The Leiden Nonischemic Cardiomyopathy Study
Condition: Cardiomyopathy, Dilated; Tachycardia, Ventricular; Ventricular Fibrillation
MeSH terms: Cardiomyopathies; Tachycardia; Ventricular Fibrillation; Tachycardia, Ventricular; Cardiomyopathy, Dilated
Study type: Observational

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.
    


Intervention name(s): Transthoracic echocardiography; Exercise test; 24-hour Holter electrocardiogram; Contrast-enhanced magnetic resonance imaging; 123-iodine metaiodobenzylguanidine imaging; Blood samples; Genetic analysis; Invasive electrophysiological study; Endomyocardial biopsy; Intraoperative biopsy; Intraoperative mapping and/or ablation
Intervention type(s): Other; Other; Other; Other; Other; Other; Genetic; Procedure; Procedure; Procedure; Procedure
Intervention MeSH terms: 3-Iodobenzylguanidine
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Patients with nonischemic cardiomyopathy and controls who are admitted to the hospital
      
Biospecimen description: 
      Per patient:

      Blood samples (40 mL) Ventricular biopsies
    
Keywords: Cardiomyopathy, Dilated; Tachycardia, Ventricular; Ventricular Fibrillation; Arrhythmias, Cardiac/etiology; Arrhythmias, Cardiac/physiopathology; Magnetic Resonance Imaging; 3-Iodobenzylguanidine/diagnostic use; Sympathetic Nervous System/radionuclide imaging; Electrophysiologic Techniques, Cardiac; Biopsy; Genetic Testing; Echocardiography; Electrocardiography, Ambulatory; Exercise Test