The purpose of this study is to determine the effectiveness of Ranolazine for the treatment chest pain from disease of small vessels of the heart also known as 'microvascular angina'.

The Yale Chest Pain Center (CPC) is a unique clinical lab that provides an integrated interdisciplinary research team, access to high volume of chest pain patients largely free of coronary disease (93%) as well state of the art diagnostics including cardiac PET and a sophisticated system for serum processing and banking facilities. The CPC cohort represents a unique population with unrecognized microvascular disease and is often only accessible through the ED. We propose a one-year pilot study to understand the mechanisms of angina relief by Ranolazine (n=20) in patients with microvessel disease in the ED population as compared to controls (n=10) at baseline and at 1-month. In addition, changes in pain scores and function as measured by Seattle Angina Questionnaire (SAQ), recidivism and costs will be measured and correlated with changes in coronary flow reserve (CFR). Serum samples will be obtained and banked for future marker analysis as intermediate surrogates of outcomes.

Primary aim: To compare changes in coronary flow reserve as measured by cardiac PET in patients receiving Ranolazine versus controls.

Secondary aim: To determine if Ranolazine changes Seattle Angina Questionnaire (SAQ) scores in association with changes in Coronary Flow Reserve (CFR) versus controls.

Exploratory aim: To compare composite rate of return visits (office, emergency department and hospitalization) for chest pain within 4-weeks of enrollment between patients with and without Ranolazine.

Inclusion Criteria:

• Patients admitted to the Yale ED CPC
• ≥ 30 years age
• chest pain or angina equivalent as their chief complaint within 24 hours of enrollment
• Coronary Flow Reserve(CFR) <2.5 on PET scan in the ED.

Exclusion Criteria:

• Acute coronary syndrome
• Prior evidence of obstructive heart disease (history of Percutaneous Transluminal Coronary Angioplasty (PTCA), Coronary Artery Bypass Grafting (CABG) or calcium score > 10 on PET scan)
• Resting blood pressure of systolic >180/110 mm Hg or <100/40
• known cardiomyopathy or heart failure
• currently on dialysis
• creatinine clearance <30 ml/min
• liver cirrhosis
• significant aortic stenosis (murmur on exam)
• active use of cocaine or amphetamine
• current use of potent CYP3A4 inducers or inhibitors (such as ketoconazole, clarithromycin, HIV protease inhibitors)
• baseline QTc > 580 msec
• use of drugs that prolong QTc (Haldol, erythromycin)
• pregnancy
• inability to read or understand English
• suffering from a condition that precludes interview (i.e. cognitive or communication impairment).

Small sample size with higher than expected dropout rates.