10.1 Diagnosing ANOCA/INOCA and Treating MINOCA in the Interventional Laboratory

Problem Presenter: Tim Henry

These proceedings summarize the educational activity of the 18th Biennial Meeting of the International Andreas Gruentzig Society held January 27 to 30, 2026, in Puerto Ayora, Santa Cruz, Ecuador.

Faculty Disclosures     Sponsors

2026 IAGS Summary Document

Statement of problem or issue

Angina can be caused by: (1) epicardial coronary artery disease; (2) microvascular disease; (3) vasoconstrictive disease (vasoreactivity); and (4) several miscellaneous conditions such as myocardial bridges, etc.[1-4] Although often considered as separate entities, many patients have combinations of these abnormalities present in varying proportions. To design effective treatment strategies it is critical to understand properly the underlying mechanism of angina. It is becoming increasingly clear that the microvasculature plays a critical role in many pf the unmet clinical needs in cardiovascular disease.

Gaps in current knowledge

Clinical areas where microvascular disease and vasoreactivity play key roles include:

• ANOCA (angina with non-obstructed coronary arteries).
• INOCA (ischemia with non-obstructed coronary arteries.
• MINOCA (myocardial infarction with non-obstructed coronary arteries.
• HFpEF (approximately 75% have microvascular dysfunction).
• STEMI/NSTEMI with MVO (microvascular obstruction – 60% of anterior MI patients have MVO resulting in worse long-term prognosis).
• Post-PCI and post-CTO angina: 20-40% of patients have ongoing angina, At times due to incomplete revascularization or diffuse disease, but frequently it involves microvascular disease or vasoconstriction.
• Refractory angina: Frequently involves bot epicardial and microvascular disease.
• Long COVID – microvascular dysfunction plays a key role.
• Hypertrophic cardiomyopathy (HCM) – microvascular dysfunction frequently is the cause of angina.

In order to understand and characterize the etiology of ongoing angina despite medical therapy, invasive coronary functional physiology testing (ICFT) is often required.[1-4] The ICFT is performed using adenosine infusion to assess endothelium independent function, acetylcholine (Ach) to assess endothelium-dependent function (low dose ACh), and epicardial coronary vasospasm (high dose Ach). Challenges remain regarding the best method to assess microvascular function (doppler ultrasound versus bolus thermodilution versus continuous thermodilution, with several novel methods under investigation), and technical issues (radial versus femoral access, pre- or post-nitroglycerin, and ad hoc versus elective off medications).

Possible solutions or future directions

We know from the CorMicA randomized clinical trial that ICFT-guided therapy is superior to empiric treatment only (Ford TJ, et al).[5] This was confirmed by the ILIAS ANOCA trial and the AID-ANGIO study for ANOCA/INOCA, and by the PROMISE trial for MINOCA.[6-9]

MINOCA is another large knowledge gap area. MINOCA is not a specific diagnosis, but rather an umbrella descriptive term that covers multiple underlying mechanisms that can lead to myocardial infarction (MI) without significant epicardial atherosclerotic obstruction. Some of these mechanisms are listed below:

• Coronary microvascular disease.
• Coronary artery vasospasm.
• Plaque erosion.
• Coronary thromboembolism.
• Spontaneous coronary artery dissection.
• Myocarditis.
• Takotsubo syndrome (autonomic neurovascular dysfunction).
• Nonischemic cardiomyopathies.

Future approaches will be based on studies designed to understand the appropriate medications for specific phenotypes.[2,3,8] Current medications include nitrates, beta-blockers, calcium channel antagonists, statins, angiotensin receptor blockers and converting enzyme inhibitors, and ranolazine. Non-medication lifestyle therapies include exercise, weight loss, psychotherapy, and meditation. Novel device-based therapies to be investigated include transcutaneous nerve stimulation and stellate ganglion blockade, external counterpulsation, and coronary sinus reducer implantation.

References

1. Taqueti VR, Di Carli MF. Coronary Microvascular Disease Pathogenic Mechanisms and Therapeutic Options: JACC State-of-the-Art Review. J Am Coll Cardiol. 2018 Nov 27;72(21):2625-2641. doi: 10.1016/j.jacc.2018.09.042. PMID: 30466521.
2. Samuels BA, et al; Microvascular Network (MVN). Comprehensive Management of ANOCA, Part 1-Definition, Patient Population, and Diagnosis: JACC State-of-the-Art Review. J Am Coll Cardiol. 2023 Sep 19;82(12):1245-1263. doi: 10.1016/j.jacc.2023.06.043. PMID: 37704315.
3. Smilowitz NR, et al; Microvascular Network (MVN). Comprehensive Management of ANOCA, Part 2-Program Development, Treatment, and Research Initiatives: JACC State-of-the-Art Review. J Am Coll Cardiol. 2023 Sep 19;82(12):1264-1279. doi: 10.1016/j.jacc.2023.06.044. PMID: 37704316.
4. de Silva R, et al. Refractory angina: mechanisms and stratified treatment in obstructive and non-obstructive chronic myocardial ischaemic syndromes. Eur Heart J. 2025 Oct 7;46(38):3738-3757. doi: 10.1093/eurheartj/ehaf284. PMID: 40590516.
5. Ford TJ, et al. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial. J Am Coll Cardiol. 2018 Dec 11;72(23 Pt A):2841-2855. doi: 10.1016/j.jacc.2018.09.006. Epub 2018 Sep 25. PMID: 30266608.
6. Boerhout CKM, et al. Coronary function testing vs angiography alone to guide treatment of angina with non-obstructive coronary arteries: the ILIAS ANOCA trial. Eur Heart J. 2025 Nov 7;46(42):4396-4406. doi: 10.1093/eurheartj/ehaf580. PMID: 40796241.
7. Jerónimo A, et al. Comprehensive diagnosis in chronic coronary syndromes combining angiography and intracoronary testing: the AID-ANGIO study. EuroIntervention. 2025 Jan 6;21(1):35-45. doi: 10.4244/EIJ-D-24-00499. PMID: 39773829.
8. Douglas PS, et al. Survival After Initial Stress Testing vs Anatomic Testing in Suspected Coronary Artery Disease: Long-Term Follow-Up of the PROMISE Randomized Clinical Trial. JAMA Cardiol. 2025 Oct 1;10(10):1050-1054. doi: 10.1001/jamacardio.2025.2882. PMID: 40864459.
9. Vrints C, et al; ESC Scientific Document Group. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024 Sep 29;45(36):3415-3537. doi: 10.1093/eurheartj/ehae177. Erratum in: Eur Heart J. 2025 Apr 22;46(16):1565. doi: 10.1093/eurheartj/ehaf079. PMID: 39210710.