Image-Based Prediction of Ventricular Tachycardia Events in Non-ischemic Cardiomyopathy

NCT ID: NCT06730464

Last Updated: 2024-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2024-10-07

Study Completion Date

2027-02-23

Brief Summary

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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

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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)

Conditions

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Dilated Cardiomyopathy Arrhythmogenic Cardiomyopathy Ventricular Arrhythmia Hypertrophic Cardiomyopathies

Keywords

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Dilated cardiomyopathy Non-dilated left ventricular cardiomyopathy (NDLVC) border zone channels ventricular arrhythmias

Study Design

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Observational Model Type

COHORT

Study Time Perspective

OTHER

Study Groups

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Patients with non ischemic cardiomyopathies

Patients will only be recruited if they fulfill ALL the inclusion criteria:

1. Age \> 18 years.
2. 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
3. Life expectancy of \> 1 year with a good functional status.
4. Signed informed consent.
5. CMR already performed or scheduled for clinical purpose (standard clinical practice).
6. No VA events at the time of the 1st LGE-CMR study.

No interventions assigned to this group

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Humanitas Research Hospital IRCCS, Rozzano-Milan

OTHER

Sponsor Role collaborator

Hospital de La Luz

OTHER

Sponsor Role collaborator

Hospitales Universitarios Virgen del Rocio

UNKNOWN

Sponsor Role collaborator

Centro Medico Teknon

OTHER

Sponsor Role lead

Responsible Party

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Antonio Berruezo, MD, PhD

Head of Arrhythmia Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Humanitas Research Hospital (Rozzano - Milan, Italy)

Milan, Italy, Italy

Site Status RECRUITING

Hospital de la Luz

Lispon, Portugal, Portugal

Site Status RECRUITING

Teknon Medical Center

Barcelona, Barcelona, Spain

Site Status RECRUITING

Virgen del Rocio University Hospital

Seville, Sevilla, Spain

Site Status RECRUITING

Countries

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Italy Portugal Spain

Facility Contacts

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Diego Penela, MD, PhD

Role: primary

Antonio Miguel Ferreira, MD, PhD

Role: primary

Antonio Berruezo, MD, PhD

Role: primary

Juan Acosta, MD, PhD

Role: primary

References

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Other Identifiers

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IMPROVE-NICM

Identifier Type: -

Identifier Source: org_study_id