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No Reflow-phenomenon: from Current State of the Art to Future Perspectives

1. Anthea Hospital, GVM Care & Research. Cardiology Department;
2. Unità Operativa Cardiologia Universitaria, Azienda Ospedaliero-Universitaria Policlinico di Bari, Bari, Italy;
3. Unità Operativa Cardiologia, Ospedale Bonomo, Andria, Italy;
4. Città di Lecce Hospital, GVM Care & Research. Cardiology Department

Special Issues: Coronary artery disease and role of percutaneous interventions

Early and successful myocardial reperfusion with primary percutaneous coronary intervention (pPCI) is the optimal therapy for patients presenting with ST segment elevation myocardial infarction (STEMI). Despite successful epicardial reopening of the infarct related artery, myocardial perfusion may not be restored in up to 40-50% of patients. This phenomenon, referred to as no-reflow (NR), recognizes several pathogenetic components including distal atherothrombotic embolization, ischaemic injury, reperfusion damage, intramyocardial hemorrhage and individual susceptibility of coronary microcirculation. However the complexity of pathogenesis remains still unclear. Moreover, cause NR plays a crucial role in patients prognosis, accurate detection is critical and multiple novel diagnostic modalities has been recently assessed.The NR phenomenon represents a challenge in the management of STEMI patients and has recently captured a growing interest of both basic scientists and interventional cardiologists. Although relevant efforts to transfer into real world practice new therapeutic strategies, to date there is still weak evidence of clinical improvement in this setting. Several strategies of prevention and treatment of NR have been proposed in the clinical arena including pharmacological and mechanical interventions. Nevertheless, the complexity of the phenomenon makes extremely unlikely for a single therapy to be effective. Understanding the interaction between the components of this pathway, along with exploring newer and more effective agents may enable patients to be treated with the most appropriate therapy.
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References

1. Hamm CW, Bassand JP, Agewall S, et al. (2011) ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation. Eur Heart J 32: 2999-3054.    

2. Rezkalla SH, Kloner RA (2008) Coronary no-reflow phenomenon: from the experimental laboratory to the cardiac catheterization laboratory. Catheter Cardiovasc Interv 72: 950-957.    

3. Eeckhout E, Kern MJ (2001) The coronary no-reflow phenomenon: a review of mechanisms and therapies. Eur Heart J 22: 729-739    

4. Wu KC, Zerhouni EA, Judd RM, et al. (1998) Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation 97: 765-772.    

5. Brosh D, Assali AR, Mager A, et al. (2007) Effect of no-reflow during primary percutaneous coronary intervention for acute myocardial infarction on six-month mortality. Am J Cardiol 99: 442-445.    

6. Bolognese L, Carrabba N, Parodi G, et al. (2004) Impact of microvascular dysfunction on left ventricular remodeling and long-term clinical outcome after primary coronary angioplasty for acute myocardial infarction. Circulation 109: 1121-1126.    

7. Ndrepepa G, Tiroch K, Fusaro M, et al. (2010) A 5-year prognostic value of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction. J Am Coll Cardiol 55: 2383-2389.    

8. Kloner RA, Ganote CE, Jennings RB (1974) The "no-reflow" phenomenon after temporary coronary occlusion in the dog. J Clin Invest 54: 1496-1508.    

9. Galiuto L, Lombardo A, Maseri A, et al. (2003) Temporal evolution and functional outcome of no reflow: sustained and spontaneously reversible patterns following successful coronary recanalisation. Heart 89: 731-737.    

10. Limbruno U, De CM, Pistolesi S, et al. (2005) Distal embolization during primary angioplasty: histopathologic features and predictability. Am Heart J 150: 102-108    

11. Bahrmann P, Werner GS, Heusch G, et al. (2007) Detection of coronary microembolization by Doppler ultrasound in patients with stable angina pectoris undergoing elective percutaneous coronary interventions. Circulation 115: 600-608    

12. Kleinbongard P, Bose D, Baars T, et al. (2011) Vasoconstrictor potential of coronary aspirate from patients undergoing stenting of saphenous vein aortocoronary bypass grafts and its pharmacological attenuation. Circ Res 108: 344-352    

13. Tranum-Jensen J, Janse MJ, Fiolet WT, et al. (1981) Tissue osmolality, cell swelling, and reperfusion in acute regional myocardial ischemia in the isolated porcine. Circ Res 49: 364-381.    

14. Yellon DM, Hausenloy DJ (2007) Myocardial reperfusion injury. N Engl J Med 357: 1121-1135.    

15. Paradies G, Petrosillo G, Pistolese M, et al. (2004) Decrease in mitochondrial complex I activity in ischemic/reperfused rat heart: involvement of reactive oxygen species and cardiolipin. Circ Res 94: 53-59.    

16. Petrosillo G, Di Venosa N, Moro N, et al. (2011) In vivo hyperoxic preconditioning protects against rat-heart ischemia/reperfusion injury by inhibiting mitochondrial permeability transition pore opening and cytochrome c release. Free Radic Biol Med 50: 477-483.    

17. Lefer AM, Tsao PS, Aoki N, et al. (1990) Mediation of cardioprotection by transforming growth factor-beta. Science 249: 61-64.    

18. Furuichi K, Wada T, Iwata Y, et al. (2006) Interleukin-1-dependent sequential chemokine expression and inflammatory cell infiltration in ischemia-reperfusion injury. Crit Care Med 34: 2447-2455.    

19. Basso C, Rizzo S, Thiene G (2010) The metamorphosis of myocardial infarction following coronary recanalization. Cardiovasc Pathol 19: 22-28.    

20. Collet JP, Montalescot G (2005) The acute reperfusion management of STEMI in patients with impaired glucose tolerance and type 2 diabetes. Diabetes Vasc Dis Res 2: 136-143.    

21. Golino P, Maroko PR, Carew TE (1987) The effect of acute hypercholesterolemia on myocardial infarct size and the no-reflow phenomenon during coronary occlusion-reperfusion. Circulation 75: 292-298.    

22. Ishihara M (2012) Acute hyperglycemia in patients with acute myocardial infarction. Cric J 76: 563-571.

23. Gibson CM, Ryan KA, Murphy SA, et al. (1998) Impaired coronary blood flow in nonculprit arteries in the setting of acute myocardial infarction. The TIMI Study Group. Thrombolysis in myocardial infarction. J Am Coll Cardiol 34: 974-982.

24. Araszkiewicz A, Lesiak M, Grajek S, et al. (2007) Effect of microvascular reperfusion on prognosis and left ventricular function in anterior wall myocardial infarction treated with primary angioplasty. Int J Cardiol 114: 183-187.    

25. Lepper W, Sieswerda GT, Vanoverschelde JL, et al. (2001) Predictive value of markers of myocardial reperfusion in acute myocardial infarction for follow-up left ventricular function. Am J Cardiol 88: 1358-1363.    

26. Vicente J, Mewton N, Croisille P, et al. (2009) Comparison of the angiographic myocardial blush grade with delayed-enhanced cardiac magnetic resonance for the assessment of microvascular obstruction in acute myocardial infarctions. Catheter Cardiovasc Interv 74: 1000-1007.    

27. Uetani T, Amano T, Kumagai S, et al. (2009) Intracoronary electrocardiogram recording with a bare-wire system: perioperative ST-segment elevation in the intracoronary electrocardiogram is associated with myocardial injury after elective coronary stent implantation. JACC Cardiovasc Interv 2: 127-135.    

28. Mather AN, Fairbairn TA, Artis NJ, et al. (2011) Timing of cardiovascular MR imaging after acute myocardial infarction: effect on estimates of infarct characteristics and prediction of late ventricular remodeling. Radiology 261: 116-126.    

29. Lund GK, Stork A, Saeed M, et al. (2004) Acute myocardial infarction: evaluation with first-pass enhancement and delayed enhancement MR imaging compared with 201Tl SPECT imaging. Radiology 232: 49-57.    

30. Nijveldt R, Beek AM, Hirsch A, et al. (2008) Functional recovery after acute myocardial infarction: comparison between angiography, electrocardiography, and cardiovascular magnetic resonance measures of microvascular injury. J Am Coll Cardiol 52: 181-189.    

31. Greaves K, Dixon SR, Fejka M, et al. (2003) Myocardial contrast echocardiography is superior to other known modalities for assessing myocardial reperfusion after acute myocardial infarction. Heart 89: 139-144.    

32. Tanaka A, Kawarabayashi T, Nishibori Y, et al. (2002) No-reflow phenomenon and lesion morphology in patients with acute myocardial infarction. Circulation 105: 2148-2152.    

33. Watanabe T, Nanto S, Uematsu M, et al. (2003) Prediction of no-reflow phenomenon after successful percutaneous coronary intervention in patients with acute myocardial infarction: intravascular ultrasound findings. Circ J 67: 667-671.    

34. Wu X, Mintz GS, Xu K, et al. (2011) The relationship between attenuated plaque identified by intravascular ultrasound and no-reflow after stenting in acute myocardial infarction: the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial. JACC Cardiovasc Interv 4: 495-502.

35. Tanaka A, Imanishi T, Kitabata H, et al. (2009) Lipid-rich plaque and myocardial perfusion after successful stenting in patients with non-ST-segment elevation acute coronary syndrome: an optical coherence tomography study. Eur Heart J 30: 1348-1355.    

36. Svilaas T, Vlaar PJ, van der Horst IC, et al. (2008) Thrombus aspiration during primary percutaneous coronary intervention. N Engl J Med 358: 557-567.    

37. Frobert O, Lagerqvist B, Olivecrona GK, et al. (2013) TASTE Trial. Thrombus aspiration during ST-segment elevation myocardial infarction. N Engl J Med 369: 1587-1597.

38. Jolly SS, Cairns JA, Yusuf S, et al. (2015) TOTAL Investigators. Randomized trial of primary PCI with or without routine manual thrombectomy. N Engl J Med 372: 1389-1398.

39. Puymirat E, Aissaoui N, Cottin Y, et al. (2014) Effect of coronary thrombus aspiration during primary percutaneous coronary intervention on one-year survival (from the FAST-MI 2010 registry). Am J Cardiol 114: 1651-1657.    

40. Kilic S, Ottervanger JP, Dambrink JH, et al. (2014) Myocardial Infarction Study Group. The effect of thrombus aspiration during primary percutaneous coronary intervention on clinical outcome in daily clinical practice. Thromb Haemost 111: 165-171.

41. Jones DA, Rathod KS, Gallagher S, et al. (2015) Manual thrombus aspiration is not associated with reduced mortality in patients treated with primary percutaneous coronary intervention: an observational study of 10,929 patients with ST-segment elevation myocardial infarction from the London Heart Attack Group. JACC Cardiovasc Interv 8: 575-584.    

42. Siudak Z, Mielecki W, Dziewierz A, et al. (2015) No long-term clinical benefit from manual aspiration thrombectomy in ST-elevation myocardial infarction patients. Data from NRDES registry. Catheter Cardiovasc Interv 85: E16-E22.    

43. De Rosa S, Cirillo P, De Luca G, et al. (2007) Rheolytic thrombectomy during percutaneous coronary intervention improves long-term outcome in high-risk patients with acute myocardial infarction. J Interv Cardiol 20: 292-298.    

44. Mehta SK, Frutkin AD, Milford-Beland S, et al. (2007) Utilization of distal embolic protection in saphenous vein graft interventions (an analysis of 19,546 patients in the American College of Cardiology-National Cardiovascular Data Registry). Am J Cardiol 100: 1114-1118.    

45. Baim DS, Wahr D, George B, et al. (2002) Randomized trial of a distal embolic protection device during percutaneous intervention of saphenous vein aorto-coronary bypass grafts. Circulation 105: 1285-1290.

46. Heusch G, Kleinbongard P, Bose D, et al. (2009) Coronary microembolization: from bedside to bench and back to bedside. Circulation 120: 1822-1836.    

47. Ali A, Cox D, Dib N, et al. (2006) 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 48: 244-252.    

48. Stone GW, Abizaid A, Silber S, et al. (2012) Prospective, randomized,multicenter evaluation of a polyethylene terephthalate micronet mesh-covered stent (MGuard) in ST-segment elevation myocardial infarction: the master trial. J Am Coll Cardiol S0735-1097: 04506-8.

49. Dudek D, Brener SJ, Rakowski T, et al. (2014) Efficacy of an embolic protection stent as a function of delay to reperfusion in st-segment elevation myocardial infarction (from the MASTER Trial). Am J Cardiol 114: 1485-1489.    

50. Thiele H, Schindler K, Friedenberger J, et al. (2008) 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 118: 49-57.    

51. Bartorelli AL, Trabattoni D, Galli S, et al. (1999) Successful dissolution of occlusive coronary thrombus with local administration of abciximab during PTCA. Catheter Cardiovasc Interv 48: 211-213.    

52. Kakkar AK, Moustapha A, Hanley HG, et al. (2004) Comparison of intracoronary vs. intravenous administration of abciximab in coronary stenting. Catheter Cardiovasc Interv 61: 31-34.

53. Stone GW, Maehara A, Witzenbichler B, et al. (2012) Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial. JAMA 307: 1817-1826.    

54. Thiele H, Wohrle J, Hambrecht R, et al. (2012) Intracoronary vs. intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial. Lancet 379: 923-931.

55. De Rosa S, Caiazzo G, Torella D, et al. (2012) Intracoronary abciximab reduces death and major adverse cardiovascular events in acute coronary syndromes: A meta-analysis of clinical trials. Int J Cardiol 7-5273(12)01631-2.

56. Van't Hof AW, Ten Berg J, Heestermans T, et al. (2008) Ongoing Tirofiban in myocardial infarction evaluation (On-TIME) 2 study group. Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial. Lancet 372: 537-546.

57. Authors/Task Force members, Windecker S, Kolh P, Alfonso F, et al. (2014) 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 35: 2541-2619.    

58. Morikawa S, Takabe W, Mataki C, et al. (2002) The effect of statins on mRNA levels of genes related to inflammation, coagulation, and vascular constriction in HUVEC. Human umbilical vein endothelial cells. J Atheroscler Thromb 9: 178-183.    

59. Oduncu V, Tanalp AC, Erkol A, et al. (2011) Impact of chronic pre-treatment of statins on the level of systemic inflammation and myocardial perfusion in patients undergoing primary angioplasty. Am J Cardiol 107: 179-185.    

60. Iwakura K, Ito H, Kawano S, et al. (2006) Chronic pretreatment of statins is associated with the reduction of the no-reflow phenomenon in the patients with reperfused acute myocardial infarction. Eur Heart J 27: 534-539.    

61. Lyu T, Zhao Y, Zhang T, et al. (2013) Effect of statin pretreatment on myocardial perfusion in patients undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis. Clin Cardiol 36: E17-24.    

62. Navarese EP, Kowalewski M, Andreotti F, et al. (2014) Meta-analysis of time-related benefits of statin therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol 113: 1753-1764.    

63. Ross AM, Gibbons RJ, Stone GW, et al. (2005) 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: 1775-1780.    

64. Niccoli G, Rigattieri S, De Vita MR, et al. (2013) Open-label, randomized, placebo-controlled evaluation of intracoronary adenosine or nitroprusside after thrombus aspiration during primary percutaneous coronary intervention for the prevention of microvascular obstruction in acute myocardial infarction: the REOPEN-AMI study (Intracoronary Nitroprusside Versus Adenosine in Acute Myocardial Infarction). JACC Cardiovasc Interv 6: 580-589.    

65. Nazir SA, Khan JN, Mahmoud IZ, et al. (2014) The REFLO-STEMI trial comparing intracoronary adenosine, sodium nitroprusside and standard therapy for the attenuation of infarct size and microvascular obstruction during primary percutaneous coronary intervention: study protocol for a randomised controlled trial.Trials 15: 371.    

66. Ishii H, Ichimiya S, Kanashiro M, et al. (2005) Impact of a single intravenous administration of nicorandil before reperfusion in patients with ST segment-elevation myocardial infarction. Circulation 112: 1284-1288.    

67. Vijayalakshmi K, Whittaker VJ, Kunadian B, et al. (2006) Prospective, randomized controlled trial to study the effect of intracoronary injection of verapamil and adenosine on coronary blood flow during percutaneous coronary intervention in patients with acute coronary syndromes. Heart 92: 1278-1284.    

68. Michaels AD, Appleby M, Otten MH, et al. (2002) Pretreatment with intragraft verapamil prior to percutaneous coronary intervention of saphenous vein graft lesions: results of the randomized, controlled vasodilator prevention on no-reflow (VAPOR) trial. J Invasive Cardiol 14: 299-302.

69. Su Q, Li L, Liu Y (2013) Short-term effect of verapamil on coronary no-reflow associated with percutaneous coronary intervention in patients with acute coronary syndrome: a systematic review and meta-analysis of randomized controlled trials. Clin Cardiol 36: E11-16.    

70. Piot C, Croisille P, Staat P, et al (2008) Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med 359: 473-481.    

71. Dominguez-Rodriguez A, Abreu-Gonzalez P, Garcia-Gonzalez MJ, et al. (2007) A unicenter, randomized, double-blind, parallel-group, placebo-controlled study of Melatonin as an Adjunct in patients with acute myocaRdial Infarction undergoing primary Angioplasty TheMelatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial: study design and rationale. Contemp Clin Trials 28: 532-539.    

72. Kloner RA, Hale SL, Dai W, et al. (2012) Reduction of ischemia/reperfusion injury with bendavia, a mitochondria-targeting cytoprotective Peptide. J Am Heart Assoc 1: e001644.

73. Kandzari DE, Hasselblad V, Tcheng JE, et al (2004) Improved clinical outcome with abciximab therapy in acute myocardial infarction: a systematic overview of randomized clinical trials. Am Heart J 147: 457-462.    

74. Amit G, Cafri C, Yaroslavtsev S, et al. (2006) Intracoronary nitroprusside for the prevention of the no-reflow phenomenon after primary percutaneous coronary intervention in acute myocardial infarction. A randomized, double-blind, placebo-controlled clinical trial. Am Heart J 152: 887.e9-14.

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