The Leiden Nonischemic Cardiomyopathy Study

Completed

• Conditions: Tachycardia, Ventricular; Ventricular Fibrillation; Cardiomyopathy, Dilated
• Interventions: Other: Transthoracic echocardiography; Other: Exercise test; Other: 24-hour Holter electrocardiogram; Other: Contrast-enhanced magnetic resonance imaging; Other: 123-iodine metaiodobenzylguanidine imaging; Other: Blood samples; Genetic: Genetic analysis; Procedure: Invasive electrophysiological study; Procedure: Intraoperative biopsy; Procedure: Endomyocardial biopsy; Procedure: Intraoperative mapping and/or ablation

• Registration Number: NCT01940081
• Lead Sponsor: Leiden University Medical Center

Brief Summary

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

Not available

Study Timeline

• Study Start: 2011-10
• Study First Submitted: 2013-08-29
• Study First Submitted QC: 2013-09-07
• Study First Posted: 2013-09-11
• Primary Completion: 2019-09
• Study Completion: 2019-09
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-19
• Last Update Posted: 2020-02-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 148

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Group A: Nonischemic cardiomyopathy - not admitted for surgery	24-hour Holter electrocardiogram	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
Group A: Nonischemic cardiomyopathy - not admitted for surgery	Transthoracic echocardiography	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
Group A: Nonischemic cardiomyopathy - not admitted for surgery	Exercise test	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
Group A: Nonischemic cardiomyopathy - not admitted for surgery	123-iodine metaiodobenzylguanidine imaging	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
Group A: Nonischemic cardiomyopathy - not admitted for surgery	Invasive electrophysiological study	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
Group B: Nonischemic cardiomyopathy -admitted for surgery	123-iodine metaiodobenzylguanidine imaging	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)
Group C: Controls	Transthoracic echocardiography	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
Group C: Controls	24-hour Holter electrocardiogram	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
Group C: Controls	Blood samples	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
Group B: Nonischemic cardiomyopathy -admitted for surgery	Exercise test	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)
Group A: Nonischemic cardiomyopathy - not admitted for surgery	Genetic analysis	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
Group C: Controls	Exercise test	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
Group C: Controls	Contrast-enhanced magnetic resonance imaging	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
Group A: Nonischemic cardiomyopathy - not admitted for surgery	Contrast-enhanced magnetic resonance imaging	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
Group B: Nonischemic cardiomyopathy -admitted for surgery	Contrast-enhanced magnetic resonance imaging	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)
Group B: Nonischemic cardiomyopathy -admitted for surgery	Genetic analysis	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)
Group B: Nonischemic cardiomyopathy -admitted for surgery	Intraoperative biopsy	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)
Group A: Nonischemic cardiomyopathy - not admitted for surgery	Blood samples	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
Group B: Nonischemic cardiomyopathy -admitted for surgery	24-hour Holter electrocardiogram	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)
Group B: Nonischemic cardiomyopathy -admitted for surgery	Blood samples	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)
Group B: Nonischemic cardiomyopathy -admitted for surgery	Intraoperative mapping and/or ablation	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)
Group C: Controls	Intraoperative biopsy	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
Group A: Nonischemic cardiomyopathy - not admitted for surgery	Endomyocardial biopsy	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
Group B: Nonischemic cardiomyopathy -admitted for surgery	Transthoracic echocardiography	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)
Group B: Nonischemic cardiomyopathy -admitted for surgery	Invasive electrophysiological study	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)

Primary Outcome Measures

Name	Time	Method
Inducibility of ventricular arrhythmias	Baseline electrophysiological study
Type of induced ventricular arrhythmias	Baseline electrophysiological study
Spontaneous ventricular arrhythmias	Up to 10 years
Type of spontaneous ventricular arrhythmias	Up to 10 years

Secondary Outcome Measures

Name	Time	Method
LV function/dimensions/compact fibrosis deterioration as assessed by 123-I MIBG imaging and/or CE-MRI	18 months
Hospital admissions for heart failure	Up to 10 years
Cardiac mortality	Up to 10 years
All-cause mortality	Up to 10 years

Trial Locations

Locations (1)

Dept. of Cardiology, Leiden University Medical Center; 🇳🇱 Leiden, Netherlands