The Effects of Ranolazine on Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction

I. Inclusion Criteria

• Age > 18 years old
• Diagnosis of Heart Failure (HF) with Preserved Ejection Fraction (PEF)
• Signs or symptoms of heart failure (breathlessness, pulmonary congestion, edema, fatigue), NYHA (New York Heart Association) Class II-III HF AND
• LVEF (Left Ventricular Ejection Fraction) > 45% AND
• Evidence of elevated LV filling pressures
• E/e-prime (E/e') mitral ratio > 8. Mitral E/e' ratio has been proposed as a noninvasive measure of left ventricular filling pressure.
• Brain natiuretic peptide (BNP) > 80 pg/mL. BNP is biomarker of ventricular wall stress.
• Pulmonary Artery systolic pressure estimated at > 35 mm Hg on echocardiography
• Stable medical management for at least 1 month

II. Exclusion Criteria

• Inability to perform 6 minute walk (6MW) test or 6 minute walk distance > 550 meters at baseline
• Inability to perform the Naughton protocol exercise test, or an absolute contraindication to exercise testing
• Decompensated heart failure
• Clinically significant valvular disease or congenital cardiac defects
• Clinical diagnosis of Chronic obstructive pulmonary disease (COPD) or significant lung pathology
• Prior treatment with ranolazine
• Percutaneous coronary intervention within the past 6 months or planned intervention during the study period
• Acute coronary syndrome within the prior 2 months
• Presence of uncorrected perfusion defects on stress testing
• Presence of angina
• Any rhythm other than sinus
• Electrocardiogram measured QTc interval > 500 msec
• Clinically significant hepatic impairment (ALT/AST > 3x upper limit of normal)
• Participation in another investigational drug or device study within 1 month prior to screening
• Females of childbearing potential
• Current treatment with potent inhibitors of hepatic cytochrome P450 (CYP) enzyme complex pathways affecting drug metabolism (e.g. ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir)
• Current treatment with CYP3A and/or P-Glycoprotein (Pgp) inducers (e.g. rifampin, rifampicin, carbamazepine, St. John's wort)
• Any other conditions that in the opinion of the investigators are likely to prevent compliance with the study protocol or pose a safety concern if the subject participates in the study.