The Leiden Nonischemic Cardiomyopathy Study

NCT ID: NCT01940081

Last Updated: 2020-02-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

148 participants

Study Classification

OBSERVATIONAL

Study Start Date

2011-10-31

Study Completion Date

2019-09-30

Brief Summary

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Rationale: 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.

Objectives: 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 NICM.

Hypothesis: Improved understanding of the substrate and mechanisms of VA in NICM may allow more effective, individualized and substrate-based therapies to be developed.

Study design: A prospective cohort study.

Study population: The study population will consist of three groups (A, B and C): NICM patients with documented VA, suspected VA or intermediate to high risk for VA (according to established criteria) who are not referred for cardiac surgery (group A), NICM patients with documented VA, suspected VA or a high risk for VA who are referred for cardiac surgery (group B) and a control group consisting of patients without NICM who are referred for cardiac surgery (group C).

Evaluation: 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). If CE-MRI is performed in another hospital, additional recordings will be performed in our hospital. Additionally, blood samples (arterial, cardiac venous and peripheral venous) for collagen turnover markers will be taken from all patients. 123-iodine metaiodobenzylguanidine (123-I MIBG) 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.

Intervention: In group B, intra-operative mapping and cryo-ablation and postoperative electrophysiologic study will be performed in patients with subepicardial late enhancement on MRI or induced VA suspected for an subepicardial origin.

Main study parameters/endpoints: The main study parameters are extent, location and pattern of fibrosis on imaging and in biopsy specimens. The main study endpoints are inducibility of VA, type of induced VA, spontaneous VA and type of spontaneous VA.

Detailed Description

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Conditions

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Cardiomyopathy, Dilated Tachycardia, Ventricular Ventricular Fibrillation

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Group A: Nonischemic cardiomyopathy - not admitted for surgery

Patients with nonischemic cardiomyopathy with:

* documented ventricular arrhythmia or
* suspected ventricular arrhythmia (e.g. because of out-of-hospital cardiac arrest, palpitations or syncope) or
* high risk for ventricular arrhythmia (LVEF ≤ 35%) or
* intermediate risk for ventricular arrhythmia (LVEF ≤ 50% and late enhancement on contrast-enhanced MRI)

who are not admitted for cardiac surgery

Transthoracic echocardiography

Intervention Type OTHER

Exercise test

Intervention Type OTHER

24-hour Holter electrocardiogram

Intervention Type OTHER

Contrast-enhanced magnetic resonance imaging

Intervention Type OTHER

123-iodine metaiodobenzylguanidine imaging

Intervention Type OTHER

Blood samples

Intervention Type OTHER

Genetic analysis

Intervention Type GENETIC

Invasive electrophysiological study

Intervention Type PROCEDURE

Endomyocardial biopsy

Intervention Type PROCEDURE

Group B: Nonischemic cardiomyopathy -admitted for surgery

Patients with nonischemic cardiomyopathy with:

* documented ventricular arrhythmia or
* suspected ventricular arrhythmia (e.g. because of out-of-hospital cardiac arrest, palpitations or syncope) or
* high risk for ventricular arrhythmia (LVEF ≤ 35%)

who are admitted for cardiac surgery (e.g., mitral valve annuloplasty or CorCap)

Transthoracic echocardiography

Intervention Type OTHER

Exercise test

Intervention Type OTHER

24-hour Holter electrocardiogram

Intervention Type OTHER

Contrast-enhanced magnetic resonance imaging

Intervention Type OTHER

123-iodine metaiodobenzylguanidine imaging

Intervention Type OTHER

Blood samples

Intervention Type OTHER

Genetic analysis

Intervention Type GENETIC

Invasive electrophysiological study

Intervention Type PROCEDURE

Intraoperative biopsy

Intervention Type PROCEDURE

Intraoperative mapping and/or ablation

Intervention Type PROCEDURE

Group C: Controls

Patients without nonischemic cardiomyopathy (controls) who are admitted for:

* Coronary artery bypass graft surgery and who do not have prior myocardial infarction
* Aortic valve replacement

Transthoracic echocardiography

Intervention Type OTHER

Exercise test

Intervention Type OTHER

24-hour Holter electrocardiogram

Intervention Type OTHER

Contrast-enhanced magnetic resonance imaging

Intervention Type OTHER

Blood samples

Intervention Type OTHER

Intraoperative biopsy

Intervention Type PROCEDURE

Interventions

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Transthoracic echocardiography

Intervention Type OTHER

Exercise test

Intervention Type OTHER

24-hour Holter electrocardiogram

Intervention Type OTHER

Contrast-enhanced magnetic resonance imaging

Intervention Type OTHER

123-iodine metaiodobenzylguanidine imaging

Intervention Type OTHER

Blood samples

Intervention Type OTHER

Genetic analysis

Intervention Type GENETIC

Invasive electrophysiological study

Intervention Type PROCEDURE

Endomyocardial biopsy

Intervention Type PROCEDURE

Intraoperative biopsy

Intervention Type PROCEDURE

Intraoperative mapping and/or ablation

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Nonischemic cardiomyopathy
* Documented ventricular arrhythmia, suspected ventricular arrhythmia (e.g. because of out-of-hospital cardiac arrest, palpitations or syncope) or high risk for ventricular arrhythmias (LVEF ≤ 35%) or intermediate risk for ventricular arrhythmias (LVEF ≤ 50% and late enhancement on contrast-enhanced MRI)
* Admission not for cardiac surgery


* Nonischemic cardiomyopathy
* Documented ventricular arrhythmia or suspected ventricular arrhythmia (e.g. because of out-of-hospital cardiac arrest, palpitations or syncope) or high risk for ventricular arrhythmia (LVEF ≤ 35%)
* Admission for cardiac surgery (e.g., mitral valve annuloplasty or CorCap)


\- Patients undergoing aortic valve replacement or coronary artery bypass graft surgery

Exclusion Criteria

* Age \< 18 years or \> 80 years
* Inadequate patient competence
* Pregnancy
* Inability to comply with the protocol due to haemodynamic instability


\- Other cardiomyopathy (e.g., prior myocardial infarction, infiltrative cardiac disease such as sarcoidosis, amyloidosis or Chagas cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia, hypertrophic cardiomyopathy, non-compaction cardiomyopathy and congenital heart disease)


* Nonischemic cardiomyopathy
* Prior myocardial infarction
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Leiden University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Katja Zeppenfeld

Prof. dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Dept. of Cardiology, Leiden University Medical Center

Leiden, , Netherlands

Site Status

Countries

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Netherlands

References

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Piers SR, Androulakis AF, Yim KS, van Rein N, Venlet J, Kapel GF, Siebelink HM, Lamb HJ, Cannegieter SC, Man SC, Zeppenfeld K. Nonsustained Ventricular Tachycardia Is Independently Associated With Sustained Ventricular Arrhythmias in Nonischemic Dilated Cardiomyopathy. Circ Arrhythm Electrophysiol. 2022 Feb;15(2):e009979. doi: 10.1161/CIRCEP.121.009979. Epub 2022 Jan 28.

Reference Type DERIVED
PMID: 35089806 (View on PubMed)

Other Identifiers

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Cardiomyopathy study

Identifier Type: -

Identifier Source: org_study_id

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