Clinical trial NCT06730464: Image-Based Prediction of Ventricular Tachycardia Events in Non-ischemic Cardiomyopathy
Official title: Image-Based Prediction of Ventricular Tachycardia Events in Non-ischemic Cardiomyopathy, an International Multicenter Study - [The IMPROVE-NICM Study]
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Dilated Cardiomyopathy
Arrhythmogenic Cardiomyopathy
Ventricular Arrhythmia
Hypertrophic Cardiomyopathies
Keywords: Dilated cardiomyopathy
Non-dilated left ventricular cardiomyopathy (NDLVC)
border zone channels
ventricular arrhythmias
Lead sponsor: Centro Medico Teknon
Sponsor class: OTHER
Collaborators: name: Humanitas Research Hospital IRCCS, Rozzano-Milan
name: Hospital de La Luz
name: Hospitales Universitarios Virgen del Rocio
First posted: 2024-12-12
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with dilated cardiomyopathy (DCM) or Non-dilated left ventricular cardiomyopathy (NDLVC) or Post-myocarditis cardiomyopathy

Brief summary: Risk stratification for sudden cardiac death (SCD) in patients with non-ischemic cardiomyopathy (NICM) remains suboptimal. Although current guidelines rely on severe left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) \< 35%) as key predictor of arrhythmic risk and clinical indication of prophylactic implantable cardioverter defibrillator (ICD), this approach seems inadequate, since registries report that only a minority of NICM ICD carriers experience an appropriate ICD shock during follow-up, whereas out-of-hospital cardiac arrests (OHCA) occur in patients with LVEF\>35% in up to 80% of cases. Moreover, pivotal primary prevention trials (DANISH trial, long-term outcome of the SCD-HeFT trial) failed to demonstrate a net mortality benefit of ICD in patients with NICM.

As for most structural heart diseases (SHD), scar-related reentry has been addressed as the pathophysiological mechanism of ventricular arrhythmias (VAs) in patients with NICM, with fibrotic tissue being the substrate of this reentry. Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is the gold standard for the non-invasive visualization and characterization of the myocardial fibrosis and according to retrospective studies is detected in nearly 30% of patients with NICM.

In latest years, several studies and subsequent metanalyses have explored the correlation between CMR-detected LGE and occurrence of VAs, showing that presence, extent, location (septal vs lateral) and patten (focal vs multifocal vs ring-like) of non-ischemic fibrosis help in stratifying arrhythmic risk.

Nonetheless, scar heterogeneity (that is, inherent composition of dense scars vs border zone (BZ), presence of strands of viable myocardium within the scar) has been indicated as a potential novel predictor of VAs. In a recent prospective multicenter registry on patients with class I indication for cardiac resynchronization therapy (CRT) (\>60% with NICM), not only scar mass, but even border zone (BZ) mass and presence of BZ channels were identified as independent predictors for VT occurrence in NICM patients.

This BZ mass and BZ channels can be automatically identified using a commercially available, post-processing imaging platform named ADAS 3D LV (ADAS3D Medical SL, Barcelona, Spain), with FDA 510(k) Clearance and CE Mark approval. Thus, CMR-derived BZ mass might be used as an automatically reproducible criterium to reclassify those patients with NICM at highest risk for developing VAs/SCD in a relatively short period of at least 2 years.

In the present cohort study, the investigators sought to: i) evaluate the usefulness of CMR-derived BZ mass measurement and identification of heterogeneous tissue channels (HTC) (among other scar characteristics derived from image post-processing) to predict the occurrence of VT events in an international, retrospective, multicenter, unselected series of patients with NICM without previous arrhythmia evidence (main study); ii) subsequently validate these predictors of VT occurrence in a prospectively-collected multicenter cohort study (substudy 1); iii) retrospectively evaluate in the subset of patients with \> 1 LGE-CMR performed as part of standard clinical practice if any change in BZ mass and HTC presence occurs over time and if this correlates with occurrence of VAs (substudy 2).

Detailed description: Primary objective To analyze the composite outcome of SCD or sustained VT (either treated by an ICD or documented by any diagnostic method) in patients with NICM and no previous arrhythmia evidence, according to their risk classification by means of number of HCT and BZ mass.

Secondary objectives Substudy 1

To validate the variables retrospectively identified to be predictors of SCD or sustained VT in a prospective cohort of consecutively enrolled patients with NICM and no previous arrhythmia evidence.

Substudy 2 To retrospectively evaluate the evolution of scar characteristics over time and their prognostic implication in the subset of patients fulfilling eligibility criteria of the main project with at least 2 LGE-CMRs available as part of their clinical follow-up.

Main study, substudy 1 and 2

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

* LVEF
* Scar mass
* BZC mass
* Core mass
* Scar location
* Scar pattern
* Age
* Genotype (when this data is available)

Eligibility criteria: Inclusion Criteria:

* Diagnosis of non-ischemic heart disease involving the left ventricle, irrespectively of LVEF. This diagnosis includes:

  1. Dilated cardiomyopathy (DCM)
  2. Non-dilated left ventricular cardiomyopathy (NDLVC)
  3. Post-myocarditis cardiomyopathy
* Life expectancy of \> 1 year with a good functional status.
* Signed informed consent.
* At least one late gadolinium enhancement-cardiac magnetic resonance (LGE-CMR) already performed.
* No VA events at the time of the 1st LGE-CMR study.

Exclusion Criteria:

* Pregnancy.
* Life expectancy of \< 1 year, or bad functional status (NYHA IV functional class).
* Other concomitant structural heart diseases (e.g. ischemic, congenital, arrhythmogenic right ventricular cardiomyopathy etc.)
* No LGE-CMR at time of enrollment or LGE-CMR data not available.
* Previously documented sustained ventricular arrhythmias at the time of 1st 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: From the inclusion date (first CMR date) up to 100 months
Secondary outcomes:
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Humanitas Research Hospital (Rozzano - Milan, Italy)
city: Lispon
country: Portugal
facility: Hospital de la Luz
city: Barcelona
country: Spain
facility: Teknon Medical Center
city: Sevilla
country: Spain
facility: Virgen del Rocio University Hospital
Study officials:
References:
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