The Leiden Nonischemic Cardiomyopathy Study

Leiden University Medical Center (LUMC)

Status: Completed

Conditions: Cardiomyopathy, Dilated; Ventricular Fibrillation; Tachycardia, Ventricular

Treatments: Other: 123-iodine metaiodobenzylguanidine imaging; Other: Exercise test; Procedure: Endomyocardial biopsy; Procedure: Intraoperative biopsy; Other: Contrast-enhanced magnetic resonance imaging; Other: Blood samples; Other: Transthoracic echocardiography; Genetic: Genetic analysis; Procedure: Intraoperative mapping and/or ablation; Procedure: Invasive electrophysiological study; Other: 24-hour Holter electrocardiogram

Study type: Observational

Funder types: Other

Identifiers

NCT01940081

Cardiomyopathy study

Details and patient eligibility

About

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.

Enrollment: 148 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria, group A:

• 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

Inclusion criteria, group B:

• 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)

Inclusion criteria, group C:

• Patients undergoing aortic valve replacement or coronary artery bypass graft surgery

Exclusion criteria, all groups:

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

Exclusion Criteria, groups A and B:

• 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)

Exclusion criteria, group C:

• Nonischemic cardiomyopathy
• Prior myocardial infarction

Trial design

148 participants in 3 patient groups

Group A: Nonischemic cardiomyopathy - not admitted for surgery

Description:

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

Treatment:

Other: 123-iodine metaiodobenzylguanidine imaging

Other: Transthoracic echocardiography

Procedure: Invasive electrophysiological study

Other: Contrast-enhanced magnetic resonance imaging

Other: 24-hour Holter electrocardiogram

Genetic: Genetic analysis

Other: Blood samples

Procedure: Endomyocardial biopsy

Other: Exercise test

Group B: Nonischemic cardiomyopathy -admitted for surgery

Description:

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)

Treatment:

Other: 123-iodine metaiodobenzylguanidine imaging

Other: Transthoracic echocardiography

Procedure: Invasive electrophysiological study

Other: Contrast-enhanced magnetic resonance imaging

Other: 24-hour Holter electrocardiogram

Genetic: Genetic analysis

Procedure: Intraoperative mapping and/or ablation

Procedure: Intraoperative biopsy

Other: Blood samples

Other: Exercise test

Group C: Controls

Description:

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

Treatment:

Other: Transthoracic echocardiography

Other: Contrast-enhanced magnetic resonance imaging

Other: 24-hour Holter electrocardiogram

Procedure: Intraoperative biopsy

Other: Blood samples

Other: Exercise test