Suboptimal reperfusion after primary percutaneous coronary intervention in acute ST elevation myocardial infarction
- C Michael Gibson, MS, MD
C Michael Gibson, MS, MD
- Professor of Medicine
- Harvard Medical School
- Joseph P Carrozza, MD
Joseph P Carrozza, MD
- Vice President
- Steward Cardiovascular Network
- Professor of Medicine
- Tufts University School of Medicine
- Roger J Laham, MD
Roger J Laham, MD
- Associate Professor of Medicine
- Harvard Medical School
Coronary reperfusion after acute ST-elevation myocardial infarction (STEMI) improves patient outcomes. This can be achieved by primary percutaneous coronary intervention (PCI), usually with stenting, or fibrinolytic therapy. Primary PCI is preferred if it can be performed (door-to-balloon time) within 90 to 120 minutes of presentation to the hospital because of greater efficacy in achieving coronary perfusion and better clinical outcomes. (See "Primary percutaneous coronary intervention versus fibrinolysis in acute ST elevation myocardial infarction: Clinical trials", section on 'Primary PCI versus fibrinolytic trials'.)
The efficacy of revascularization with primary PCI can be assessed using the Thrombolysis in Myocardial Infarction (TIMI) flow grading system (originally developed to assess reperfusion after fibrinolysis) (table 1). Trials of fibrinolytic therapy have shown that the clinical benefits of reperfusion correlate with the restoration of TIMI grade 3 (normal) epicardial coronary flow (figure 1A-B), which is only attained in 50 to 60 percent of patients [1-5]. (See "Fibrinolytic (thrombolytic) agents in acute ST elevation myocardial infarction: Markers of efficacy", section on 'TIMI flow grade'.)
Attainment of TIMI 3 flow is much more common with primary PCI, being achieved in 93 to 96 percent in the PAMI and CADILLAC trials of more than 5400 patients [6,7]. However, some patients do not recover normal epicardial flow despite the absence of vessel obstruction. This phenomenon is called no-reflow and is a predictor of worse outcome. (See 'No-reflow phenomenon' below.)
Issues related to suboptimal reperfusion after primary PCI will be reviewed here. Other issues related to primary PCI and the clinical use of fibrinolytic therapy are discussed separately. (See "Primary percutaneous coronary intervention in acute ST elevation myocardial infarction: Determinants of outcome" and "Fibrinolysis for acute ST elevation myocardial infarction: Initiation of therapy".)
Suboptimal reperfusion after primary percutaneous coronary intervention (PCI) may be caused by one or more of several factors, including:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- GUSTO investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993; 329:673.
- Simes RJ, Topol EJ, Holmes DR Jr, et al. Link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial reperfusion. Importance of early and complete infarct artery reperfusion. GUSTO-I Investigators. Circulation 1995; 91:1923.
- Ross AM, Coyne KS, Moreyra E, et al. Extended mortality benefit of early postinfarction reperfusion. GUSTO-I Angiographic Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Trial. Circulation 1998; 97:1549.
- Vogt A, von Essen R, Tebbe U, et al. Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: retrospective analysis of four German multicenter studies. J Am Coll Cardiol 1993; 21:1391.
- Karagounis L, Sorensen SG, Menlove RL, et al. Does thrombolysis in myocardial infarction (TIMI) perfusion grade 2 represent a mostly patent artery or a mostly occluded artery? Enzymatic and electrocardiographic evidence from the TEAM-2 study. Second Multicenter Thrombolysis Trial of Eminase in Acute Myocardial Infarction. J Am Coll Cardiol 1992; 19:1.
- Mehta RH, Harjai KJ, Cox D, et al. Clinical and angiographic correlates and outcomes of suboptimal coronary flow inpatients with acute myocardial infarction undergoing primary percutaneous coronary intervention. J Am Coll Cardiol 2003; 42:1739.
- Stone GW, Grines CL, Cox DA, et al. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med 2002; 346:957.
- De Luca G, van 't Hof AW, de Boer MJ, et al. Impaired myocardial perfusion is a major explanation of the poor outcome observed in patients undergoing primary angioplasty for ST-segment-elevation myocardial infarction and signs of heart failure. Circulation 2004; 109:958.
- Brodie BR, Stuckey TD, Hansen C, et al. Relation between electrocardiographic ST-segment resolution and early and late outcomes after primary percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2005; 95:343.
- Rezkalla SH, Kloner RA. Coronary No-reflow Phenomenon. Curr Treat Options Cardiovasc Med 2005; 7:75.
- Eeckhout E, Kern MJ. The coronary no-reflow phenomenon: a review of mechanisms and therapies. Eur Heart J 2001; 22:729.
- Henriques JP, Zijlstra F, Ottervanger JP, et al. Incidence and clinical significance of distal embolization during primary angioplasty for acute myocardial infarction. Eur Heart J 2002; 23:1112.
- Prasad A, Stone GW, Stuckey TD, et al. Impact of diabetes mellitus on myocardial perfusion after primary angioplasty in patients with acute myocardial infarction. J Am Coll Cardiol 2005; 45:508.
- Timmer JR, van der Horst IC, de Luca G, et al. Comparison of myocardial perfusion after successful primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction with versus without diabetes mellitus. Am J Cardiol 2005; 95:1375.
- 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 2000; 36:1202.
- Piana RN, Paik GY, Moscucci M, et al. Incidence and treatment of 'no-reflow' after percutaneous coronary intervention. Circulation 1994; 89:2514.
- Dibra A, Mehilli J, Dirschinger J, et al. Thrombolysis in myocardial infarction myocardial perfusion grade in angiography correlates with myocardial salvage in patients with acute myocardial infarction treated with stenting or thrombolysis. J Am Coll Cardiol 2003; 41:925.
- 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 1996; 93:1993.
- Tarantini G, Cacciavillani L, Corbetti F, et al. Duration of ischemia is a major determinant of transmurality and severe microvascular obstruction after primary angioplasty: a study performed with contrast-enhanced magnetic resonance. J Am Coll Cardiol 2005; 46:1229.
- Iwakura K, Ito H, Kawano S, et al. Predictive factors for development of the no-reflow phenomenon in patients with reperfused anterior wall acute myocardial infarction. J Am Coll Cardiol 2001; 38:472.
- Kondo M, Nakano A, Saito D, Shimono Y. Assessment of "microvascular no-reflow phenomenon" using technetium-99m macroaggregated albumin scintigraphy in patients with acute myocardial infarction. J Am Coll Cardiol 1998; 32:898.
- Hearse DJ, Bolli R. Reperfusion induced injury: manifestations, mechanisms, and clinical relevance. Cardiovasc Res 1992; 26:101.
- Kloner RA, Rude RE, Carlson N, et al. Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: which comes first? Circulation 1980; 62:945.
- Bonderman D, Teml A, Jakowitsch J, et al. Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque. Blood 2002; 99:2794.
- Gregorini L, Marco J, Kozàkovà M, et al. Alpha-adrenergic blockade improves recovery of myocardial perfusion and function after coronary stenting in patients with acute myocardial infarction. Circulation 1999; 99:482.
- Yu Y, Ohmori K, Chen Y, et al. Effects of pravastatin on progression of glucose intolerance and cardiovascular remodeling in a type II diabetes model. J Am Coll Cardiol 2004; 44:904.
- Kawaguchi R, Oshima S, Jingu M, et al. Usefulness of virtual histology intravascular ultrasound to predict distal embolization for ST-segment elevation myocardial infarction. J Am Coll Cardiol 2007; 50:1641.
- Gibson CM, Cannon CP, Murphy SA, et al. 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 2002; 105:1909.
- Haager PK, Christott P, Heussen N, et al. Prediction of clinical outcome after mechanical revascularization in acute myocardial infarction by markers of myocardial reperfusion. J Am Coll Cardiol 2003; 41:532.
- Kawamoto T, Yoshida K, Akasaka T, et al. Can coronary blood flow velocity pattern after primary percutaneous transluminal coronary angioplasty [correction of angiography] predict recovery of regional left ventricular function in patients with acute myocardial infarction? Circulation 1999; 100:339.
- 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 1996; 94:1269.
- Furber AP, Prunier F, Nguyen HC, et al. Coronary blood flow assessment after successful angioplasty for acute myocardial infarction predicts the risk of long-term cardiac events. Circulation 2004; 110:3527.
- 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 2000; 101:2368.
- Taylor AJ, Al-Saadi N, Abdel-Aty H, et al. Detection of acutely impaired microvascular reperfusion after infarct angioplasty with magnetic resonance imaging. Circulation 2004; 109:2080.
- Baks T, van Geuns RJ, Biagini E, et al. Effects of primary angioplasty for acute myocardial infarction on early and late infarct size and left ventricular wall characteristics. J Am Coll Cardiol 2006; 47:40.
- Levine GN, Bates ER, Blankenship JC, et al. 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. J Am Coll Cardiol 2016; 67:1235.
- Jolly SS, Cairns JA, Yusuf S, et al. Randomized trial of primary PCI with or without routine manual thrombectomy. N Engl J Med 2015; 372:1389.
- Fröbert O, Lagerqvist B, Olivecrona GK, et al. Thrombus aspiration during ST-segment elevation myocardial infarction. N Engl J Med 2013; 369:1587.
- Lagerqvist B, Fröbert O, Olivecrona GK, et al. Outcomes 1 year after thrombus aspiration for myocardial infarction. N Engl J Med 2014; 371:1111.
- Svilaas T, Vlaar PJ, van der Horst IC, et al. Thrombus aspiration during primary percutaneous coronary intervention. N Engl J Med 2008; 358:557.
- Kumbhani DJ, Bavry AA, Desai MY, et al. Role of aspiration and mechanical thrombectomy in patients with acute myocardial infarction undergoing primary angioplasty: an updated meta-analysis of randomized trials. J Am Coll Cardiol 2013; 62:1409.
- Jolly SS, James S, Džavík V, et al. Thrombus Aspiration in ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration. Circulation 2017; 135:143.
- Burzotta F, De Vita M, Gu YL, et al. Clinical impact of thrombectomy in acute ST-elevation myocardial infarction: an individual patient-data pooled analysis of 11 trials. Eur Heart J 2009; 30:2193.
- Ali A, Cox D, Dib N, et al. Rheolytic thrombectomy with percutaneous coronary intervention for infarct size reduction in acute myocardial infarction: 30-day results from a multicenter randomized study. J Am Coll Cardiol 2006; 48:244.
- Migliorini A, Stabile A, Rodriguez AE, et al. Comparison of AngioJet rheolytic thrombectomy before direct infarct artery stenting with direct stenting alone in patients with acute myocardial infarction. The JETSTENT trial. J Am Coll Cardiol 2010; 56:1298.
- Kastrati A, Byrne RA, Schömig A. Is it time to jettison complex mechanical thrombectomy in favor of simple manual aspiration devices? J Am Coll Cardiol 2010; 56:1307.
- Stone GW, Webb J, Cox DA, et al. Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction: a randomized controlled trial. JAMA 2005; 293:1063.
- Gick M, Jander N, Bestehorn HP, et al. Randomized evaluation of the effects of filter-based distal protection on myocardial perfusion and infarct size after primary percutaneous catheter intervention in myocardial infarction with and without ST-segment elevation. Circulation 2005; 112:1462.
- Kelbaek H, Terkelsen CJ, Helqvist S, et al. Randomized comparison of distal protection versus conventional treatment in primary percutaneous coronary intervention: the drug elution and distal protection in ST-elevation myocardial infarction (DEDICATION) trial. J Am Coll Cardiol 2008; 51:899.
- Schömig A, Kastrati A. Distal embolic protection in patients with acute myocardial infarction: attractive concept but no evidence of benefit. JAMA 2005; 293:1116.
- Gorog DA, Foale RA, Malik I. Distal myocardial protection during percutaneous coronary intervention: when and where? J Am Coll Cardiol 2005; 46:1434.
- Limbruno U, De Caterina R. EMERALD, AIMI, and PROMISE: is there still a potential for embolic protection in primary PCI? Eur Heart J 2006; 27:1139.
- Mizote I, Ueda Y, Ohtani T, et al. Distal protection improved reperfusion and reduced left ventricular dysfunction in patients with acute myocardial infarction who had angioscopically defined ruptured plaque. Circulation 2005; 112:1001.
- Neumann FJ, Blasini R, Schmitt C, et al. Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation 1998; 98:2695.
- Costantini CO, Stone GW, Mehran R, et al. Frequency, correlates, and clinical implications of myocardial perfusion after primary angioplasty and stenting, with and without glycoprotein IIb/IIIa inhibition, in acute myocardial infarction. J Am Coll Cardiol 2004; 44:305.
- Aung Naing K, Li L, Su Q, Wu T. Adenosine and verapamil for no-reflow during primary percutaneous coronary intervention in people with acute myocardial infarction. Cochrane Database Syst Rev 2013; :CD009503.
- Gu YL, Kampinga MA, Wieringa WG, et al. Intracoronary versus intravenous administration of abciximab in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention with thrombus aspiration: the comparison of intracoronary versus intravenous abciximab administration during emergency reperfusion of ST-segment elevation myocardial infarction (CICERO) trial. Circulation 2010; 122:2709.
- Thiele H, Schindler K, Friedenberger J, et al. Intracoronary compared with intravenous bolus abciximab application in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: the randomized Leipzig immediate percutaneous coronary intervention abciximab IV versus IC in ST-elevation myocardial infarction trial. Circulation 2008; 118:49.
- Prati F, Capodanno D, Pawlowski T, et al. Local delivery versus intracoronary infusion of abciximab in patients with acute coronary syndromes. JACC Cardiovasc Interv 2010; 3:928.
- Sezer M, Oflaz H, Gören T, et al. Intracoronary streptokinase after primary percutaneous coronary intervention. N Engl J Med 2007; 356:1823.
- Iwakura K, Ito H, Kawano S, et al. Chronic pre-treatment of statins is associated with the reduction of the no-reflow phenomenon in the patients with reperfused acute myocardial infarction. Eur Heart J 2006; 27:534.
- Lee CH, Wong HB, Tan HC, et al. Impact of reversibility of no reflow phenomenon on 30-day mortality following percutaneous revascularization for acute myocardial infarction-insights from a 1,328 patient registry. J Interv Cardiol 2005; 18:261.
- Hillegass WB, Dean NA, Liao L, et al. Treatment of no-reflow and impaired flow with the nitric oxide donor nitroprusside following percutaneous coronary interventions: initial human clinical experience. J Am Coll Cardiol 2001; 37:1335.
- Wang HJ, Lo PH, Lin JJ, et al. Treatment of slow/no-reflow phenomenon with intracoronary nitroprusside injection in primary coronary intervention for acute myocardial infarction. Catheter Cardiovasc Interv 2004; 63:171.
- Barcin C, Denktas AE, Lennon RJ, et al. Comparison of combination therapy of adenosine and nitroprusside with adenosine alone in the treatment of angiographic no-reflow phenomenon. Catheter Cardiovasc Interv 2004; 61:484.
- Werner GS, Lang K, Kuehnert H, Figulla HR. Intracoronary verapamil for reversal of no-reflow during coronary angioplasty for acute myocardial infarction. Catheter Cardiovasc Interv 2002; 57:444.
- Marzilli M, Orsini E, Marraccini P, Testa R. Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction. Circulation 2000; 101:2154.
- Berger PB, Ellis SG, Holmes DR Jr, et al. Relationship between delay in performing direct coronary angioplasty and early clinical outcome in patients with acute myocardial infarction: results from the global use of strategies to open occluded arteries in Acute Coronary Syndromes (GUSTO-IIb) trial. Circulation 1999; 100:14.
- Yamamuro A, Akasaka T, Tamita K, et al. Coronary flow velocity pattern immediately after percutaneous coronary intervention as a predictor of complications and in-hospital survival after acute myocardial infarction. Circulation 2002; 106:3051.
- Bolognese L, Carrabba N, Parodi G, et al. Impact of microvascular dysfunction on left ventricular remodeling and long-term clinical outcome after primary coronary angioplasty for acute myocardial infarction. Circulation 2004; 109:1121.
- Gibson CM, Cannon CP, Murphy SA, et al. Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation 2000; 101:125.
- Stone GW, Peterson MA, Lansky AJ, et al. Impact of normalized myocardial perfusion after successful angioplasty in acute myocardial infarction. J Am Coll Cardiol 2002; 39:591.
- RISK FACTORS
- NO-REFLOW PHENOMENON
- - Thrombectomy
- - Distal embolic protection devices
- - Direct stenting
- - Systemic GP IIb/IIIa inhibitors
- - Intracoronary infusions
- Vasodilator therapies
- Antithrombotic/thrombolytic therapies
- - Chronic statin therapy
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS