Abbreviations
- ANOCA (angina with nonobstructive coronary arteries)
- ASCVD (atherosclerotic cardiovascular disease)
- CAD (coronary artery disease)
- CFT (coronary function testing)
- CMD (coronary microvascular dysfunction)
- IHD (ischemic heart disease)
- MB (myocardial bridging)
Introduction
Every year, more than 10 million people in the United States seek evaluation for suspected ischemic heart disease (IHD). Cardiovascular disease is a leading cause of morbidity and mortality in women, but significant disparities exist in evaluation and management. In the last 60 years, the overall population mortality rate due to atherosclerotic coronary artery disease (CAD) has declined by almost 50%; however, in women the rate of decline has been substantially lower. Furthermore, the frequency of hospitalizations for acute myocardial infarction in young women (35-54 years) has increased from 21% in 1995-1999 to 31% in 2010-2014, compared to a relatively stable frequency in young men (from 30% to 33%).
Historically, the evaluation of suspected cardiac chest pain, or angina pectoris, has focused on identifying myocardial ischemia caused by obstructive CAD; however, nearly 50% of patients undergoing invasive coronary angiography for suspected IHD are found to have no obstructive CAD or no coronary arteries with ≥50% stenosis. Instead, prior studies have suggested that 3 to 4 million people in the United States suffer from angina with nonobstructive coronary arteries (ANOCA). ANOCA is an umbrella term defined by the presence of anginal chest pain with either normal epicardial coronal arteries or coronary arteries with nonobstructive CAD. It encompasses coronary vasomotor disorders including coronary microvascular dysfunction (CMD), coronary vasospasm, endothelial dysfunction, symptomatic myocardial bridging (MB), and other nonatherosclerotic disorders. ANOCA endotypes may occur in isolation or as mixed syndromes, and they may exist in combination with CAD, which can be diffuse and missed with invasive angiography without intravascular imaging. Additionally, atherosclerosis of any degree can impair endothelial function and contribute to development of ANOCA. Although CAD is the leading cause of mortality in both men and women, women are more likely than men to suffer from ANOCA.
Routine cardiovascular testing, which focuses on the evaluation of obstructive CAD, is less likely to define the underlying diagnosis in ANOCA, creating a diagnostic disparity for women with stable IHD. According to the 2021 American Heart Association and American College of Cardiology guideline for the evaluation and diagnosis of chest pain, assessment of patients with angina should start with an estimation of the pretest probability of atherosclerotic CAD, and additional diagnostic testing may be advised to rule out obstructive CAD. Although there is a growing array of testing options that can shed light on ANOCA, including invasive coronary function testing (CFT) and positron emission tomography (PET) myocardial perfusion imaging (MPI), evaluation of ANOCA is usually considered only after CAD is excluded. Additionally, these tests remain out of reach of many practicing clinicians, with variation in clinician awareness, site availability, insurance coverage, and patient preference regarding exposure to radiation or contrast dye, additional noninvasive tests, or repeat invasive procedures. As a result, many women with underlying ANOCA or mixed CAD/coronary vasomotor disorders are likely to be misdiagnosed, have a delayed diagnosis, and experience persistent symptoms. For example, in one study of 112 women with nonobstructive CAD entering a multidisciplinary women’s health center, 64% of patients did not have a specific diagnosis prior to entering the center, and 71% received a new or changed diagnosis after undergoing further testing. In another study of 297 women with a self-reported diagnosis of ANOCA, almost 78% were told that their symptoms were noncardiac prior to receiving the correct diagnosis.
Testing that can elucidate the specific subtype of ANOCA is important given the prevalence and increased morbidity and mortality associated with these disorders in women. A study of 297 women with ANOCA found that after symptom onset, women reported lower functional capacity and adverse effects on home life, social life, mental health, interpersonal relationships, and work. Furthermore, a meta-analysis of 6631 patients with and without CMD described a 4-fold increase in mortality and a 5-fold increase in major cardiovascular events in patients with CMD. Recent studies such as the randomized CORonary MICrovascular Angina (CorMicA) trial have demonstrated significant improvement in symptom burden and quality of life with stratified medical therapy based on the identification of the underlying vasomotor disorder. Although it seems intuitive that an accurate diagnosis allows patients to understand their condition and is essential for guiding therapy, stratified medical therapy rarely occurs in clinical practice.
The objective of this review is to introduce subtypes of ANOCA as commonly encountered syndromes in women with angina and to provide a practical diagnostic algorithm for ANOCA.
