Ranolazine and Microvascular Angina by PET in the Emergency Department

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).