Microvascular Obstruction. Underlying Pathophysiology and Clinical Diagnosis

Journal of the American College of Cardiology

Volumn 55, Issue 16, 2010, Pages 1649-1660

  Bekkers, Sebastiaan C A M ^a   Yazdani, Saami K ^b   Virmani, Renu ^b   Waltenberger, Johannes ^a  

^a MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

^b CVPATH INSTITUTE   (United States)

Author keywords

diagnosis; imaging; microvascular obstruction (MVO); myocardial infarction; pathophysiology; review

Indexed keywords

ACETYLSALICYLIC ACID; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CLOPIDOGREL; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; FIBRIN; FIBRINOGEN RECEPTOR ANTAGONIST; FIBRINOLYTIC AGENT; GLYCERYL TRINITRATE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LOW MOLECULAR WEIGHT HEPARIN;

ACUTE HEART INFARCTION; ANGIOCARDIOGRAPHY; BLOOD FLOW VELOCITY; CAPILLARY FLOW; CELL DAMAGE; CONTRAST ECHOCARDIOGRAPHY; CORONARY ARTERY ATHEROSCLEROSIS; CORONARY ARTERY BLOOD FLOW; ELECTROCARDIOGRAPHY; ENDOTHELIUM CELL; FIBRINOLYTIC THERAPY; HEART INFARCTION; HEART INFARCTION SIZE; HEART MUSCLE CELL; HEART MUSCLE INJURY; HEART MUSCLE ISCHEMIA; HEART MUSCLE REPERFUSION; HUMAN; LEUKOCYTE ACTIVATION; MICROANGIOPATHY; NEUTROPHIL CHEMOTAXIS; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOPHYSIOLOGY; PERCUTANEOUS CORONARY INTERVENTION; PRIORITY JOURNAL; PROGNOSIS; REPERFUSION INJURY; REVIEW; THROMBOCYTE ACTIVATION;

CORONARY CIRCULATION; CORONARY STENOSIS; DIAGNOSTIC IMAGING; HUMANS; MICROCIRCULATION; REGIONAL BLOOD FLOW; REPRODUCIBILITY OF RESULTS;

EID: 77950573904     PISSN: 07351097     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jacc.2009.12.037     Document Type: Review

References (94)

1. The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 329 (1993) 673-682
2. Ito H., Tomooka T., Sakai N., et al. Lack of myocardial perfusion immediately after successful thrombolysis. A predictor of poor recovery of left ventricular function in anterior myocardial infarction. Circulation 85 (1992) 1699-1705
3. Kloner R.A., Ganote C.E., and Jennings R.B. The "no-reflow" phenomenon after temporary coronary occlusion in the dog. J Clin Invest 54 (1974) 1496-1508
4. Gerber B.L., Rochitte C.E., Melin J.A., et al. Microvascular obstruction and left ventricular remodeling early after acute myocardial infarction. Circulation 101 (2000) 2734-2741
5. Hombach V., Grebe O., Merkle N., et al. Sequelae of acute myocardial infarction regarding cardiac structure and function and their prognostic significance as assessed by magnetic resonance imaging. Eur Heart J 26 (2005) 549-557
6. Piana R.N., Paik G.Y., Moscucci M., et al. Incidence and treatment of 'no-reflow' after percutaneous coronary intervention. Circulation 89 (1994) 2514-2518
7. Wu K.C., Zerhouni E.A., Judd R.M., et al. Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation 97 (1998) 765-772
8. Roe M.T., Ohman E.M., Maas A.C., et al. Shifting the open-artery hypothesis downstream: the quest for optimal reperfusion. J Am Coll Cardiol 37 (2001) 9-18
9. Yellon D.M., and Hausenloy D.J. Myocardial reperfusion injury. N Engl J Med 357 (2007) 1121-1135
10. Buja L.M. Myocardial ischemia and reperfusion injury. Cardiovasc Pathol 14 (2005) 170-175
11. Stanley W.C. Cardiac energetics during ischaemia and the rationale for metabolic interventions. Coron Artery Dis 12 Suppl 1 (2001) S3-S7
12. Reimer K.A., Lowe J.E., Rasmussen M.M., and Jennings R.B. The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs. Circulation 56 (1977) 786-794
13. Jennings R.B., Steenbergen Jr. C., and Reimer K.A. Myocardial ischemia and reperfusion. Monogr Pathol 37 (1995) 47-80
14. Kloner R.A., Rude R.E., Carlson N., Maroko P.R., DeBoer L.W., and Braunwald E. Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: which comes first?. Circulation 62 (1980) 945-952
15. Reimer K.A., and Jennings R.B. The changing anatomic reference base of evolving myocardial infarction. Underestimation of myocardial collateral blood flow and overestimation of experimental anatomic infarct size due to tissue edema, hemorrhage and acute inflammation. Circulation 60 (1979) 866-876
16. Virmani R., Forman M.B., and Kolodgie F.D. Myocardial reperfusion injury. Histopathological effects of perfluorochemical. Circulation 81 (1990) IV57-IV68
17. Velasco C.E., Turner M., Inagami T., et al. Reperfusion enhances the local release of endothelin after regional myocardial ischemia. Am Heart J 128 (1994) 441-451
18. Piper H.M., Garcia-Dorado D., and Ovize M. A fresh look at reperfusion injury. Cardiovasc Res 38 (1998) 291-300
19. Eeckhout E., and Kern M.J. The coronary no-reflow phenomenon: a review of mechanisms and therapies. Eur Heart J 22 (2001) 729-739
20. Maxwell S.R., and Lip G.Y. Reperfusion injury: a review of the pathophysiology, clinical manifestations and therapeutic options. Int J Cardiol 58 (1997) 95-117
21. Braunwald E., and Kloner R.A. Myocardial reperfusion: a double-edged sword?. J Clin Invest 76 (1985) 1713-1719
22. Engler R.L., Dahlgren M.D., Morris D.D., Peterson M.A., and Schmid-Schonbein G.W. Role of leukocytes in response to acute myocardial ischemia and reflow in dogs. Am J Physiol 251 (1986) H314-H323
23. Babior B.M. The respiratory burst of phagocytes. J Clin Invest 73 (1984) 599-601
24. Erbel R., and Heusch G. Coronary microembolization. J Am Coll Cardiol 36 (2000) 22-24
25. Kawano H., Hayashida T., Ohtani H., et al. Histopathological findings of the no-reflow phenomenon following coronary intervention for acute coronary syndrome. Int Heart J 46 (2005) 327-332
26. Saber R.S., Edwards W.D., Bailey K.R., McGovern T.W., Schwartz R.S., and Holmes Jr. D.R. Coronary embolization after balloon angioplasty or thrombolytic therapy: an autopsy study of 32 cases. J Am Coll Cardiol 22 (1993) 1283-1288
27. Davies M.J., Thomas A.C., Knapman P.A., and Hangartner J.R. Intramyocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac death. Circulation 73 (1986) 418-427
28. Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion. Circulation 71 (1985) 699-708
29. Frink R.J., Rooney Jr. P.A., Trowbridge J.O., and Rose J.P. Coronary thrombosis and platelet/fibrin microemboli in death associated with acute myocardial infarction. Br Heart J 59 (1988) 196-200
30. Hong M.K., Popma J.J., Pichard A.D., et al. Clinical significance of distal embolization after transluminal extraction atherectomy in diffusely diseased saphenous vein grafts. Am Heart J 127 (1994) 1496-1503
31. Kaplan B.M., Benzuly K.H., Kinn J.W., et al. Treatment of no-reflow in degenerated saphenous vein graft interventions: comparison of intracoronary verapamil and nitroglycerin. Cathet Cardiovasc Diagn 39 (1996) 113-118
32. Stone G.W., Webb J., Cox D.A., et al. Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction: a randomized controlled trial. JAMA 293 (2005) 1063-1072
33. Silva-Orrego P., Colombo P., Bigi R., et al. Thrombus aspiration before primary angioplasty improves myocardial reperfusion in acute myocardial infarction: the DEAR-MI (Dethrombosis to Enhance Acute Reperfusion in Myocardial Infarction) study. J Am Coll Cardiol 48 (2006) 1552-1559
34. Henriques J.P., Zijlstra F., Ottervanger J.P., et al. Incidence and clinical significance of distal embolization during primary angioplasty for acute myocardial infarction. Eur Heart J 23 (2002) 1112-1117
35. Ambrosio G., Weisman H.F., Mannisi J.A., and Becker L.C. Progressive impairment of regional myocardial perfusion after initial restoration of postischemic blood flow. Circulation 80 (1989) 1846-1861
36. Judd R.M., Lugo-Olivieri C.H., Arai M., et al. Physiological basis of myocardial contrast enhancement in fast magnetic resonance images of 2-day-old reperfused canine infarcts. Circulation 92 (1995) 1902-1910
37. Villanueva F.S. Myocardial contrast echocardiography in acute myocardial infarction. Am J Cardiol 90 (2002) 38J-47J
38. Reffelmann T., and Kloner R.A. Microvascular reperfusion injury: rapid expansion of anatomic no reflow during reperfusion in the rabbit. Am J Physiol Heart Circ Physiol 283 (2002) H1099-H1107
39. Rochitte C.E., Lima J.A., Bluemke D.A., et al. Magnitude and time course of microvascular obstruction and tissue injury after acute myocardial infarction. Circulation 98 (1998) 1006-1014
40. Kennedy J.W., Ritchie J.L., Davis K.B., Stadius M.L., Maynard C., and Fritz J.K. The western Washington randomized trial of intracoronary streptokinase in acute myocardial infarction. A 12-month follow-up report. N Engl J Med 312 (1985) 1073-1078
41. Brener S.J., Moliterno D.J., Aylward P.E., et al. Reperfusion after primary angioplasty for ST-elevation myocardial infarction: predictors of success and relationship to clinical outcomes in the APEX-AMI angiographic study. Eur Heart J 29 (2008) 1127-1135
42. Morishima I., Sone T., Okumura K., et al. Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction. J Am Coll Cardiol 36 (2000) 1202-1209
43. Gibson C.M., Murphy S.A., Rizzo M.J., et al. Thrombolysis In Myocardial Infarction (TIMI) Study Group. Relationship between TIMI frame count and clinical outcomes after thrombolytic administration. Circulation 99 (1999) 1945-1950
44. Iwakura K., Ito H., Takiuchi S., et al. Alternation in the coronary blood flow velocity pattern in patients with no reflow and reperfused acute myocardial infarction. Circulation 94 (1996) 1269-1275
45. Lepper W., Hoffmann R., Kamp O., et al. Assessment of myocardial reperfusion by intravenous myocardial contrast echocardiography and coronary flow reserve after primary percutaneous transluminal coronary angioplasty [correction of angiography] in patients with acute myocardial infarction. Circulation 101 (2000) 2368-2374
46. Furber A.P., Prunier F., Nguyen H.C., Boulet S., Delepine S., and Geslin P. Coronary blood flow assessment after successful angioplasty for acute myocardial infarction predicts the risk of long-term cardiac events. Circulation 110 (2004) 3527-3533
47. Gibson C.M., Cannon C.P., Murphy S.A., et al. Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation 101 (2000) 125-130
48. van't Hof A.W., Liem A., Suryapranata H., Hoorntje J.C., de Boer M.J., Zijlstra F., and Zwolle Myocardial Infarction Study Group. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Circulation 97 (1998) 2302-2306
49. Gibson C.M., Cannon C.P., Murphy S.A., Marble S.J., Barron H.V., and Braunwald E. Relationship of the TIMI myocardial perfusion grades, flow grades, frame count, and percutaneous coronary intervention to long-term outcomes after thrombolytic administration in acute myocardial infarction. Circulation 105 (2002) 1909-1913
50. Henriques J.P., Zijlstra F., van't Hof A.W., et al. Angiographic assessment of reperfusion in acute myocardial infarction by myocardial blush grade. Circulation 107 (2003) 2115-2119
51. Kaul S. Coronary angiography cannot be used to assess myocardial perfusion in patients undergoing reperfusion for acute myocardial infarction. Heart 86 (2001) 483-484
52. Villanueva F.S., Glasheen W.P., Sklenar J., and Kaul S. Assessment of risk area during coronary occlusion and infarct size after reperfusion with myocardial contrast echocardiography using left and right atrial injections of contrast. Circulation 88 (1993) 596-604
53. Ito H., Okamura A., Iwakura K., et al. Myocardial perfusion patterns related to thrombolysis in myocardial infarction perfusion grades after coronary angioplasty in patients with acute anterior wall myocardial infarction. Circulation 93 (1996) 1993-1999
54. Greaves K., Dixon S.R., Fejka M., et al. Myocardial contrast echocardiography is superior to other known modalities for assessing myocardial reperfusion after acute myocardial infarction. Heart 89 (2003) 139-144
55. Ito H., Maruyama A., Iwakura K., et al. Clinical implications of the 'no reflow' phenomenon. A predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction. Circulation 93 (1996) 223-228
56. Porter T.R., Li S., Oster R., and Deligonul U. The clinical implications of no reflow demonstrated with intravenous perfluorocarbon containing microbubbles following restoration of Thrombolysis In Myocardial Infarction (TIMI) 3 flow in patients with acute myocardial infarction. Am J Cardiol 82 (1998) 1173-1177
57. Lima J.A., Judd R.M., Bazille A., Schulman S.P., Atalar E., and Zerhouni E.A. Regional heterogeneity of human myocardial infarcts demonstrated by contrast-enhanced MRI. Potential mechanisms. Circulation 92 (1995) 1117-1125
58. Orn S., Manhenke C., Greve O.J., et al. Microvascular obstruction is a major determinant of infarct healing and subsequent left ventricular remodelling following primary percutaneous coronary intervention. Eur Heart J 30 (2009) 1978-1985
59. Nijveldt R., Hofman M.B., Hirsch A., et al. Assessment of microvascular obstruction and prediction of short-term remodeling after acute myocardial infarction: cardiac MR imaging study. Radiology 250 (2009) 363-370
60. Yan A.T., Gibson C.M., Larose E., et al. Characterization of microvascular dysfunction after acute myocardial infarction by cardiovascular magnetic resonance first-pass perfusion and late gadolinium enhancement imaging. J Cardiovasc Magn Reson 8 (2006) 831-837
61. Simonetti O.P., Kim R.J., Fieno D.S., et al. An improved MR imaging technique for the visualization of myocardial infarction. Radiology 218 (2001) 215-223
62. Kim R.J., Fieno D.S., Parrish T.B., et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 100 (1999) 1992-2002
63. Wu K.C., Kim R.J., Bluemke D.A., et al. Quantification and time course of microvascular obstruction by contrast-enhanced echocardiography and magnetic resonance imaging following acute myocardial infarction and reperfusion. J Am Coll Cardiol 32 (1998) 1756-1764
64. Lund G.K., Stork A., Saeed M., et al. Acute myocardial infarction: evaluation with first-pass enhancement and delayed enhancement MR imaging compared with 201Tl SPECT imaging. Radiology 232 (2004) 49-57
65. Bekkers S.C., Backes W.H., Kim R.J., et al. Detection and characteristics of microvascular obstruction in reperfused acute myocardial infarction using an optimized protocol for contrast-enhanced cardiovascular magnetic resonance imaging. Eur Radiol 19 (2009) 2904-2912
66. Nijveldt R., Beek A.M., Hirsch A., et al. Functional recovery after acute myocardial infarction: comparison between angiography, electrocardiography, and cardiovascular magnetic resonance measures of microvascular injury. J Am Coll Cardiol 52 (2008) 181-189
67. Barbash G.I., Roth A., Hod H., et al. Rapid resolution of ST elevation and prediction of clinical outcome in patients undergoing thrombolysis with alteplase (recombinant tissue-type plasminogen activator): results of the Israeli Study of Early Intervention in Myocardial Infarction. Br Heart J 64 (1990) 241-247
68. de Lemos J.A., Antman E.M., Giugliano R.P., et al. ST-segment resolution and infarct-related artery patency and flow after thrombolytic therapy. Thrombolysis in Myocardial Infarction (TIMI) 14 investigators. Am J Cardiol 85 (2000) 299-304
69. Schroder R., Dissmann R., Bruggemann T., et al. Extent of early ST segment elevation resolution: a simple but strong predictor of outcome in patients with acute myocardial infarction. J Am Coll Cardiol 24 (1994) 384-391
70. de Lemos J.A., and Braunwald E. ST segment resolution as a tool for assessing the efficacy of reperfusion therapy. J Am Coll Cardiol 38 (2001) 1283-1294
71. Feldman L.J., Coste P., Furber A., et al. Incomplete resolution of ST-segment elevation is a marker of transient microcirculatory dysfunction after stenting for acute myocardial infarction. Circulation 107 (2003) 2684-2689
72. van't Hof A.W., Liem A., de Boer M.J., Zijlstra F., and Zwolle Myocardial infarction Study Group. Clinical value of 12-lead electrocardiogram after successful reperfusion therapy for acute myocardial infarction. Lancet 350 (1997) 615-619
73. Bekkers S.C., Lemmert M.E., Schalla S., et al. ST segment resolution after reperfusion therapy for acute myocardial infarction is related to microvascular obstruction (abstr). Circulation 116 Suppl II (2007) II425
74. Santoro G.M., Valenti R., Buonamici P., et al. Relation between ST-segment changes and myocardial perfusion evaluated by myocardial contrast echocardiography in patients with acute myocardial infarction treated with direct angioplasty. Am J Cardiol 82 (1998) 932-937
75. Syed M.A., Borzak S., Asfour A., et al. Single lead ST-segment recovery: a simple, reliable measure of successful fibrinolysis after acute myocardial infarction. Am Heart J 147 (2004) 275-280
76. Zeymer U., Schroder R., Tebbe U., Molhoek G.P., Wegscheider K., and Neuhaus K.L. Noninvasive detection of early infarct vessel patency by resolution of ST-segment elevation in patients with thrombolysis for acute myocardial infarction; results of the angiographic substudy of the Hirudin for Improvement of Thrombolysis (HIT)-4 trial. Eur Heart J 22 (2001) 769-775
77. Cooper H.A., de Lemos J.A., Morrow D.A., et al. Minimal ST-segment deviation: a simple, noninvasive method for identifying patients with a patent infarction-related artery after fibrinolytic administration. Am Heart J 144 (2002) 790-795
78. Krucoff M.W., Johanson P., Baeza R., Crater S.W., and Dellborg M. Clinical utility of serial and continuous ST-segment recovery assessment in patients with acute ST-elevation myocardial infarction: assessing the dynamics of epicardial and myocardial reperfusion. Circulation 110 (2004) e533-e539
79. Gorgels A.P., Vos M.A., Letsch I.S., et al. Usefulness of the accelerated idioventricular rhythm as a marker for myocardial necrosis and reperfusion during thrombolytic therapy in acute myocardial infarction. Am J Cardiol 61 (1988) 231-235
80. Gressin V., Gorgels A., Louvard Y., Lardoux H., and Bigelow R. ST-segment normalization time and ventricular arrhythmias as electrocardiographic markers of reperfusion during intravenous thrombolysis for acute myocardial infarction. Am J Cardiol 71 (1993) 1436-1439
81. Wehrens X.H., Doevendans P.A., Ophuis T.J., and Wellens H.J. A comparison of electrocardiographic changes during reperfusion of acute myocardial infarction by thrombolysis or percutaneous transluminal coronary angioplasty. Am Heart J 139 (2000) 430-436
82. Svilaas T., Vlaar P.J., van der Horst I.C., et al. Thrombus aspiration during primary percutaneous coronary intervention. N Engl J Med 358 (2008) 557-567
83. Amado L.C., Kraitchman D.L., Gerber B.L., et al. Reduction of "no-reflow" phenomenon by intra-aortic balloon counterpulsation in a randomized magnetic resonance imaging experimental study. J Am Coll Cardiol 43 (2004) 1291-1298
84. Sjauw K.D., Engstrom A.E., Vis M.M., et al. A systematic review and meta-analysis of intra-aortic balloon pump therapy in ST-elevation myocardial infarction: should we change the guidelines?. Eur Heart J 30 (2009) 459-468
85. Antman E.M., Giugliano R.P., Gibson C.M., et al., The TIMI 14 Investigators. Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. Circulation 99 (1999) 2720-2732
86. de Lemos J.A., Antman E.M., Gibson C.M., et al. Abciximab improves both epicardial flow and myocardial reperfusion in ST-elevation myocardial infarction. Observations from the TIMI 14 trial. Circulation 101 (2000) 239-243
87. Kunichika H., Ben-Yehuda O., Lafitte S., Kunichika N., Peters B., and DeMaria A.N. Effects of glycoprotein IIb/IIIa inhibition on microvascular flow after coronary reperfusion. A quantitative myocardial contrast echocardiography study. J Am Coll Cardiol 43 (2004) 276-283
88. Montalescot G., Barragan P., Wittenberg O., et al. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med 344 (2001) 1895-1903
89. Taniyama Y., Ito H., Iwakura K., et al. Beneficial effect of intracoronary verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction. J Am Coll Cardiol 30 (1997) 1193-1199
90. Prasad A., Stone G.W., Stuckey T.D., et al. Relation between leucocyte count, myonecrosis, myocardial perfusion, and outcomes following primary angioplasty. Am J Cardiol 99 (2007) 1067-1071
91. Shandelya S.M., Kuppusamy P., Herskowitz A., Weisfeldt M.L., and Zweier J.L. Soluble complement receptor type 1 inhibits the complement pathway and prevents contractile failure in the postischemic heart. Evidence that complement activation is required for neutrophil-mediated reperfusion injury. Circulation 88 (1993) 2812-2826
92. Galiuto L., DeMaria A.N., del Balzo U., et al. Ischemia-reperfusion injury at the microvascular level: treatment by endothelin A-selective antagonist and evaluation by myocardial contrast echocardiography. Circulation 102 (2000) 3111-3116
93. Babbitt D.G., Virmani R., and Forman M.B. Intracoronary adenosine administered after reperfusion limits vascular injury after prolonged ischemia in the canine model. Circulation 80 (1989) 1388-1399
94. Ross A.M., Gibbons R.J., Stone G.W., Kloner R.A., and Alexander R.W. A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II). J Am Coll Cardiol 45 (2005) 1775-1780