Implantable Cardioverter Defibrillators - Improving Risk Stratification (ICD-IRS)

This study has been completed.
Sponsor:
Collaborators:
Leicester Cardiovascular Biomedical Research Unit
Da Vinci Health Technology Innovation Network
Sorin Group
Information provided by (Responsible Party):
University Hospitals, Leicester
ClinicalTrials.gov Identifier:
NCT01944514
First received: September 12, 2013
Last updated: September 19, 2013
Last verified: September 2013
  Purpose

Worldwide three million people a year die from sudden cardiac death (SCD). In most cases there is no warning and the heart is stopped by a sudden arrhythmia. We know that some people are at high risk of sudden cardiac death and can prevent their deaths with an implantable cardioverter defibrillator (ICD) that is implanted in a minor operation.

However, most people who die from sudden cardiac death are not found to be at high risk by our current risk markers and 40% of the people who have ICDs do not have therapy within the first 4 years after implant. We need new and better ways of identifying people who are at high risk of sudden cardiac death so that we can prevent their deaths with ICDs. Our understanding of the electrical signals in the heart has increased considerably in recent years; in no small part this is due to our Principal Investigator Professor Andre Ng's basic science work. This study aims to take the understanding of action potential duration (APD) restitution gained through our work and other studies in humans and in computer simulations and translate it into a fresh way of assessing risk of sudden cardiac death.

This study will carefully examine electrical activity, using APD restitution, in the hearts of patients who are having ICDs fitted because of their high risk of sudden cardiac death and combine this with a detailed heart scan, assessment of autonomic nervous system and gene expression data. We will then follow these patients up to see who benefits from their ICD. This wide ranging information will give us as complete a picture as possible of the factors that cause sudden cardiac death. We hope to use this to identify better predictors of sudden cardiac death.

The study hypotheses are as follows:

Primary

  1. Regional Restitution Instability Index (R2I2) will be significantly higher in patients reaching the endpoint of ventricular endpoint / sudden cardiac death than in those not.
  2. An R2I2 cut-off of 1.03 will partition patients into high and low risk groups.

    Secondary

  3. Peri-infarct zone mass in grams will be significantly higher in patients reaching the endpoint of ventricular endpoint / sudden cardiac death than in those not.

Condition
Sudden Cardiac Death
Implantable Defibrillator User
Myocardial Infarction
Arrhythmias, Cardiac

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Improving Risk Stratification of Patients for Implantable Cardioverter Defibrillators Through Electrophysiological Tests, Cardiac Magnetic Resonance Imaging, Autonomic Function Tests, RNA Analysis and Plasma Biomarkers.

Resource links provided by NLM:


Further study details as provided by University Hospitals, Leicester:

Primary Outcome Measures:
  • Regional Restitution Instability Index [ Time Frame: 18months - 2years ] [ Designated as safety issue: No ]
    Regional Restitution Instability Index (R2I2) is a measure of electrical instability. R2I2 is calculated as the mean of the standard deviation of the residuals from the mean gradients for each ECG lead across a range of diastolic intervals. An R2I2 cut-off of 1.03 (no units) will partition the study population into high and low risk groups.


Secondary Outcome Measures:
  • Peri-infarct zone [ Time Frame: 18months-2 years ] [ Designated as safety issue: No ]
    Peri-infarct zone is calculated from cardiac magnetic resonance imaging scans with late gadolinium enhancement. The full width half maximum technique will be used and Peri-infarct zone assessed using peri-infarct zone mass in grams.


Biospecimen Retention:   Samples Without DNA

Fresh frozen plasma


Enrollment: 92
Study Start Date: January 2010
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Ischaemic cardiomyopathy group
Patients with ischaemic cardiomyopathy attending for ICD implantation / Ventricular tachycardia stimulation testing as part of ICD risk stratification
Non-ischaemic cohort
Patients attending for ICD implantation / ventricular tachycardia stimulation test who do not have ischaemic cardiomyopathy.
Control group
Patients attending for electrophysiological study with no conditions that place them at risk of sudden cardiac death.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Ischaemic cardiomyopathy cohort: patients with a history of myocardial infarction attending for ICD implantation / Ventricular tachycardia stimulation test.

Non-Ischaemic cohort: patients without a history of myocardial infarction attending for ICD implantation / Ventricular tachycardia stimulation test.

Control group: Patients with normal hearts and no conditions / family history that increases risk of sudden cardiac death attending for an electrophysiological study.

Criteria

Inclusion Criteria:

  • Attending for ICD implantation under NICE criteria or attending for an ICD box-change procedure or attending for an Electrophysiological test as part of NICE assessment for ICD implantation
  • Age >18
  • History of ischaemic heart disease or non-ischaemic cardiomyopathy or inherited sudden cardiac death syndrome.

Exclusion Criteria:

  • <28 days since acute coronary syndrome / cardiac surgery
  • Unable to give informed consent
  • Women who are pregnant / planning pregnancy
  • Contraindication for defibrillator safety margin test

    • Haemodynamic instability
    • Severe valvular heart disease
    • Symptomatic, severe, coronary artery disease
    • Recent stroke
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01944514

Sponsors and Collaborators
University Hospitals, Leicester
Leicester Cardiovascular Biomedical Research Unit
Da Vinci Health Technology Innovation Network
Sorin Group
Investigators
Principal Investigator: G. Andre Ng, MBCHb, PhD University of Leicester
  More Information

Publications:
Responsible Party: University Hospitals, Leicester
ClinicalTrials.gov Identifier: NCT01944514     History of Changes
Other Study ID Numbers: UHL-10824: ICD-IRS
Study First Received: September 12, 2013
Last Updated: September 19, 2013
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University Hospitals, Leicester:
Action potential duration restitution
Ventricular arrhythmia
Sudden cardiac death
Peri-infarct zone
Electrocardiogram

Additional relevant MeSH terms:
Arrhythmias, Cardiac
Death
Infarction
Myocardial Infarction
Death, Sudden, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Ischemia
Necrosis
Myocardial Ischemia
Vascular Diseases
Heart Arrest
Death, Sudden

ClinicalTrials.gov processed this record on April 17, 2014