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The reason the articles are here is for the purpose to educate the public about Coronary Microvascular Disease. As a public service, we are providing some source material.


2017 American Heart Association, Inc. – White Paper

Ischemia and No Obstructive Coronary Artery Disease (INOCA)
Developing Evidence-Based Therapies and Research Agenda for the next Decade
By:    C. Noel Bairey Merz, MD
         Carl J. Pepine, MD
         Mary Norine Walsh, MD
         Jerome L. Fleg, MD

The Women’s Ischemia Syndrome Evaluation (WISE) Study: protocol design, methodology and feasibility report

The Women’s Ischemia Syndrome Evaluation (WISE) is a National Heart, Lung and Blood Institute-sponsored, four-center study designed to:
1. Optimize symptom evaluation and diagnostic testing for ischemic heart disease
2. Explore mechanisms for symptoms and myocardial ischemia in the absence of epicardial coronary artery stenosis
3. Evaluate the influence of reproductive hormones on symptoms and diagnostic test response

Accurate diagnosis of ischemic heart disease in women is a major challenge to physicians, and the role reproductive hormones play in this diagnostic uncertainty is unexplored. Moreover, the significance and pathophysiology of ischemia in the absence of significant epicardial coronary stenosis is unknown.

Coronary Microvascular Dysfunction

In the last two decades, a number of studies reported that abnormalities in the coronary microcirculation function and structure may occur in patients without obstructive atherosclerosis, in patients with risk factors, with myocardial diseases, as well as in obstructive atherosclerosis. 

Coronary microvascular dysfunction may be iatrogenic and is an important risk marker, contributing to the pathogenesis of cardiovascular and myocardial diseases.  Due to its importance, it becomes a therapeutic target.  This article presents an update on the clinical relevance of coronary microvascular dysfunction in different clinical situations.









Coronary Endothelial Dysfunction, Obesity and Metabolic Syndrome

To define the impact of metabolic syndrome (MetS) and obesity on coronary vascular function, with the hypothesis that subjects with MetS will have endothelial dysfunction.

Obesity or the metabolic syndrome (MetS) is associated with a higher risk of diabetes and coronary artery disease (CAD). Endothelial dysfunction is a common casual pathway in the initiation and progression of CAD.

Syndrome X and Microvascular Coronary Dysfunction

A 44-year old woman is referred for worsening chest pain since 2007, with abnormal stress testing in May 2008, followed by coronary angiography in June 2008.  She had several prior hospitalizations to evaluate possible myocardial infraction, and 1 with an elevated troponin level in 2001.  She has a history of breast cancer in 2007.  She currently reports daily exertional substernal chest pain that radiates to her left arm and hand that is relieved with rest.  She works as an undercover police officer, frequently has to chase suspects, and is concerned about being able to do her job.  A review of cardiac risk factors is negative.  She takes tamoxifen with vitamins, and her physical examination and resting ECG are normal.  Review of the prior coronary angiography confirm absence of obstructive coronary disease and normal left ventricular function.

To further evaluate the basis for her symptoms, she underwent coronary reactivity testing (CRT), which demonstrated a limited coronary flow reserve (CFR) to adenosine and coronary blood flow reserve as well as coronary artery constriction with acetylcholine, indicative of endothelial dysfunction.  Adenosine stress cardiac magnetic resonance imaging was consistent with microvascular coronary dysfunction.

Microvascular Coronary Dysfunction in Women – Pathophysiology, Diagnosis, and Management

Women exhibit a greater symptom burden, more functional disability, and a higher prevalence of no obstructive coronary artery disease (CAD) compared to men when evaluated for signs and symptoms for myocardial ischemia.  Microvascular Coronary Dysfunction (MCD) defined as limited coronary flow reserve (CFR) and/or coronary endothelial dysfunction is the predominant etiological mechanism of ischemia in women with the triad of persistent chest pain, no obstructive CAD, and ischemia evidenced by stress testing.  Evidence shows that approximately 50% of these patients have physiologic of MCD.  MCD is associated with a 2.5% annual major adverse event rate that includes death, nonfatal MI, nonfatal stroke and congestive heart failure.  Although tests such as adenosine stress cardiac magnetic resonance imaging (CMRI) may be a useful noninvasive method to predict subendocardial ischemia, the gold standard test to diagnose MCD is an invasive Coronary Reactivity Testing (CRT).  Early identification of MCD by CRT may be beneficial in prognostication and stratifying these patients for optimal medical therapy.  Currently, understanding of MCD pathophysiology can be used to guide diagnosis and therapy.  Continued research in MCD is needed to further advance our understanding.

Angina in Women without Obstructive Coronary Artery Disease

A staggering number of women undergo coronary angiography each year due to angina symptoms, only to discover “normal” findings.  It is now appreciated that these women face significant greater morbidity than once believed, with an uncertain treatment course and high rates of medical utilization.  The pathophysiology of chest pain in women without obstructive coronary disease represents a heterogeneous mix:  some have cardiac chest pain that is non-ischemic, others have chest pain due to microvascular ischemia or abnormal pain sensation, and still others have chest pain of non-cardiac origin.  All of these women suffer from symptoms of chest pain; however, the prognosis and therapeutic options differ widely.  The following is a concise review of the epidemiology, prognosis, disease mechanisms, and treatment options for chest pain in women without obstructive coronary artery disease (CAD).