The following are key points to remember from a state-of-the-art review on comprehensive management of angina with nonobstructive coronary arteries (ANOCA):

1. There is an important distinction between ANOCA (angina with nonobstructive coronary arteries) and INOCA (ischemia with nonobstructive coronary arteries). The demonstration of ischemia is not a prerequisite for the diagnosis of ANOCA as many patients presenting with angina or an anginal equivalent such as shortness of breath may have negative stress tests, including exercise treadmill, stress echocardiography, and nuclear stress tests. ANOCA is a working diagnosis.
2. The majority (>60%) of patients with ANOCA have angina provoked by physical exertion and/or emotional stress, and resolving with rest, whereas the remainder have angina sporadically or at rest, or have an anginal equivalent such as shortness of breath. Symptoms are stable (although may wax and wane) and have usually been present for ≥3 months, with no other clearly identified etiology. Patients with ANOCA tend to be younger, have fewer risk factors than those with obstructive coronary artery disease, and are more likely to be women.
3. Many patients with ANOCA have normal findings on conventional diagnostic testing. The absence does not exclude the presence of coronary microvascular dysfunction. The assessment of coronary flow reserve (CFR) by cardiac magnetic resonance or positron emission tomography has a Class 2a recommendation in symptomatic patients in the 2021 multisociety guideline for the evaluation and diagnosis of chest pain.
4. For invasive testing, patient preparation and vascular access are important to focus on and specific drugs are used such as adenosine to induce hyperemia and acetylcholine to induce vasospasm and endothelial dysfunction. If radial access is used, avoid the use of a calcium channel blocker (CCB), which could mask spasm with acetylcholine administration—an important consideration. The left anterior descending artery is preferred for routine use of invasive testing. A minimum of six-lead electrocardiography is used for continuous monitoring during the challenge.
5. There are four important endotypes of ANOCA to be recognized: 1) Abnormal CFR and microvascular resistance. This endotype is associated with a variety of coronary risk factors including increasing age, hypertension, diabetes, and dyslipidemia, which may reflect underlying subclinical atherosclerosis. 2) Isolated abnormal CFR. This endotype is usually characterized by increased basal cerebral blood flow and normal hyperemic flow. 3) Abnormal index of microcirculatory resistance/hyperemic microvascular resistance. 4) Normal CFR and microvascular resistance. These endotypes have variable prognostic significance.
6. Ideally, management of patients with ANOCA should occur at centers with coronary function testing expertise that can appropriately identify, test, and treat these complex patients, and improve care by integrating expert clinical staff, invasive and noninvasive diagnostic modalities, and clinical resources to ensure high-quality longitudinal follow-up. These patients benefit from a multidisciplinary care team that includes an interventional cardiovascular disease specialist with expertise in coronary microvascular dysfunction assessment, provocative testing for coronary spasm and myocardial bridge testing, and a noninvasive cardiologist with expertise in noninvasive ANOCA testing.
7. Pharmacotherapy for coronary microvascular dysfunction: Exercise training, mental relaxation, weight loss, and cardiac rehabilitation have been associated with improvements in symptoms, exercise capacity, time to angina, and quality of life (QoL). First-line agents include the beta-blockers, angiotensin-converting enzyme inhibitors, statins, and lifestyle measures. Second- and third-line agents, ranolazine, CCBs, long-acting nitrates, ivabradine, and L-arginine can be used with limited efficacy and results.
8. Pharmacotherapy for coronary spasm: CCBs should be used first-line for epicardial coronary spasm and may be beneficial for microvascular spasm. When angina persists despite a single CCB, dihydropyridine and non-dihydropyridine CCBs may be used in combination for additional antianginal effect, as tolerated by blood pressure and heart rate. Short-acting nitrates and statin medications can be important adjuncts to first-line therapy. Second- and third-line agents include cilostazol and cyproheptadine.
9. For those patients with myocardial bridging as the cause, surgical approaches can be attempted after failure of pharmacotherapy. Surgical unroofing is currently the treatment of choice for symptomatic patients who fail medical management because it aims to correct the underlying pathology and is effective in improving symptoms and QoL.
10. There are a few clinical trials testing novel medications and invasive management of patients with ANOCA. Endothelial receptor antagonist, transcutaneous electrical nerve stimulation, enhanced external counterpulsation, coronary sinus reducer therapy, and cell-based therapy are emerging precision medicine models that require further assessment.
11. There is a need for collaborative research initiatives to improve clinical care in ANOCA. Clinical trials and national and international registries focused on clinical characteristics, harmonious data collection, standardization of protocols to assess effectiveness of therapies and long-term outcomes are needed to advance the care of these patients.

Note: The key points also include information from part 2 of this article: Smilowitz NR, et al. Comprehensive Management of ANOCA, Part 2—Program Development, Treatment, and Research Initiatives: JACC State-of-the-Art Review. J Am Coll Cardiol 2023;82:1264-79; https://www.jacc.org/doi/10.1016/j.jacc.2023.06.044.

Clinical Topics: Prevention, Stable Ischemic Heart Disease, Chronic Angina

Keywords: Chest Pain, Microvascular Angina, Myocardial Ischemia, Patient Care Team, Primary Prevention

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