The Leiden Nonischemic Cardiomyopathy Study
The Leiden Nonischemic Cardiomyopathy Study
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.
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