The ultimate goal of the consortium is to use state-of-the-art imaging, genetics, and machine-learning techniques to identify NCCM patients at risk for severe arrhythmia or stroke and guide preventive therapy using personalized risk scores
ID
Source
Brief title
Condition
- Myocardial disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
We hypothesize integrated analysis of clinical, genetic and imaging variables
will improve outcome prediction in patients with NCCM. At 5 centers, 600
patients with suspected NCCM by joint adjudication will be comprehensively
phenotyped and followed for up to 3 years. Independent core labs will perform
comprehensive structural and functional evaluation of clinical echo and MRI
exams. Adverse events are adjudicated by an independent event committee.
Machine-learning techniques for complex multi-parameter predictions will be
applied to develop predictive models for arrhythmic events, thromboembolic
events and composite outcomes. Performance will be compared to currently used
risk models and guideline-based criteria for ICD implantation and
anticoagulation.
Secondary outcome
We hypothesize that high-resolution cardiac CT can discover structural
differences between pathological non-compaction and benign hyper-trabeculation,
independent of quantity. From the original cohort (Aim 1), 300 adult patients
with suspected NCCM will undergo cardiac CT and advanced computational
analytics including hypothesis-based features (thrombogenic cavities), measures
of trabecular density and complexity, as well as hypothesis-free image
interpretations of the non-compacted myocardium using artificial intelligence
(radiomics), as demonstrated in our preliminary studies. Interactions between
structure and function will be investigated using regional co-registration of
CT and echo/MRI data. We will determine the incremental predictive value of the
structural CT features to the models from the primary outcome.
Background summary
Non-compaction cardiomyopathy (NCCM), also known as left ventricular
non-compaction (LVNC), is a heterogeneous myocardial disorder characterized by
ventricular myocardium comprising of a diminished compacted outer layer and
extensive non-compacted inner muscular layer. A specific genetic mutations or
histopathological substrate that defines NCCM has not yet been identified.
Although the true prevalence of NCCM is unknown, non-compaction is reported in
0.05-0.24% of adult echocardiograms, and in up to 4% of patients with reduced
left ventricular (LV) function. Clinically, NCCM can manifest as LV dysfunction
and heart failure, and many patients ultimately require heart transplantation.
Life-threatening ventricular tachyarrhythmias occur in 38-47% of NCCM
patients.Stroke and other systemic emboli occur in 9-24%, which is thought to
be due to deep recesses and contractile dysfunction promoting thrombus
formation. Recognition and treatment of high-risk NCCM patients is important,
but it is also crucial to avoid the burden, risk and cost of (indefinite)
anticoagulation and ICDs in those unlikely to benefit. Increased non-compaction
detection rates in adults have created an urgent unmet clinical need for better
risk stratification and more effective allocation of impactful preventive
therapies.
Study objective
The ultimate goal of the consortium is to use state-of-the-art imaging,
genetics, and machine-learning techniques to identify NCCM patients at risk for
severe arrhythmia or stroke and guide preventive therapy using personalized
risk scores
Study design
This is a prospective, multicenter observational study to identify clinical,
genetic and imaging predictors of clinical outcome in patients with suspected
non-compaction cardiomyopathy. Written informed consent will be obtained from
all study participants. The total project duration is 5 years. Patient
enrollment and CT examinations will be performed in the first 4 years. CT
examinations will be performed on FDA approved equipment and no investigational
drugs will be used. There is no diagnostic or therapeutic intervention that
will affect standard patient management. The primary endpoints include past and
prospective embolic, arrhythmic and heart failure events as assessed by an
Events Adjudication Committee.
Study burden and risks
In addition to standard clinical diagnostic an therapeutic interventions,
bloodsamples (incl genetic tests) will be taken, Quality of life questionnaires
will be completed at baseline and follow-up and a subgroup of patients (approx.
50%) will undergo a cardiac CT scan.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
• >=18 years old
• Hypertrabeculation of the left ventricle fulfilling the echo-based Jenni
criteria of NCCM
• Cardiac MRI examination performed or planned for clinical purposes
Exclusion criteria
Exclusion criteria to the study (Aim 1):
• Complex congenital disease, neuromuscular disorders or isolated RV
non-compaction
• Inability to provide informed consent
• Contra-indications to MRI
Exclusion criteria to the cardiac CT exam (Aim 2):
• 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
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL73728.078.21 |