Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis (MARINA)

The purpose of this study is to look at the effects of the drug Ranolazine compared to Placebo on symptoms of chest pain or chest tightness (known as angina), exercise endurance and ability, and changes in blood flow to the very small arteries of the heart (known as coronary microvascular function) in patients who do not have significant blockages in their major heart arteries. Ranolazine is a drug that is already approved by the FDA for angina, but it may be particularly effective in people with disease in their tiny heart vessels (known as coronary microvascular disease).

This trial aims to enroll 50 patients with angina who undergo baseline bicycle exercise testing with monitoring of the heart's electrical activity and oxygen consumption (known as cardiopulmonary exercise test) and coronary angiogram (taking pictures of the heart arteries through small hollow tubes placed through the wrist or groin). If severe blockages in the main arteries are not found then testing for coronary microvascular function will be performed. Subsequently, participants will then be randomized 50/50 to either Ranolazine or Placebo. After taking the study drug for 12 weeks, they will then repeat the cardiopulmonary exercise test and the coronary angiogram with testing for microvascular function.

Heart disease is the most common cause of death in the world. Most of our understanding of heart disease has involved the large heart arteries (epicardial arteries); however, disease of the very small heart arteries (coronary microvasculature) likely precedes the development of epicardial disease and represents the "base of the iceberg" of cardiovascular disease. Yet, we do not understand how dysfunctional microvasculature leads to reduced blood flow, symptoms and adverse outcomes.

Coronary microvascular disease results from a combination of structural and functional abnormalities, so it is important to have reliable diagnostic tools that do not rely solely on imaging. The gold-standard for testing involves hemodynamic (blood circulation) measurements such as coronary flow reserve (CFR) and hyperemic microcirculatory resistance (HMR) that take place in the cardiac catheterization laboratory.

Ranolazine is a relatively new U.S Food and Drug Administration-approved medicine to help with angina (chest pain). There are no publications on the effect of Ranolazine on HMR.

Eligibility Criteria:
Inclusion Criteria:

* History of typical angina or effort-induced anginal symptoms and are currently experiencing angina at least once per week
* Abnormal stress ECG, exercise stress imaging, or pharmacological stress imaging
* Non-obstructive coronary artery disease as defined by lesion stenosis ≤ 50% in any artery as visualized by diagnostic angiography

Exclusion Criteria:

* Inability to provide informed consent
* Active Myocardial Infarction
* History of coronary artery bypass grafting
* Diagnosis of other specific cardiac disease such as severe valvular heart disease, cardiomyopathy, or variant angina
* Left Ventricular Ejection Fraction (LVEF) \< 30%
* Known renal insufficiency (CrCl \< 30 mL/min) or on dialysis
* Contraindications to the use of Ranolazine