Study to Compare TWA Test and EPS Test for Predicting Patients at Risk for Life-threatening Heart Rhythms (ABCD Study)
Study to Compare TWA Test and EPS Test for Predicting Patients at Risk for Life-threatening Heart Rhythms (ABCD Study)
The ABCD clinical study is 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. Patients undergo both the TWA test and EP study and receive an Implantable
 Cardioverter Defibrillator (ICD)if either of the tests show the patient is at risk. The
 patient is then followed for 2 years. The incidence of a ventricular tachyarrhythmia events
 and total mortality are to be evaluated over the duration of the study.
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.

 This is a prospective, multi-center study to demonstrate the following:

 PRIMARY HYPOTHESIS: a TWA test directed therapy is equivalent to EPS directed therapy in
 predicting VTEs in patients with ischemic heart disease, LVEF less than 0.40, and
 asymptomatic non-sustained ventricular tachycardia. The study will determine whether the
 positive predictive value of TWA test directed therapy is equivalent to the positive
 predictive value of EPS directed therapy. The study will also determine whether the negative
 predictive value of TWA test directed therapy is equivalent to the negative predictive value
 of EPS directed therapy. The positive groups under TWA test directed therapy will be compared
 with the positive groups under EPS directed therapy, and the negative groups under TWA
 directed therapy will be compared with the negative groups under EPS directed therapy.
 SECONDARY HYPOTHESIS: The study will determine whether the positive predictive value of a TWA
 test (not including indeterminates) is equivalent to the positive predictive value of an EPS
 in predicting future VTEs. The study will also determine whether the negative predictive
 value of a TWA test (not including indeterminates) is equivalent to the negative predictive
 value of an EPS in predicting future VTEs. The TWA test positive groups will be compared with
 the EPS positive groups, and the TWA test negative groups will be compared with the EPS
 negative groups. The secondary hypothesis will also be tested against the primary endpoint
 defined above.
Inclusion Criteria:

 Patients with no previous history of life threatening ventricular arrhythmias or
 symptomatic non-sustained VT, and who meet the following inclusion criteria may be enrolled
 in the study:

 1. Ischemic heart disease as documented by any of the following: previous myocardial
 infarction (documented by 2 out of 3 of the following: history, ECG, and/or cardiac
 enzymes), prior PTCA or CABG; angina with a positive exercise or pharmacological
 stress test; angina with a greater than 50% occlusion of any coronary artery, left
 ventricular dysfunction that can be attributed to angiographically documented coronary
 artery disease

 2. LVEF less than 0.40 as determined by echocardiography, radionuclide or contrast
 ventriculography within six months of enrollment.

 3. Non-sustained ventricular tachycardia within 6 months of enrollment, defined as
 greater than 3 consecutive premature ventricular contractions having at least three
 consecutive intervals with a cycle length at or below 550 ms, and with the entire
 episode lasting less than 30 seconds. This episode should be associated with either no
 symptoms, or palpitations alone. An episode of NSVT associated with any symptoms
 (other than palpitations) does not satisfy inclusion criteria for the trial.

 4. The patient is 18 years of age or older.

 5. In the judgement of the principal investigator, the patient is capable of undergoing a
 sub-maximal treadmill exercise test to a heart rate of 120 bpm.

 6. The patient has signed the latest IRB approved informed consent form.

 Exclusion Criteria:

 Patients meeting any of the following exclusion criteria will not be eligible for
 enrollment:

 1. The patient is unable to give informed consent.

 2. The patient is known to have had a cardiac arrest or sustained life threatening
 ventricular arrhythmias, other than in the setting of an acutely reversible cause
 (e.g., acute phase MI, drug intoxication).

 3. The patient has had an EPS or TWA test at any time and for any reason prior to being
 screened and consented for this trial.

 4. The patient has unstable coronary artery disease.

 5. The patient has contraindications to ICD implantation.

 6. A submaximal exercise test is contraindicated.

 7. The patient has persistent atrial fibrillation or flutter.

 8. The patient is less than 28 days post MI, post CABG, or post coronary angioplasty.

 9. The patient has an LVEF 0.40, but no evidence of ischemic heart disease as defined by
 section 4.1.

 10. The patient has NYHA functional Class IV congestive heart failure symptoms at the time
 of enrollment.

 11. The patient is on any class 1 or 3 antiarrhythmic drug.

 12. The patient is participating in a study of another investigational device or drug. If,
 in the opinion of the investigator, this would not interfere with this study, the
 eligibility of such a patient should be discussed with the primary investigators of
 the ABCD trial, Drs. Rosenbaum or Costantini.

 13. The patient has any other significant medical condition or acute illness that in the
 opinion of the investigator precludes participation.

 14. The patient has a previous history of syncope, unless the episode was clearly not
 caused by a ventricular tachyarrhythmia.

 15. The patient has a life expectancy of less than one year from any cause.

 16. The patient has a positive pregnancy test.

 17. The patient is not geographically stable or is unable to comply with the follow up
 schedule.