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

NCT06730464 | Recruiting DMC

• 1 other identifier: IMPROVE-NICM
• Study Type: observational
• Target: 500
• Locations: 3 countries
• Sites: 4

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).

Conditions

Dilated Cardiomyopathy; Arrhythmogenic Cardiomyopathy; Ventricular Arrhythmia; Hypertrophic Cardiomyopathies

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of patients presenting one of sudden cardiac death, sustained ventricular arrhythmia, or defibrillator therapy.

  The primary endpoint will be the clinical composite of sudden cardiac death, or any sustained ventricular arrhythmia, or defibrillator therapy

  From the inclusion date (first CMR date) up to 100 months

Study Arms (1)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with dilated cardiomyopathy (DCM) or Non-dilated left ventricular cardiomyopathy (NDLVC) or Post-myocarditis cardiomyopathy

You may qualify if:

• Diagnosis of non-ischemic heart disease involving the left ventricle, irrespectively of LVEF. This diagnosis includes:
• Dilated cardiomyopathy (DCM)
• Non-dilated left ventricular cardiomyopathy (NDLVC)
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centro Medico Teknon: lead
• Humanitas Research Hospital IRCCS, Rozzano-Milan: collaborator
• Hospital de La Luz: collaborator
• Hospitales Universitarios Virgen del Rocio: collaborator

Study Sites (4)

Humanitas Research Hospital (Rozzano - Milan, Italy)

Milan, Italy, 20089, Italy

RECRUITING

Hospital de la Luz

Lispon, Portugal, 1500-650, Portugal

RECRUITING

Teknon Medical Center

Barcelona, Barcelona, 08022, Spain

RECRUITING

Virgen del Rocio University Hospital

Seville, Sevilla, 41013, Spain

RECRUITING

Related Publications (15)

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MeSH Terms

Conditions

Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Arrhythmia Department

Study Record Dates

• First Submitted: December 2, 2024
• First Posted: December 12, 2024
• Study Start: October 7, 2024
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): February 23, 2027
• Last Updated: December 12, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); ES (2); PT (1)