International Consortium for Multimodality Phenotyping in Adults With Non-compaction (NONCOMPACT)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Compaction Cardiomyopathy
• Intervention / Treatment: Diagnostic test: Echocardiography; Diagnostic test: Magnetic resonance imaging (MRI); Diagnostic test: Computed tomography (CT)

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands, 3015GD
    • Erasmus Medical Center
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

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

Exclusion Criteria (general cohort):

• 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.

Exclusion Criteria (cardiac CT examination):

• 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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; Standard echocardiography exam performed as part of clinical management.; Diagnostic test: Magnetic resonance imaging (MRI); Standard comprehensive cardiac MRI exam of the heart performed as part of clinical management.; Diagnostic test: Computed tomography (CT); ECG-triggered, contrast-enhanced CT scan of the heart performed for research purposes in eligible study participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of hard heart failure related adverse events	Heart failure death, cardiac transplantation or mechanical circulatory support	Up to 4 years after enrollment
Incidence of composite of hard adverse events	Hard embolic, arrhythmic and heart failure related adverse events (as described above)	Up to 4 years after enrollment
Incidence of all embolic adverse events	Hard embolic adverse events or transient neurologic event without objective infarction	Up to 4 years after enrollment
Incidence of all arrhythmic adverse events	Hard arrhythmic adverse events or syncope without recorded arrhythmia	Up to 4 years after enrollment
Incidence of all heart failure related adverse events	Hard heart failure related adverse events or resynchronization therapy, heart failure hospital admission	Up to 4 years after enrollment
Incidence of composite of adverse events	All embolic, arrhythmic or heart failure related adverse events (as described above)	Up to 4 years after enrollment

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: University of Pennsylvania; The Cleveland Clinic; Erasmus Medical Center; Seoul National University Hospital
• Investigators: Principal Investigator: Koen Nieman, MD, PhD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2030

Study Registration Dates

• First Submitted: June 5, 2020
• First Submitted That Met QC Criteria: June 5, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Genetics; Prognosis; Magnetic resonance imaging; Computed tomography; Echocardiography
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Cardiomyopathies; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Diagnostic Techniques, Cardiovascular; Radiography; Heart Function Tests; Cardiac Imaging Techniques; Ultrasonography; Image Interpretation, Computer-Assisted; Radiographic Image Enhancement; Image Enhancement; Photography; Tomography, X-Ray; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Echocardiography
• Other Study ID Numbers: 56001; SSU00099737 (Other Identifier: Advarra Single IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified datasets will be created and maintained on a public website in a password-protected area, where the frequency of use of the datasets can be monitored by Stanford and NHLBI.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No