Implantable Cardioverter Defibrillators - Improving Risk Stratification

NCT ID: NCT01944514

Last Updated: 2013-09-20

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 92 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-01-31

Brief 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.

Conditions

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

Keywords

Action potential duration restitution; Ventricular arrhythmia; Sudden cardiac death; Peri-infarct zone; Electrocardiogram

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Ischaemic cardiomyopathy group

Patients with ischaemic cardiomyopathy attending for ICD implantation / Ventricular tachycardia stimulation testing as part of ICD risk stratification

No interventions assigned to this group

Non-ischaemic cohort

Patients attending for ICD implantation / ventricular tachycardia stimulation test who do not have ischaemic cardiomyopathy.

No interventions assigned to this group

Control group

Patients attending for electrophysiological study with no conditions that place them at risk of sudden cardiac death.

No interventions assigned to this group

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Leicester

OTHER

Sponsor Role: collaborator

Da Vinci Health Technology Innovation Network

OTHER

Sponsor Role: collaborator

LivaNova

INDUSTRY

Sponsor Role: collaborator

University Hospitals, Leicester

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

G. Andre Ng, MBCHb, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Leicester

References

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.

Reference Type: BACKGROUND

PMID: 23130163 (View on PubMed)

Nicolson WB, McCann GP, Smith MI, Sandilands AJ, Stafford PJ, Schlindwein FS, Samani NJ, Ng GA. Prospective evaluation of two novel ECG-based restitution biomarkers for prediction of sudden cardiac death risk in ischaemic cardiomyopathy. Heart. 2014 Dec;100(23):1878-85. doi: 10.1136/heartjnl-2014-305672. Epub 2014 Aug 4.

Reference Type: DERIVED

PMID: 25092878 (View on PubMed)

Other Identifiers

UHL-10824: ICD-IRS

Identifier Type: -

Identifier Source: org_study_id