1) To improve our understanding of the underlying pro-arrhythmic substrate and electrophysiologic mechanisms of VA in NICM, and to develop individualized treatment for VA based on the identified substrate. 2) To improve risk stratification for VA…
ID
Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are extent, location and pattern of fibrosis in
biopsy specimens, in-vitro electrophysiological properties of biopsy specimens
and electroanatomical mapping results. The main study endpoints are
inducibility of VA, type of induced VA, spontaneous VA and type of spontaneous
VA.
Secondary outcome
Secondary study parameters:
- CE-MRI
- 123-I MIBG/MIBI imaging
- Collagen turnover markers
- Electroanatomical mapping findings: low voltage, late potentials,
fragmentation and progressive conduction delay during extrastimuli
- Fibrosis (e.g. percentage of fibrotic cells and extracellular matrix) in
biopsy specimens
Secondary study endpoints:
- Heart failure
- Cardiac mortality
- All-cause mortality.
- Disease progression (as assessed by 123-I MIBG/MIBI-scans and MRI-scans).
Background summary
Sudden cardiac death, mainly caused by ventricular arrhythmias (VA), is a major
cause of morbidity and mortality in non-ischemic cardiomyopathy (NICM).
Therapies that effectively prevent VA are lacking. Improved understanding of
the substrate and mechanisms of VA in NICM may allow more effective,
individualized and substrate-based therapies to be developed. In addition, risk
stratification in NICM needs to be improved so that therapies can be allocated
more efficiently.
Study objective
1) To improve our understanding of the underlying pro-arrhythmic substrate and
electrophysiologic mechanisms of VA in NICM, and to develop individualized
treatment for VA based on the identified substrate. 2) To improve risk
stratification for VA and sudden cardiac death in NICM based on substrate
characteristics. 3) To evaluate disease progression in non-ischemic
cardiomyopathy.
Study design
A prospective cohort study. All patients will be evaluated according to current
standards for patients with NICM. Evaluation will include 24h-Holter,
echocardiography, coronary angiogram and contrast-enhanced MRI (CE-MRI).
Additionally, blood samples (arterial, cardiac venous and peripheral venous)
for collagen turnover markers will be taken from all patients. 123-iodine
metaiodobenzylguadinine (123-I MIBG) and methoxyisobutylisonitrile (MIBI)
imaging, electrophysiologic study and endomyocardial biopsy will be performed
in group A and B. Intra-operative biopsy will be performed in group B and C. An
overview of all procedures and clinical indications is provided in appendix A.
Study burden and risks
The majority of patients in group A will not be exposed to additional risks.
Only a minority of patients in group A and B will be exposed to minor
additional risks associated with femoral artery access for blood sampling,
electrophysiologic study and endomyocardial biopsy. All patients in group A and
B will be exposed to radiation during 123-I MIBG/MIBI imaging. All patients in
group B will be exposed to additional risks of intra-operative mapping,
ablation and biopsy. Patients in group C will all be exposed to additional
risks of CE-MRI and intra-operative biopsy. Details on risks are provided in
appendix B and an overview of risks is provided in appendix C. Nevertheless,
risks involved in this study are outweighed by substantial benefit that this
study may provide for these, and future patients, which is outlined below.
Postbus 9600
2300 RC Leiden
NL
Postbus 9600
2300 RC Leiden
NL
Listed location countries
Age
Inclusion criteria
A) NICM patients with
- documented VA or
- suspected VA (e.g. because of out-of-hospital cardiac arrest, palpitations or syncope) or
- high risk for VA (LVEF * 35% and NYHA functional class II or III*) or
- intermediate risk for VA (LVEF * 50%* and late enhancement on CE-MRI)
who are not admitted for cardiac surgery;B) NICM patients with
- documented VA or
- suspected VA (e.g. because of out-of-hospital cardiac arrest, palpitations or syncope) or
- high risk for VA (LVEF * 35% and NYHA functional class II or III*)
who are admitted for cardiac surgery (e.g., mitral valve annuloplasty or CorCap)
C) Non-NICM patients (controls) who are admitted for
- Coronary artery bypass graft surgery and who do not have prior myocardial infarction.
- Aortic valve replacement.
Exclusion criteria
Exclusion criteria are as follows:;- Age < 18 years or > 80 years
- Inadequate patient competence
- Pregnancy
- Inability to comply with the protocol due to haemodynamic instability
- Non-NICM (e.g., prior myocardial infarction, infiltrative cardiac disease such as sarciodosis, amyloidosis or Chagas cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia, hypertrophic cardiomyopathy, non-compaction cardiomyopathy and congenital heart disease);Exclusion criteria for CE-MRI:
- According to the safety guidelines for MR-imaging. These can be found on Albinusnet: MRI / Veiligheidsrichtlijnen voor MR-imaging, http://albinusnet.lumc.nl/home/reg/pro/1010/60711030322284).;Exclusion criteria for blood sampling:
- Haemoglobin < 6.0 mmol/L
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL37472.058.11 |
| OMON | NL-OMON28325 |