Clinical trial NCT06730607: Image-Based Prediction of Ventricular Tachycardias in Post-Myocarditis Patients: an International Multicenter Case-control Study
Official title: Image-Based Prediction of Ventricular Tachycardia Events in Post-Myocarditis Patients: an International Multicenter Case-control Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Myocarditis
Ventricular Arrhythmia
Keywords: myocarditis
ventricular arrhythmias
sudden cardiac death
cardiac magnetic resonance
Lead sponsor: Centro Medico Teknon
Sponsor class: OTHER
First posted: 2024-12-12
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with previous myocarditis and a cardiac magnetic resonance performed at least 6 months after the diagnosis

Brief summary: Ventricular arrhythmias (VAs) are frequently associated with structural heart diseases (SHD) such as myocardial infarction, myocarditis, and non-ischemic cardiomyopathies. Myocardial fibrotic tissue plays a central role in the genesis and the maintenance of re-entrant VAs associated with post-myocarditis sequelae and late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) has proven to be a useful tool for the non-invasive characterization of the scarred tissue and the underlying arrhythmogenic substrate. Moreover, a post-processing imaging platform named ADAS 3D LV (ADAS3D Medical SL, Barcelona, Spain) allows to analyze the CMR-derived data and to characterize the scar architecture, differentiating between dense (scar core zone) and more diffuse (border zone \[BZ\]) fibrosis, and identifying the BZ channels (BZCs) that are strands of healthy myocardial tissue within zones of unexcitable tissue and connect areas of normal myocardium. It was described that BZCs could serve as slow-conducting reentrant pathways and are critical to entail VA in ischemic and non-ischemic heart disease. However, the pathophysiological role and the correlation between scar architecture and VAs in post-myocarditis patients is yet to be defined.

To date, the standard-of-care evaluation for primary prevention implantable cardioverter-defibrillator (ICD) therapy is LVEF-based, leading to the fact that the contemporary rate of appropriated therapies is very low. Moreover, events may also occur in patients with normal to moderately depressed LVEF, which is particularly relevant, as it constitutes the most prevalent population of patients exposed to an increased risk of VAs. Multiple studies reported that LGE at CMR is a strong and specific predictor of VT occurrence and sudden death in post-myocarditis patients. There were reported cases in which even after the normalization of LVEF, the extension of LGE, the scar architecture, and the presence of BZCs at cMR analysis are determinants of the arrhythmic risk in post-myocarditis patients.

The Investigators sought to evaluate the usefulness of CMR-derived scar architecture analysis to predict the occurrence of VT events in an international, multicenter, case-control study on unselected post-myocarditis patients without previous arrhythmia evidence. Aim of the study is also to assess the net reclassification improvement (NRI) for the indication of primary prevention ICD implantation using CMR data and post-processing data as compared to LVEF-based indication

Detailed description: Research hypothesis

The composite outcome is:

* sudden cardiac death, sustained VT, syncopal VT or appropriate ICD therapy (ATP and/or shock) in ICD carriers in primary prevention, or
* sudden cardiac death, sustained VT, syncopal VT detected by any diagnostic test (i.e., 24 h Holter monitoring, prolonged Holter monitoring, urgency ECG etc.) in no ICD-carriers.

Our research hypothesis is that the composite outcome will be higher in those patients with greater scar mass and BZC mass.

Primary objective To analyze the composite outcome of sudden cardiac death or sustained ventricular tachycardia (either treated by an ICD or documented by any diagnostic method) in post-myocarditis patients with no previous arrhythmia evidence, according to their risk classification by means of BZC mass.

Secondary objectives

To analyze the relationship between the primary outcome and other variables:

* LVEF
* Scar mass
* BZ mass
* Core mass
* Presence and number of tissue channels within the scar, as detected by cardiac CT
* Age
* Time since myocarditis

Eligibility criteria: Inclusion Criteria:

1. Age \> 18 years.
2. Myocarditis diagnosis \> 6 months before the inclusion in the study.
3. Signed informed consent.
4. CMR performed \> 6 months after myocarditis diagnosis

Exclusion Criteria:

* Age \< 18 years.
* Pregnancy.
* Other concomitant structural heart diseases (e.g. congenital, non-ischemic, etc.)
* Active myocarditis
* Myocarditis diagnosis \< 6 months
* Previously documented sustained ventricular arrhythmias.
* Impossibility or contraindications to undergo LGE-CMR.
* Concomitant investigation treatments.
* Medical, geographical and social factors that make study participation impractical, and inability to give written informed consent. Patient's refusal to participate in the study.

Primary outcomes:
measure: Number of patients presenting one of sudden cardiac death, sustained ventricular arrhythmia, or defibrillator therapy.
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: Humanitas Research Hospital
state: Milan
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
city: Barcelona
country: Spain
facility: Teknon Medical Center
Study officials:
References:
citation: Acosta J, Fernandez-Armenta J, Borras R, Anguera I, Bisbal F, Marti-Almor J, Tolosana JM, Penela D, Andreu D, Soto-Iglesias D, Evertz R, Matiello M, Alonso C, Villuendas R, de Caralt TM, Perea RJ, Ortiz JT, Bosch X, Serra L, Planes X, Greiser A, Ekinci O, Lasalvia L, Mont L, Berruezo A. Scar Characterization to Predict Life-Threatening Arrhythmic Events and Sudden Cardiac Death in Patients With Cardiac Resynchronization Therapy: The GAUDI-CRT Study. JACC Cardiovasc Imaging. 2018 Apr;11(4):561-572. doi: 10.1016/j.jcmg.2017.04.021. Epub 2017 Aug 2.
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citation: Peretto G, Sala S, Rizzo S, Palmisano A, Esposito A, De Cobelli F, Campochiaro C, De Luca G, Foppoli L, Dagna L, Thiene G, Basso C, Della Bella P. Ventricular Arrhythmias in Myocarditis: Characterization and Relationships With Myocardial Inflammation. J Am Coll Cardiol. 2020 Mar 10;75(9):1046-1057. doi: 10.1016/j.jacc.2020.01.036.