This study is being done to determine if Ranolazine treatment improves coronary microcirculation function among patients with coronary microcirculation dysfunction. We are also looking to learn if symptomatic improvement of chest pain during treatment with Ranalozine is related to improved coronary microcirculation function.

Inclusion Criteria:

• - Patients with subjective symptoms of ischemia without flow limiting angiographic CAD (<50% epicardial coronary stenosis) and abnormal IMR (>20 U).

• Definition of ischemia (any one):

  • chest pain with dynamic ischemic ECG changes (t wave inversions or > 1 mm ST depressions
  • Exercise treadmill testing induced chest pain with ≥1 mm of downsloping or flat ST segment depression during exercise or recovery; ≥2 mm of ischemic ST depression at a low workload (stage 2 or less or ≤130 beats/min); early onset (stage 1) or prolonged duration (>5 min) of ST depression; multiple leads (>5) with ST depression
  • Nuclear stress perfusion defect > 10%
  • Stress echocardiogram with stress induced wall motion abnormality

Exclusion Criteria:

• - Age < 18 yrs
• Flow Limiting epicardial CAD >50%
• Life expectancy < 6 months
• Recent (<1 week) myocardial infarction or positive biomarkers
• Severe aortic stenosis
• Contraindications to IMR testing including inability to utilize antithrombotic therapy and/or intravenous adenosine
• Contraindications to Ranolazine therapy:
• Patients with known hepatic insufficiency, prolonged QT or renal failure (GFR < 60)
• use of drugs that inhibit CYP3A such as diltiazem, verapamil, ketoconazole, macrolides and HIV protease inhibitors
• Pregnancy, breastfeeding
• Patients taking drugs which prolong QT interval

1 year