The Effects of Ranolazine on CPET Parameters in Ischemic Cardiomyopathy Patients (ERIC)

Selected patients will undergo a CPET evaluation. The initial CPET will identify patients
with underlying ischemia and serve as a baseline study. Ischemia will be assessed using: 1)
peak VO2: measures the peak transport of O2 to the tissues when O2 extraction from the blood
is maximal; 2) the anaerobic threshold (AT): measures the sustainable work capacity in units
of VO2; 3) the O2-pulse measurements at the AT peak VO2: estimate stroke volume at those
levels of exercise; and 4) the relationship of O2 uptake to work rate (ΔVO2/ΔWR): provides
information on the ability of the cardiac output to increase. Patients whoseCPET results
meet the criteria for ischemia will be started on Ranexa 500mg BID and advanced within one
week +/-4 days to 1000mg BID. A second CPET will be performed after 4 weeks +/- 4 days of
maximum therapy. CPET results before and after therapy will undergo a statistical
comparison. The initial off treatment CPET measurement will serve as the control to assess
changes found during therapy. No medication changes or revascularization procedures will
occur during the study. If patients require and undergo a medication change or a
revascularization procedure, they will be excluded from the study.

Patients will be contacted at the completion of week one prior to up titration, then at the
end of week two to ensure tolerance and compliance with the 1000mg BID dose. Patients will
perform the second CPET study at week four +/- 1 week. The trial medication will be assessed
and counted to ensure that patients have taken there allotted pill count for the duration of
the study. Patients who are found to be noncompliant of less than 80% will be excluded from
the study.

Inclusion Criteria:

- Patients > 18 years of age will be enrolled in the trial.

- Stable patients without hospitalizations, medication changes or cardiac intervention
within one month of the study will be enrolled.

- Patients must be able to complete the CPET protocol and must have demonstrable
ischemia on the initial CPET evaluation.

- Patients must have a documented ejection fraction < 40%

a. LV function can be assessed via: i. Echocardiogram ii. MUGA or Nuclear Perfusion
Scan iii. Left ventriculogram

- Patients must be Ranexa naive and without contraindication for Ranexa therapy.

Exclusion Criteria:

- QTc>500 msec on resting EKG

- Hepatic Impairment (Child-Pugh class A, B or C)

- Have received prior treatment with ranolazine

- Treatment with QT prolonging drugs as class 1A (e.g., quinidine), class III (e.g.,
sotalol, dofetilide) anti-arrhythmics, amiodarone and anti-psychotics (e.g.,
thioridazine, ziprasidone)

- Treatment with potent or moderately potent CYP3A inhibitors including ketoconazole
and other azole antifungals, diltiazem, verapamil, macrolide antibiotics, HIV
protease inhibitors or consumption of grapefruit juice or grapefruit juice containing
products

- Have participated in another trial of an investigational device or drug within 30
days of screening

- Have end stage renal disease requiring dialysis

- Have any chronic illness likely to effect compliance with the protocol

- Have second or third degree atrioventricular block in the absence of a functioning
ventricular pacemaker

- Have uncontrolled clinically significant cardiac arrhythmias, or a history of
ventricular fibrillation, torsade de pointes, or other life-threatening ventricular
arrhythmias

- Uncontrolled HTN defined as BP > /= 160/100 mm Hg