Implantable Cardioverter Defibrillators - Improving Risk Stratification

Myocardial Infarction Clinical Trial

— ICD-IRS  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01944514
• Other study ID #: UHL-10824: ICD-IRS
• Status: Completed
• Phase: N/A
• First received: September 12, 2013
• Last updated: September 19, 2013
• Start date: January 2010

Study information

• Verified date: September 2013
• Source: University Hospitals, Leicester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Observational

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. primary completion date: November 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

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

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
University Hospitals, Leicester	Da Vinci Health Technology Innovation Network, LivaNova, University of Leicester

References & Publications (1)

Nicolson WB, McCann GP, Brown PD, Sandilands AJ, Stafford PJ, Schlindwein FS, Samani NJ, Ng GA. A novel surface electrocardiogram-based marker of ventricular arrhythmia risk in patients with ischemic cardiomyopathy. J Am Heart Assoc. 2012 Aug;1(4):e001552. doi: 10.1161/JAHA.112.001552. Epub 2012 Aug 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Regional Restitution Instability Index	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.	18months - 2years	No
Secondary	Peri-infarct zone	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.	18months-2 years	No