Ischemia and no obstructive coronary arteries in patients with stable ischemic heart disease

Abstract

A large proportion of patients with suspected obstructive coronary artery disease (CAD) is found to have ischemia with no obstructive coronary artery disease (INOCA). Based on current evidence, these patients are at increased risk of adverse cardiovascular events, even though they have no obstructive CAD. Importantly, INOCA is associated with recurrent clinical presentations with chest pain, impaired functional capacity, reduced health-related quality of life, and high healthcare costs. Underlying coronary microvascular dysfunction (CMD), through endothelium-dependent and independent mechanisms contribute to these adverse outcomes in INOCA. While non-invasive and invasive diagnostic testing has typically focused on identification of obstructive CAD in symptomatic patients, functional testing to detect coronary epicardial and microvascular dysfunction should be considered in those with INOCA who have persistent angina. Current diagnostic methods to clarify functional abnormalities and treatment strategies for epicardial and/or microvascular dysfunction in INOCA are reviewed.

Keywords: Atherosclerosis; Coronary artery disease; Functional imaging; Ischemic heart disease.

Figure 1.. Mechanisms Contributing to INOCA

In addition to epicardial atherosclerosis and epicardial coronary vasospasm, CMD is a major cause of abnormal coronary blood flow regulation. CMD-related functional and structural mechanisms contribute to impaired blood flow and ischemia. CAD: coronary artery disease; CMD: coronary microvascular dysfunction; VSMC: vascular smooth muscle cell. Created with BioRender.com.

Figure 2.. Abnormal Coronary Vascular Function in INOCA and Outcomes

In women with no obstructive coronary artery disease, functional coronary angiography identifies those at higher risk for adverse events and angina hospitalizations. Epicardial coronary vascular reactivity can impact microvascular resistance to flow. A majority of patients with low coronary flow reserve also had abnormal epicardial coronary artery response to acetylcholine, and these pathways are inter-related. Reprinted with Permission from AlBadri et al.

Figure 3.. Therapeutic Considerations in CMD Management

Treatment of CMD and associated abnormal vasoreactivity includes traditional anti-anginal medications to lower myocardial oxygen demand, as well as medications that improve endothelial function. Anti-nociceptive strategies can be helpful given the role of enhanced pain perception described in a subset of CMD subjects. ACE-I: angiotensin converting enzyme-inhibitors; EECP: Enhanced external counter pulsation *Patients may have overlapping abnormal pathways with low coronary flow reserve + smooth muscle dysfunction.