Coronary Arterial Function and Disease in Women With No Obstructive Coronary Arteries

Abstract

Ischemic heart disease (IHD) is the leading cause of mortality in women. While traditional cardiovascular risk factors play an important role in the development of IHD in women, women may experience sex-specific IHD risk factors and pathophysiology, and thus female-specific risk stratification is needed for IHD prevention, diagnosis, and treatment. Emerging data from the past 2 decades have significantly improved the understanding of IHD in women, including mechanisms of ischemia with no obstructive coronary arteries and myocardial infarction with no obstructive coronary arteries. Despite this progress, sex differences in IHD outcomes persist, particularly in young women. This review highlights the contemporary understanding of coronary arterial function and disease in women with no obstructive coronary arteries, including coronary anatomy and physiology, mechanisms of ischemia with no obstructive coronary arteries and myocardial infarction with no obstructive coronary arteries, noninvasive and invasive diagnostic strategies, and management of IHD.

Keywords: coronary disease; coronary vessels; myocardial infarction; risk factors; sex characteristics.

Figure 1.. Normal Structure and Function of Coronary Macro- and Microcirculation.

Reprinted from Taqueti VR et al with permission.

Figure 2.. Coronary Vascular Dysfunction Mechanisms in Ischemia and No Obstructive Coronary Artery Disease.

CBF, coronary blood flow; CFR, coronary flow reserve; hMR, hyperemic index of microcirculatory resistance. Reprinted from de Silva R et al with permission.

Figure 3.. Noninvasive Diagnosis of Ischemic Heart Disease in Women.

Schematic of the ischemic cascade, a sequence of pathophysiologic events associated with CAD, and noninvasive multimodality imaging approaches for the evaluation of IHD in women. Anatomy-based (CCTA) and quantitative functional (CFR) imaging probes earlier events in the cascade than dose conventional testing, and as such may be especially useful in the evaluation of women. CCTA, coronary computed tomography angiography; CFR, coronary flow reserve; MPI, myocardial perfusion imaging; SE, stress echocardiography; ETT, exercise treadmill testing. Adapted from Taqueti VR et al with permission.

Figure 4.. Stratified Medical Therapy Using Invasive Coronary Function Testing in INOCA.

The Coronary Microvascular Angina (CorMicA) Trial randomized patients with angina and no obstructive CAD to invasive coronary function testing linked to stratified medical therapy or standard care. Invasive coronary function testing included assessment of coronary flow reserve (CFR), index of microcirculatory resistance (IMR), fractional flow reserve (FFR), and vasoreactivity testing with acetylcholine (Ach) and nitroglycerin (GTN). Stratified medical therapy based on diagnosis of microvascular angina, vasospastic angina, vs noncardiac chest pain was associated with improved angina and quality of life. Reprinted from Ford TJ et al with permission.

Figure 5.. “Traffic light” clinical algorithm for the diagnosis of MINOCA.

CAD, coronary artery disease; FFR, fractional flow reserve; LV, left ventricular; MINOCA, myocardial infarction with no obstructive coronary arteries; SCAD, spontaneous coronary artery dissection. Reprinted from Tamis-Holland JE et al with permission.

Figure 6.. The Diverse Pathogenesis of Myocardial Infarction and Ischemia in Women.

While obstructive atherosclerosis is the most common etiology of MI and ischemia in women, it is just the tip of the iceberg when considering the diverse pathological mechanisms of coronary arterial function and disease in women. Coronary microvascular dysfunction and coronary vasospasm are common causes of ischemia with no obstructive coronary arteries (INOCA). Spontaneous coronary artery dissection (SCAD) is a cause of MI that can have an obstructive or nonobstructive angiographic appearance. MI in the setting of no obstructive coronary arteries (MINOCA) can be attributed to coronary vasospasm (epicardial or microvascular), thromboembolism, plaque rupture, or plaque erosion. Elevated troponin in women may also be due to non-MI etiologies, including myocarditis, nonischemic cardiomyopathy, and Takotsubo Syndrome. INOCA, ischemia with no obstructive coronary arteries; MI, myocardial infarction; MINOCA, myocardial infarction with no obstructive coronary arteries; SCAD, spontaneous coronary artery dissection. (Illustration credit: Julia Huang and Ben Smith).