Ischemia With Nonobstructive Coronary Artery Disease

Figure 1. Clinical Diagnostic Flow of INOCA Ischemic heart disease is suspected when patients have symptoms and/or signs of ischemic heart disease. When there is no flow-limiting obstructive coronary artery disease, ischemia with nonobstructive coronary arteries (INOCA) should be suspected. CT = computed tomography.

Figure 2. Coronary Anatomy and Possible Causes of INOCA The coronary arterial system is composed of 3 compartments: epicardial coronary arteries, prearterioles, and arterioles. Each compartment has different sizes and functions with uninterrupted borders. Myocardial ischemia can originate from any part of this coronary arterial system. INOCA = ischemia with non-obstructive coronary arteries.

Figure 3. Schematic Concept of Invasive Physiologic Indexes Invasive physiologic indexes are helpful in identifying the presence of myocardial ischemia and discriminating the mechanisms of myocardial ischemia. Fractional flow reserve (FFR) or nonhyperemic pressure ratio (NHPR) reflects the degree of flow limitation caused by epicardial coronary artery lesions, and the index of microcirculatory resistance (IMR) or hyperemic microvascular resistance (HMR) represents the status of the microcirculatory system. Coronary flow reserve (CFR) is influenced by both macrovascular and microvascular disease status.

Figure 4. Representative Cases for INOCA (A) Masked diffuse disease. Invasive coronary angiography showed an insignificant coronary lesion at the proximal left anterior descending (LAD) artery. However, FFR was 0.73 with a gradual step-up at pressure pull back tracing. Intracoronary ultrasound showed diffuse atherosclerotic plaque at the proximal LAD. (B) Coronary microvascular disease. Invasive coronary angiography showed insignificant epicardial coronary stenosis. FFR was 0.91 at the distal LAD artery, but CFR was 1.8 and IMR was 51 U. (C) Epicardial vasospastic angina. Baseline angiography showed spastic coronary arteries. After intravenous ergonovine infusion, the patient complained of severe chest pain, and significant coronary spasms (>90% constriction) occurred in the LAD and right coronary arteries, whereas the electrocardiogram showed significant ST-segment elevation. (D) Microvascular vasospastic angina. The ergonovine provocation test showed diffuse insignificant epicardial artery constriction (<90%). However, the patient complained of severe chest pain, and the electrocardiogram showed significant ST-segment elevation at inferior leads. Abbreviations as in Figures 2 and 3.

Figure 5. Occurrence and Overlap of INOCA Endotypes There are several endotypes of ischemia with nonobstructive coronary arteries (INOCA), and multiple mechanisms can coexist in patients with INOCA.

Central Illustration. Identifying Mechanisms of Ischemia With Nonobstructive Coronary Arteries With Invasive Coronary Angiography A systematic approach to diagnose ischemia with nonobstructive coronary arteries (INOCA) and define the underlying mechanisms is presented. The first step is excluding flow-limiting epicardial coronary artery disease using invasive coronary angiography. Invasive physiologic assessment using fractional flow reserve (FFR) or nonhyperemic pressure ratio (NHPR) and/or invasive coronary imaging is helpful. After excluding the presence of ischemia-causing epicardial lesions, comprehensive physiologic assessments should be performed to identify the microvascular dysfunction. Finally, provocation tests are helpful in the diagnosis of vasospastic angina. HMR = hyperemic microvascular resistance; IMR = index of microvascular resistance.