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Myocardial infarction with non-obstructive coronary artery disease (MINOCA): the role of microvascular disease

Commented by ESC Working Group on Coronary Pathophysiology & Microcirculation

Pathophysiology and Mechanisms

According to the fourth universal definition of myocardial infarction (UDMI), myocardial infarction with non-obstructive coronary artery disease (MINOCA) is define by classical criteria of myocardial infarction (MI), the absence of stenosis ≥50% in a major epicardial artery demonstrated on coronary angiography1 and no clinically overt specific cause for the acute presentation other than acute MI2. Since the knowledge of underlying pathophysiological mechanisms of MINOCA has developed significantly over the last decade, a key role is mainly occupied by the coronary microvascular disease (CMD)3. The coronary microcirculation has a fundamental role in the regulation of coronary blood flow in response to cardiac oxygen requirements. As a matter of fact, endothelial and smooth muscle cell dysfunction are commonly present in patients with MINOCA and CMD. In this setting, the functional assessment of the microcirculation has become one of the most interesting techniques in the evaluation of MINOCA, as CMD is highly prevalent and has significant unmet clinical need.

As shown in the Lindahl et al’s review, the invasive tests of coronary artery function should be used more often whenever possible in Cath labs, as they represent the true gold-standard4 in the evaluation of CMD. Both the use of guidewire-based measurement of coronary flow reserve (CFR) and intracoronary Acetylcholine testing for endothelium-dependent coronary microvascular spasm, should be used to assess CMD dysfunction5. Given the limitations of these techniques such as their time-consuming complexity and their invasiveness, we encourage the usage of positron emission tomography (PET) and cardiac magnetic resonance imaging (CMR) as discussed in this review. Through the measurements of myocardial blood flow and coronary flow reserve, PET is the reference standard for non-invasive assessment of CMD6. As shown in scientific Literature, CMR imaging and PET has a satisfactory concordance regarding vascular territories7. In our opinion, CT coronary angiography could be a future tool for evaluation of CMD, as myocardial first-pass dynamic CT allows for semi-quantitative assessment of Myocardial blood flow and Myocardial perfusion reserve8-9. However, there have been very few studies investigating its ability to detect CMD and it has not been validated. The main advantage of CT would be the ability to combine anatomical and functional imaging in one imaging examination, reducing the need for additional investigations.

There is no published randomised clinical trial on treatment of MINOCA, although there is one ongoing randomised clinical trial evaluating the usage of beta-blockers and ACE-inhibitor/angiotensin receptor blocker (MINOCA-BAT trial) 10. Nowadays, the medical treatment is based on low-dose aspirin4-14 and statins, which are associated with a reduction of MACE and mortality11-14, as well as ACE-I and ARB 12-14, while there is not any strong evidence that support the use of DAPT, beta-blockers or calcium channel blockers. As shown in the Lindahl et al’s review, the benefits of non-pharmacological treatments are even more uncertain; however, He et al showed the beneficial effect of moderate continuous training program on long term all-cause mortality. 13 Moreover, it’s fundamental to treat risk factors in any MINOCA patients. The deep and complete knowledge of pathophysiological pathways of MINOCA patients with CMD, could led to new and effective therapies that could help to cure this pathology.


  1. Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol. 2018;72:2231-64.
  2. Agewall S, Beltrame JF, Reynolds HR, Niessner A, Rosano G, Caforio AL, De Caterina R, Zimarino M, Roffi M, Kjeldsen K, Atar D, Kaski JC, Sechtem U, Tornvall P; WG on Cardiovascular Pharmacotherapy. ESC working group position paper on myocardial infarction with non-obstructive coronary arteries. Eur Heart J. 2017;38:143-53.
  3. Tamis-Holland JE, Jneid H, Reynolds HR, Agewall S, Brilakis ES, Brown TM, Lerman A, Cushman M, Kumbhani DJ, Arslanian-Engoren C, Bolger AF, Beltrame JF; American Heart Association Interventional Cardiovascular Care Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Epidemiology and Prevention; and Council on Quality of Care and Outcomes Research. Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease: A Scientific Statement From the American Heart Association. Circulation. 2019; 139:e891-908.
  4. Marie A. Guerraty Arterioscler Thromb Vasc Biol;2020 Dec;40(12):2815-2817.
  5. Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, FunckBrentano C, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: The Task Force for the Diagnosis and Management of Chronic Coronary Syndromes of the European Society of Cardiology (ESC). Eur Heart J 2020;41:407-77.
  6. Dilsizian V, Bacharach SL, Beanlands RS, Bergmann SR, Delbeke D, Dorbala S, Gropler RJ, Knuuti J, Schelbert HR, Travin MI. ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures. J Nucl Cardiol. 2016;23:1187-226.
  7. Everaars H, van Diemen PA, Bom MJ, Schumacher SP, de Winter RW, van de Ven PM, Raijmakers PG, Lammertsma AA, Hofman MBM, van der Geest RJ, Götte MJ, van Rossum AC, Nijveldt R, Danad I, Driessen RS, Knaapen P. Comparison between quantitative cardiac magnetic resonance perfusion imaging and [15O]H2O positron emission tomography. Eur J Nuc Med Mol Imaging. 2020;47:1688-97.
  8. Branch KR, Haley RD, Bittencourt MS, Patel AR, Hulten E, Blankstein R. Myocardial computed tomography perfusion. Cardiovasc Diagn Ther 2017;7:452-62. 49. Ho K-T, Ong H-Y, Tan G, Yong Q-W. Dynamic CT myocardial perfusion measurements of resting and hyperaemic blood flow in low-risk subjects with 128-slice dual-source CT. Eur Heart J Cardiovasc Imaging 2015;16:300-6
  9. Ho K-T, Ong H-Y, Tan G, Yong Q-W. Dynamic CT myocardial perfusion measurements of resting and hyperaemic blood flow in low-risk subjects with 128-slice dual-source CT. Eur Heart J Cardiovasc Imaging 2015;16:300-6.
  10. Nordenskjöld AM, Agewall S, Atar D, Baron T, Beltrame J, Bergström O, Erlinge D, Gale CP, López-Pais J, Jernberg T, Johansson P, Ravn-Fisher A, Reynolds HR, Somaratne JB, Tornvall P, Lindahl B. Randomized evaluation of beta-blocker and ACE-inhibitor/angiotensin receptor blocker treatment in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA-BAT): Rationale and design. Am Heart J. 2021;231:96-104.
  11. Abdu FA, Liu L, Mohammed AQ, Xu B, Yin G, Xu S, Xu Y, Che W. Effect of Secondary Prevention Medication on the Prognosis in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease. J Cardiovasc Pharmacol. 2020;76:678-83.
  12. Paolisso P, Bergamaschi L, Saturi G, D’Angelo EC, Magnani I, Toniolo S, et al. Secondary prevention medical therapy and outcomes in patients with myocardial infarction with non-obstructive coronary artery disease. Front Pharmacol 2020;10:1606.
  13. ] He CJ, Zhu CY, Zhu YJ, Zou ZX, Wang SJ, Zhai CL, et al. Effect of exercise-based cardiac rehabilitation on clinical outcomes in patients with myocardial infarction in the absence of obstructive coronary artery disease (MINOCA). Int J Cardiol 2020;315:9–14
  14. Sucato V, Testa G, Puglisi S, Evola S, Galassi AR, Novo G. Myocardial infarction with non-obstructive coronary arteries (MINOCA): Intracoronary imaging-based diagnosis and management. J Cardiol. 2021 May;77(5):444-451
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

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