CONTEMPORARY DIAGNOSIS OF CORONARY MICROVASCULAR DYSFUNCTION IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Keywords:
coronary microcirculation; acute myocardial infarction
Abstract
Coronary microvascular dysfunction (CMD) is encountered in up to 50% of patients presenting with ST-segment elevation acute myocardial infarction (STEMI) and treated with primary percutaneous coronary intervention (PCI). The current reference standard to diagnose microvascular injury in this setting is cardiac magnetic resonance (CMR) imaging. The extent of microvascular injury, termed microvascular obstruction (MVO) on CMR, increases over time after recanalization of the infarct-related artery (IRA), until it reaches its peak around day 3, and it subsides by day 10. Most of the current research evaluated MVO on CMR on days 2-7 after primary PCI, and showed its association with cardiac death and heart failure independently of the infarct size. As microvascular injury becomes a new therapeutic target in STEMI, given the plateauing mortality curves despite widespread access to timely reperfusion, the question of early diagnosis of CMD grows in importance. To this end, invasive coronary microcirculation assessment in the recanalized IRA immediately after primary PCI, has been tested in terms of its association with MVO and infarct size on CMR, as well as its ability to predict adverse clinical outcomes. Both invasive thermodilution- and Doppler wire-derived indices of microvascular resistance were successful in stratifying patients according to the risk of cardiac death and heart failure in the follow-up. Recently, a coronary angiography-based method, which unlike thermodilution and Doppler derives indices of microvascular resistance from a computational dynamics software and does not require additional wiring of the epicardial artery, has demonstrated the ability to predict adverse clinical outcomes. The described diagnostic tools for stratification of patients according to the risk of CMD and consequently impaired prognosis after STEMI, still remain a subject of on-going research, in terms of both the most relevant cut offs for different indices and the optimal time point of assessment.
References
Literature:
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9. Ndrepepa G, Cassese S, Scalamogna M, Lahu S, Aytekin A, Xhepa E, et al. Association of De Ritis Ratio with Prognosis in Patients with Coronary Artery Disease and Aminotransferase Activity within and outside the Healthy Values of Reference Range. J Clin Med. 2023;12(9).
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29. Carrick D, Haig C, Carberry J, May VTY, McCartney P, Welsh P, et al. Microvascular resistance of the culprit coronary artery in acute ST-elevation myocardial infarction. JCI Insight. 2016;1(6):e85768.
30. Konijnenberg LSF, Damman P, Duncker DJ, Kloner RA, Nijveldt R, van Geuns RM, et al. Pathophysiology and diagnosis of coronary microvascular dysfunction in ST-elevation myocardial infarction. Cardiovasc Res. 2020;116(4):787-805.
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1. Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720-826.
2. Milasinovic D, Mladenovic D, Zaharijev S, Mehmedbegovic Z, Marinkovic J, Jelic D, et al. Prognostic impact of non-culprit chronic total occlusion over time in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Eur Heart J Acute Cardiovasc Care. 2021;10(9):990-8.
3. Pedersen F, Butrymovich V, Kelbaek H, Wachtell K, Helqvist S, Kastrup J, et al. Short- and long-term cause of death in patients treated with primary PCI for STEMI. J Am Coll Cardiol. 2014;64(20):2101-8.
4. Cung TT, Morel O, Cayla G, Rioufol G, Garcia-Dorado D, Angoulvant D, et al. Cyclosporine before PCI in Patients with Acute Myocardial Infarction. N Engl J Med. 2015;373(11):1021-31.
5. Niccoli G, Montone RA, Ibanez B, Thiele H, Crea F, Heusch G, et al. Optimized Treatment of ST-Elevation Myocardial Infarction. Circ Res. 2019;125(2):245-58.
6. Galli M, Niccoli G, De Maria G, Brugaletta S, Montone RA, Vergallo R, et al. Coronary microvascular obstruction and dysfunction in patients with acute myocardial infarction. Nat Rev Cardiol. 2023.
7. Milasinovic D, Nedeljkovic O, Maksimovic R, Sobic-Saranovic D, Dukic D, Zobenica V, et al. Coronary Microcirculation: The Next Frontier in the Management of STEMI. J Clin Med. 2023;12(4).
8. Ito H. No-reflow phenomenon and prognosis in patients with acute myocardial infarction. Nat Clin Pract Cardiovasc Med. 2006;3(9):499-506.
9. Ndrepepa G, Cassese S, Scalamogna M, Lahu S, Aytekin A, Xhepa E, et al. Association of De Ritis Ratio with Prognosis in Patients with Coronary Artery Disease and Aminotransferase Activity within and outside the Healthy Values of Reference Range. J Clin Med. 2023;12(9).
10. Ito H, Tomooka T, Sakai N, Yu H, Higashino Y, Fujii K, et al. Lack of myocardial perfusion immediately after successful thrombolysis. A predictor of poor recovery of left ventricular function in anterior myocardial infarction. Circulation. 1992;85(5):1699-705.
11. de Waha S, Patel MR, Granger CB, Ohman EM, Maehara A, Eitel I, 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):3502-10.
12. Del Buono MG, Montone RA, Camilli M, Carbone S, Narula J, Lavie CJ, et al. Coronary Microvascular Dysfunction Across the Spectrum of Cardiovascular Diseases: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021;78(13):1352-71.
13. Bulluck H, Dharmakumar R, Arai AE, Berry C, Hausenloy DJ. Cardiovascular Magnetic Resonance in Acute ST-Segment-Elevation Myocardial Infarction: Recent Advances, Controversies, and Future Directions. Circulation. 2018;137(18):1949-64.
14. Ndrepepa G, Kastrati A. Coronary No-Reflow after Primary Percutaneous Coronary Intervention-Current Knowledge on Pathophysiology, Diagnosis, Clinical Impact and Therapy. J Clin Med. 2023;12(17).
15. Eitel I, de Waha S, Wohrle J, Fuernau G, Lurz P, Pauschinger M, et al. Comprehensive prognosis assessment by CMR imaging after ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2014;64(12):1217-26.
16. Stone GW, Selker HP, Thiele H, Patel MR, Udelson JE, Ohman EM, et al. Relationship Between Infarct Size and Outcomes Following Primary PCI: Patient-Level Analysis From 10 Randomized Trials. J Am Coll Cardiol. 2016;67(14):1674-83.
17. Symons R, Pontone G, Schwitter J, Francone M, Iglesias JF, Barison A, et al. Long-Term Incremental Prognostic Value of Cardiovascular Magnetic Resonance After ST-Segment Elevation Myocardial Infarction: A Study of the Collaborative Registry on CMR in STEMI. JACC Cardiovasc Imaging. 2018;11(6):813-25.
18. van Kranenburg M, Magro M, Thiele H, de Waha S, Eitel I, Cochet A, et al. Prognostic value of microvascular obstruction and infarct size, as measured by CMR in STEMI patients. JACC Cardiovasc Imaging. 2014;7(9):930-9.
19. Reinstadler SJ, Stiermaier T, Reindl M, Feistritzer HJ, Fuernau G, Eitel C, et al. Intramyocardial haemorrhage and prognosis after ST-elevation myocardial infarction. Eur Heart J Cardiovasc Imaging. 2019;20(2):138-46.
20. Carrick D, Haig C, Ahmed N, Rauhalammi S, Clerfond G, Carberry J, et al. Temporal Evolution of Myocardial Hemorrhage and Edema in Patients After Acute ST-Segment Elevation Myocardial Infarction: Pathophysiological Insights and Clinical Implications. J Am Heart Assoc. 2016;5(2).
21. Doucette JW, Corl PD, Payne HM, Flynn AE, Goto M, Nassi M, et al. Validation of a Doppler guide wire for intravascular measurement of coronary artery flow velocity. Circulation. 1992;85(5):1899-911.
22. Pijls NH, De Bruyne B, Smith L, Aarnoudse W, Barbato E, Bartunek J, et al. Coronary thermodilution to assess flow reserve: validation in humans. Circulation. 2002;105(21):2482-6.
23. Everaars H, de Waard GA, Driessen RS, Danad I, van de Ven PM, Raijmakers PG, et al. Doppler Flow Velocity and Thermodilution to Assess Coronary Flow Reserve: A Head-to-Head Comparison With [(15)O]H(2)O PET. JACC Cardiovasc Interv. 2018;11(20):2044-54.
24. Garot P, Pascal O, Simon M, Monin JL, Teiger E, Garot J, et al. Impact of microvascular integrity and local viability on left ventricular remodelling after reperfused acute myocardial infarction. Heart. 2003;89(4):393-7.
25. Takahashi T, Hiasa Y, Ohara Y, Miyazaki S, Ogura R, Miyajima H, et al. Usefulness of coronary flow reserve immediately after primary coronary angioplasty for acute myocardial infarction in predicting long-term adverse cardiac events. Am J Cardiol. 2007;100(5):806-11.
26. van de Hoef TP, Bax M, Meuwissen M, Damman P, Delewi R, de Winter RJ, et al. Impact of coronary microvascular function on long-term cardiac mortality in patients with acute ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv. 2013;6(3):207-15.
27. Ahn SG, Hung OY, Lee JW, Lee JH, Youn YJ, Ahn MS, et al. Combination of the Thermodilution-Derived Index of Microcirculatory Resistance and Coronary Flow Reserve Is Highly Predictive of Microvascular Obstruction on Cardiac Magnetic Resonance Imaging After ST-Segment Elevation Myocardial Infarction. JACC Cardiovasc Interv. 2016;9(8):793-801.
28. Carrick D, Haig C, Ahmed N, Carberry J, Yue May VT, McEntegart M, 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):1833-47.
29. Carrick D, Haig C, Carberry J, May VTY, McCartney P, Welsh P, et al. Microvascular resistance of the culprit coronary artery in acute ST-elevation myocardial infarction. JCI Insight. 2016;1(6):e85768.
30. Konijnenberg LSF, Damman P, Duncker DJ, Kloner RA, Nijveldt R, van Geuns RM, et al. Pathophysiology and diagnosis of coronary microvascular dysfunction in ST-elevation myocardial infarction. Cardiovasc Res. 2020;116(4):787-805.
31. Aarnoudse W, Fearon WF, Manoharan G, Geven M, van de Vosse F, Rutten M, et al. Epicardial stenosis severity does not affect minimal microcirculatory resistance. Circulation. 2004;110(15):2137-42.
32. Melikian N, Vercauteren S, Fearon WF, Cuisset T, MacCarthy PA, Davidavicius G, et al. Quantitative assessment of coronary microvascular function in patients with and without epicardial atherosclerosis. EuroIntervention. 2010;5(8):939-45.
33. Bulluck H, Foin N, Cabrera-Fuentes HA, Yeo KK, Wong AS, Fam JM, et al. Index of Microvascular Resistance and Microvascular Obstruction in Patients With Acute Myocardial Infarction. JACC Cardiovasc Interv. 2016;9(20):2172-4.
34. Fearon WF, Low AF, Yong AS, McGeoch R, Berry C, Shah MG, et al. Prognostic value of the Index of Microcirculatory Resistance measured after primary percutaneous coronary intervention. Circulation. 2013;127(24):2436-41.
35. Maznyczka AM, Oldroyd KG, Greenwood JP, McCartney PJ, Cotton J, Lindsay M, et al. Comparative Significance of Invasive Measures of Microvascular Injury in Acute Myocardial Infarction. Circ Cardiovasc Interv. 2020;13(5):e008505.
36. De Maria GL, Alkhalil M, Wolfrum M, Fahrni G, Borlotti A, Gaughran L, et al. Index of Microcirculatory Resistance as a Tool to Characterize Microvascular Obstruction and to Predict Infarct Size Regression in Patients With STEMI Undergoing Primary PCI. JACC Cardiovasc Imaging. 2019;12(5):837-48.
37. Jeyaprakash P, Mikhail P, Ford TJ, Pathan F, Berry C, Negishi K. Index of Microcirculatory Resistance to predict microvascular obstruction in STEMI: A systematic review and meta-analysis. Catheter Cardiovasc Interv. 2024;103(2):249-59.
38. Maznyczka AM, Oldroyd KG, McCartney P, McEntegart M, Berry C. The Potential Use of the Index of Microcirculatory Resistance to Guide Stratification of Patients for Adjunctive Therapy in Acute Myocardial Infarction. JACC Cardiovasc Interv. 2019;12(10):951-66.
39. El Farissi M, Zimmermann FM, De Maria GL, van Royen N, van Leeuwen MAH, Carrick D, et al. The Index of Microcirculatory Resistance After Primary PCI: A Pooled Analysis of Individual Patient Data. JACC Cardiovasc Interv. 2023;16(19):2383-92.
40. Scarsini R, De Maria GL, Borlotti A, Kotronias RA, Langrish JP, Lucking AJ, et al. Incremental Value of Coronary Microcirculation Resistive Reserve Ratio in Predicting the Extent of Myocardial Infarction in Patients with STEMI. Insights from the Oxford Acute Myocardial Infarction (OxAMI) Study. Cardiovasc Revasc Med. 2019;20(12):1148-55.
41. Maznyczka AM, Carrick D, Oldroyd KG, James-Rae G, McCartney P, Greenwood JP, et al. Thermodilution-derived temperature recovery time: a novel predictor of microvascular reperfusion and prognosis after myocardial infarction. EuroIntervention. 2021;17(3):220-8.
42. Yew SN, Carrick D, Corcoran D, Ahmed N, Carberry J, Teng Yue May V, et al. Coronary Thermodilution Waveforms After Acute Reperfused ST-Segment-Elevation Myocardial Infarction: Relation to Microvascular Obstruction and Prognosis. J Am Heart Assoc. 2018;7(15):e008957.
43. Everaars H, de Waard GA, Schumacher SP, Zimmermann FM, Bom MJ, van de Ven PM, et al. Continuous thermodilution to assess absolute flow and microvascular resistance: validation in humans using [15O]H2O positron emission tomography. Eur Heart J. 2019;40(28):2350-9.
44. Williams RP, de Waard GA, De Silva K, Lumley M, Asrress K, Arri S, et al. Doppler Versus Thermodilution-Derived Coronary Microvascular Resistance to Predict Coronary Microvascular Dysfunction in Patients With Acute Myocardial Infarction or Stable Angina Pectoris. Am J Cardiol. 2018;121(1):1-8.
45. Jin X, Yoon MH, Seo KW, Tahk SJ, Lim HS, Yang HM, et al. Usefulness of Hyperemic Microvascular Resistance Index as a Predictor of Clinical Outcomes in Patients with ST-Segment Elevation Myocardial Infarction. Korean Circ J. 2015;45(3):194-201.
46. Teunissen PF, de Waard GA, Hollander MR, Robbers LF, Danad I, Biesbroek PS, et al. Doppler-derived intracoronary physiology indices predict the occurrence of microvascular injury and microvascular perfusion deficits after angiographically successful primary percutaneous coronary intervention. Circ Cardiovasc Interv. 2015;8(3):e001786.
47. Escaned J, Flores A, Garcia-Pavia P, Segovia J, Jimenez J, Aragoncillo P, et al. Assessment of microcirculatory remodeling with intracoronary flow velocity and pressure measurements: validation with endomyocardial sampling in cardiac allografts. Circulation. 2009;120(16):1561-8.
48. Patel N, Petraco R, Dall'Armellina E, Kassimis G, De Maria GL, Dawkins S, et al. Zero-Flow Pressure Measured Immediately After Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Provides the Best Invasive Index for Predicting the Extent of Myocardial Infarction at 6 Months: An OxAMI Study (Oxford Acute Myocardial Infarction). JACC Cardiovasc Interv. 2015;8(11):1410-21.
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Published
2025/10/30
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