The Leiden Nonischemic Cardiomyopathy Study

Ventricular Fibrillation Clinical Trial

Official title:

The Leiden Nonischemic Cardiomyopathy Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01940081
• Other study ID #: Cardiomyopathy study
• Status: Completed
• Start date: October 2011
• Est. completion date: September 2019

Study information

• Verified date: February 2020
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 148
• Est. completion date: September 2019
• Est. primary completion date: September 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Tachycardia
• Tachycardia, Ventricular
• Ventricular Fibrillation

Intervention

Other:
• Transthoracic echocardiography

• Exercise test

• 24-hour Holter electrocardiogram

• Contrast-enhanced magnetic resonance imaging

• 123-iodine metaiodobenzylguanidine imaging

• Blood samples

Genetic:
• Genetic analysis

Procedure:
• Invasive electrophysiological study

• Endomyocardial biopsy

• Intraoperative biopsy

• Intraoperative mapping and/or ablation

Locations

Country	Name	City	State
Netherlands	Dept. of Cardiology, Leiden University Medical Center	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inducibility of ventricular arrhythmias		Baseline electrophysiological study
Primary	Type of induced ventricular arrhythmias		Baseline electrophysiological study
Primary	Spontaneous ventricular arrhythmias		Up to 10 years
Primary	Type of spontaneous ventricular arrhythmias		Up to 10 years
Secondary	Hospital admissions for heart failure		Up to 10 years
Secondary	Cardiac mortality		Up to 10 years
Secondary	All-cause mortality		Up to 10 years
Secondary	LV function/dimensions/compact fibrosis deterioration as assessed by 123-I MIBG imaging and/or CE-MRI		18 months