Multimodal and Multidisciplinary Approach to Optimize Diagnostic, Prognostic, and Therapeutic Management of Patients with Non-ischemic Cardiomyopathies and Arrhythmogenic-inflammatory Phenotypes: a Multicenter, Observational, Retrospective and Prospective Registry Study.

Recruiting

Conditions: Non-ischemic Cardiomyopathy
Dilated Cardiomyopathy (DCM)
Hypertrophic Cardiomyopathy (HCM)
Restrictive Cardiomyopathy
Arrhythmogenic Cardiomyopathy (AC, ARVD/C)
Left Ventricular Noncompaction
Arrhythmogenic Mitral Valve Prolapse
Peripartum Cardiomyopathy
Anderson-Fabry Disease
Arrhythmic and Inflammatory Non-ischemic Cardiomyopathy

Registration Number: NCT06607471

Lead Sponsor: Scientific Institute San Raffaele

Brief Summary: Non-ischemic cardiomyopathies (NICM) represent a heterogeneous group of pathologies characterized by absence of obstructive disease of the epicardial coronary vessels and distinct structural and functional changes of the myocardium. The main identified forms include dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), and arrhythmogenic cardiomyopathy proper (ACM). More recently, further forms of cardiomyopathy have been described, less common and not uniquely classifiable, including: uncompressed myocardium (LVNC), peripartum cardiomyopathy (PPCM), structural correlates of arrhythmogenic mitral valve prolapse (AMVP), Anderson-Fabry disease (AFD), NICM associated with multi- system neuromuscular or autoimmune diseases, lysosomal diseases, glycogenosis, mitochondrial cytopathies and canal diseases with structural substrates. Finally, there are "overlap" forms, characterized by the sharing in the same subject of characteristic aspects of two or more of the above- mentioned diseases; and of the "undefined" forms, which to date do not reach the diagnostic criteria for any of the above-mentioned diseases.

To the best of current knowledge, there are two points discovered in scientific research, namely the description of the arrhythmogenic and "inflammatory" phenotypes in a broad sense, which are summarized here with the acronym AINICM. In detail:

1. Arrhythmic manifestations account for the arrhythmogenic component of AINICM, which is not limited to ACM proper. In fact, most of the above diseases have a non-arrhythmic clinical presentation and a prevailing tendency to evolve towards a picture of cardiovascular decompensation. Although sudden arrhythmic death has been described throughout the spectrum of AINICM, early arrhythmic manifestations of such diseases have an unknown prevalence, an uncertain association with different disease genotypes and phenotypes, and still uncertain predictivity of long-term arrhythmic risk. At the same time, optimal diagnostic and therapeutic pathways in arrhythmias associated with AINICM are still being studied.

2. Myocardial inflammation (M-Infl) accounts for the inflammatory component of AINICM, and has recently been described in association with many AINICM on a genetic basis, including undefined and arrhythmic forms. The data is of high interest not only in the diagnostic, but also in prognostic and therapeutic field. In fact, on the one hand the presence of M-Infl seems to have a physio- pathological role in AINICM; on the other, as already known in myocarditis, the optimal therapeutic paths of arrhythmias may differ in patients with and without M-Infl; in particular, also in the light of the preliminary data available in adult and paediatric AINICM, the inflammatory forms are expected to respond better to immunosuppressive therapy, the arrhythmogenic ones to an ablative therapy with frequent need of implantation of cardiac devices.

Based on the clinical presentation, NICM patients will be divided into arrhythmic (AINICM) and non-arrhythmic patients as study and control groups , respectively. The AINICM group will include presentation with ventricular fibrillation (VF), either sustained or non-sustained ventricular tachycardia (VT; NSVT), frequent premature ventricular complexes (PVC), supraventricular arrhythmias (SVA) and bradyarrhythmias (BA). Clinical presentations other than arrhythmic, including chest pain and heart failure, will define the control group. In parallel, as shown in Figure 1, patients with any evidence of M-Infl will be compared with those showing no signs of M-Infl.

Detailed Description: This study aims to collect clinical data of both retrospective and prospective patients with suspected or proven NICMs in a registry. The scope of the registry is to answer multiple unsolved questions in the field of AINICM as described below:

1. Improving the diagnostic workup. While genetic test and cardiac magnetic resonance (CMR) constitute the gold standard dagnostic techniques for NICM, it is known that; A) the yield of genetic test is low in NICM; B) the diagnostic performance of CMR may be limited in AINICM, because of cardiac device-related artifacts and/or irregular heartbeat. In this setting, alternative diagnostic techniques, namely computed tomography (CT) scan, positron emission tomography (PET), electroanatomical map (EAM) and endomyocardial biopsy (EMB) may be clinically helpful, as recommended for the investigation of many arrhythmogenic substrates.

2. Identifying disease-specific signatures. Genotype-phenoype associations are expected to benefit from a multimodal and multiparametric approach, in order to allow etiology-specific features in AINICM. Most of the current signatures are limited to combined genotype-CMR studies. Signatures would likely benefit from implementing additional parameters, including arrhythmia features and myocadial inflammatory status.

3. Working our models for risk prediction. Outcomes and arrhythmic risk stratification remain uncertain for most NICM. Based on an advanced multimodal workup, multiparametric risk scores may be created and subsequenlty validated, in order to predict the arrhythmic risk of specific cardiomyopathies. This would improve and refine the scores currently available for a limited number of NICM, such as HCM, classic right ventricular ACM, or cardiomyopathies secondary to LMNA gene mutation. Parameters from clinical arrhythmology and cardiac electrophysiology, as well as those related to inflammation, may improve the current status of the art about risk prediction.

4. Tailoring treatment strategies. A multimodal (i.e. by use of multiple diagnostic techniques) and multidisciplinary (i.e. by means of a team of cardiac electrophysiologists, cardiologists, radiologists, geneticists, immunologists, cardiac pathologists, pediatricians) model may help improving therapeutic strategies in AINICM, as already demonstrated in myocarditis. In detail, treatment options will include guideline-directed cardiological treatment, implantable cardiac devices, antiarrhythmic drugs, immunomodulating agents and catheter ablation of arrhythmias. In this setting, the coordinating center is an internationally recognized third-level referral center for the management of ventricular arrhythmias, and already has advanced facilities, including a dedicated multidisciplinary disease unit for myocarditis and inflammatory cardiomyopathies. In this setting, preliminary evidence suggests a potential benefit from targeting M-Infl even in NICM and AINICM.

5. Allowing direct comparison among specific NICM subgroups. Extensive inclusion criteria, allowing the entry of all NICM in a common registry with homogeneous variables would enable the direct comparison of different AINICM types, by means of multiparametric and multimodal characterization, for the first time including both the electrophysiological and inflammatory viewpoints. This is expected to significantly advance the status of knowledge in the field of NICM.

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 15000

Inclusion Criteria

Written informed consent. For pediatric patients, consent will be obtained by parents, according to the laws applicable in each of the participating countries.
Clinical suspicion of NICM, and/or proven diagnosis of any NICM and/or genotype consistent with any NICM.

NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.

Exclusion Criteria

Absent informed consent.
Proven diagnosis of cardiac disease alternative to NICM.
Lack of diagnostic workup suitable for diagnosing NICM, detecting arrhythmias, or detecting M-Infl.
For patients retrospectively enrolled: lack of active status of follow-up at the enrolling center.

Study & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) amongst different diagnostic techniques in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At year 30	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) amongst different diagnostic techniques in overlapping phenotypes	At year 30	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) amongst different diagnostic techniques in undefined phenotypes	At year 30	Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value
Assessment of prevalence of M-Inf in RCM, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of M-Inf in ACM, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of M-Inf in LVNC, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of M-Inf in AMVP, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of M-Inf in PPCM, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of M-Inf in AFD, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of M-Inf in storage and dysmetabolic diseases, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of M-Inf in mitochondrial diseases, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of M-Inf in channelopathies with structural changes, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of arrhythmogenic substrates in DCM, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of arrhythmogenic substrates in HCM, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of arrhythmogenic substrates in RCM, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of arrhythmogenic substrates in ACM, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of arrhythmogenic substrates in LVNC, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of arrhythmogenic substrates in AMVP, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of arrhythmogenic substrates in PPCM, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of arrhythmogenic substrates in AFD, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of arrhythmogenic substrates in storage and dysmetabolic diseases, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of arrhythmogenic substrates in mitochondrial diseases, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of arrhythmogenic substrates in channelopathies with structural changes, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of arrhythmogenic substrates in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of overlapping phenotypes, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of undefined phenotypes, as defined by multimodal diagnostic workup	At year 30	The multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Identification of DCM-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Identification of HCM-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Identification of RCM-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Identification of ACM-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Identification of LVNC-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Identification of AMVP-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Identification of PPCM-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Identification of AFD-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Identification of storage and dysmetabolic diseases-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Identification of mitochondrial diseases-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Identification of channelopathies with structural changes-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Identification of cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Identification of overlapping phenotypes-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Identification of undefined phenotypes-specific signatures	At year 30	Identification of disease-specific signatures of diagnosis, etiology, genotype, clinical presentation, arrhythmia type, myocardial inflammation, outcomes, and response to treatment.
Differences in incidence of major events during follow-up in different NICMs	At year 30	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearanc e/recurrence of M-Infl. NICMs include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Occurrence of major cardiac events in DCM	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Occurrence of major cardiac events in HCM	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Occurrence of major cardiac events in RCM	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Occurrence of major cardiac events in ACM	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Occurrence of major cardiac events in LVNC	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Occurrence of major cardiac events in AMVP	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Occurrence of major cardiac events in PPCM	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Occurrence of major cardiac events in AFD	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Occurrence of major cardiac events in storage and dysmetabolic diseases	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Occurrence of major cardiac events in mitochondrial diseases	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Occurrence of major cardiac events in channelopathies with structural changeschannelopathies with structural changes	At 1 year	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Occurrence of major cardiac events in channelopathies with structural changes	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Occurrence of major cardiac events in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Occurrence of major cardiac events in overlapping phenotypes	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in DCM	At 30years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in HCM	At 30 years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in RCM	At 30 years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in ACM	At 30 years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in LVNC	At 30 years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in AMVP	At 30 years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in PPCM	At 30 years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in AFD	At 30 years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in storage and dysmetabolic diseases	At 30 years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in mitochondrial diseases	At 30 years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in channelopathies with structural changes	At 30 years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in overlapping phenotypes	At 30 years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Evaluation of efficacy of treatment, defined based on the incidence of major events during follow-up in undefined phenotypes	At 30 years	Real world efficacy (by comparison of outcomes in patients receiving distinct treatment options) and safety profile (complications, side effects) of every therapeutic strategy, either alone or in combination. Major events are defined as all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Inf.
Assessment of diagnostic accuracy (in terms of true/false positive/negative rates) amongst different diagnostic techniques in DCM	At year 30	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) amongst different diagnostic techniques in HCM	At year 30	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) amongst different diagnostic techniques in RCM	At year 30	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) amongst different diagnostic techniques in ACM	At year 30	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) amongst different diagnostic techniques in LVNC	At year 30	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) amongst different diagnostic techniques in AMVP	At year 30	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) amongst different diagnostic techniques in PPCM	At year 30	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) amongst different diagnostic techniques in AFD	At year 30	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) amongst different diagnostic techniques in storage and dysmetabolic diseases	At year 30	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) amongst different diagnostic techniques in mitochondrial diseases	At year 30	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) amongst different diagnostic techniques in channelopathies with structural changes	At year 30	Diagnostic concordance in terms of sensitivity, specificity, positive predictive value, negative predictive value
Assessment of prevalence of M-Inf in DCM, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of M-Inf in HCM, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of M-Inf in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of M-Inf in overlapping phenotypes, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Assessment of prevalence of M-Inf in undefined phenotypes, as defined by multimodal diagnostic workup	At year 30	Multimodal diagnostic workup is a combination of genetic tests, different techniques of cardiac imaging, laboratory tests and biomarkers, histology, and electrophysiological tools, collecting all the clinical variables in a registry
Occurrence of major cardiac events in undefined phenotypes	At 30 years	all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl.

Secondary Outcome Measures

Name	Time	Method
Identification of genetic, circulatory, tissue, cellular, metabolic, molecular, immunologic or multiomic factors with any role in etiology, clinical presentation, diagnosis, prognosis, response to treatment	At 30 years	This will be assessed either in the presence or in the absence of defined NICMs. NICMs include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Assessment of the diagnostic yield of different techniques of arrhythmia monitoring in NICMs	At 30 years	NICMs include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Prevalence of inflammatory activity (presence; type; quantification; pattern) in NICM	At 30 years	Prevalence of inflammatory activity (presence; type; quantification; pattern) in NICMs, which include but not limit to DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Prevalence of inflammatory activity (presence; type; quantification; pattern) in DCM	At 30 years	presence; type; quantification; pattern
Prevalence of inflammatory activity (presence; type; quantification; pattern) in HCM	At 30 years	presence; type; quantification; pattern
Prevalence of inflammatory activity (presence; type; quantification; pattern) in RCM	At 30 years	presence; type; quantification; pattern
Prevalence of inflammatory activity (presence; type; quantification; pattern) in ACM	At 30 years	presence; type; quantification; pattern
Prevalence of inflammatory activity (presence; type; quantification; pattern) in LVNC	At 30 years	presence; type; quantification; pattern
Prevalence of inflammatory activity (presence; type; quantification; pattern) in AMVP	At 30 years	presence; type; quantification; pattern
Prevalence of inflammatory activity (presence; type; quantification; pattern) in PPCM	At 30 years	presence; type; quantification; pattern
Prevalence of inflammatory activity (presence; type; quantification; pattern) in storage and dysmetabolic diseases	At 30 years	presence; type; quantification; pattern
Prevalence of inflammatory activity (presence; type; quantification; pattern) in mitochondrial diseases	At 30 years	presence; type; quantification; pattern
Prevalence of inflammatory activity (presence; type; quantification; pattern) in channelopathies with structural changes	At 30 years	presence; type; quantification; pattern
Prevalence of inflammatory activity (presence; type; quantification; pattern) in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years	presence; type; quantification; pattern
Prevalence of inflammatory activity (presence; type; quantification; pattern) in overlapping phenotypes	At 30 years	presence; type; quantification; pattern
Analysis of correlation between M-Infl and arrhythmia type and ECG features in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, neuromuscular, mitochondrial, toxic, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Analysis of correlation between M-Infl and arrhythmia type and ECG features in DCM	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between M-Infl and arrhythmia type and ECG features in HCM	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between M-Infl and arrhythmia type and ECG features in RCM	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between M-Infl and arrhythmia type and ECG features in ACM	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between M-Infl and arrhythmia type and ECG features in LVNC	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between M-Infl and arrhythmia type and ECG features in AMVP	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between M-Infl and arrhythmia type and ECG features in PPCM	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between M-Infl and arrhythmia type and ECG features in AFD	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between M-Infl and arrhythmia type and ECG features in storage and dysmetabolic diseases	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between M-Infl and arrhythmia type and ECG features in mitochondrial diseases	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between M-Infl and arrhythmia type and ECG features in channelopathies with structural changes	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between M-Infl and arrhythmia type and ECG features in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between M-Infl and arrhythmia type and ECG features in overlapping phenotypes	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between M-Infl and arrhythmia type and ECG features in undefined phenotypes	At 30 years	correlation between M-Infl and arrhythmia type and ECG features
Analysis of correlation between EMB sampling site and localization of substrate abnormalities at imaging (including substrate-guided EMB or alternative biopsy techniques) in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, neuromuscular, mitochondrial, toxic, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge
Analysis of correlation between EMB sampling site and localization of substrate abnormalities at imaging (including substrate-guided EMB or alternative biopsy techniques) in DCM	At 30 years	correlation between EMB sampling site and localization of substrate
Analysis of correlation between EMB sampling site and localization of substrate abnormalities at imaging (including substrate-guided EMB or alternative biopsy techniques) in HCM	At 30 years	correlation between EMB sampling site and localization of substrate
Analysis of correlation between EMB sampling site and localization of substrate abnormalities at imaging (including substrate-guided EMB or alternative biopsy techniques) in RCM	At 30 years	correlation between EMB sampling site and localization of substrate
Analysis of correlation between EMB sampling site and localization of substrate abnormalities at imaging (including substrate-guided EMB or alternative biopsy techniques) in ACM	At 30 years	correlation between EMB sampling site and localization of substrate
Analysis of correlation between EMB sampling site and localization of substrate abnormalities at imaging (including substrate-guided EMB or alternative biopsy techniques) in LVNC	At 30 years	correlation between EMB sampling site and localization of substrate
Analysis of correlation between EMB sampling site and localization of substrate abnormalities at imaging (including substrate-guided EMB or alternative biopsy techniques) in AMVP	At 30 years	correlation between EMB sampling site and localization of substrate
Analysis of correlation between EMB sampling site and localization of substrate abnormalities at imaging (including substrate-guided EMB or alternative biopsy techniques) in PPCM	At 30 years	correlation between EMB sampling site and localization of substrate
Analysis of correlation between EMB sampling site and localization of substrate abnormalities at imaging (including substrate-guided EMB or alternative biopsy techniques) in AFD	At 30 years	correlation between EMB sampling site and localization of substrate
Analysis of correlation between EMB sampling site and localization of substrate abnormalities at imaging (including substrate-guided EMB or alternative biopsy techniques) in storage and dysmetabolic diseases and mitochondrial diseases	At 30 years	correlation between EMB sampling site and localization of substrate
Analysis of correlation between EMB sampling site and localization of substrate abnormalities at imaging (including substrate-guided EMB or alternative biopsy techniques) in channelopathies with structural changes	At 30 years	correlation between EMB sampling site and localization of substrate
Analysis of correlation between EMB sampling site and localization of substrate abnormalities at imaging (including substrate-guided EMB or alternative biopsy techniques) in cardiomyopathies associated with systemic, rheumatologic, neuromuscular diseases	At 30 years	correlation between EMB sampling site and localization of substrate
Analysis of correlation between EMB sampling site and localization of substrate abnormalities at imaging (including substrate-guided EMB or alternative biopsy techniques) in overlapping and/or undefined phenotypes	At 30 years	correlation between EMB sampling site and localization of substrate
Diagnostic yield of EMB guided by electroanatomical map in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Diagnostic yield of EMB guided by electroanatomical map in DCM	At 30 years	Investestigating the role of EMB guided by electroanatomical map in diagnosis
Diagnostic yield of EMB guided by electroanatomical map in HCM	At 30 years	Investestigating the role of EMB guided by electroanatomical map in diagnosis
Diagnostic yield of EMB guided by electroanatomical map in RCM	At 30 years	Investestigating the role of EMB guided by electroanatomical map in diagnosis
Diagnostic yield of EMB guided by electroanatomical map in ACM	At 30 years	Investestigating the role of EMB guided by electroanatomical map in diagnosis
Diagnostic yield of EMB guided by electroanatomical map in LVNC	At 30 years	Investestigating the role of EMB guided by electroanatomical map in diagnosis
Diagnostic yield of EMB guided by electroanatomical map in AMVP	At 30 years	Investestigating the role of EMB guided by electroanatomical map in diagnosis
Diagnostic yield of EMB guided by electroanatomical map in PPCM	At 30 years	Investestigating the role of EMB guided by electroanatomical map in diagnosis
Diagnostic yield of EMB guided by electroanatomical map in AFD	At 30 years	Investestigating the role of EMB guided by electroanatomical map in diagnosis
Diagnostic yield of EMB guided by electroanatomical map in storage and dysmetabolic diseases, mitochondrial diseases, channelopathies with structural changes, and cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years	Investestigating the role of EMB guided by electroanatomical map in diagnosis
Diagnostic yield of EMB guided by electroanatomical map in overlapping and/or undefined phenotypes	At 30 years	Investestigating the role of EMB guided by electroanatomical map in diagnosis
Diagnostic performance of CT scan and/or PET in NICMs, especially when CMR is not feasible	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Comparison between CMR/CT scan/PET/EAM findings (including fusion imaging) and advanced imaging techniques at echocardiogram in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Analysis of association between M-Infl and arrhythmogenic substrates (cause, types, localization, extension, features, outcomes, response to treatment) in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Evaluation of healing timing of M-Infl in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Association between substrate abnormalities localizations (as assessed by second level imaging techniques) and arrhythmias (type, characteristics and origin site) in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Analysis of association between arrhythmia and inflammation type/features with any other diagnostic exam performed at baseline or during FU	At 30 years	The diagnostic exams mainly include EMB, CMR/CT scan/PET, echocardiogram, stress tests, blood exams, genetic/blood/tissue/cell/molecular/multiomic biomarkers. This analysis regards but not limits to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Analysis of diagnostic accuracy (sensitivity, specificity, positive and negative predictive values) and safety in different diagnostic techniques (EMB, CMR, CT scan, PET; EAM) in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Prevalence of genetic variants (pathogenic, likely-pahogenic, of unknown significance) in NICMs showing distinct arrhythmic phenotypes, M-Infl and scar patterns	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Genotype-phenotype correlations, as assessed by multimodal and multiparametric diagnostic workup in NICMs (i.e. analysis of association between genotypes and distinct imaging/electrocardiographic/inflammatory/laboratory patterns in patients with NICMs)	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Evaluation of coronary microvascular disease in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Assessment of myocardial ischemia in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Assessment of autoimmunity in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Identification of any abnormality (genetic, histological, circulating) involving the intercalated disks as known arrhythmogenic players in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Assessment of hemodynamic changes in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Multimodal multiparametric imaging investigation of NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Evaluation of differential diagnosis between NICMs and other cardiac diseases	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Identification of biomarkers of inflammatory stage (acute vs. chronic; active vs. previous) in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Analysis of correlation between local and systemic/peripheral inflammation in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Analysis of the concordance/discordance between the diagnostic findings observed in NICMs by means of distinct techniques, namely EMB and imaging (CMR, CT scan, PET, EAM, echocardiogram)	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Investigation of infectious, toxicologic, and immunologic factors associated with NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Diagnostic value of extracardiac diagnostic techniques in NICMs	At 30 years	NICMs include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Occurrence of minor events in DCM	At 30 years	non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Occurrence of minor events in HCM	At 30 years	non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Occurrence of minor events in RCM	At 30 years	non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Occurrence in minor events in RCM	At 25 years	non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Occurrence of minor events in ACM	At 30 years	non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Occurrence of minor events in distinct cardiomyopathic phenotypes that have been described in some diseases	At 30 years	left ventricular noncompaction (LVNC), arrhythmogenic mitral valve prolapse (AMVP), peripartum cardiomyopathy (PPCM), Anderson-Fabry disease (AFD), storage and dysmetabolic diseases, mitochondrial diseases, channelopathies with structural changes, and cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases. Minor events include non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Occurrence of minor events in distinct cardiomyopathic phenotypes have been described in some diseases	At 5 years	left ventricular noncompaction (LVNC), arrhythmogenic mitral valve prolapse (AMVP), peripartum cardiomyopathy (PPCM), Anderson-Fabry disease (AFD), storage and dysmetabolic diseases, mitochondrial diseases, channelopathies with structural changes, and cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases. Minor events include non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Occurrence of minor events in overlapping and undefined phenotypes	At 30 years	non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Identification of biomarkers associated with treatment response for NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Identification of cost-effective multimodal and multiparametric risk scores for NICMs	At 30 years	These risk scores will be aimed but not limit to obtain the maximal capability of discriminating heterogeneous outcomes by means of the minimal number of predictors and/or the minimal number of exams and/or the chepest/safest exams. NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Assessment of the prognostic value of arrhythmias in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Assessment of the predictive value of electrophysiological study and electroanatomical arrhythmogenic substrates in risk stratification of NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Assessment of the prognostic value of M-Infl in NICMs, i.e. association with major events	At 30 years	Major events include all-cause death, cardiac death, extra-cardiac disease related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Validation of the reproducibility of existing risk factors and risk stratification scores for NICMs in a real-world population, i.e. verification of their role in predicting major events	At 30 years	Major events include all-cause death, cardiac death, extra-cardiac disease related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Refinement of risk factors and risk stratification scores for NICMs, i.e. working out of models integrating known and new risk factors for the prediction of major events	At 30 years	Major events include all-cause death, cardiac death, extra-cardiac disease related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Elaboration of new risk scores for NICMs, also based on modern technologies of machine learning and artificial intelligence, by identifying the most effective combination of prognostic variables capable of predicting major events	At 30 years	Major events include all-cause death, cardiac death, extra-cardiac disease related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Validation of new models in control patient cohorts, i.e. verification of their role in predicting major events	At 30 years	Major events include all-cause death, cardiac death, extra-cardiac disease related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Assessment of epidemiology signatures in DCM	At 30 years
Assessment of epidemiology signatures in HCM	At 30 years
Assessment of epidemiology signatures in RCM	At 30 years
Assessment of epidemiology signatures in ACM	At 30 years
Assessment of epidemiology signatures in LVNC	At 30 years
Assessment of epidemiology signatures in AMVP	At 30 years
Assessment of epidemiology signatures in PPCM	At 30 years
Assessment of epidemiology signatures in AFD	At 30 years
Assessment of epidemiology signatures in storage and dysmetabolic diseases	At 30 years
Assessment of epidemiology signatures in mitochondrial diseases	At 30 years
Assessment of epidemiology signatures in channelopathies with structural changes	At 30 years
Assessment of epidemiology signatures in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years
Assessment of epidemiology signatures in overlapping and undefined phenotypes	At 30 years
Assessment of etiology signatures in DCM	At 30 years
Assessment of etiology signatures in HCM	At 30 years
Assessment of etiology signatures in RCM	At 30 years
Assessment of etiology signatures in ACM	At 30 years
Assessment of etiology signatures in LVNC	At 30 years
Assessment of etiology signatures in AMVP	At 30 years
Assessment of etiology signatures in PPCM	At 30 years
Assessment of etiology signatures in AFD	At 30 years
Assessment of etiology signatures in storage and dysmetabolic diseases	At 30 years
Assessment of etiology signatures in mitochondrial diseases	At 30 years
Assessment of etiology signatures in channelopathies with structural changes	At 30 years
Evaluation of efficacy of treatment, defined based on the incidence of minor events during follow-up in AMVP Efficacy of pharmacological antiarrhythmic treatment on major and minor events	At 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Evaluation of efficacy of treatment, defined based on the incidence of minor events during follow-up in PPCM Efficacy of pharmacological antiarrhythmic treatment on major and minor events	At 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Evaluation of efficacy of treatment, defined based on the incidence of minor events during follow-up in AFD Efficacy of pharmacological antiarrhythmic treatment on major and minor events	At 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Evaluation of efficacy of treatment, defined based on the incidence of minor events during follow-up in storage and dysmetabolic diseases Efficacy of pharmacological antiarrhythmic treatment on major and minor events	At 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Evaluation of efficacy of treatment, defined based on the incidence of minor events during follow-up in mitochondrial diseases Efficacy of pharmacological antiarrhythmic treatment on major and minor events	At 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Evaluation of efficacy of treatment, defined based on the incidence of minor events during follow-up in channelopathies with structural changes Efficacy of pharmacological antiarrhythmic treatment on major and minor events	At 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Evaluation of efficacy of pharmacological antiarrhythmic treatment on major and minor events in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Evaluation of efficacy of treatment, defined based on the incidence of minor events during follow-up in overlapping and undefined phenotypes Efficacy of pharmacological antiarrhythmic treatment on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatment on arrhythmic and inflammatory outcomes, as well as on major and minor events in DCM	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatment on arrhythmic and inflammatory outcomes, as well as on major and minor events in HCM	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatment on arrhythmic and inflammatory outcomes, as well as on major and minor events in RCM	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatment on arrhythmic and inflammatory outcomes, as well as on major and minor events in ACM	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatment on arrhythmic and inflammatory outcomes, as well as on major and minor events in LVNC	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatment on arrhythmic and inflammatory outcomes, as well as on major and minor events in AMVP	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatment on arrhythmic and inflammatory outcomes, as well as on major and minor events in PPCM	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatment on arrhythmic and inflammatory outcomes, as well as on major and minor events in AFD	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatment on arrhythmic and inflammatory outcomes, as well as on major and minor events in storage and dysmetabolic diseases, mitochondrial diseases, channelopathies with structural changes	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatment on arrhythmic and inflammatory outcomes, as well as on major and minor events in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatment on arrhythmic and inflammatory outcomes, as well as on major and minor events in overlapping and undefined phenotypes	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Identification of criteria for device implants (PM, ICD, S-ICD, CRT-D...) in NICMs patients	By 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Identification of the most suitable therapeutic strategies based on indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes	By 30 years	This applies to NICM patients with supraventricular arrhythmias, bradyarrhythmias, or ventricular arrhythmias, with or without M-Inf. NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Identification of the best candidates to multidisciplinary management of NICMs	By 30 years	by identification of the subgroups of patients showing the maximal effects (i.e. lowest incidence of major and minor adverse events) and the minimal risks (i.e. lowest incidence of side effects) following application of multidisciplinary care. NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Indication and timing for device (ICD, CRT-D) implant in primary prevention, based on multidisciplinary, multimodal, multiparametric risk assessment in NICMs, and in relation to different general and etiology-dependent treatments	By 30 years	by identification of the subgroups of patients showing the maximal effects (i.e. lowest incidence of major and minor adverse events) and the minimal risks (i.e. lowest incidence of side effects) following application of multidisciplinary care. NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Efficacy of multidisciplinary patient - tailored approach for the management of inflammation and comorbidities in DCM patients, i.e. effects on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of multidisciplinary patient - tailored approach for the management of inflammation and comorbidities in HCM patients, i.e. effects on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of multidisciplinary patient - tailored approach for the management of inflammation and comorbidities in RCM patients, i.e. effects on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of multidisciplinary patient - tailored approach for the management of inflammation and comorbidities in PPCM patients, i.e. effects on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of multidisciplinary patient - tailored approach for the management of inflammation and comorbidities in AMVP patients, i.e. effects on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of multidisciplinary patient - tailored approach for the management of inflammation and comorbidities in AFD patients, i.e. effects on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of multidisciplinary patient - tailored approach for the management of inflammation and comorbidities in storage and dysmetabolic diseases patients, i.e. effects on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of multidisciplinary patient - tailored approach for the management of inflammation and comorbidities in mitochondrial diseases patients, i.e. effects on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of multidisciplinary patient - tailored approach for the management of inflammation and comorbidities in cardiomyopathies associated with overlapping and undefined phenotypes patients, i.e. effects on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of support treatment, optimal cardiological treatment, and treatment options for heart failure in DCM patients, , i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of support treatment, optimal cardiological treatment, and treatment options for heart failure in RCM patients, , i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of support treatment, optimal cardiological treatment, and treatment options for heart failure in ACM patients, , i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of support treatment, optimal cardiological treatment, and treatment options for heart failure in LVNC patients, , i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of support treatment, optimal cardiological treatment, and treatment options for heart failure in AMVP patients, , i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of support treatment, optimal cardiological treatment, and treatment options for heart failure in PPCM patients, , i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of support treatment, optimal cardiological treatment, and treatment options for heart failure in AFD patients, , i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of support treatment, optimal cardiological treatment, and treatment options for heart failure in storage and dysmetabolic diseases patients, , i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of support treatment, optimal cardiological treatment, and treatment options for heart failure in mitochondrial diseases patients, , i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of support treatment, optimal cardiological treatment, and treatment options for heart failure in channelopathies with structural change patients, , i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of support treatment, optimal cardiological treatment, and treatment options for heart failure in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases patients, , i.e. effects on major and minor events	By 30 years	Analysis of safety, i.e. incidence of adverse reactions. Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of support treatment, optimal cardiological treatment, and treatment options for heart failure in overlapping and undefined phenotypes patients, , i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of immunomodulatory, immunosuppressive and anti-inflammatory therapy, including biological targeted therapy in DCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of immunomodulatory, immunosuppressive and anti-inflammatory therapy, including biological targeted therapy in RCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of immunomodulatory, immunosuppressive and anti-inflammatory therapy, including biological targeted therapy in AMVP i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of immunomodulatory, immunosuppressive and anti-inflammatory therapy, including biological targeted therapy in PPCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of immunomodulatory, immunosuppressive and anti-inflammatory therapy, including biological targeted therapy in AFD i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of immunomodulatory, immunosuppressive and anti-inflammatory therapy, including biological targeted therapy in mitochondrial diseases i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of immunomodulatory, immunosuppressive and anti-inflammatory therapy, including biological targeted therapy in storage and dysmetabolic diseases i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of immunomodulatory, immunosuppressive and anti-inflammatory therapy, including biological targeted therapy in channelopathies with structural changes i.e. effects on major and minor events.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes). Analysis of safety, i.e. incidence of adverse reactions. Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of immunomodulatory, immunosuppressive and anti-inflammatory therapy, including biological targeted therapy in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases i.e. effects on major and minor events.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes). Analysis of safety, i.e. incidence of adverse reactions. Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of immunomodulatory, immunosuppressive and anti-inflammatory therapy, including biological targeted therapy in overlapping and undefined phenotypes i.e. effects on major and minor events.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes). Analysis of safety, i.e. incidence of adverse reactions. Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology -specific treatments, including those aimed to target extra - cardiac disease manifestations in DCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatments, including those aimed to target extra-cardiac disease manifestations in HCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatments, including those aimed to target extra-cardiac disease manifestations in RCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatments, including those aimed to target extra-cardiac disease manifestations in ACM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatments, including those aimed to target extra-cardiac disease manifestations in LVNC i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatments, including those aimed to target extra-cardiac disease manifestations in AMVP i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatments, including those aimed to target extra-cardiac disease manifestations in PPCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatments, including those aimed to target extra-cardiac disease manifestations in mitochondrial diseases i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatments, including those aimed to target extra-cardiac disease manifestations in channelopathies with structural changes i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatments, including those aimed to target extra-cardiac disease manifestations in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases i.e. effects on major and minor events.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Analysis of safety, i.e. incidence of adverse reactions. Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of replacement therapy, molecular therapy, gene therapy in HCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of replacement therapy, molecular therapy, gene therapy in RCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of replacement therapy, molecular therapy, gene therapy in ACM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of replacement therapy, molecular therapy, gene therapy in LVNC i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of replacement therapy, molecular therapy, gene therapy in AFD i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of replacement therapy, molecular therapy, gene therapy in storage and dysmetabolic diseases, mitochondrial diseases i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of replacement therapy, molecular therapy, gene therapy in channelopathies with structural changes i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of replacement therapy, molecular therapy, gene therapy in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of replacement therapy, molecular therapy, gene therapy in overlapping and undefined phenotypes i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of heart transplantation and other treatment for end-stage heart failure in DCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of heart transplantation and other treatment for end-stage heart failure in HCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of heart transplantation and other treatment for end-stage heart failure in RCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of heart transplantation and other treatment for end-stage heart failure in PPCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of heart transplantation and other treatment for end-stage heart failure in AFD i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of heart transplantation and other treatment for end-stage heart failure in storage and dysmetabolic diseases, mitochondrial diseases i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of heart transplantation and other treatment for end-stage heart failure in channelopathies with structural changes i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of heart transplantation and other treatment for end-stage heart failure in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases i.e. effects on major and minor events.	By 30 years	Analysis of safety, i.e. incidence of adverse reactions. Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of heart transplantation and other treatment for end-stage heart failure in overlapping and undefined phenotypes i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of surgical or hemodynamic procedures in DCM, i.e. effects on major and minor event i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of surgical or hemodynamic procedures in HCM, i.e. effects on major and minor event i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of surgical or hemodynamic procedures in RCM, i.e. effects on major and minor event i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of surgical or hemodynamic procedures in ACM, i.e. effects on major and minor event i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of surgical or hemodynamic procedures in LVNC, i.e. effects on major and minor event i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of surgical or hemodynamic procedures in AMVP, i.e. effects on major and minor event i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of surgical or hemodynamic procedures in PPCM, i.e. effects on major and minor event i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of surgical or hemodynamic procedures in AFD, i.e. effects on major and minor event i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of surgical or hemodynamic procedures in storage and dysmetabolic diseases, mitochondrial diseases, i.e. effects on major and minor event i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of surgical or hemodynamic procedures in channelopathies with structural changes, i.e. effects on major and minor event i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Invasive and noninvasive investigation of arrhythmogenic substrates in NICMs	At 30 years	NICMs include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Investigation of ablation of cardiac arrhythmias (indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) in NICMs	By 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Role of ablation (any technique) on arrhythmic outcomes in NICMs, in all patients, as well as in subgroups with and without arrhythmias and MInfl	By 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Indications and optimal timing for any electrophysiological or interventional procedures in HCM, i.e. comparison of incidence of major and minor events in patients undergoing treatment at different timings	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Indications and optimal timing for any electrophysiological or interventional procedures in ACM, i.e. comparison of incidence of major and minor events in patients undergoing treatment at different timings	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Indications and optimal timing for any electrophysiological or interventional procedures in LVNC, i.e. comparison of incidence of major and minor events in patients undergoing treatment at different timings	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Indications and optimal timing for any electrophysiological or interventional procedures in AMVP, i.e. comparison of incidence of major and minor events in patients undergoing treatment at different timings	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Indications and optimal timing for any electrophysiological or interventional procedures in PPCM, i.e. comparison of incidence of major and minor events in patients undergoing treatment at different timings	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Indications and optimal timing for any electrophysiological or interventional procedures in AFD, i.e. comparison of incidence of major and minor events in patients undergoing treatment at different timings	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Indications and optimal timing for any electrophysiological or interventional procedures in storage and dysmetabolic diseases, i.e. comparison of incidence of major and minor events in patients undergoing treatment at different timings	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Indications and optimal timing for any electrophysiological or interventional procedures in mitochondrial diseases, i.e. comparison of incidence of major and minor events in patients undergoing treatment at different timings	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Indications and optimal timing for any electrophysiological or interventional procedures in channelopathies with structural changes, i.e. comparison of incidence of major and minor events in patients undergoing treatment at different timings	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Indications and optimal timing for any electrophysiological or interventional procedures rheumatologic or neuromuscular diseases	By 30 years	i.e. comparison of incidence of major and minor events in patients undergoing treatment at different timings. Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Indications and optimal timing for any electrophysiological or interventional procedures in overlapping and undefined phenotypes, i.e. comparison of incidence of major and minor events in patients undergoing treatment at different timings	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Assessment of etiology signatures in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years
Assessment of etiology signatures in overlapping and undefined phenotypes	At 30 years
Assessment of pathophysiology signatures in DCM	At 30 years
Assessment of pathophysiology signatures in HCM	At 30 years
Assessment of pathophysiology signatures in RCM	At 30 years
Assessment of pathophysiology signatures in ACM	At 30 years
Assessment of pathophysiology signatures in LVNC	At 30 years
Assessment of pathophysiology signatures in AMVP	At 30 years
Assessment of pathophysiology signatures in PPCM	At 30 years
Assessment of pathophysiology signatures in AFD	At 30 years
Assessment of pathophysiology signatures in storage and dysmetabolic diseases	At 30 years
Assessment of pathophysiology signatures in mitochondrial diseases	At 30 years
Assessment of pathophysiology signatures in channelopathies with structural changes	At 5 years
Assessment of genotype-phenotype signatures in HCM	At 30 years
Assessment of genotype-phenotype signatures in RCM	At 30 years
Assessment of genotype-phenotype signatures in channelopathies with structural changes	At 30 years
Assessment of genotype-phenotype signatures in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years
Assessment of genotype-phenotype signatures in overlapping and undefined phenotypes	At 30 years
Assessment of arrhythmia signatures in DCM	At 30 years
Assessment of arrhythmia signatures in HCM	At 5 years
Assessment of arrhythmia signatures in RCM	Every 10 years
Assessment of arrhythmia signatures in ACM	Every 30 years
Assessment of arrhythmia signatures in LVNC	At 30 years
Assessment of arrhythmia signatures in AMVP	At 30 years
Assessment of arrhythmia signatures in PPCM	At 30 years
Assessment of arrhythmia signatures in AFD	At 30 years
Assessment of arrhythmia signatures in storage and dysmetabolic diseases	At 30 years
Assessment of arrhythmia signatures in mitochondrial diseases	At 30 years
Assessment of arrhythmia signatures in channelopathies with structural changes	At 30 years
Assessment of arrhythmia signatures in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years
Assessment of arrhythmia signatures in overlapping and undefined phenotype	At 30 years
Assessment of M-Infl signatures in DCM	At 30 years
Assessment of M-Infl signatures in HCM	At 30 years
Assessment of M-Infl signatures in ACM	At 30 years
Assessment of M-Infl signatures in LVNC	At 30 years
Assessment of M-Infl signatures in storage and dysmetabolic diseases	At 30 years
Assessment of M-Infl signatures in mitochondrial diseases	At 30 years
Assessment of M-Infl signatures in channelopathies with structural changes	At 30 years
Assessment of M-Infl signatures in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years
Assessment of M-Infl signatures in overlapping and undefined phenotypes	At 30 years
Assessment of extracardiac signatures in DCM	At 30 years
Assessment of extracardiac signatures in HCM	At 30 years
Assessment of extracardiac signatures in ACM	At 30 years
Assessment of extracardiac signatures in LVNC	At 30 years
Assessment of extracardiac signatures in AMVP	At 30 years
Assessment of extracardiac signatures in PPCM	At 30 years
Assessment of extracardiac signatures in AFD	At 30 years
Assessment of extracardiac signatures in storage and dysmetabolic diseases	At 30 years
Assessment of extracardiac signatures in mitochondrial diseases	At 30 years
Assessment of extracardiac signatures in channelopathies with structural changes	At 30 years
Assessment of extracardiac signatures in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years
Assessment of extracardiac signatures in overlapping and undefined phenotypes	At 30 years
Assessment of multidisciplinary, multimodal, multiparametric diagnostic signatures in DCM	At 30 years
Assessment of multidisciplinary, multimodal, multiparametric diagnostic signatures in HCM	At 30 years
Assessment of multidisciplinary, multimodal, multiparametric diagnostic signatures in RCM	At 30 years
Assessment of multidisciplinary, multimodal, multiparametric diagnostic signatures in ACM	At 30 years
Assessment of multidisciplinary, multimodal, multiparametric diagnostic signatures in storage and dysmetabolic diseases, mitochondrial diseases, channelopathies with structural changes	At 30 years
Assessment of multidisciplinary, multimodal, multiparametric diagnostic signatures in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years
Assessment of multidisciplinary, multimodal, multiparametric diagnostic signatures in overlapping and undefined phenotypes	At 30 years
Assessment of laboratory, tissue, cell, metabolic or multiomic signatures in DCM	At 30 years
Assessment of laboratory, tissue, cell, metabolic or multiomic signatures in HCM	At 30 years
Assessment of laboratory, tissue, cell, metabolic or multiomic signatures in ACM	At 30 years
Assessment of laboratory, tissue, cell, metabolic or multiomic signatures in LVNC	At 30 years
Assessment of laboratory, tissue, cell, metabolic or multiomic signatures in AMVP	At 30 years
Assessment of laboratory, tissue, cell, metabolic or multiomic signatures in AFD	At 30 years
Assessment of laboratory, tissue, cell, metabolic or multiomic signatures in storage and dysmetabolic diseases, mitochondrial diseases, channelopathies with structural changes	At 30 years
Assessment of laboratory, tissue, cell, metabolic or multiomic signatures in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years
Assessment of laboratory, tissue, cell, metabolic or multiomic signatures in overlapping and undefined phenotypes	At 30 years
Assessment of prognostic signatures in DCM	At 30 years
Assessment of prognostic signatures in HCM	At 30 years
Assessment of prognostic signatures in RCM	At 30 years
Assessment of prognostic signatures in ACM	At 30 years
Assessment of prognostic signatures in LVNC	At 30 years
Assessment of prognostic signatures in AMVP	At 30 years
Assessment of prognostic signatures in PPCM	At 30 years
Assessment of prognostic signatures in AFD	At 30 years
Assessment of prognostic signatures in storage and dysmetabolic diseases, mitochondrial diseases, channelopathies with structural changes, and cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years
Assessment of prognostic signatures in overlapping and undefined phenotypes	At 30 years
Assessment of response to treatment signatures in DCM	At 30 years
Assessment of response to treatment signatures in HCM	At 30 years
Assessment of response to treatment signatures in RCM	At 30 years
Assessment of response to treatment signatures in ACM	At 30 years
Assessment of response to treatment signatures in LVNC	At 30 years
Assessment of response to treatment signatures in AMVP	At 30 years
Assessment of response to treatment signatures in PPCM	At 30 years
Assessment of response to treatment signatures in AFD	At 30 years
Evaluation of efficacy of treatment, defined based on the incidence of minor events during follow-up in DCM Efficacy of pharmacological antiarrhythmic treatment on major and minor events	At 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Assessment of pathophysiology signatures in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years
Assessment of pathophysiology signatures in overlapping and undefined phenotypes	At 30 years
Assessment of genotype-phenotype signatures in DCM	At 30 years
Assessment of genotype-phenotype signatures in ACM	At 30 years
Assessment of genotype-phenotype signatures in LVNC	At 30 years
Assessment of genotype-phenotype signatures in AMVP	At 30 years
Assessment of genotype-phenotype signatures in PPCM	At 30 years
Assessment of genotype-phenotype signatures in AFD	At 30 years
Assessment of genotype-phenotype signatures in storage and dysmetabolic diseases	At 30 years
Assessment of genotype-phenotype signatures in mitochondrial diseases	At 30 years
Assessment of M-Infl signatures in RCM	At 30 years
Assessment of M-Infl signatures in AMVP	At 30 years
Assessment of M-Infl signatures in PPCM	At 30 years
Assessment of M-Infl signatures in AFD	At 30 years
Assessment of extracardiac signatures in RCM	At 30 years
Assessment of laboratory, tissue, cell, metabolic or multiomic signatures in RCM	At 30 years
Assessment of laboratory, tissue, cell, metabolic or multiomic signatures in PPCM	At 30 years
Assessment of response to treatment signatures in storage and dysmetabolic diseases, mitochondrial diseases, channelopathies with structural changes, and cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years
Assessment of response to treatment signatures in overlapping and undefined phenotypes	At 30 years
Prevalence of inflammatory activity (presence; type; quantification; pattern) in undefined phenotypes	At 30 years	presence; type; quantification; pattern
Assessment of abnormalities in myocardial structure, function, perfusion, and metabolism in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Assessment of non-ischemic myocardial fibrotic scar (presence; type; quantification; pattern; distribution; extension) in NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, dysmetabolic, mitochondrial, toxic, neuromuscular, rheumatological/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Description of the natural history of overall and specific forms of NICM, showing distinct arrhythmic phenotypes, M-Infl and scar patterns.	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Identification of prognostic genetic, circulatory, tissue, cellular, metabolic, molecular, immunologic or multiomic biomarkers for NICMs	At 30 years	NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Evaluation of efficacy of treatment, defined based on the incidence of minor events during follow-up in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases	At 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of multidisciplinary patient - tailored approach for the management of inflammation and comorbidities in ACM patients, i.e. effects on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of multidisciplinary patient - tailored approach for the management of inflammation and comorbidities in LVNC patients, i.e. effects on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of multidisciplinary patient - tailored approach for the management of inflammation and comorbidities in channelopathies with structural changes patients, i.e. effects on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of multidisciplinary patient - tailored approach for the management of inflammation and comorbidities in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases patients, i.e. effects on major and minor events	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of support treatment, optimal cardiological treatment, and treatment options for heart failure in HCM patients, , i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of immunomodulatory, immunosuppressive and anti-inflammatory therapy, including biological targeted therapy in HCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of immunomodulatory, immunosuppressive and anti-inflammatory therapy, including biological targeted therapy in ACM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of immunomodulatory, immunosuppressive and anti-inflammatory therapy, including biological targeted therapy in LVNC i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatments, including those aimed to target extra-cardiac disease manifestations in AFD i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatments, including those aimed to target extra-cardiac disease manifestations in storage and dysmetabolic diseases i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of etiology-specific treatments, including those aimed to target extra-cardiac disease manifestations in overlapping and undefined phenotypes i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of replacement therapy, molecular therapy, gene therapy in DCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of replacement therapy, molecular therapy, gene therapy in AMVP i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of replacement therapy, molecular therapy, gene therapy in PPCM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of heart transplantation and other treatment for end-stage heart failure in ACM i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of heart transplantation and other treatment for end-stage heart failure in LVNC i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of heart transplantation and other treatment for end-stage heart failure in AMVP i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of surgical or hemodynamic procedures in cardiomyopathies associated with systemic rheumatologic or neuromuscular diseases, i.e. effects on major and minor event i.e. effects on major and minor events.	By 30 years	Analysis of safety, i.e. incidence of adverse reactions. Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Efficacy of surgical or hemodynamic procedures in overlapping and undefined phenotypes, i.e. effects on major and minor event i.e. effects on major and minor events. Analysis of safety, i.e. incidence of adverse reactions.	By 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Investigation of cardiac device implant in primary and secondary prevention, in all patients, as well as in subgroups with and without M-Infl in NICMs	By 30 years	(indications, patient selection, timing, risk-to-benefit ratio, side effects, duration, challenges, relationships with outcomes) NICMs will include but not limit to: DCM, HCM, RCM, ACM, inflammatory, infiltrative, toxic, dysmetabolic, mitochondrial, neuromuscular, rheumatologic/autoimmune cardiomyopathies, channelopathies with structural substrates, LVNC, PPCM, AMVP, AFD, athlete's heart, undefined and overlap cardiomyopathies. Additional diseases of the NICM spectrum will be included in parallel with the advance of the current knowledge.
Evaluation of efficacy of treatment, defined based on the incidence of minor events during follow-up in HCM Efficacy of pharmacological antiarrhythmic treatment on major and minor events	At 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Evaluation of efficacy of treatment, defined based on the incidence of minor events during follow-up in RCM Efficacy of pharmacological antiarrhythmic treatment on major and minor events	At 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Evaluation of efficacy of treatment, defined based on the incidence of minor events during follow-up in ACM Efficacy of pharmacological antiarrhythmic treatment on major and minor events	At 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.
Evaluation of efficacy of treatment, defined based on the incidence of minor events during follow-up in LVNC Efficacy of pharmacological antiarrhythmic treatment on major and minor events	At 30 years	Major events: all-cause death, cardiac death, extra-cardiac disease-related death, major ventricular arrhythmias (ventricular tachycardia, fibrillation, appropriate ICD therapy), advanced atrioventricular blocks, heart transplantation, end-stage heart failure, disease-related hospitalizations, left/right ventricular systolic dysfunction, presence/persistence/clearance/recurrence of M-Infl. Minor events: non-sustained ventricular arrhythmias, supraventricular arrhythmias, other bradyarrhythmias, any structural/functional myocardial abnormality detectable by multimodal diagnostic workup, abnormal laboratory, tissue or multiomic biomarkers, all-cause hospitalizations, disease costs, complications related to disease management, extra-cardiac disease-related non-fatal endpoints.

Trial Locations

Locations (1): IRCCS San Raffaele Scientific Institute
🇮🇹
Milan, Milano, Italy
IRCCS San Raffaele Scientific Institute
🇮🇹Milan, Milano, Italy
Giovanni Peretto, MD
Contact
+39 0226437482
peretto.giovanni@hsr.it
Simone Sala, MD
Contact
+39 0226437483
sala.simone@hsr.it

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Multimodal and Multidisciplinary Approach to Optimize Diagnostic, Prognostic, and Therapeutic Management of Patients with Non-ischemic Cardiomyopathies and Arrhythmogenic-inflammatory Phenotypes: a Multicenter, Observational, Retrospective and Prospective Registry Study.

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