Clinical trial NCT01940081: The Leiden Nonischemic Cardiomyopathy Study
Official title: The Leiden Nonischemic Cardiomyopathy Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiomyopathy, Dilated
Tachycardia, Ventricular
Ventricular Fibrillation
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
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2013-09-11
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with nonischemic cardiomyopathy and controls who are admitted to the hospital

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.


Eligibility 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

Primary outcomes:
measure: Inducibility of ventricular arrhythmias
timeFrame: Baseline electrophysiological study
measure: Type of induced ventricular arrhythmias
timeFrame: Baseline electrophysiological study
measure: Spontaneous ventricular arrhythmias
timeFrame: Up to 10 years
measure: Type of spontaneous ventricular arrhythmias
timeFrame: Up to 10 years
Secondary outcomes:
measure: Hospital admissions for heart failure
timeFrame: Up to 10 years
measure: Cardiac mortality
timeFrame: Up to 10 years
measure: All-cause mortality
timeFrame: Up to 10 years
measure: LV function/dimensions/compact fibrosis deterioration as assessed by 123-I MIBG imaging and/or CE-MRI
timeFrame: 18 months
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Dept. of Cardiology, Leiden University Medical Center
Study officials:
References:
citation: Piers SR, Androulakis AF, Yim KS, van Rein N, Venlet J, Kapel GF, Siebelink HM, Lamb HJ, Cannegieter SC, Man SC, Zeppenfeld K. Nonsustained Ventricular Tachycardia Is Independently Associated With Sustained Ventricular Arrhythmias in Nonischemic Dilated Cardiomyopathy. Circ Arrhythm Electrophysiol. 2022 Feb;15(2):e009979. doi: 10.1161/CIRCEP.121.009979. Epub 2022 Jan 28.