Image-Based Prediction of Ventricular Tachycardia Events in Non-ischemic Cardiomyopathy (IMPROVE-NICM)

December 8, 2024 updated by: Antonio Berruezo, MD, PhD, Centro Medico Teknon

Image-Based Prediction of Ventricular Tachycardia Events in Non-ischemic Cardiomyopathy, an International Multicenter Study - [The IMPROVE-NICM Study]

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).

Study Overview

Status

Recruiting

Conditions

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)

Study Type

Observational

Enrollment (Estimated)

500

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20089
        • Recruiting
        • Humanitas Research Hospital (Rozzano - Milan, Italy)
        • Contact:
  • Portugal
      • Lispon, Portugal, 1500-650
        • Recruiting
        • Hospital de la Luz
        • Contact:
  • Spain
      • Barcelona, Spain, 08022
      • Sevilla, Spain, 41013

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

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

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients presenting one of sudden cardiac death, sustained ventricular arrhythmia, or defibrillator therapy.
Time Frame: From the inclusion date (first CMR date) up to 100 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centro Medico Teknon

Collaborators

Hospitales Universitarios Virgen del Rocío
Hospital de La Luz
Humanitas Research Hospital IRCCS, Rozzano-Milan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 7, 2024

Primary Completion (Estimated)

October 30, 2026

Study Completion (Estimated)

February 23, 2027

Study Registration Dates

First Submitted

December 2, 2024

First Submitted That Met QC Criteria

December 8, 2024

First Posted (Estimated)

December 12, 2024

Study Record Updates

Last Update Posted (Estimated)

December 12, 2024

Last Update Submitted That Met QC Criteria

December 8, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMPROVE-NICM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Dilated Cardiomyopathy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Luxembourg

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe