
This study has multiple aims.
To compare EMB with noninvasive diagnostic techniques (CMR, DECT, PET scan, either alone or in association).
To assess the role of blood biomarkers for identification of aetiology, predisposition, prognosis, response to treatment, inflammatory activity, clinical presentation.
To describe myocarditis presenting with arrhythmias, with special focus on ventricular arrhythmias at different myocarditis stages and in different clinical contexts. To validate and generalize the leader hospital model for optimal diagnostic and therapeutical management of arrhythmias in myocarditis patients (given the role of the leader hospital as an international referral center for arrhythmias ablation and management).
To evaluate the timing needed for myocarditis healing in different patients subgroups, as assessed by noninvasive imaging techniques (CMR, DECT, PET scan), either alone or in association.
To compare patients subgroups of myocarditis, in terms of epidemiology, aetiology, prognosis, and diagnostic-therapeutical strategies. Among the others, the main study subgroups will be:
- Arrhythmic vs. non-arrhythmic myocarditis. B. Arrhythmic myocarditis subgroups. C. Non-arrhythmic myocarditis subgroups (i.e.: fulminant, acute coronary syndrome-like, pericarditis-like, heart failure, non-ischaemic dilated/hypokinetic cardiomyopathies of unknown aetiology…).
- Infectious vs. autoimmune vs. toxic myocarditis. E. Myocarditis treated by aetiology-based treatment vs. isolated cardiac medical treatment.
- Myocarditis at different disease stages: acute, hyperacute, fulminant, chronic active, post-inflammatory, or active vs. previous vs. non-myocarditis.
- Myocarditis presenting as organ-specific diseases vs. in the context of a genetic disorder or systemic disease.
- Myocarditis vs. peri-myocarditis/myo-pericarditis. I. Other analyses.
Any adult patient with clinically suspected myocarditis, of any clinical presentation and any degree of severity, will be considered as suitable for study enrollment.
Patients will undergo diagnostic and therapeutical strategies considered as clinically indicated in a patient-tailored manner, as suggested by international guidelines recommendations and best local clinical practice. Patients will be free of either accepting or refusing any diagnostic or therapeutical proposal. Whenever accepted, data will be simply collected and analyzed.
Based on clinical presentation, patients will be divided into two groups, arrhythmic (group A) and non-arrhythmic (group NA, including any other clinical presentation).
Independently of A/NA groups, all patients will undergo optimal diagnostic and therapeutic strategies, as summarized in panel A. In parallel, special diagnostic and therapeutical strategies will be performed in patients with arrhythmic presentation or evidence of arrhythmias, as shown in panel B. Proposed flowcharts (Panels A and B) represent only an approximate algorithm. Exceptions can be made in single cases, based on clinical indications.
Panel A - Diagnostic and therapeutical workup in all patients. Independently of groups (A/NA), all patients will undergo optimal diagnostic and therapeutical workup, guided by updated scientific evidence merged with the clinical experience of the center.
Baseline diagnostic workup will include: complete blood exams, 12-leads ECG, continuous telemetric monitoring, transthoracic doppler echocardiogram, coronary artery imaging (coronary angiography or CT scan). Any other clinically relevant diagnostic test will be collected.
In life-threatening presentations (cardiogenic shock or malignant arrhythmias), support treatment by optimal medical therapy, inotropic or mechanical circulatory support, and acute-phase arrhythmia management (including cardioversion, defibrillation, or temporary pacing) will be performed, as indicated, before completing diagnostic workup.
Final diagnosis of myocarditis will include, whenever applicable:
- For stable patients: 1) a second-level imaging technique (CMR as first choice; and/or DECT, PET, or multiple/fusion imaging techniques, based on clinical indications); followed by: 2) EMB, whenever clinically indicated. Blood exams for aetiology screening will be personalized upon clinical indications.
- For unstable patients: EMB only, as recommended. Blood exams for aetiology screening will be personalized upon clinical indications.
Diagnostic criteria for myocarditis, as assessed by any diagnostic technique, will be defined based on international scientific evidence and will be constantly updated. Similar considerations apply to myocarditis staging and aetiology definition. Whenever not available at local institutions, diagnostic exams can be performed and analyzed at external centers.
All patients with myocarditis (or any alternative final diagnosis), will undergo standard cardiological optimal medical treatment (COMT), as indicated. By converse, aetiology-dependent treatment will be performed only in patients with a final diagnosis of any active (acute, fulminant, chronic active) myocarditis of defined aetiology (EMB-proved). Multidisciplinary assessment, including infective disease specialists (in viral/infective myocarditis), immunologists (in non-infective/autoimmune myocarditis) or any other specialist as needed, will be used to identify indications to treatment, drug choice (either approved or with a justified unapproved indication), treatment duration and safety profile, aiming at the best patients\' interest. Toxic myocarditis will be treated accordingly, by evaluating the opportunity of withdrawing pathogenic noxa.
This protocol will not interfere with local best clinical practice. Patients with non-active myocarditis (previous or healed) or with non-myocarditis, will undergo \"standard FU\"; (see below). Patients with active myocarditis will undergo \"intensive FU\"; (see below).
Independently of FU modalities, diagnostic reassessment will be considered in the presence of at least one of the following instability criteria: a) new unexplained cardiac symptoms (dyspnoea, chest pain, syncope, palpitation); b) new unexplained increase in troponin or natriuretic peptides; c) new imaging abnormal signs; d) new unexplained clinically relevant arrhythmias. Diagnostic reassessment will include second-level imaging and/or EMB, as shown above. Subsequent therapeutical workup will be in line with the above explanations. In stable patients or undergone myocarditis healing, exercise stress test will be obtained, whenever possible.
Panel B - Diagnostic and therapeutical workup of patients with arrhythmias In parallel with (and independently of) Panel A content, patients with arrhythmias (group A) will undergo specific diagnostic and therapeutical management for arrhythmias, as a result of the integration between international guidelines recommendations and the experience of an international referral center for arrhythmia management and ablation.
To oversimplify, 4 groups of patients will be considered.
Group 1: major ventricular arrhythmias, including haemodynamically unstable VT (hu-VT) and ventricular fibrillation (VF).
After electrical stabilization and support treatment (panel A), indication to secondary prevention ICD implant will be multiparametric and patient-tailored. In patients with active myocarditis, subcutaneous ICD (S-ICD) or wearable CD (WCD) will be considered. Antiarrhythmic drugs will be considered in all Group 1 patients. In addition, all Group 1 patients will undergo COMT and aetiology-dependent treatment whenever applicable (panel A). Ablation of ventricular arrhythmias will be considered in patients with severe arrhythmic presentation, or symptomatic, or refractory to optimal medical treatment. Electrophysiological study (EPS) may be used in selected cases. A cardiac resynchronization therapy with defibrillator function (CRT-D) will replace ICD whenever indicated.
Group 2: other ventricular arrhythmias, including high-burden (hb) premature ventricular complexes (PVC); nonsustained VT (NSVT); haemodynamically stable VT (hs-VT).
Whenever clinically indicated, Group 2 patients will undergo invasive EPS (or in alternative noninvasive programmed ventricular stimulation in ICD carriers) to stratify arrhythmic risk. Patients with positive EPS will undergo ICD (or S-ICD/WCD) as in Group 1. Patients with negative EPS, as well as Group 2 cases not undergoing EPS, will undergo watchful waiting strategy (always with an intensive FU) with or without loop recorder implant: in these cases, ICD (or S-ICD/WCD) will be implanted only following documentation of relevant VA in FU. In addition, all Group 2 patients will undergo antiarrhythmic treatment, COMT and aetiology-dependent treatment whenever applicable (panel A). In symptomatic or drug-refractory cases, ablation of ventricular arrhythmias will be considered. A CRT-D will replace ICD whenever indicated.
Group 3: bradyarrhythmias, including advanced (2nd type II or 3rd degree) atrioventricular block (AVB); critical sinus pauses from sinus node disease (SND).
After electrical stabilization and support treatment (panel A), including the use of temporary pacemaker as a bridge-to-decision, patients will undergo watchful waiting strategy or definitive device implant. Instead of a pacemaker (PM), ICD will be considered in the presence of high-risk criteria for ventricular tachyarrhythmias, including: a) overlap with Group 1 presentation; b) overlap with Group 2 presentation, especially in the presence of positive EPS; c) other indications for primary prevention ICD implant (severe systolic dysfunction); d) signs of increased tachyarrhythmic risk (scar signs); e) patients with special aetiologies leading to an increased tachyarrhythmic risk (i.e: cardiac sarcoid, giant cell myocarditis, Chagas disease, overlapping genetic syndromes). In addition, all Group 3 patients will undergo COMT and aetiology-dependent treatment whenever applicable (panel A). A CRT-D or a CRT-P will replace ICD or PM, respectively, whenever indicated.
Group 4: supraventricular arrhythmias, including atrial fibrillation (AF); atrial flutter (AFlu); atrial tachycardia (AT).
Following acute-phase rate control (RaC), stable rhythm control (RyC) strategy will be considered as the therapeutical target, together with appropriate anticoagulation, as needed. Normal sinus rhythm will be obtained through either electrical or pharmacological cardioversion. In patients with unsuccessful attempts of sinus rhythm conversion, optimal treatment of active myocarditis will be considered as a primary target. Following myocarditis healing, in the presence of persistent arrhythmias, patients will be considered for RyC via electrical or pharmacological cardioversion. Transcatheter ablation will be an option for patients with drug-symptomatic, recurrent or refractory arrhythmias. Permanent RaC strategy will be considered only in non responders. Widespread use of implantable loop recorders will apply, as clinically indicated. In addition, all Group 4 patients will undergo COMT and aetiology-dependent treatment whenever applicable (panel A).
Aims in detail. Aim 1 Comparison between EMB and second level imaging findings (N=1000)
Primary:
Diagnostic concordance
Secondary:
Inflammatory activity (presence; type; quantification) Fibrosis (presence; type; quantification) Coronary microvascular disease Comparison between EMB sampling site and abnormal substrate localization at imaging (including substrate-guided EMB or alternative biopsy techniques) Role of EMB guided by electroanatomical map Diagnostic performance of DECT and/or PET, especially when CMR is contraindicated Comparison between CMR/DECT findings and PET scan (including fusion imaging) or advanced imaging techniques including strain analysis at echocardiogram Comparison between substrate abnormalities localizations (as assessed by second level imaging techniques) and arrhythmias (type, characteristics and origin site) Comparison among different diagnostic techniques (EMB, CMR/DECT, PET) in terms of safety and diagnostic accuracy Evaluation of differential diagnosis with other cardias diseases, and particularly with arrhythmogenic cardiomyopathy of any localization (left, right, biventricular, to identify updated diagnostic criteria) Comparison between information provided by all the techniques above, and data from electroanatomical mapping (EAM) Other analyses
Aim 2 Evaluation of blood exams and biomarkers (N=1000)
Primary:
Identification of diagnostic biomarkers Identification of aetiology biomarkers
Secondary:
Cardiac and inflammatory biomarkers evaluation in different myocarditis subtypes Identification of biomarkers of inflammatory stage (acute vs. chronic; active vs. previous) Comparison between local and systemic/peripheral inflammation Correlations with EMB and second-level imaging (CMR, DECT, PET…) findings Identification of genetic factors with any role in predisposition, prognosis, response to treatment, or any other correlation, either in the presence or in the absence of underlying cardiomyopathy or autoimmune/inflammatory disease Identification of prognostic biomarkers Identification of biomarkers associated with treatment response Evaluation of any tissue/organ damage or associated comorbidities Study of cardiac autoantibodies Study of any cell, tissue, genetic or circulating biomarker Correlations with clinical presentations Other analyses
Aim 3 Validation of optimal management of arrhythmic myocarditis (N=1000)
Primary:
Evaluation of effects on major endpoints
Secondary:
Evaluation of effects on minor endpoints Role of electrophysiological study in risk stratification Role of loop recorders in arrhythmia monitoring Role of transcatheter ablation (any technique) on arrhythmic outcomes Identification of optimal timing for any electrophysiological/device procedure Role of pharmacological antiarrhythmic treatment Role of aetiology-specific treatment on arrhythmic outcomes Identification of criteria for device implants (PM, ICD, S-ICD, CRT-D…) in myocarditis patients Validation of therapeutic strategies and their optimal timing in patients with supraventricular arrhythmias, bradyarrhythmias, or ventricular arrhythmias Correlation between arrhythmia type/features with any other diagnostic exam performed at baseline or during FU (mainly EMB, CMR/DECT/PET, echocardiogram, stress tests, blood exams, genetic/blood/tissue/cell biomarkers) Indications and timing for device (ICD, CRT-D) implant in primary prevention, based on multiparametric risk assessment, and in relation to different general and aetiology-dependent treatments Other analyses
Aim 4 Evaluation of healing timing in myocarditis (N=500) Primary Any degree of recovery by 3, 6, 9, 12 and 12 months Secondary Comparison of healing times in treated vs. untreated patients Correlations between healing times and clinical presentation types Correlations between healing times and any biomarker Correlations between healing times and any outcomes Validation of exercise stress test role after myocarditis healing Evaluation of PET scan or other diagnostic techniques as alternatives to CMR in special populations Other analyses
Aim 5 Subgroup analyses (N=500, hugely variable in each subanalysis) A vs. NA groups; A myocarditis subgroups; NA myocarditis subgroups (including fulminant); Infective vs. autoimmune vs. toxic forms; Treated by aetiology-driven therapy vs. standard cardiological treatment; Different myocarditis stages and differential diagnoses; Isolated vs. in the context o a systemic disease or genetic disease; Myocarditis vs. perimyocarditis/ myopericarditis Primary Differences in major outcomes Secondary Differences in minor outcomes Differences in any biomarker Differences in any diagnostic exam Differences in aetiology Differences in predisposition Differences in inflammatory activity Differences in pericardial involvement Differences in systemic involvement Differences in arrhythmias types and features Differences in clinical presentation Differences in treatment response, including novel treatments Validation of local aetiology/pathophysiology-dependent treatments Validation of biomarkers and imaging techniques in monitoring response to treatment Identification of optimal follow-up timeline Other analyses
- Conditions
- Myocarditis, Ventricular Arrhythmia, Inflammatory Cardiomyopathy, Genetic Predisposition, Autoimmunity, Arrhythmia
- Being tested
- support treatment, cardiac medical treatment, aetiology-specific treatment, device implant, arrhythmia 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
- Medical subject headings
- Myocarditis, Genetic Predisposition to Disease, Autoimmune Diseases, Arrhythmias, Cardiac, Cardiomyopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
support treatment, cardiac medical treatment, aetiology-specific treatment, device implant, arrhythmia ablationOther
Treatment will be patient-tailored, integrating international guidelines recommendation and the experience of the center where enrollment takes place.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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) Receives: 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 Receives: Other: support treatment, cardiac medical treatment, aetiology-specific treatment, device implant, arrhythmia ablation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of major cardiac events
death; cardiac death; malignant ventricular arrhythmias ( = VT, VF, appropriate ICD therapy); heart transplantation; end-stage heart failure
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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:
- 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.
Measured: 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:
- 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.
Measured: 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:
- 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.
Measured: 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:
- 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.
Measured: 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:
- 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.
Measured: 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:
- 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.
Measured: 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:
- 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.
Measured: By 10-year follow-up
Secondary outcomes (105)
Occurrence of minor arrhythmic events
NSVT; PVC burden; supraventricular arrhythmias; bradyarrhythmias
Measured: At baseline assessment and through study completion (up to 10 years)
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).
Measured: At baseline assessment and through study completion (up to 10 years)
Any modification in clinical parameters
Signs and symptoms related to cardiac or multisystemic disease, as assessed by dedicated questionnaires.
Measured: By 10-year follow-up
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).
Measured: By 10-year follow-up
Any modification in exercise peak heart rate
Reporting changes in exercise peak heart rate (beats per minute) by any cardiac or cardiopulmonary stress test, by comparing follow-up results with baseline performance
Measured: By 10-year follow-up
Any modification in exercise peak systolic blood pressure
Reporting changes in exercise peak systolic blood pressure (mmHg) by any cardiac or cardiopulmonary stress test, by comparing follow-up results with baseline performance
Measured: By 10-year follow-up
Any modification in exercise walking distance
Reporting changes in exercise walking distance (meters) by any cardiac or cardiopulmonary stress test, by comparing follow-up results with baseline performance
Measured: By 10-year follow-up
Any modification in exercise oxygen consumption
Reporting changes in exercise oxygen consumption (l/min) by any cardiac or cardiopulmonary stress test, by comparing follow-up results with baseline performance
Measured: By 10-year follow-up
Any modification in exercise-induced arrhythmias
Reporting changes in exercise-induced arrhythmias (type) by any cardiac or cardiopulmonary stress test, by comparing follow-up results with baseline performance
Measured: By 10-year follow-up
Identification of the prevalence of associated diseases
Identification of any comorbidity associated with myocarditis (qualitative description)
Measured: By 10-year follow-up
Any modification in arrhythmia burden
Change in daily and monthly arrhythmia burden quantification, as compared to baseline assessment
Measured: By 10-year follow-up
Any modification in arrhythmia morphology
Change in 12-lead ECG morphology (QRS axis) of arrhythmias, as compared to baseline assessment
Measured: By 10-year follow-up
Any modification in arrhythmia regularity
Change in arrhythmia cycle length regularity, as compared to baseline
Measured: By 10-year follow-up
Any modification in arrhythmia tolerance
Change in arrhythmia hemodynamic tolerance (presence or absence of syncope), as compared to baseline assessment
Measured: By 10-year follow-up
Prevalence of coronary circulation abnormalities
Reporting the prevalence of any anatomical or functional abnormality found at: coronary angiography; CT scan; histology; provocative stress tests, nuclear medicine techniques
Measured: By 10-year follow-up
Prevalence of electrophysiological study
Reporting prevalence of electrophysiological study in the population, including indication and timing.
Measured: By 10-year follow-up
Results of electrophysiological study
Reporting the results of electrophysiological study (inducibility of ventricular tachycardia or fibrillation), including the association with occurrence of arrhythmias (ventricular tachycardia, ventricular fibrillation, appropriate ICD therapy) during follow-up.
Measured: By 10-year follow-up
Prevalence of ventricular arrhythmia ablation
Reporting prevalence of ventricular arrhythmia ablation in the population, including indication and timing.
Measured: By 10-year follow-up
Results of ventricular arrhythmia ablation
Reporting the results of ventricular arrhythmia ablation (inducibility of ventricular tachycardia or fibrillation at the end of the procedure), including the association with occurrence of arrhythmias (ventricular tachycardia, ventricular fibrillation, appropriate ICD therapy) during follow-up.
Measured: By 10-year follow-up
Prevalence of supraventricular arrhythmia ablation
Reporting prevalence of supraventricular arrhythmia ablation (atrial fibrillation, atrial flutter, atrial tachycardia) in the population, including indication and timing.
Measured: By 10-year follow-up
Results of supraventricular arrhythmia ablation
Reporting the results of supraventricular arrhythmia ablation by assessing the occurrence of supraventricular arrhythmias (atrial fibrillation, atrial flutter, atrial tachycardia) during follow-up.
Measured: By 10-year follow-up
Prevalence of cardiac device implants
Reporting prevalence of cardiac device implants (pacemakers, ICD, CRT-P, CRT-D, WCD, S-ICD, implantable loop recorders) in the population, including indication and timing.
Measured: By 10-year follow-up
Comparison of arrhythmia detection by continuous vs. non-continuous monitoring
Assessment of the occurrence of arrhythmias detected by continuous arrhythmia monitoring (pacemakers, ICD, CRT-P, CRT-D, WCD, S-ICD, implantable loop recorders) as compared to those detected by non-continuous arrhythmia monitoring (Holter ECG).
Measured: By 10-year follow-up
Assessment of the withdrawal timing of non-permanent cardiac devices
Reporting the time of witrhdrawal of non-permanent cardiac devices (WCD, S-ICD, loop recorders).
Measured: By 10-year follow-up
Prevalence of CT scan
Reporting prevalence of CT scan in the population, including indication and timing.
Measured: By 10-year follow-up
Results of CT scan
Reporting the results of CT scan (number of positive results; both in absolute, and as compared to the other imaging techniques)
Measured: By 10-year follow-up
Prevalence of PET scan
Reporting prevalence of PET scan in the population, including indication, type and timing.
Measured: By 10-year follow-up
Results of PET scan
Reporting the results of PET scan (number of positive results; both in absolute, and as compared to the other imaging techniques)
Measured: By 10-year follow-up
Prevalence of electroanatomical mapping
Reporting prevalence of electroanatomical mapping in the population, including indication and timing.
Measured: By 10-year follow-up
Results of electroanatomical mapping
Reporting the results of electroanatomical mapping (number of positive results; both in absolute, and as compared to the other imaging techniques)
Measured: By 10-year follow-up
Prevalence of stress tests
Reporting prevalence of stress tests, including indication, type (ECG; echocardiogram; scintigraphy; CMR; 6-minute walking test; cardiac rehabilitation programs; cardiopulmonary stress test) and timing.
Measured: By 10-year follow-up
Results of stress tests - ECG
Reporting the results of stress tests (prevalence of ST segment modification) in the population, including the association with major outcomes (malignant ventricular arrhythmias; heart failure requiring intravenous diuretics, hospitalization, or heart transplantation).
Measured: By 10-year follow-up
Results of stress tests - wall motion abnormalities
Reporting the results of stress tests (prevalence of wall motion abnromalities by either echocardiogram, scintigraphy or CMR) in the population, including the association with major outcomes (malignant ventricular arrhythmias; heart failure requiring intravenous diuretics, hospitalization, or heart transplantation).
Measured: By 10-year follow-up
Results of stress tests - coronary flow reserve
Reporting the results of stress tests (prevalence of reduced coronary flow reserve, as assessed by either scintigraphy, CMR, or PET scan) in the population, including the association with major outcomes (malignant ventricular arrhythmias; heart failure requiring intravenous diuretics, hospitalization, or heart transplantation).
Measured: By 10-year follow-up
Myocarditis recurrences
Reporting of any myocarditis recurrences (either clinically-suspected, biomarker-proven, CMR or second level imaging-proven, or EMB-proven); comparison with first myocarditis episode; investigation of underlying aetiology.
Measured: At baseline assessment (including past medical history) and through study completion (up to 10 years)
Response to treatment - systolic function
Comparison of any change in left ventricular ejection fraction (LVEF) in patients undergoing different treatment strategy:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Response to treatment - malignant ventricular arrhythmias
Comparison of any change in the incidence of malignant ventricular arrhythmias (= VT, VF, appropriate ICD therapy) in patients undergoing different treatment strategy:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Prognostic risk stratification - malignant ventricular arrhythmias
Identification of independent predictors of malignant ventricular arrhythmias (= VT, VF, appropriate ICD therapy) during follow-up in the population, as assessed by either univariable or multivariable risk stratification models.
Measured: Through study completion (up to 10 years)
Prognostic risk stratification - heart failure
Identification of independent predictors of heart failure (= hospitalization for acute heart failure, heart transplantation, left ventricular ejection fraction below 35%) during follow-up in the population, as assessed by either univariable or multivariable risk stratification models.
Measured: Through study completion (up to 10 years)
Prognostic risk stratification - cardiac death
Identification of independent predictors of cardiac death during follow-up in the population, as assessed by either univariable or multivariable risk stratification models.
Measured: Through study completion (up to 10 years)
Description of multidisciplinary workup models
Description of types and number of physicians from different medical specializations involved in the management of myocarditis patients.
Measured: At baseline assessment and through study completion (up to 10 years)
Prognostic impact of multidisciplinary workup models
Comparison of outcomes (cardiac death, heart failure, malignant ventricular arrhythmias) between patients managed by single vs. multiple physicians.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison between EMB and second level imaging findings in detecting myocardial inflammation
Reporting myocardial inflammation (presence; type; quantification) in EMB vs. second level imaging techniques
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison between EMB and second level imaging findings in detecting myocardial fibrosis
Reporting myocardial fibrosis (presence; type; quantification) in EMB vs. second level imaging techniques
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison between EMB and second level imaging findings in detecting coronary microvascular disease
Reporting coronary microvascular disease (presence; type) in EMB vs. second level imaging techniques
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison between EMB sampling site and abnormal substrate localization at imaging
Descriprion of EMB sampling site in relation to the localization of abnormal substrate as assessed by second level imaging techniques
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison between substrate-guided vs. standard EMB sampling. Substrate defined by any second level imaging technique (CMR, PET, DECT, electroanatomical mapping). EMB sampling performed at any cardiac site.
Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison between different second level imaging findings
Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value. Comparison of substrate abnormalities (localization; pattern; extension; distribution) as found by different second level imaging techniques, including CMR, DECT, PET, electroanatomical mapping, and echocardiogram (including fusion imaging). Scar definition, characterization and composition.Texture analysis.Other analyses.
Measured: At baseline assessment and through study completion (up to 10 years)
Associations between arrhythmia morphology and substrate localization
Identification of association (sensitivity, specificity, positive predictive value, negative predictive value) between arrhythmia morphology pattern (right superior; right inferior; left superior; left inferios - as assessed by 12-lead ECG) and substrate localization (anterior; septal; lateral; inferior - as defined by any second level imaging technique including CMR, PET, DECT, electroanatomical mapping).
Measured: At baseline assessment and through study completion (up to 10 years)
Associations between arrhythmia morphology and inflammatory stage
Identification of association (sensitivity, specificity, positive predictive value, negative predictive value) between arrhythmia mophology (monomorphic vs. polymorphic, as assessed by 12-lead ECG) and inflammatory stage (active vs. nonactive, as assessed by any technique including EMB, CMR, PET, DECT, electroanatomical mapping, troponin)
Measured: At baseline assessment and through study completion (up to 10 years)
Associations between arrhythmia regularity and inflammatory stage
Identification of association (sensitivity, specificity, positive predictive value, negative predictive value) between arrhythmia regularity (regular vs. irregular, as assessed by 12-lead ECG) and inflammatory stage (active vs. nonactive, as assessed by any technique including EMB, CMR, PET, DECT, electroanatomical mapping, troponin)
Measured: At baseline assessment and through study completion (up to 10 years)
Prevalence of adverse effects associated with EMB
Reporting the prevalence of adverse effects (death; pericardial effusion; vascular complications) associated with EMB.
Measured: At baseline assessment and through study completion (up to 10 years)
Prevalence of adverse effects associated with immunosuppressive therapy
Reporting the prevalence of adverse effects (death; infections; diarrhea; myeloid, renal and liver toxicity) associated with immunosuppressive therapy.
Measured: At baseline assessment and through study completion (up to 10 years)
Prevalence of overlap syndromes and differential diagnoses
Reporting the prevalence of overlap syndromes and/or differential diagnoses with other primary or acquired cardias diseases other than myocarditis, including: arrhythmogenic cardiomyopathy (right, left, biventricular), dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, noncompaction cardiomyopathy, toxic cardiomyopathy, ischemic cardiomyopathy; other genetic or acquired human diseases.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison between histology abnormalities and arrhythmias
Reporting the prevalence of any histological abnormality (normal vs. abnormal findings at either immunohistochemical, molecular, or ultrastructural analysis at EMB) in patients with arrhythmic vs. nonarrhythmic presentations of myocarditis.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison between genetic test results and myocarditis features
Description, in genotyped patients, of any association (in terms of sensitivity, specificity, positive predictive value, negative predictive value) between genetic test results and myocarditis features (clinical presentation, associated diseases, findings at baseline workup, prognosis, and response to treatment).
Measured: At baseline assessment and through study completion (up to 10 years)
Corrrelation between troponin abnormalities and follow-up occurrence of malignant ventricular arrhythmias
Reporting the association (in terms of sensitivity, specificity, positive predictive value, negative predictive value) between troponin abnormalities (ng/l) and occurrence of malignant ventricular arrhythmias (= VT, VF, appropriate ICD therapy).
Measured: At baseline assessment and through study completion (up to 10 years)
Corrrelation between troponin abnormalities and follow-up occurrence of heart failure
Reporting the association (in terms of sensitivity, specificity, positive predictive value, negative predictive value) between troponin abnormalities (ng/l) and occurrence of heart failure (= hospitalization for acute heart failure, heart transplantation, left ventricular ejection fraction below 35%).
Measured: At baseline assessment and through study completion (up to 10 years)
Corrrelation between NTproBNP abnormalities and follow-up occurrence of malignant ventricular arrhythmias
Reporting the association (in terms of sensitivity, specificity, positive predictive value, negative predictive value) between NTproBNP abnormalities (pg/ml) and occurrence of malignant ventricular arrhythmias (= VT, VF, appropriate ICD therapy).
Measured: At baseline assessment and through study completion (up to 10 years)
Corrrelation between NTproBNP abnormalities and follow-up occurrence of heart failure
Reporting the association (in terms of sensitivity, specificity, positive predictive value, negative predictive value) between NTproBNP abnormalities (pg/ml) and occurrence of heart failure (= hospitalization for acute heart failure, heart transplantation, left ventricular ejection fraction below 35%).
Measured: At baseline assessment and through study completion (up to 10 years)
Corrrelation between C-reactive protein abnormalities and follow-up occurrence of malignant ventricular arrhythmias
Reporting the association (in terms of sensitivity, specificity, positive predictive value, negative predictive value) between C-reactive protein abnormalities (mg/l) and occurrence of malignant ventricular arrhythmias (= VT, VF, appropriate ICD therapy).
Measured: At baseline assessment and through study completion (up to 10 years)
Corrrelation between C-reactive protein abnormalities and follow-up occurrence of heart failure
Reporting the association (in terms of sensitivity, specificity, positive predictive value, negative predictive value) between C-reactive protein abnormalities (mg/l) and occurrence of heart failure (= hospitalization for acute heart failure, heart transplantation, left ventricular ejection fraction below 35%).
Measured: At baseline assessment and through study completion (up to 10 years)
Corrrelation between histological abnormalities and follow-up occurrence of malignant ventricular arrhythmias
Reporting the association (in terms of sensitivity, specificity, positive predictive value, negative predictive value) between histological abnormalities (any abnormality including immunohistochemical, molecular, and ultrastructural findings) and occurrence of malignant ventricular arrhythmias (= VT, VF, appropriate ICD therapy).
Measured: At baseline assessment and through study completion (up to 10 years)
Corrrelation between histological abnormalities and follow-up occurrence of heart failure
Reporting the association (in terms of sensitivity, specificity, positive predictive value, negative predictive value) between histological abnormalities (any abnormality including immunohistochemical, molecular, and ultrastructural findings) and occurrence of heart failure (= hospitalization for acute heart failure, heart transplantation, left ventricular ejection fraction below 35%).
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of minor arrhythmic events in patients undergoing different
Evaluation of the occurrence of minor arrhythmic events (NSVT; PVC burden; supraventricular arrhythmias; bradyarrhythmias) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of left ventricular end-diastolic volume in patients undergoing different therapeutic strategies
Evaluation of left ventricular end-diastolic volume (LVEDVi, ml/m2) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of right ventricular end-diastolic volume in patients undergoing
Evaluation of right ventricular end-diastolic volume (RVEDVi, ml/m2) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of left ventricular ejection fraction in patients undergoing different therapeutic strategies
Evaluation of left ventricular ejection fraction (LVEF, %) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of right ventricular ejection fraction in patients undergoing different therapeutic strategies
Evaluation of left ventricular ejection fraction (RVEF, %) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of biventricular global longitudinal strain in patients undergoing different therapeutic strategies
Evaluation of biventricular global longitudinal strain (GLS, %) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of left atrial volume in patients undergoing different therapeutic strategies
Evaluation of left atrial volume (LAVi, ml/m2) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of left ventricular diastolic dysfunction in patients undergoing different therapeutic strategies
Evaluation of diastolic dysfunction (E/E\' ratio) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of pericardial abnormalities in patients undergoing different therapeutic strategies
Prevalence of pericardial abnormalities (presence of pericardial effusion) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of valvular abnormalities in patients undergoing different therapeutic strategies
Prevalence of valvular abnormalities (presence of valvular disease) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of CMR abnormalities in patients undergoing different therapeutic strategies
Prevalence of CMR abnormalities (classic and modern Lake Louise Criteria) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of DECT abnormalities in patients undergoing different therapeutic strategies
Prevalence of DECT abnormalities (classic and modern Lake Louise Criteria) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of PET abnormalities in patients undergoing different therapeutic strategies
Prevalence of PET abnormalities (abnormal FDG or ammonia uptake) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of electroanatomical mapping abnormalities in patients undergoing different therapeutic strategies
Prevalence of electroanatomical mapping abnormalities (low-voltage areas) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of symptoms in patients undergoing different therapeutic strategies
Prevalence of symptoms in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of exercise tolerance in patients undergoing different therapeutic strategies
Change in exercise tolerance (New York Heart Association class) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of troponin in patients undergoing different therapeutic strategies
Change in troponin values (ng/l) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of NTproBNP in patients undergoing different therapeutic strategies
Change in NTproBNP values (pg/ml) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of C-reactive protein in patients undergoing different therapeutic strategies
Change in C-reactive protein values (mg/l) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of arrhythmia burden in patients undergoing different therapeutic strategies
Change in arrhythmia burden (daily and montly incidence of arrhythmias) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of arrhythmia morphology in patients undergoing different therapeutic strategies
Change in arrhythmia morphology (monomorphic vs. polymorphic) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of arrhythmia regularity in patients undergoing different therapeutic strategies
Change in arrhythmia regularity (regular vs. irregular) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of arrhythmia tolerance in patients undergoing different therapeutic strategies
Change in arrhythmia tolerance (presence vs. absence of syncope) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Evaluation of myocarditis healing time in patients undergoing different therapeutic strategies
Assessment of myocarditis healing time (months) in patient groups differing for:
1-General cardiac treatment. 2-Specific aetiology-driven treatment. 3-Cardiac device implant. 4-Arrhythmia ablation.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of the incidence of minor arrhythmic events in different patient subgroups
Evaluation of the occurrence of minor arrhythmic events (NSVT; PVC burden; supraventricular arrhythmias; bradyarrhythmias) in different patient groups:
- 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of left ventricular ejection fraction in different patient subgroups
Evaluation of left ventricular ejection fraction (LVEF, %) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups. 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of CMR abnormalities in different patient subgroups
Evaluation of CMR abnormalities (Lake Louise criteria positivity) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups. 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of DECT abnormalities in different patient subgroups
Evaluation of DECT abnormalities (delayed enhancement positivity) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups. 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of PET abnormalities in different patient subgroups
Evaluation of PET abnormalities (abnormal FDG or ammonia uptake) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups. 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of electroanatomical abnormalities in different patient subgroups
Evaluation of electroanatomical mapping abnormalities (low-voltage areas/abnormal electrograms) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups. 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of troponin abnormalities in different patient subgroups
Evaluation of troponin abnormalities (ng/l) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups. 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of NTproBNP abnormalities in different patient subgroups
Evaluation of NTproBNP abnormalities (pg/ml) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups. 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of C-reactive protein abnormalities in different patient subgroups
Evaluation of C-reactive protein abnormalities (mg/l) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups. 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of autoantibodies abnormalities in different patient subgroups
Evaluation of autoantibodies (U/l) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups. 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of genetic test abnormalities in different patient subgroups
Evaluation of genetic test abnormalities (mutations) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups. 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of histological abnormalities in different patient subgroups
Evaluation of histological abnormalities (presence/absence of abnormal findings at either immunohistochemical, molecular, or ultrastructural analyses) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups. 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of exercise tolerance in different patient subgroups
Evaluation of exercise tolerance (New York heart Association class) in different patient groups: A. Arrhythmic myocarditis subgroups (1-4). B. Non-arrhythmic myocarditis subgroups. 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of arrhythmia burden in different patient subgroups
Evaluation of arrhythmia burden (daily and monthly incidence of arrhythmias) 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of arrhythmia morphology in different patient subgroups
Evaluation of 12-lead arrhythmia morphology (QRS axis) and their modification 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of arrhythmia regularity in different patient subgroups
Evaluation of arrhythmia regularity (cycle length variability) and their modification 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Comparison of myocarditis healing time in different patient subgroups
Evaluation of myocarditis healing time (months) 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.
Measured: At baseline assessment and through study completion (up to 10 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start1 Jan 2013
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for MyocarditisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Other
- Enrolment
- 20 participants (estimated)
- Target duration
- 30 Years
Sponsor and investigators
- Lead sponsor
- Scientific Institute San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovanni Peretto, Scientific Institute San Raffaele
- Investigators
- Paolo Della Bella, MD, Study chair, San Raffaele Scientific Institute, Milan, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06591260
- Sponsor's protocol ID
- MYOPED
- Acronym
- MYOPED
- Status last verified
- Sep 2024
- First submitted
- 7 Sep 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Requests will be evaluated case by case by the PI.
Publications
Frustaci A, Russo MA, Chimenti C. Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study. Eur Heart J. 2009 Aug;30(16):1995-2002. doi: 10.1093/eurheartj/ehp249. Epub 2009 Jun 25.
PubMed 19556262Mason JW, O'Connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME, Moon TE. A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators. N Engl J Med. 1995 Aug 3;333(5):269-75. doi: 10.1056/NEJM199508033330501.
PubMed 7596370Schultheiss HP, Piper C, Sowade O, Waagstein F, Kapp JF, Wegscheider K, Groetzbach G, Pauschinger M, Escher F, Arbustini E, Siedentop H, Kuehl U. Betaferon in chronic viral cardiomyopathy (BICC) trial: Effects of interferon-beta treatment in patients with chronic viral cardiomyopathy. Clin Res Cardiol. 2016 Sep;105(9):763-73. doi: 10.1007/s00392-016-0986-9. Epub 2016 Apr 25.
PubMed 27112783Ammirati E, Moroni F, Sormani P, Peritore A, Milazzo A, Quattrocchi G, Cipriani M, Oliva F, Giannattasio C, Frigerio M, Roghi A, Camici PG, Pedrotti P. Quantitative changes in late gadolinium enhancement at cardiac magnetic resonance in the early phase of acute myocarditis. Int J Cardiol. 2017 Mar 15;231:216-221. doi: 10.1016/j.ijcard.2016.11.282. Epub 2016 Nov 23.
PubMed 27913009Antunes S, Esposito A, Palmisanov A, Colantoni C, de Cobelli F, Del Maschio A. Characterization of normal and scarred myocardium based on texture analysis of cardiac computed tomography images. Annu Int Conf IEEE Eng Med Biol Soc. 2016 Aug;2016:4161-4164. doi: 10.1109/EMBC.2016.7591643.
PubMed 28269199Ammirati E, Cipriani M, Lilliu M, Sormani P, Varrenti M, Raineri C, Petrella D, Garascia A, Pedrotti P, Roghi A, Bonacina E, Moreo A, Bottiroli M, Gagliardone MP, Mondino M, Ghio S, Totaro R, Turazza FM, Russo CF, Oliva F, Camici PG, Frigerio M. Survival and Left Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis. Circulation. 2017 Aug 8;136(6):529-545. doi: 10.1161/CIRCULATIONAHA.117.026386. Epub 2017 Jun 2.
PubMed 28576783Friedrich MG, Sechtem U, Schulz-Menger J, Holmvang G, Alakija P, Cooper LT, White JA, Abdel-Aty H, Gutberlet M, Prasad S, Aletras A, Laissy JP, Paterson I, Filipchuk NG, Kumar A, Pauschinger M, Liu P; International Consensus Group on Cardiovascular Magnetic Resonance in Myocarditis. Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol. 2009 Apr 28;53(17):1475-87. doi: 10.1016/j.jacc.2009.02.007.
PubMed 19389557Rivers E, Worth A, Thrasher AJ, Burns SO. How I manage patients with Wiskott Aldrich syndrome. Br J Haematol. 2019 May;185(4):647-655. doi: 10.1111/bjh.15831. Epub 2019 Mar 12.
PubMed 30864154Guariso G, Gasparetto M. Treating children with inflammatory bowel disease: Current and new perspectives. World J Gastroenterol. 2017 Aug 14;23(30):5469-5485. doi: 10.3748/wjg.v23.i30.5469.
PubMed 28852307Rodriguez-Gonzalez M, Ruiz-Gonzalez E, Castellano-Martinez A. Anakinra as rescue therapy for steroid-dependent idiopathic recurrent pericarditis in children: case report and literature review. Cardiol Young. 2019 Feb;29(2):241-243. doi: 10.1017/S1047951118002020. Epub 2018 Dec 4.
PubMed 30511600Fung RCM, Hon KL, Leung AKC. Acute Myocarditis in Children: An Overview of Treatment and Recent Patents. Recent Pat Inflamm Allergy Drug Discov. 2020;14(2):106-116. doi: 10.2174/1872213X14666200204103714.
PubMed 32013855Kindermann I, Barth C, Mahfoud F, Ukena C, Lenski M, Yilmaz A, Klingel K, Kandolf R, Sechtem U, Cooper LT, Bohm M. Update on myocarditis. J Am Coll Cardiol. 2012 Feb 28;59(9):779-92. doi: 10.1016/j.jacc.2011.09.074.
PubMed 22361396Priori SG, Blomstrom-Lundqvist C. 2015 European Society of Cardiology Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death summarized by co-chairs. Eur Heart J. 2015 Nov 1;36(41):2757-9. doi: 10.1093/eurheartj/ehv445.
PubMed 26745817Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, Fu M, Helio T, Heymans S, Jahns R, Klingel K, Linhart A, Maisch B, McKenna W, Mogensen J, Pinto YM, Ristic A, Schultheiss HP, Seggewiss H, Tavazzi L, Thiene G, Yilmaz A, Charron P, Elliott PM; European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2013 Sep;34(33):2636-48, 2648a-2648d. doi: 10.1093/eurheartj/eht210. Epub 2013 Jul 3.
PubMed 23824828
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06591260
- Acronym / sponsor ID
- MYOPED / MYOPED
- Conditions
- Myocarditis, Ventricular Arrhythmia, Inflammatory Cardiomyopathy, Genetic Predisposition, Autoimmunity, Arrhythmia
- Keywords
- Myocarditis, Ventricular arrhythmias, Arrhythmias, Arrhythmogenic inflammatory cardiomyopathy, Endomyocardial biopsy, Cardiac magnetic resonance, Ablation, Positron emission tomography
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Scientific Institute San RaffaeleUniversity, hospital or other
- Study start
- 1 Jan 2013 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 19 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study, previously designed as a single-center experience, is multicenter, observational and both retrospective and prospective.
Retrospective phase includes all clinical data occurring before the index event (hospitalization or clinically suspected myocarditis) and myocarditis diagnosis. Prospective phase includes all data following index event and myocarditis diagnosis.
This study has multiple aims.
To compare EMB with noninvasive diagnostic techniques (CMR, DECT, PET scan, either alone or in association).
To assess the role of blood biomarkers for identification of aetiology, predisposition, prognosis, response to treatment, inflammatory activity, clinical presentation.
To describe myocarditis presenting with arrhythmias, with special focus on ventricular arrhythmias at different myocarditis stages and in different clinical contexts. To validate and generalize the leader hospital model for optimal diagnostic and therapeutical management of arrhythmias in myocarditis patients (given the role of the leader hospital as an international referral center for arrhythmias ablation and management).
To evaluate the timing needed for myocarditis healing in different patients subgroups, as assessed by noninvasive imaging techniques (CMR, DECT, PET scan), either alone or in association.
To compare patients subgroups of myocarditis, in terms of epidemiology, aetiology, prognosis, and diagnostic-therapeutical strategies. Among the others, the main study subgroups will be:
- Arrhythmic vs. non-arrhythmic myocarditis. B. Arrhythmic myocarditis subgroups. C. Non-arrhythmic myocarditis subgroups (i.e.: fulminant, acute coronary syndrome-like, pericarditis-like, heart failure, non-ischaemic dilated/hypokinetic cardiomyopathies of unknown aetiology…).
- Infectious vs. autoimmune vs. toxic myocarditis. E. Myocarditis treated by aetiology-based treatment vs. isolated cardiac medical treatment.
- Myocarditis at different disease stages: acute, hyperacute, fulminant, chronic active, post-inflammatory, or active vs. previous vs. non-myocarditis.
- Myocarditis presenting as organ-specific diseases vs. in the context of a genetic disorder or systemic disease.
- Myocarditis vs. peri-myocarditis/myo-pericarditis. I. Other analyses.
Any adult patient with clinically suspected myocarditis, of any clinical presentation and any degree of severity, will be considered as suitable for study enrollment.
Patients will undergo diagnostic and therapeutical strategies considered as clinically indicated in a patient-tailored manner, as suggested by international guidelines recommendations and best local clinical practice. Patients will be free of either accepting or refusing any diagnostic or therapeutical proposal. Whenever accepted, data will be simply collected and analyzed.
Based on clinical presentation, patients will be divided into two groups, arrhythmic (group A) and non-arrhythmic (group NA, including any other clinical presentation).
Independently of A/NA groups, all patients will undergo optimal diagnostic and therapeutic strategies, as summarized in panel A. In parallel, special diagnostic and therapeutical strategies will be performed in patients with arrhythmic presentation or evidence of arrhythmias, as shown in panel B. Proposed flowcharts (Panels A and B) represent only an approximate algorithm. Exceptions can be made in single cases, based on clinical indications.
Panel A - Diagnostic and therapeutical workup in all patients. Independently of groups (A/NA), all patients will undergo optimal diagnostic and therapeutical workup, guided by updated scientific evidence merged with the clinical experience of the center.
Baseline diagnostic workup will include: complete blood exams, 12-leads ECG, continuous telemetric monitoring, transthoracic doppler echocardiogram, coronary artery imaging (coronary angiography or CT scan). Any other clinically relevant diagnostic test will be collected.
In life-threatening presentations (cardiogenic shock or malignant arrhythmias), support treatment by optimal medical therapy, inotropic or mechanical circulatory support, and acute-phase arrhythmia management (including cardioversion, defibrillation, or temporary pacing) will be performed, as indicated, before completing diagnostic workup.
Final diagnosis of myocarditis will include, whenever applicable:
- For stable patients: 1) a second-level imaging technique (CMR as first choice; and/or DECT, PET, or multiple/fusion imaging techniques, based on clinical indications); followed by: 2) EMB, whenever clinically indicated. Blood exams for aetiology screening will be personalized upon clinical indications.
- For unstable patients: EMB only, as recommended. Blood exams for aetiology screening will be personalized upon clinical indications.
Diagnostic criteria for myocarditis, as assessed by any diagnostic technique, will be defined based on international scientific evidence and will be constantly updated. Similar considerations apply to myocarditis staging and aetiology definition. Whenever not available at local institutions, diagnostic exams can be performed and analyzed at external centers.
All patients with myocarditis (or any alternative final diagnosis), will undergo standard cardiological optimal medical treatment (COMT), as indicated. By converse, aetiology-dependent treatment will be performed only in patients with a final diagnosis of any active (acute, fulminant, chronic active) myocarditis of defined aetiology (EMB-proved). Multidisciplinary assessment, including infective disease specialists (in viral/infective myocarditis), immunologists (in non-infective/autoimmune myocarditis) or any other specialist as needed, will be used to identify indications to treatment, drug choice (either approved or with a justified unapproved indication), treatment duration and safety profile, aiming at the best patients\' interest. Toxic myocarditis will be treated accordingly, by evaluating the opportunity of withdrawing pathogenic noxa.
This protocol will not interfere with local best clinical practice. Patients with non-active myocarditis (previous or healed) or with non-myocarditis, will undergo \"standard FU\"; (see below). Patients with active myocarditis will undergo \"intensive FU\"; (see below).
Independently of FU modalities, diagnostic reassessment will be considered in the presence of at least one of the following instability criteria: a) new unexplained cardiac symptoms (dyspnoea, chest pain, syncope, palpitation); b) new unexplained increase in troponin or natriuretic peptides; c) new imaging abnormal signs; d) new unexplained clinically relevant arrhythmias. Diagnostic reassessment will include second-level imaging and/or EMB, as shown above. Subsequent therapeutical workup will be in line with the above explanations. In stable patients or undergone myocarditis healing, exercise stress test will be obtained, whenever possible.
Panel B - Diagnostic and therapeutical workup of patients with arrhythmias In parallel with (and independently of) Panel A content, patients with arrhythmias (group A) will undergo specific diagnostic and therapeutical management for arrhythmias, as a result of the integration between international guidelines recommendations and the experience of an international referral center for arrhythmia management and ablation.
To oversimplify, 4 groups of patients will be considered.
Group 1: major ventricular arrhythmias, including haemodynamically unstable VT (hu-VT) and ventricular fibrillation (VF).
After electrical stabilization and support treatment (panel A), indication to secondary prevention ICD implant will be multiparametric and patient-tailored. In patients with active myocarditis, subcutaneous ICD (S-ICD) or wearable CD (WCD) will be considered. Antiarrhythmic drugs will be considered in all Group 1 patients. In addition, all Group 1 patients will undergo COMT and aetiology-dependent treatment whenever applicable (panel A). Ablation of ventricular arrhythmias will be considered in patients with severe arrhythmic presentation, or symptomatic, or refractory to optimal medical treatment. Electrophysiological study (EPS) may be used in selected cases. A cardiac resynchronization therapy with defibrillator function (CRT-D) will replace ICD whenever indicated.
Group 2: other ventricular arrhythmias, including high-burden (hb) premature ventricular complexes (PVC); nonsustained VT (NSVT); haemodynamically stable VT (hs-VT).
Whenever clinically indicated, Group 2 patients will undergo invasive EPS (or in alternative noninvasive programmed ventricular stimulation in ICD carriers) to stratify arrhythmic risk. Patients with positive EPS will undergo ICD (or S-ICD/WCD) as in Group 1. Patients with negative EPS, as well as Group 2 cases not undergoing EPS, will undergo watchful waiting strategy (always with an intensive FU) with or without loop recorder implant: in these cases, ICD (or S-ICD/WCD) will be implanted only following documentation of relevant VA in FU. In addition, all Group 2 patients will undergo antiarrhythmic treatment, COMT and aetiology-dependent treatment whenever applicable (panel A). In symptomatic or drug-refractory cases, ablation of ventricular arrhythmias will be considered. A CRT-D will replace ICD whenever indicated.
Group 3: bradyarrhythmias, including advanced (2nd type II or 3rd degree) atrioventricular block (AVB); critical sinus pauses from sinus node disease (SND).
After electrical stabilization and support treatment (panel A), including the use of temporary pacemaker as a bridge-to-decision, patients will undergo watchful waiting strategy or definitive device implant. Instead of a pacemaker (PM), ICD will be considered in the presence of high-risk criteria for ventricular tachyarrhythmias, including: a) overlap with Group 1 presentation; b) overlap with Group 2 presentation, especially in the presence of positive EPS; c) other indications for primary prevention ICD implant (severe systolic dysfunction); d) signs of increased tachyarrhythmic risk (scar signs); e) patients with special aetiologies leading to an increased tachyarrhythmic risk (i.e: cardiac sarcoid, giant cell myocarditis, Chagas disease, overlapping genetic syndromes). In addition, all Group 3 patients will undergo COMT and aetiology-dependent treatment whenever applicable (panel A). A CRT-D or a CRT-P will replace ICD or PM, respectively, whenever indicated.
Group 4: supraventricular arrhythmias, including atrial fibrillation (AF); atrial flutter (AFlu); atrial tachycardia (AT).
Following acute-phase rate control (RaC), stable rhythm control (RyC) strategy will be considered as the therapeutical target, together with appropriate anticoagulation, as needed. Normal sinus rhythm will be obtained through either electrical or pharmacological cardioversion. In patients with unsuccessful attempts of sinus rhythm conversion, optimal treatment of active myocarditis will be considered as a primary target. Following myocarditis healing, in the presence of persistent arrhythmias, patients will be considered for RyC via electrical or pharmacological cardioversion. Transcatheter ablation will be an option for patients with drug-symptomatic, recurrent or refractory arrhythmias. Permanent RaC strategy will be considered only in non responders. Widespread use of implantable loop recorders will apply, as clinically indicated. In addition, all Group 4 patients will undergo COMT and aetiology-dependent treatment whenever applicable (panel A).
Aims in detail. Aim 1 Comparison between EMB and second level imaging findings (N=1000)
Primary:
Diagnostic concordance
Secondary:
Inflammatory activity (presence; type; quantification) Fibrosis (presence; type; quantification) Coronary microvascular disease Comparison between EMB sampling site and abnormal substrate localization at imaging (including substrate-guided EMB or alternative biopsy techniques) Role of EMB guided by electroanatomical map Diagnostic performance of DECT and/or PET, especially when CMR is contraindicated Comparison between CMR/DECT findings and PET scan (including fusion imaging) or advanced imaging techniques including strain analysis at echocardiogram Comparison between substrate abnormalities localizations (as assessed by second level imaging techniques) and arrhythmias (type, characteristics and origin site) Comparison among different diagnostic techniques (EMB, CMR/DECT, PET) in terms of safety and diagnostic accuracy Evaluation of differential diagnosis with other cardias diseases, and particularly with arrhythmogenic cardiomyopathy of any localization (left, right, biventricular, to identify updated diagnostic criteria) Comparison between information provided by all the techniques above, and data from electroanatomical mapping (EAM) Other analyses
Aim 2 Evaluation of blood exams and biomarkers (N=1000)
Primary:
Identification of diagnostic biomarkers Identification of aetiology biomarkers
Secondary:
Cardiac and inflammatory biomarkers evaluation in different myocarditis subtypes Identification of biomarkers of inflammatory stage (acute vs. chronic; active vs. previous) Comparison between local and systemic/peripheral inflammation Correlations with EMB and second-level imaging (CMR, DECT, PET…) findings Identification of genetic factors with any role in predisposition, prognosis, response to treatment, or any other correlation, either in the presence or in the absence of underlying cardiomyopathy or autoimmune/inflammatory disease Identification of prognostic biomarkers Identification of biomarkers associated with treatment response Evaluation of any tissue/organ damage or associated comorbidities Study of cardiac autoantibodies Study of any cell, tissue, genetic or circulating biomarker Correlations with clinical presentations Other analyses
Aim 3 Validation of optimal management of arrhythmic myocarditis (N=1000)
Primary:
Evaluation of effects on major endpoints
Secondary:
Evaluation of effects on minor endpoints Role of electrophysiological study in risk stratification Role of loop recorders in arrhythmia monitoring Role of transcatheter ablation (any technique) on arrhythmic outcomes Identification of optimal timing for any electrophysiological/device procedure Role of pharmacological antiarrhythmic treatment Role of aetiology-specific treatment on arrhythmic outcomes Identification of criteria for device implants (PM, ICD, S-ICD, CRT-D…) in myocarditis patients Validation of therapeutic strategies and their optimal timing in patients with supraventricular arrhythmias, bradyarrhythmias, or ventricular arrhythmias Correlation between arrhythmia type/features with any other diagnostic exam performed at baseline or during FU (mainly EMB, CMR/DECT/PET, echocardiogram, stress tests, blood exams, genetic/blood/tissue/cell biomarkers) Indications and timing for device (ICD, CRT-D) implant in primary prevention, based on multiparametric risk assessment, and in relation to different general and aetiology-dependent treatments Other analyses
Aim 4 Evaluation of healing timing in myocarditis (N=500) Primary Any degree of recovery by 3, 6, 9, 12 and 12 months Secondary Comparison of healing times in treated vs. untreated patients Correlations between healing times and clinical presentation types Correlations between healing times and any biomarker Correlations between healing times and any outcomes Validation of exercise stress test role after myocarditis healing Evaluation of PET scan or other diagnostic techniques as alternatives to CMR in special populations Other analyses
Aim 5 Subgroup analyses (N=500, hugely variable in each subanalysis) A vs. NA groups; A myocarditis subgroups; NA myocarditis subgroups (including fulminant); Infective vs. autoimmune vs. toxic forms; Treated by aetiology-driven therapy vs. standard cardiological treatment; Different myocarditis stages and differential diagnoses; Isolated vs. in the context o a systemic disease or genetic disease; Myocarditis vs. perimyocarditis/ myopericarditis Primary Differences in major outcomes Secondary Differences in minor outcomes Differences in any biomarker Differences in any diagnostic exam Differences in aetiology Differences in predisposition Differences in inflammatory activity Differences in pericardial involvement Differences in systemic involvement Differences in arrhythmias types and features Differences in clinical presentation Differences in treatment response, including novel treatments Validation of local aetiology/pathophysiology-dependent treatments Validation of biomarkers and imaging techniques in monitoring response to treatment Identification of optimal follow-up timeline Other analyses
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Target follow-up
- 30 Years
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arrhythmic (A) | – | Other: support treatment, cardiac medical treatment, aetiology-specific treatment, device implant, arrhythmia ablationArrhythmic 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). |
| Nonarrhythmic (NA) | – | Other: support treatment, cardiac medical treatment, aetiology-specific treatment, device implant, arrhythmia ablationNonarrhythmic 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) |
| Subgroups | – | Other: support treatment, cardiac medical treatment, aetiology-specific treatment, device implant, arrhythmia ablationFor 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 |
Who may qualify
- Ages
- 0 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- 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.
Key inclusion criteria (4 listed)
- Written informed consent.
- Age \< 18 years.
- Clinically suspected myocarditis.
- Enrollment performed by one of the participating Centers.
Key exclusion criteria (2 listed)
- Absence of written informed consent.
- Age \> 18 years (adults)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| support treatment, cardiac medical treatment, aetiology-specific treatment, device implant, arrhythmia ablationTreatment will be patient-tailored, integrating international guidelines recommendation and the experience of the center where enrollment takes place. | Other | Arrhythmic (A), Nonarrhythmic (NA), Subgroups |
Primary outcome
Occurrence of major cardiac events
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Validation of optimal management of arrhythmic myocarditis by comparing the occurrence of major cardiac events in patients undergoing different therapeutic strategies - Primary
Time frame: 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.
Evaluation of healing timing in myocarditis - Primary
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
105 secondary outcomes
Occurrence of minor arrhythmic events
Time frame: At baseline assessment and through study completion (up to 10 years)
Any modification in imaging parameters
Time frame: At baseline assessment and through study completion (up to 10 years)
Any modification in clinical parameters
Time frame: By 10-year follow-up
Any modification in New York Heart Association class
Time frame: By 10-year follow-up
Any modification in exercise peak heart rate
Time frame: By 10-year follow-up
Any modification in exercise peak systolic blood pressure
Time frame: By 10-year follow-up
Any modification in exercise walking distance
Time frame: By 10-year follow-up
Any modification in exercise oxygen consumption
Time frame: By 10-year follow-up
Any modification in exercise-induced arrhythmias
Time frame: By 10-year follow-up
Identification of the prevalence of associated diseases
Time frame: By 10-year follow-up
Any modification in arrhythmia burden
Time frame: By 10-year follow-up
Any modification in arrhythmia morphology
Time frame: By 10-year follow-up
Any modification in arrhythmia regularity
Time frame: By 10-year follow-up
Any modification in arrhythmia tolerance
Time frame: By 10-year follow-up
Prevalence of coronary circulation abnormalities
Time frame: By 10-year follow-up
Prevalence of electrophysiological study
Time frame: By 10-year follow-up
Results of electrophysiological study
Time frame: By 10-year follow-up
Prevalence of ventricular arrhythmia ablation
Time frame: By 10-year follow-up
Results of ventricular arrhythmia ablation
Time frame: By 10-year follow-up
Prevalence of supraventricular arrhythmia ablation
Time frame: By 10-year follow-up
Results of supraventricular arrhythmia ablation
Time frame: By 10-year follow-up
Prevalence of cardiac device implants
Time frame: By 10-year follow-up
Comparison of arrhythmia detection by continuous vs. non-continuous monitoring
Time frame: By 10-year follow-up
Assessment of the withdrawal timing of non-permanent cardiac devices
Time frame: By 10-year follow-up
Prevalence of CT scan
Time frame: By 10-year follow-up
Results of CT scan
Time frame: By 10-year follow-up
Prevalence of PET scan
Time frame: By 10-year follow-up
Results of PET scan
Time frame: By 10-year follow-up
Prevalence of electroanatomical mapping
Time frame: By 10-year follow-up
Results of electroanatomical mapping
Time frame: By 10-year follow-up
Prevalence of stress tests
Time frame: By 10-year follow-up
Results of stress tests - ECG
Time frame: By 10-year follow-up
Results of stress tests - wall motion abnormalities
Time frame: By 10-year follow-up
Results of stress tests - coronary flow reserve
Time frame: By 10-year follow-up
Myocarditis recurrences
Time frame: At baseline assessment (including past medical history) and through study completion (up to 10 years)
Response to treatment - systolic function
Time frame: At baseline assessment and through study completion (up to 10 years)
Response to treatment - malignant ventricular arrhythmias
Time frame: At baseline assessment and through study completion (up to 10 years)
Prognostic risk stratification - malignant ventricular arrhythmias
Time frame: Through study completion (up to 10 years)
Prognostic risk stratification - heart failure
Time frame: Through study completion (up to 10 years)
Prognostic risk stratification - cardiac death
Time frame: Through study completion (up to 10 years)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Background: PubMed 19556262Frustaci A, Russo MA, Chimenti C. Randomized study on the efficacy of immunosuppressive therapy in patients with virus-negative inflammatory cardiomyopathy: the TIMIC study. Eur Heart J. 2009 Aug;30(16):1995-2002. doi: 10.1093/eurheartj/ehp249. Epub 2009 Jun 25.
- Background: PubMed 7596370Mason JW, O'Connell JB, Herskowitz A, Rose NR, McManus BM, Billingham ME, Moon TE. A clinical trial of immunosuppressive therapy for myocarditis. The Myocarditis Treatment Trial Investigators. N Engl J Med. 1995 Aug 3;333(5):269-75. doi: 10.1056/NEJM199508033330501.
- Background: PubMed 27112783Schultheiss HP, Piper C, Sowade O, Waagstein F, Kapp JF, Wegscheider K, Groetzbach G, Pauschinger M, Escher F, Arbustini E, Siedentop H, Kuehl U. Betaferon in chronic viral cardiomyopathy (BICC) trial: Effects of interferon-beta treatment in patients with chronic viral cardiomyopathy. Clin Res Cardiol. 2016 Sep;105(9):763-73. doi: 10.1007/s00392-016-0986-9. Epub 2016 Apr 25.
- Background: PubMed 27913009Ammirati E, Moroni F, Sormani P, Peritore A, Milazzo A, Quattrocchi G, Cipriani M, Oliva F, Giannattasio C, Frigerio M, Roghi A, Camici PG, Pedrotti P. Quantitative changes in late gadolinium enhancement at cardiac magnetic resonance in the early phase of acute myocarditis. Int J Cardiol. 2017 Mar 15;231:216-221. doi: 10.1016/j.ijcard.2016.11.282. Epub 2016 Nov 23.
- Background: PubMed 28269199Antunes S, Esposito A, Palmisanov A, Colantoni C, de Cobelli F, Del Maschio A. Characterization of normal and scarred myocardium based on texture analysis of cardiac computed tomography images. Annu Int Conf IEEE Eng Med Biol Soc. 2016 Aug;2016:4161-4164. doi: 10.1109/EMBC.2016.7591643.
- Background: PubMed 28576783Ammirati E, Cipriani M, Lilliu M, Sormani P, Varrenti M, Raineri C, Petrella D, Garascia A, Pedrotti P, Roghi A, Bonacina E, Moreo A, Bottiroli M, Gagliardone MP, Mondino M, Ghio S, Totaro R, Turazza FM, Russo CF, Oliva F, Camici PG, Frigerio M. Survival and Left Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis. Circulation. 2017 Aug 8;136(6):529-545. doi: 10.1161/CIRCULATIONAHA.117.026386. Epub 2017 Jun 2.
- Background: PubMed 19389557Friedrich MG, Sechtem U, Schulz-Menger J, Holmvang G, Alakija P, Cooper LT, White JA, Abdel-Aty H, Gutberlet M, Prasad S, Aletras A, Laissy JP, Paterson I, Filipchuk NG, Kumar A, Pauschinger M, Liu P; International Consensus Group on Cardiovascular Magnetic Resonance in Myocarditis. Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J Am Coll Cardiol. 2009 Apr 28;53(17):1475-87. doi: 10.1016/j.jacc.2009.02.007.
- Background: PubMed 30864154Rivers E, Worth A, Thrasher AJ, Burns SO. How I manage patients with Wiskott Aldrich syndrome. Br J Haematol. 2019 May;185(4):647-655. doi: 10.1111/bjh.15831. Epub 2019 Mar 12.
- Background: PubMed 28852307Guariso G, Gasparetto M. Treating children with inflammatory bowel disease: Current and new perspectives. World J Gastroenterol. 2017 Aug 14;23(30):5469-5485. doi: 10.3748/wjg.v23.i30.5469.
- Background: PubMed 30511600Rodriguez-Gonzalez M, Ruiz-Gonzalez E, Castellano-Martinez A. Anakinra as rescue therapy for steroid-dependent idiopathic recurrent pericarditis in children: case report and literature review. Cardiol Young. 2019 Feb;29(2):241-243. doi: 10.1017/S1047951118002020. Epub 2018 Dec 4.
- Background: PubMed 32013855Fung RCM, Hon KL, Leung AKC. Acute Myocarditis in Children: An Overview of Treatment and Recent Patents. Recent Pat Inflamm Allergy Drug Discov. 2020;14(2):106-116. doi: 10.2174/1872213X14666200204103714.
- Background: PubMed 22361396Kindermann I, Barth C, Mahfoud F, Ukena C, Lenski M, Yilmaz A, Klingel K, Kandolf R, Sechtem U, Cooper LT, Bohm M. Update on myocarditis. J Am Coll Cardiol. 2012 Feb 28;59(9):779-92. doi: 10.1016/j.jacc.2011.09.074.
- Individual participant dataSharing planned: Undecided. Requests will be evaluated case by case by the PI.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Paolo Della Bella, MD study chair
San Raffaele Scientific Institute, Milan, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Myocarditis and Ventricular Arrhythmia, run by Scientific Institute San Raffaele at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giovanni Peretto, MD (+39 0226437482, peretto.giovanni@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of major cardiac events (time frame: By 12-month follow-up). The study lists 69 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06591260, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.