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.

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.

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
• Inflammatory (Non-Arrhythmic) Non-ischemic Cardiomyopathy
• Nonischemic Cardiomyopathy Sensu Strictu (Non-inflammatory, Non-arrhythmic)
• Major Ventricular Arrhythmias, I.e. Sustained Ventricular Tachycardia, Ventricular Fibrillation, or Appropriate Therapy of Cardiac Device (defibrillators)
• Overlapping Phenotype
• Undefined Phenotypes

Interventions

OTHER

Support treatment, cardiac medical treatment, aetiology-specific treatment, device implant, arrhythmia ablation

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

OTHER

Support treatment, cardiac medical treatment, aetiology-specific treatment

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

Sponsors & Collaborators

• Scientific Institute San Raffaele

  lead OTHER

Principal Investigators

• Paolo Della Bella, MD · San Raffaele Scientific Institute, Milan, Italy

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-01-30

Primary Completion

2035-12-31

Completion

2035-12-31

Countries

• Italy

Study Locations