Ranolazine Implantable Cardioverter-Defibrillator Trial

Inclusion Criteria:

1,440 high-risk patients with ischemic/nonischemic cardiomyopathy who receive their ICDs asstandard of care for primary or secondary prevention of mortality following approvedindications for ICD therapy. High-risk patients will be defined as: Secondary Prevention Patients Subjects with ischemic or nonischemic cardiomyopathy,qualified for or with existing ICD (or CRT-D) after documented VT/VF or cardiac arrest (secondary prevention of mortality). Secondary prevention subjects with existing implantsare eligible regardless of when the implant was received (subjects could be recruited fromoutpatient clinics or from inpatient activity including during re-implant or otherprocedures). Primary Prevention Patients

1. Patients with primary prevention indications for ischemic or non-ischemiccardiomyopathy with EF≤35%, with existing devices (ICD/CRT-D), regardless of when thedevice was implanted, who have experienced at least ONE episode of VT/VF appropriatelytreated with ICD therapy (ATP or shock) or had untreated NSVT lasting at least 10beats with heart rate of at least 170 bpm, documented by electrogram of theirimplanted device.

2. Patients with ischemic or non-ischemic cardiomyopathy with EF≤35%, who have beenimplanted within the last 2 years (initial ICD/CRT-D implants, including upgrades frompacemakers) who have NOT experienced VT/VF treated with ICD therapy (ATP or shock),AND who have one of the following additional criteria: BUN≥26 mg/dl or QRS>120ms orAtrial Fibrillation or NSVT documented by ECG/Holter or >500 Ventricular PrematureBeats (VPBs)documented in a 24-hour Holter.

• Stable optimal pharmacologic therapy for the cardiac condition

• Age: equal to 21 years without upper limit

Exclusion Criteria:

• Patient receiving first device with coronary artery bypass graft surgery within thelast 3 calendar months prior to date consent obtained

• Patients receiving first device with percutaneous coronary intervention within thelast 1 calendar month prior to date consent obtained

• Patient receiving first device with enzyme-positive myocardial infarction with thepast 3 calendar months prior to date consent obtained

• Patient receiving first device with angiographic evidence of coronary disease who arecandidates for coronary revascularization and are likely to undergo coronary arterybypass graft surgery or percutaneous coronary intervention in the foreseeable future

• Patient in NYHA Class IV

• Patients receiving prophylactic ablation of ventricular substrate

• Patients with preexisting QTc prolongation >550ms

• Patients on strong CYP3A inhibitors (including ketoconazole, itraconazole,clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir and saquinavir andmoderate CYP3A inhibitors, including, diltiazem, verapamil, aprepitant, erythromycin,fluconazole and grapefruit juice or grapefruit-containing products.

• Patients on CYP3A inducers such as rifampin, rifabutin, rifapentine, phenobarbital,phenytoin, carbamazepine and St.John's wort

• Patients with inherited arrhythmia disorders such as Brugada's, ARVD, LQTS orhypertrophic cardiomyopathy

• Patient who is pregnant or plans to become pregnant during the course of the trial (patients at child bearing age who use prescribed pharmaceutical contraceptives couldbe enrolled)

• Patient with irreversible brain damage from preexisting cerebral disease

• Patient with presence of any disease, other than the patient's cardiac disease,associated with a reduced likelihood of survival for the duration of the trial, e.g.,cancer, uremia, liver failure, etc.

• Patient with chronic renal disease with creatinine >2.5 mg/dl or creatinine clearance <30 ml/min

• Patient participating in any other clinical trial

• Patient unwilling or unable to cooperate with the protocol

• Patient who lives at such a distance from the clinic that travel for follow-up visitswould be unusually difficult

• Patient who does not anticipate being a resident of the area for the scheduledduration of the trial

• Patients who are decisionally impaired adults, those of questionable capacity, andthose who cannot consent for themselves will not be recruited for this study.

• Patient unwilling to sign the consent for participation