Current therapeutic options for a well-recognized group of patients with anginal symptoms-a positive exercise tolerance testing, SPECT or perfusion defect in MRI but angiographically normal coronary arteries-are limited. The condition, referred to as microvascular angina (MVA) or cardiac syndrome X, is not as benign as originally reported-patients presenting with unstable angina and nonobstructive atherosclerotic coronary artery disease have a 2% risk of death or myocardial infarction at 30 days of follow-up. It is more common in women in whom the first presentation of angina occurs either perimenopausally or postmenopausally. Aberrant flow-mediated coronary vasomotion is pivotal in the pathogenesis (systemic) impairment in endothelial function. Indeed, some centers use systemic assessments of vascular function in their diagnostic pathways for this group of women. It was recently suggested that endothelial dysfunction may lead to myocardial ischemia.

In the present study, the investigators tested the hypothesis that udenafil offers dual benefits of improving vascular function and lessening ischemia in women with angina, perfusion defect in cardiac MRI, and normal coronary arteries.

The aim of this study is that udenafil offers dual benefits of improving vascular function and lessening ischemia in women with microvascular angina, perfusion defect in cardiac MRI, and normal coronary arteries.

The UMPIRE trial is a multi-center, prospective, randomized, placebo controlled trial, designed to evaluate the effect of udenafil in improvement of myocardial stress perfusion defect in cardiac MRI, in women patients with microvascular angina. A total of 70 patients will be randomized to udenafil(100 mg q d) or placebo treatment. The primary end point of the study is Change of perfusion defect over 25% of baseline defect in adenosine-stress cardiac MRI after 3-month treatment. The secondary endpoints of this study are change of perfusion defect less than 25% of baseline defect in adenosine-stress cardiac MRI after 3-month treatment, decrement of frequency of chest pain, improvement of ST-depression in stress test, improvement of duke score in stress test, improvement of QoL assessment by SF-36 questionnaire, improvement of sexual dysfunction assessment by BISF-W self-questionnaire and improvement of biomarkers foe endothelial function.

Inclusion Criteria:

1. MVA patients with typical symptom and positive adenosine-stress cardiac MRI and with normal coronary artery in coronary angiogram or coronary artery CT angiography.
2. Definition of positive adenosine-stress MRI: perfusion defect > 25% of transmurality ( by 2 radiologist based on visual assessment and qualitative assessment in core-lab)
3. Gender: female
4. Age: 18-80

Exclusion Criteria:

1. The patient with contraindication to MR contrast media or MR Imaging

2. LVEF < 50%

3. Any heart rhythm abnormality other than sinus rhythm

4. Valvular heart disease with more than moderate degree

5. Renal failure

6. Congestive Heart Failure

7. Myocardial infraction

8. Myocarditis

9. Congenital heart disease

10. Pericarditis

11. Variant angina (positive provocation test with Ergonovine or acetylcholine)

12. GERD (conformed by esophagogastroduodenoscopy)

13. Pregnant women with suspected, pregnant women or women with lactation

14. QT prolongation syndrome or take drugs that prolong the QT interval - Antiarrhythmics class IA; quinidine, procainamide - Antiarrhythmics class III; amiodarone, sotalol

15. Preanalytical within 30 days of screening in a clinical trial that may affect the influence of udenafil

    - Other PDE5 inhibitors (ex. Sildenafil, tadalafil)

    - Nitrates/ NO donor (ex. Nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, amyl nitrate/nitrite, sodium nitroprusside, nicorandil)

16. Preanalytical within 7 days of screening in a clinical trial that may affect the metabolism of udenafil

    • Antibacterials (ex. Erythromycin)
    • Antifungals (ex. Itraconazole, ketoconazole)
    • Antivirals (ex. Ritonavir, saquinavir, amprenavir, indinavir, nelfinavir)
    • Cimetidine
    • Grapefruit juice

17. Allergy or sensitivity with PDE 5 inhibitors

    -