International Consortium for Multimodality Phenotyping in Adults With Non-compaction

NCT04424030 | Active Not Recruiting

• 2 other identifiers: 56001SSU00099737
• Study Type: observational
• Target: 600
• Locations: 3 countries
• Sites: 5

Brief Summary

Non-compaction cardiomyopathy (NCCM) is a heterogeneous, poorly understood disorder characterized by a prominent inner layer of loose myocardial tissue, and associated with heart failure, stroke, severe rhythm irregularities and death. For a growing population diagnosed with NCCM there is a need for better risk stratification to appropriately allocate (or safely withhold) these impactful preventive measures. The goal of this international consortium is to improve care of patients with non-compaction cardiomyopathy. We hypothesize that comprehensive analysis of clinical, genetic, structural and functional information will improve risk stratification. In addition, we hypothesize that detailed structural analysis will allow for differentiation of pathological and benign patterns of non-compaction. In a large cohort of adult patients with suspected NCCM we will perform in-depth phenotyping, including clinical information, pedigree data, genetics, echocardiography and MRI, and follow patients for up to 3 years. We will apply machine-learning based analytics to develop predictive models and compare their performance to currently used models and treatment criteria. Secondly, in a subset of patients we will perform high-resolution cardiac CT for detailed structural characterization of the myocardial wall. We will investigate associations between myocardial structure and regional contractile function, as assessed by echo and MRI. The aim of this proposal is to identify a structural signature associated with pathological non-compaction and improve developed risk prediction models. Discovery of pathological structural signatures through innovative imaging techniques, in relation to myocardial contractility, will advance our understanding of NCCM.

Conditions

Non-Compaction Cardiomyopathy

Keywords

Echocardiography; Magnetic resonance imaging; Computed tomography; Prognosis; Genetics

Outcome Measures

Primary Outcomes (2)

• Incidence of hard embolic adverse events

  Clinical neuro/systemic embolic event by autopsy, imaging or specialist evaluation

  Up to 4 years after enrollment

• Incidence of hard arrhythmic adverse events

  Sudden death (aborted), appropriate ICD discharge or VT/VF on ECG or rhythm/device monitoring

  Up to 4 years after enrollment

Secondary Outcomes (6)

• Incidence of hard heart failure related adverse events

  Up to 4 years after enrollment

• Incidence of composite of hard adverse events

  Up to 4 years after enrollment

• Incidence of all embolic adverse events

  Up to 4 years after enrollment

• Incidence of all arrhythmic adverse events

  Up to 4 years after enrollment

• Incidence of all heart failure related adverse events

  Up to 4 years after enrollment

Study Arms (1)

Multimodality imaging

Patients who have undergone echocardiography and cardiac MRI as part of their clinical management A research cardiac CT scan will be performed in eligible participants

Diagnostic Test: Echocardiography; Diagnostic Test: Magnetic resonance imaging (MRI); Diagnostic Test: Computed tomography (CT)

Interventions

Computed tomography (CT) DIAGNOSTIC_TEST

ECG-triggered, contrast-enhanced CT scan of the heart performed for research purposes in eligible study participants.

Multimodality imaging

Echocardiography DIAGNOSTIC_TEST

Standard echocardiography exam performed as part of clinical management.

Multimodality imaging

Magnetic resonance imaging (MRI) DIAGNOSTIC_TEST

Standard comprehensive cardiac MRI exam of the heart performed as part of clinical management.

Multimodality imaging

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 hypertrabeculation of the left ventricle fulfilling echo-based criteria of non-compaction cardiomyopathy

You may qualify if:

• ≥18 years old
• Hypertrabeculation of the left ventricle fulfilling the echo-based Jenni criteria of NCCM
• Clinical cardiac MRI examination performed or planned

You may not qualify if:

• Complex congenital disease (including transposition great arteries, tetralogy of Fallot, tricuspid atresia, truncus arteriosis, single ventricle, hypoplastic left heart, pulmonary atresia, double-outlet RV), neuromuscular disorders or isolated RV non-compaction
• Inability to provide informed consent
• Contra-indications to MRI, which apply if the clinical cardiac MRI has not yet been performed at the time of study enrollment: permanent pacemakers/ICDs, MRI contrast medium allergy, significant arrhythmia with highly irregular RR intervals, severe dyspnea with inability to lay flat/breath hold, inability to communicate with the MRI technician or follow commands for any reason (psychosis, agitation, etc.), other site-specific contra-indications to clinical MRI of the heart.
• Age \<21 years
• Decompensated heart failure, or otherwise clinically unstable
• BMI\>40 kg/m2
• Pregnancy (or cannot be ruled out)
• Known iodine contrast medium allergy
• Kidney dysfunction: eGFR\<45 ml/min
• Thyroid disease: toxic multinodular goiter, Graves' disease, Hashimoto's thyroiditis

Sponsors & Collaborators

• Stanford University: lead
• The Cleveland Clinic: collaborator
• University of Pennsylvania: collaborator
• Erasmus Medical Center: collaborator
• Seoul National University Hospital: collaborator

Study Sites (5)

Stanford University

Palo Alto, California, 94304, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Erasmus Medical Center

Rotterdam, 3015GD, Netherlands

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Biospecimen

Retention: SAMPLES WITH DNA

After enrollment, blood will be drawn via venipuncture. The blood samples (35cc in total) will be centrifuged (15 minutes at 3500 RPM), after which the plasma, serum, red cells and buffy coat will be aliquoted from the vacutainers into color-coded vials. In addition to standard EDTA tubes we may include a CPT or PAX tube for more extensive analytics, or an Oragene tube for remote saliva collection. The aliquots and tubes will be stored at -70⁰C. The samples will remain at the site until analysis.

MeSH Terms

Interventions

Echocardiography; Magnetic Resonance Imaging; Tomography, X-Ray Computed

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Tomography; Image Interpretation, Computer-Assisted; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray

Study Officials

• Koen Nieman, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: June 5, 2020
• First Posted: June 9, 2020
• Study Start: January 1, 2021
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2030
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

KR (1); US (3); NL (1)