MADIT-CRT: Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy

The MADIT-CRT trial is designed to determine if combined implantable cardiac defibrillator (ICD)-cardiac resynchronization therapy (CRT-D) will reduce the risk of mortality and heart failure (HF) events by approximately 25%, in subjects who are in New York Heart Association (NYHA) functional Class II with non-ischemic or ischemic cardiomyopathy and subjects who are in NYHA functional Class I with ischemic cardiomyopathy, left ventricular dysfunction (ejection fraction \[EF\] \< or = 0.30), and prolonged intraventricular conduction (QRS duration \> or = 130 ms).

In this study, subjects will be randomized to CRT-D or ICD-only. Randomization will be stratified by clinical center and ischemic status. Approximately 60% of the subjects will be randomly assigned to receive a CRT-D with biventricular pacing, and 40% will receive an ICD only. Optimal pharmacological therapy for heart failure will be required in both treatment arms. Length of follow-up for each subject will depend on the date of entry into the study, since all subjects will be followed to a common study termination date.

Eligibility Criteria:
Inclusion Criteria:

* Ischemic heart disease defined as:

  * NYHA Class I or II for the past 3 calendar months prior to, and at the time of, enrollment;
  * one or more clinically documented (Q wave or enzyme positive) prior myocardial infarctions, but not within 3 calendar months of enrollment; and/or
  * one or more prior coronary artery bypass graft surgeries or percutaneous coronary interventions (balloon and/or stent angioplasty) but not within 3 calendar months of enrollment.

OR

* Non-ischemic heart disease including dilated cardiomyopathy characterized by a low ejection fraction and increased ventricular volume, with ventricular compliance that is normal or increased
* NYHA Class II for the past 3 calendar months prior to, and at the time of, enrollment

AND all of the following:

* Stable optimal pharmacologic therapy.
* An ejection fraction \< or = 0.30 by angiographic, radionuclide, or echocardiographic methods within one year prior to enrollment and measured during the enrollment echocardiogram obtained within 14 days prior to randomization to confirm eligibility (recommended)
* Resting QRS duration \> or = 130 ms on print-out of a current electrocardiogram (ECG) obtained within 14 days prior to randomization.
* Sinus rhythm by ECG (including right bundle branch block \[RBBB\] and first degree heart block with PR \< 250 ms.)
* Men and women 21 years of age or older (no upper-age cut off)

Exclusion Criteria:

* Existing indication for CRT
* Subjects with an implanted pacemaker
* Subjects with an existing ICD or CRT device
* Subjects in NYHA Class I with non-ischemic cardiomyopathy
* Subjects in NYHA Class III or IV in the past 3 calendar months prior to, or at the time of, enrollment
* Coronary artery bypass graft surgery or percutaneous coronary intervention (balloon and/or stent angioplasty) within the past 3 calendar months prior to enrollment
* Enzyme-positive myocardial infarction within the past 3 calendar months prior to enrollment
* Subjects with angiographic evidence of coronary disease who are candidates for coronary revascularization and are likely to undergo coronary artery bypass graft surgery or percutaneous coronary intervention in the foreseeable future
* Subjects with second or third degree heart block
* Subjects with irreversible brain damage from preexisting cerebral disease
* Women who are pregnant or plan to become pregnant during the course of the trial. Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment.
* Reversible non-ischemic cardiomyopathy such as acute viral myocarditis or discontinuation of alcohol in alcohol-induced heart disease
* Subjects with chronic atrial fibrillation within one month prior to enrollment
* Presence of any disease, other than the subject's cardiac disease, associated with a reduced likelihood of survival for the duration of the trial, e.g., cancer, uremia (blood urea nitrogen \[BUN\] \> 70 mg/dl or creatinine \> 3.0 mg/dl), liver failure, etc.
* Subjects participating in any other clinical trials
* Subjects unwilling or unable to cooperate with the protocol
* Subjects who live at such a distance from the clinic that travel for follow-up visits would be unusually difficult
* Subjects who do not anticipate being residents of the area for the scheduled duration of the trial
* Subjects unwilling to sign the consent for participation