The Leiden Nonischemic Cardiomyopathy Study

NCT01940081 | Completed

• 1 other identifier: Cardiomyopathy study
• Study Type: observational
• Target: 148
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• Hospital admissions for heart failure

  Up to 10 years

• Cardiac mortality

  Up to 10 years

• All-cause mortality

  Up to 10 years

• LV function/dimensions/compact fibrosis deterioration as assessed by 123-I MIBG imaging and/or CE-MRI

  18 months

Study Arms (3)

Group A: Nonischemic cardiomyopathy - not admitted for surgery

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

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: Endomyocardial biopsy

Group B: Nonischemic cardiomyopathy -admitted for surgery

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)

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: Intraoperative mapping and/or ablation

Group C: Controls

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

Other: Transthoracic echocardiography; Other: Exercise test; Other: 24-hour Holter electrocardiogram; Other: Contrast-enhanced magnetic resonance imaging; Other: Blood samples; Procedure: Intraoperative biopsy

Interventions

Transthoracic echocardiography OTHER

Group A: Nonischemic cardiomyopathy - not admitted for surgery; Group B: Nonischemic cardiomyopathy -admitted for surgery; Group C: Controls

Exercise test OTHER

Group A: Nonischemic cardiomyopathy - not admitted for surgery; Group B: Nonischemic cardiomyopathy -admitted for surgery; Group C: Controls

24-hour Holter electrocardiogram OTHER

Group A: Nonischemic cardiomyopathy - not admitted for surgery; Group B: Nonischemic cardiomyopathy -admitted for surgery; Group C: Controls

Contrast-enhanced magnetic resonance imaging OTHER

Group A: Nonischemic cardiomyopathy - not admitted for surgery; Group B: Nonischemic cardiomyopathy -admitted for surgery; Group C: Controls

123-iodine metaiodobenzylguanidine imaging OTHER

Group A: Nonischemic cardiomyopathy - not admitted for surgery; Group B: Nonischemic cardiomyopathy -admitted for surgery

Blood samples OTHER

Group A: Nonischemic cardiomyopathy - not admitted for surgery; Group B: Nonischemic cardiomyopathy -admitted for surgery; Group C: Controls

Genetic analysis GENETIC

Group A: Nonischemic cardiomyopathy - not admitted for surgery; Group B: Nonischemic cardiomyopathy -admitted for surgery

Invasive electrophysiological study PROCEDURE

Group A: Nonischemic cardiomyopathy - not admitted for surgery; Group B: Nonischemic cardiomyopathy -admitted for surgery

Endomyocardial biopsy PROCEDURE

Group A: Nonischemic cardiomyopathy - not admitted for surgery

Intraoperative biopsy PROCEDURE

Group B: Nonischemic cardiomyopathy -admitted for surgery; Group C: Controls

Intraoperative mapping and/or ablation PROCEDURE

Group B: Nonischemic cardiomyopathy -admitted for surgery

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with nonischemic cardiomyopathy and controls who are admitted to the hospital

You may qualify if:

• 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
• 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)
• \- Patients undergoing aortic valve replacement or coronary artery bypass graft surgery

You may not qualify if:

• Age \< 18 years or \> 80 years
• Inadequate patient competence
• Pregnancy
• Inability to comply with the protocol due to haemodynamic instability
• \- 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)
• Nonischemic cardiomyopathy
• Prior myocardial infarction

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Dept. of Cardiology, Leiden University Medical Center

Leiden, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 35089806 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Per patient: Blood samples (40 mL) Ventricular biopsies

MeSH Terms

Conditions

Cardiomyopathy, Dilated; Tachycardia, Ventricular; Ventricular Fibrillation; Arrhythmias, Cardiac

Interventions

Exercise Test; Blood Specimen Collection; Genetic Testing

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Tachycardia; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Study Record Dates

• First Submitted: August 29, 2013
• First Posted: September 11, 2013
• Study Start: October 1, 2011
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: February 20, 2020

Record last verified: 2020-02

Locations

NL (1)