Clinical trial NCT00583297: Genetic Substudy of the Alternans Before Cardioverter Defibrillator (ABCD) Trial
Official title: Identifying Genetic Markers That Predict Microvolt T-wave Alternans Status and Arrhythmia Risk in Patients With Ischemic Heart Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ventricular Tachycardia
Cardiovascular Diseases
Arrythmia
CVD
Keywords: Arrhythmia
Heart Failure
T-wave Alternans
Implanted Cardioverter Defibrillator
Biological Markers
Molecular Genetics
Corus CAD
ASGES
Age/Sex/Gene Expression Score
Gene Expression
GES
CVD
Precision Medicine
Sudden Cardiac Death
Electrophysiology Study
Cardiovascular Disease
ICD
EPS
SCD
TWA
Lead sponsor: CardioDx
Sponsor class: INDUSTRY
First posted: 2007-12-31
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The target population for the ABCD genetic sub-study includes all living individuals currently enrolled in the ABCD trial (total study enrollment=629; 566 analyzed in the trial) Participants of the ABCD trial underwent TWA and EPS testing to determine their risk for ventricular arrhythmia and most have received an implantable cardioverter defibrillator (ICD). The ABCD trial collected extensive longitudinal clinical data including medical and medication histories, incidence of ventricular arrhythmias, defibrillator shocks, other cardiovascular events, and mortality.

Brief summary: The ABCD clinical study (ClinicalTrials.gov Identifier NCT00187291) was designed to determine if a T-Wave Alternans (TWA) test is equivalent to an Electrophysiology Study (EPS) in predicting life-threatening heart rhythms in patients with ischemic heart disease, left ventricular dysfunction, and non-sustained tachycardia. The purpose of the ABCD Genetic sub-study is to identify genetic markers that predict TWA status and arrhythmia risk in this same population.

Detailed description: The primary objective of this study is to test the hypothesis that therapy directed primarily by a T wave alternans (TWA) test, measured non-invasively during exercise, is equivalent to therapy directed by an electrophysiological study (EPS) in predicting spontaneous ventricular tachyarrhythmic events (VTEs) in patients with ischemic heart disease, left ventricular dysfunction, and asymptomatic non-sustained ventricular tachycardia (NSVT). In the absence of any previous life-threatening ventricular arrhythmia (i.e., for primary prevention), ICD implantation is currently indicated in patients with ischemic heart disease, left ventricular dysfunction, asymptomatic non-sustained ventricular tachycardia, and a positive EPS. The objective of this study is to demonstrate that a TWA test directed therapy is equivalent to EPS directed therapy in guiding ICD implantation for the purpose of primary prevention of sudden cardiac death (SCD) in patients with ischemic heart disease, left ventricular dysfunction, and asymptomatic non-sustained ventricular tachycardia.

Eligibility criteria: Inclusion Criteria:

Subjects previously enrolled in the ABCD trial sponsored by St. Jude Medical (ClinicalTrials.gov Identifier NCT00187291)

* patients with ischemic heart disease
* left ventricular ejection fraction (LVEF) \< 40%
* non-sustained ventricular tachycardia

Exclusion Criteria:

Individuals who were not previously enrolled in the ABCD trial are not eligible for this genetic sub-study.

Primary outcomes:
measure: Genotype and Pre-implant T-wave alternans status.
timeFrame: two years as per original ABCD trial
Secondary outcomes:
measure: Genotype and occurrence of appropriate cardioversion
timeFrame: two years per original ABCD trial
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
Study officials:
affiliation: CardioDx, Inc.
name: Amy J Sehnert, MD
role: STUDY_DIRECTOR
affiliation: MetroHealth Medical Center
name: Elizabeth Kaufman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wilson LD, Wan X, Rosenbaum DS. Cellular alternans: a mechanism linking calcium cycling proteins to cardiac arrhythmogenesis. Ann N Y Acad Sci. 2006 Oct;1080:216-34. doi: 10.1196/annals.1380.018.
citation: Bloomfield DM, Bigger JT, Steinman RC, Namerow PB, Parides MK, Curtis AB, Kaufman ES, Davidenko JM, Shinn TS, Fontaine JM. Microvolt T-wave alternans and the risk of death or sustained ventricular arrhythmias in patients with left ventricular dysfunction. J Am Coll Cardiol. 2006 Jan 17;47(2):456-63. doi: 10.1016/j.jacc.2005.11.026. Epub 2005 Dec 15.