Advancements in the Invasive Evaluation of Coronary Microvasculature in Acute Myocardial Infarction
Main Article Content
Abstract
Coronary microvascular dysfunction represents a critical yet historically under-recognized contributor to adverse outcomes in patients with acute myocardial infarction. As contemporary revascularization strategies continue to reduce epicardial artery-related mortality, the limitations imposed by impaired microvascular perfusion have become increasingly evident. Microvascular obstruction, ischemia-reperfusion injury, and endothelial dysfunction all contribute to suboptimal myocardial recovery, despite successful epicardial intervention.
Invasive methods of assessing intravascular hemodynamics have been previously described, with identification of multiple caveats in their interpretation. Although there are multiple physiological parameters describing epicardial blood flow, coronary microvasculature evaluation has been historically limited to only a few indicators, such as coronary flow reserve and the index of microvascular resistance. Moreover, their role in the evaluation of patients remains uncertain in the case of acute coronary syndromes.
This review highlights the growing armamentarium of invasive and non-invasive techniques now available to characterize the coronary microvascular function with greater precision, with a focus on their role in acute myocardial infarction.
Article Details
How to Cite
ARANGO, Juan et al.
Advancements in the Invasive Evaluation of Coronary Microvasculature in Acute Myocardial Infarction.
Medical Research Archives, [S.l.], v. 13, n. 8, aug. 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6756>. Date accessed: 05 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i8.6756.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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20. Luo C, Long M, Hu X, et al. Thermodilution-Derived Coronary Microvascular Resistance and Flow Reserve in Patients With Cardiac Syndrome X. Circ Cardiovasc Interv. 2014;7(1):43-48. doi:10.116 1/CIRCINTERVENTIONS.113.000953
21. Melikian N, Vercauteren S, Fearon WF, et al. Quantitative assessment of coronary microvascular function in patients with and without epicardial atherosclerosis. EuroIntervention. 2010;5(8).
https://doi.org/
22. Giampaolo N, Francesco B, Leonarda G, Filippo C. Myocardial No-Reflow in Humans. JACC. 2009;54(4):281-292. doi:10.1016/j.jacc.2009.03.054
23. Ng MKC, Yeung AC, Fearon WF. Invasive Assessment of the Coronary Microcirculation. Circulation. 2006;113(17):2054-2061. doi:10.1161/CI RCULATIONAHA.105.603522
24. de Waha S, Patel MR, Granger CB, et al. Relationship between microvascular obstruction and adverse events following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: an individual patient data pooled analysis from seven randomized trials. Eur Heart J. 2017;38(47):3502-3510. doi:10.1093/eurh eartj/ehx414
25. De Maria GL, Scarsini R, Shanmuganathan M, et al. Angiography-derived index of microcirculatory resistance as a novel, pressure-wire-free tool to assess coronary microcirculation in ST elevation myocardial infarction. Int J Cardiovasc Imaging. 2020; 36(8):1395-1406. doi:10.1007/s10554-020-01831-7
26. Fearon WF, Kobayashi Y. Invasive Assessment of the Coronary Microvasculature. Circ Cardiovasc Interv. 2017;10(12):e005361. doi:10.1161/CIRCIN TERVENTIONS.117.005361
27. Carrick D, Haig C, Ahmed N, et al. Comparative Prognostic Utility of Indexes of Microvascular Function Alone or in Combination in Patients With an Acute ST-Segment–Elevation Myocardial Infarction. Circulation. 2016;134(23):1833-1847. doi:10.1161/C IRCULATIONAHA.116.022603
28. R TV, F DCM. Coronary Microvascular Disease Pathogenic Mechanisms and Therapeutic Options. JACC. 2018;72(21):2625-2641. doi:10.1016/j.jacc.2 018.09.042
29. Rehan R, Yong A, Ng M, Weaver J, Puranik R. Coronary microvascular dysfunction: A review of recent progress and clinical implications. Front Cardiovasc Med. 2023;Volume 10-2023. doi:10.33 89/fcvm.2023.1111721
30. Abramik J, Mariathas M, Felekos I. Coronary Microvascular Dysfunction and Vasospastic Angina—Pathophysiology, Diagnosis and Management Strategies. J Clin Med. 2025;14(4). doi:10.3390/jc m14041128
31. Takahashi T, Gupta A, Samuels BA, Wei J. Invasive Coronary Assessment in Myocardial Ischemia with No Obstructive Coronary Arteries. Curr Atheroscler Rep. 2023;25(10):729-740. doi:10.1007/s11883-023-01144-9
32. Christensen-Jeffries K, Couture O, Dayton PA, et al. Super-resolution Ultrasound Imaging. Ultrasound Med Biol. 2020;46(4):865-891. doi:https://doi.org/10.1016/j.ultrasmedbio.2019.11.013
33. Gallinoro E, Bertolone DT, Mizukami T, et al. Continuous vs Bolus Thermodilution to Assess Microvascular Resistance Reserve. JACC Cardiovasc Interv. 2023;16(22):2767-2777.
doi:https://doi.org/10.1016/j.jcin.2023.09.027
34. Gallinoro E, Bertolone DT, Fernandez-Peregrina E, et al. Reproducibility of bolus versus continuous thermodilution for assessment of coronary microvascular function in patients with ANOCA. EuroIntervention. 2023;19(2):e155-e166. doi:10.424 4/EIJ-D-22-00772
35. Jansen TPJ, de Vos A, Paradies V, et al. Continuous Versus Bolus Thermodilution‐Derived Coronary Flow Reserve and Microvascular Resistance Reserve and Their Association With Angina and Quality of Life in Patients With Angina and Nonobstructive Coronaries: A Head‐to‐Head Comparison. J Am Heart Assoc. 2023;12(16):e030480. doi:10.1161/J AHA.123.030480
36. De Bruyne B, Pijls NHJ, Gallinoro E, et al. Microvascular Resistance Reserve for Assessment of Coronary Microvascular Function: JACC Technology Corner. J Am Coll Cardiol. 2021;78(15):1541-1549. doi:https://doi.org/10.1016/j.jacc.2021.08.017
37. Minten L, Bennett J, McCutcheon K, et al. Optimization of Absolute Coronary Blood Flow Measurements to Assess Microvascular Function: In Vivo Validation of Hyperemia and Higher Infusion Speeds. Circ Cardiovasc Interv. 2024;17(7):e013860. doi:10.1161/CIRCINTERVENTIONS.123.013860
38. H ST, F FW, Matthieu PG, et al. Myocardial Perfusion PET for the Detection and Reporting of Coronary Microvascular Dysfunction. JACC Cardiovasc Imaging. 2023;16(4):536-548. doi:10.1016/j.jcmg.2 022.12.015
39. Fernandes J, Ferreira MJ, Leite L. Update on myocardial blood flow quantification by positron emission tomography. Revista Portuguesa de Cardiologia (English Edition). 2020;39(1):37-46. doi:https://doi.org/10.1016/j.repce.2020.03.007
40. Crooijmans C, Jansen TPJ, Meeder JG, et al. Safety, Feasibility, and Diagnostic Yield of Invasive Coronary Function Testing: Netherlands Registry of Invasive Coronary Vasomotor Function Testing. JAMA Cardiol. 2025;10(4):384-390. doi:10.1001/ja macardio.2024.5670
2. Ong P, Camici PG, Beltrame JF, et al. International standardization of diagnostic criteria for microvascular angina. Int J Cardiol. 2018;250:16-20. doi:https://doi.org/10.1016/j.ijcard.2017.08.068
3. Niccoli G, Scalone G, Lerman A, Crea F. Coronary microvascular obstruction in acute myocardial infarction. Eur Heart J. 2016;37(13):1024-1033. doi:10.1093/eurheartj/ehv484
4. Clarke JRD, Kennedy R, Lau FD, Lancaster GI, Zarich SW. Invasive evaluation of the microvasculature in acute myocardial infarction: Coronary flow reserve versus the index of microcirculatory resistance. J Clin Med. 2020;9(1). doi:10.3390/jcm9010086
5. De Bruyne B, Pijls NHJ, Smith L, Wievegg M, Heyndrickx GR. Coronary Thermodilution to Assess Flow Reserve. Circulation. 2001;104(17):2003-2006. doi:10.1161/hc4201.099223
6. Kaufmann PA, Namdar M, Matthew F, et al. Novel Doppler Assessment of Intracoronary Volumetric Flow Reserve: Validation Against PET in Patients With or Without Flow-Dependent Vasodilation. Journal of Nuclear Medicine. 2005;46 (8):1272. http://jnm.snmjournals.org/content/46/8/1272.abstract
7. Everaars H, de Waard GA, Driessen RS, et al. Doppler Flow Velocity and Thermodilution to Assess Coronary Flow Reserve: A Head-to-Head Comparison With [15O]H2O PET. JACC Cardiovasc Interv. 2018; 11(20):2044-2054. doi:https://doi.org/10.1016/j.jcin.2018.07.011
8. Perera D, Berry C, Hoole SP, et al. Invasive coronary physiology in patients with angina and non-obstructive coronary artery disease: A consensus document from the coronary microvascular dysfunction workstream of the British Heart Foundation/National Institute for Health Research Partnership. Heart. 2022;109(2):88-95. doi:10.1136/h eartjnl-2021-320718
9. Pijls NH, van Son JA, Kirkeeide RL, De Bruyne B, Gould KL. Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty. Circulation. 1993; 87(4):1354-1367. doi:10.1161/01.CIR.87.4.1354
10. Pijls NHJ, Van Gelder B, Van der Voort P, et al. Fractional Flow Reserve. Circulation. 1995;92(11): 3183-3193. doi:10.1161/01.CIR.92.11.3183
11. Ahn SG, Suh J, Hung OY, et al. Discordance Between Fractional Flow Reserve and Coronary Flow Reserve: Insights From Intracoronary Imaging and Physiological Assessment. JACC Cardiovasc Interv. 2017;10(10):999-1007. doi:https://doi.org/10.1016/j.jcin.2017.03.006
12. Sen S, Escaned J, Malik IS, et al. Development and Validation of a New Adenosine-Independent Index of Stenosis Severity From Coronary Wave–Intensity Analysis: Results of the ADVISE (ADenosine Vasodilator Independent Stenosis Evaluation) Study. J Am Coll Cardiol. 2012;59(15):1392-1402. doi:https://doi.org/10.1016/j.jacc.2011.11.003
13. Fezzi S, Huang J, Lunardi M, et al. Coronary physiology in the catheterisation laboratory: an A to Z practical guide. AsiaIntervention. 2022;8(2):86-109. doi:10.4244/AIJ-D-22-00022
14. Kogame N, Ono M, Kawashima H, et al. The Impact of Coronary Physiology on Contemporary Clinical Decision Making. JACC Cardiovasc Interv. 2020;13(14):1617-1638. doi:https://doi.org/10.1016/j.jcin.2020.04.040
15. De Maria GL, Garcia-Garcia HM, Scarsini R, et al. Novel Indices of Coronary Physiology. Circ Cardiovasc Interv. 2020;13(4):e008487. doi:10.116 1/CIRCINTERVENTIONS.119.008487
16. Fearon WF, Balsam LB, Farouque HMO, et al. Novel Index for Invasively Assessing the Coronary Microcirculation. Circulation. 2003;107(25):3129-3132. doi:10.1161/01.CIR.0000080700.98607.D1
17. Mangiacapra F, Viscusi MM, Paolucci L, et al. The Pivotal Role of Invasive Functional Assessment in Patients With Myocardial Infarction With Non-Obstructive Coronary Arteries (MINOCA). Front Cardiovasc Med. 2021;Volume 8-2021. doi:10.338 9/fcvm.2021.781485
18. Verma SK, Kumar B, Bahl VK. Aorto-ostial atherosclerotic coronary artery disease—Risk factor profiles, demographic & angiographic features. IJC Heart & Vasculature. 2016;12:26-31.
doi:https://doi.org/10.1016/j.ijcha.2016.05.016
19. Martínez GJ, Yong ASC, Fearon WF, Ng MKC. The index of microcirculatory resistance in the physiologic assessment of the coronary microcirculation. Coron Artery Dis. 2015;26. https://journals.lww.com/coronary-artery/fulltext/2015/08001/the_index_of_microcirculatory_resistance_in_the.5.aspx
20. Luo C, Long M, Hu X, et al. Thermodilution-Derived Coronary Microvascular Resistance and Flow Reserve in Patients With Cardiac Syndrome X. Circ Cardiovasc Interv. 2014;7(1):43-48. doi:10.116 1/CIRCINTERVENTIONS.113.000953
21. Melikian N, Vercauteren S, Fearon WF, et al. Quantitative assessment of coronary microvascular function in patients with and without epicardial atherosclerosis. EuroIntervention. 2010;5(8).
https://doi.org/
22. Giampaolo N, Francesco B, Leonarda G, Filippo C. Myocardial No-Reflow in Humans. JACC. 2009;54(4):281-292. doi:10.1016/j.jacc.2009.03.054
23. Ng MKC, Yeung AC, Fearon WF. Invasive Assessment of the Coronary Microcirculation. Circulation. 2006;113(17):2054-2061. doi:10.1161/CI RCULATIONAHA.105.603522
24. de Waha S, Patel MR, Granger CB, et al. Relationship between microvascular obstruction and adverse events following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: an individual patient data pooled analysis from seven randomized trials. Eur Heart J. 2017;38(47):3502-3510. doi:10.1093/eurh eartj/ehx414
25. De Maria GL, Scarsini R, Shanmuganathan M, et al. Angiography-derived index of microcirculatory resistance as a novel, pressure-wire-free tool to assess coronary microcirculation in ST elevation myocardial infarction. Int J Cardiovasc Imaging. 2020; 36(8):1395-1406. doi:10.1007/s10554-020-01831-7
26. Fearon WF, Kobayashi Y. Invasive Assessment of the Coronary Microvasculature. Circ Cardiovasc Interv. 2017;10(12):e005361. doi:10.1161/CIRCIN TERVENTIONS.117.005361
27. Carrick D, Haig C, Ahmed N, et al. Comparative Prognostic Utility of Indexes of Microvascular Function Alone or in Combination in Patients With an Acute ST-Segment–Elevation Myocardial Infarction. Circulation. 2016;134(23):1833-1847. doi:10.1161/C IRCULATIONAHA.116.022603
28. R TV, F DCM. Coronary Microvascular Disease Pathogenic Mechanisms and Therapeutic Options. JACC. 2018;72(21):2625-2641. doi:10.1016/j.jacc.2 018.09.042
29. Rehan R, Yong A, Ng M, Weaver J, Puranik R. Coronary microvascular dysfunction: A review of recent progress and clinical implications. Front Cardiovasc Med. 2023;Volume 10-2023. doi:10.33 89/fcvm.2023.1111721
30. Abramik J, Mariathas M, Felekos I. Coronary Microvascular Dysfunction and Vasospastic Angina—Pathophysiology, Diagnosis and Management Strategies. J Clin Med. 2025;14(4). doi:10.3390/jc m14041128
31. Takahashi T, Gupta A, Samuels BA, Wei J. Invasive Coronary Assessment in Myocardial Ischemia with No Obstructive Coronary Arteries. Curr Atheroscler Rep. 2023;25(10):729-740. doi:10.1007/s11883-023-01144-9
32. Christensen-Jeffries K, Couture O, Dayton PA, et al. Super-resolution Ultrasound Imaging. Ultrasound Med Biol. 2020;46(4):865-891. doi:https://doi.org/10.1016/j.ultrasmedbio.2019.11.013
33. Gallinoro E, Bertolone DT, Mizukami T, et al. Continuous vs Bolus Thermodilution to Assess Microvascular Resistance Reserve. JACC Cardiovasc Interv. 2023;16(22):2767-2777.
doi:https://doi.org/10.1016/j.jcin.2023.09.027
34. Gallinoro E, Bertolone DT, Fernandez-Peregrina E, et al. Reproducibility of bolus versus continuous thermodilution for assessment of coronary microvascular function in patients with ANOCA. EuroIntervention. 2023;19(2):e155-e166. doi:10.424 4/EIJ-D-22-00772
35. Jansen TPJ, de Vos A, Paradies V, et al. Continuous Versus Bolus Thermodilution‐Derived Coronary Flow Reserve and Microvascular Resistance Reserve and Their Association With Angina and Quality of Life in Patients With Angina and Nonobstructive Coronaries: A Head‐to‐Head Comparison. J Am Heart Assoc. 2023;12(16):e030480. doi:10.1161/J AHA.123.030480
36. De Bruyne B, Pijls NHJ, Gallinoro E, et al. Microvascular Resistance Reserve for Assessment of Coronary Microvascular Function: JACC Technology Corner. J Am Coll Cardiol. 2021;78(15):1541-1549. doi:https://doi.org/10.1016/j.jacc.2021.08.017
37. Minten L, Bennett J, McCutcheon K, et al. Optimization of Absolute Coronary Blood Flow Measurements to Assess Microvascular Function: In Vivo Validation of Hyperemia and Higher Infusion Speeds. Circ Cardiovasc Interv. 2024;17(7):e013860. doi:10.1161/CIRCINTERVENTIONS.123.013860
38. H ST, F FW, Matthieu PG, et al. Myocardial Perfusion PET for the Detection and Reporting of Coronary Microvascular Dysfunction. JACC Cardiovasc Imaging. 2023;16(4):536-548. doi:10.1016/j.jcmg.2 022.12.015
39. Fernandes J, Ferreira MJ, Leite L. Update on myocardial blood flow quantification by positron emission tomography. Revista Portuguesa de Cardiologia (English Edition). 2020;39(1):37-46. doi:https://doi.org/10.1016/j.repce.2020.03.007
40. Crooijmans C, Jansen TPJ, Meeder JG, et al. Safety, Feasibility, and Diagnostic Yield of Invasive Coronary Function Testing: Netherlands Registry of Invasive Coronary Vasomotor Function Testing. JAMA Cardiol. 2025;10(4):384-390. doi:10.1001/ja macardio.2024.5670