No reflow phenomenon
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Jennifer Giuseffi, M.D.; David M. Leder, M.D.; Ayokunle Olubaniyi, M.D.
Overview
No reflow phenomenon is the failure of blood to reperfuse an ischemic area after the physical obstruction has been removed or bypassed.[1][2] The reduced flow during percutaneous coronary intervention (PCI) is defined as the reduction in anterograde despite a patent lumen at the site of PCI, and occurs during 1-5% of PCIs. No reflow is an important predictor of mortality after PCI [3]. No reflow is a common (15%) finding during primaryangioplasty for acute MI.
The no reflow, or slow flow, phenomenon refers to inadequate myocardial perfusion with evidence of persistent myocardial ischemia of a target vessel following thrombolysis or percutaneous coronary intervention (PCI) without angiographic evidence of mechanical obstruction.
Historical Perspective
Pathophysiology
No-reflow is likely due to distal embolization of atheromatous and thrombotic debris dislodged by balloon inflation orstent implantation. Predictors of no reflow include a higher plaque burden, thrombus, lipid pools by IVUS, higherlesion elastic membrane cross-sectional area, pre-infarction angina, and TIMI flow grade 0 on the initialcoronary angiogram, among other factors. Compared to aspirates obtained from patients without no reflow, analysis of aspirates obtained from patients who developed no reflow contained more atheromatous plaque and significantly more platelet and fibrincomplex,macrophages, and cholesterol crystals. The 30-day mortality was significantly higher (27.5%) in patients with combined slow-flow and no-reflow phenomenon than in patients with normal coronary blood flow after PCI (5.3%, P < 0.001). The primary mechanism is micro-embolization of either plaque debris or thrombotic material to the distal micro-vasculature following balloon inflation or stent deployment. Another possible additional mechanism is arteriole vasospasm secondary to vasoactive agents, i.e. serotonin, adenosine diphosphate, thromboxane A2, released by the embolized platelet-rich atheromatous material. Other factors that may contribute as well include microvascular plugging with platelets or leukocytes, endothelial swelling, tissue edema compressing vasculature, oxidative stress and inflammation.
Causes
Differentiating No Reflow Phenomenon from Slow Flow
Epidemiology and Demographics
The prevalance of no flow and slow flow varies according to definition. It has been reported in anywhere from 11-30% of patients followingthrombolysis or intervention in acute myocardial infarction. However, in routine, elective coronary intervention, the prevalence has been reported to be as low as 0.6-2%. This phenomenon appears to be more frequent during interventions on saphenous vein grafts (SVG) or thrombus containing lesions as well as during the use of rotational atherectomy. Gender does not appear to play a role in this phenomenon, but it seems to occur more frequently in older patients and in those who did not experience pre-infarct angina. Admission hyperglycemia has also been associated with higher incidence of no reflow as well as worse outcomes. Lesions at high-risk for no reflow and slow flow include: diffuse atherosclerotic involvement, angiographic demonstrable thrombus, irregular or ulcerative lesions, and long lesions with large plaque volume.
Natural History, Complications and Prognosis
No reflow often appears suddenly, is associated with severe chest pain, ischemic ECG changes, and/or hemodynamic deterioration. This needs to be distinguished from slow flow, which can be caused by coronary dissection, macrothrombus formation, coronary vasospasm, or distal macroembolization. The presence of no reflow is clinically important as its presence has been associated with a five to ten fold increase in mortality, as well as a high incidence of myocardial infarction (MI), left ventricular dysfunction, ventricular arrhythmias, early congestive heart failure and cardiogenic shock.
Diagnosis
Treatment
Medical Therapy
Restore normal blood flow through epicardial coronary arteries & microvasculature to prevent persistence of myocardial ischemia. No reflow needs to be distinguished from slow flow resulting from coronary artery dissection, thrombus, coronary vasospasm, or residual stenosis. These etiologies must be excluded as part of the treatment of no reflow. Ultimately, the goals are to improve outcomes, relieve chest pain and alleviate myocardial ischemia.
Intracoronary Pharmacotherapy
Intracoronary or intragraft nitroprusside, adenosine, verapamil, nicardipine, GP IIb/IIIa inhibitors, fibrinolytic therapy and aspiration of atherosclerotic debris are some of the treatment strategies that have been used to correct the episodes of no-reflow.
Thrombus aspiration catheters may be used in high-risk patients undergoing primary PCI for STEMI with occlusion or high thrombus burden. The EXPIRA study[4] published in 2009 showed the use of a thrombus aspiration catheter in anterior STEMIpatients improves myocardial perfusion, reduces infarct size by cardiac MRI and reduces cardiac death at nine months. Care should be exercised when aspirating in the proximalLAD or proximal circumflex locations so that clot does not go down the other adjacent artery.
Distal protection devices may be used in SVGs to prevent distal embolization of clot, debris, and vasoactive mediators. However, the Enhanced Myocardial Efficacy and Recovery by Aspiration of Liberated Debris (EMERALD) and the Protection Devices in PCI Treatment of Myocardial Infarction for Salvage of Endangered Myocardium (PROMISE) trials showed inconsistent results with regards to embolic protection devices in use for primary PCI of native vessels.
Systemic glycoprotein IIb/IIIa receptor antagonists are recommended as pre-treatment in patients presenting with unstable coronary syndromes undergoing PCI. The TITAN-TIMI 34 trial showed early initiation of eptifibatide in the emergency room prior to primary PCI improved myocardial perfusion without an increased risk of bleeding.
A recent study by Zhao JL et al in 2009 showed patients presenting with acute MI and hyperglycemia had lower incidence of no reflow if they were pretreated with HMG-CoA reductase inhibitors prior to angiography.
Prevention
When intervening on high-risk lesions (see above for description), limit the amount of instrumentation within the target vessel, which includes minimizing overaggressive balloon or stent expansion. In patients undergoing rotational atherectomy, shorter runs, slower speeds and smaller initial burr size with small stepwise increases in burr size should be employed to help prevent no reflow. In addition, a cocktail of heparin, nitroglycerin and calcium channel blockers (CCB) should be infused simultaneously. Adding two arteriolar vasodilators, i.e. nicardipine and adenosine, to the flush "cocktail" may be helpful in further reducing incidence of no reflow, however traditionally the CCB used is verapamil.
ACCF/AHA/SCAI 2011 Guidelines for Percutaneous Coronary Intervention (DO NOT EDIT)[5]
No-Reflow Pharmacological Therapies (DO NOT EDIT)[5]
| Class IIa |
| "1. Administration of an intracoronary vasodilator (adenosine, calcium channel blocker, or nitroprusside) is reasonable to treat PCI-related no-reflow that occurs during primary or elective PCI.[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] (Level of Evidence: B)" |
References
- ↑ "Medscape".
- ↑ Kishi T, Yamada A, Okamatsu S, Sunagawa K (2007). "Percutaneous coronary arterial thrombectomy for acute myocardial infarction reduces no-reflow phenomenon and protects against left ventricular remodeling related to the proximal left anterior descending and right coronary artery" ([dead link] – search). Int Heart J. 48 (3): 287–302. doi:10.1536/ihj.48.287. PMID 17592194. Unknown parameter
|month=ignored (help) - ↑ Resnic FS, Wainstein M, Lee MK, Behrendt D, Wainstein RV, Ohno-Machado L; et al. (2003). "No-reflow is an independent predictor of death and myocardial infarction after percutaneous coronary intervention". Am Heart J. 145 (1): 42–6. doi:10.1067/mhj.2003.36. PMID 12514653.
- ↑ Sardella G, Mancone M, Bucciarelli-Ducci C; et al. (2009). "Thrombus aspiration during primary percutaneous coronary intervention improves myocardial reperfusion and reduces infarct size: the EXPIRA (thrombectomy with export catheter in infarct-related artery during primary percutaneous coronary intervention) prospective, randomized trial". J. Am. Coll. Cardiol. 53 (4): 309–15. doi:10.1016/j.jacc.2008.10.017. PMID 19161878. Unknown parameter
|month=ignored (help) - ↑ 5.0 5.1 Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH (2011). "2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions" (PDF). Journal of the American College of Cardiology. 58 (24): 2550–83. doi:10.1016/j.jacc.2011.08.006. PMID 22070837. Retrieved 2011-12-08. Text "PDF" ignored (help); Unknown parameter
|month=ignored (help) - ↑ Amit G, Cafri C, Yaroslavtsev S, Fuchs S, Paltiel O, Abu-Ful A, Weinstein JM, Wolak A, Ilia R, Zahger D (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". American Heart Journal. 152 (5): 887.e9–14. doi:10.1016/j.ahj.2006.05.010. PMID 17070151. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Assali AR, Sdringola S, Ghani M, Denkats AE, Yepes A, Hanna GP, Schroth G, Fujise K, Anderson HV, Smalling RW, Rosales OR (2000). <27::AID-CCD7>3.0.CO;2-0 "Intracoronary adenosine administered during percutaneous intervention in acute myocardial infarction and reduction in the incidence of "no reflow" phenomenon". Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 51 (1): 27–31, discussion 32. PMID 10973014. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Barcin C, Denktas AE, Lennon RJ, Hammes L, Higano ST, Holmes DR, Garratt KN, Lerman A (2004). "Comparison of combination therapy of adenosine and nitroprusside with adenosine alone in the treatment of angiographic no-reflow phenomenon". Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 61 (4): 484–91. doi:10.1002/ccd.20010. PMID 15065143. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Fischell TA, Haller S, Pulukurthy S, Virk IS (2008). "Nicardipine and adenosine "flush cocktail" to prevent no-reflow during rotational atherectomy". Cardiovascular Revascularization Medicine : Including Molecular Interventions. 9 (4): 224–8. doi:10.1016/j.carrev.2008.03.002. PMID 18928946. Retrieved 2011-12-15.
- ↑ Hillegass WB, Dean NA, Liao L, Rhinehart RG, Myers PR (2001). "Treatment of no-reflow and impaired flow with the nitric oxide donor nitroprusside following percutaneous coronary interventions: initial human clinical experience". Journal of the American College of Cardiology. 37 (5): 1335–43. PMID 11300444. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Huang RI, Patel P, Walinsky P, Fischman DL, Ogilby JD, Awar M, Frankil C, Savage MP (2006). "Efficacy of intracoronary nicardipine in the treatment of no-reflow during percutaneous coronary intervention". Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 68 (5): 671–6. doi:10.1002/ccd.20885. PMID 17034064. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Ito H, Taniyama Y, Iwakura K, Nishikawa N, Masuyama T, Kuzuya T, Hori M, Higashino Y, Fujii K, Minamino T (1999). "Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction". Journal of the American College of Cardiology. 33 (3): 654–60. PMID 10080465. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Kaplan BM, Benzuly KH, Kinn JW, Bowers TR, Tilli FV, Grines CL, O'Neill WW, Safian RD (1996). "Treatment of no-reflow in degenerated saphenous vein graft interventions: comparison of intracoronary verapamil and nitroglycerin". Catheterization and Cardiovascular Diagnosis. 39 (2): 113–8. doi:10.1002/(SICI)1097-0304(199610)39:2<113::AID-CCD1>3.0.CO;2-I. PMID 8922307. Unknown parameter
|month=ignored (help);|access-date=requires|url=(help) - ↑ Marzilli M, Orsini E, Marraccini P, Testa R (2000). "Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction". Circulation. 101 (18): 2154–9. PMID 10801755. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Ono H, Osanai T, Ishizaka H, Hanada H, Kamada T, Onodera H, Fujita N, Sasaki S, Matsunaga T, Okumura K (2004). "Nicorandil improves cardiac function and clinical outcome in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: role of inhibitory effect on reactive oxygen species formation". American Heart Journal. 148 (4): E15. doi:10.1016/j.ahj.2004.05.014. PMID 15459610. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Piana RN, Paik GY, Moscucci M, Cohen DJ, Gibson CM, Kugelmass AD, Carrozza JP, Kuntz RE, Baim DS (1994). "Incidence and treatment of 'no-reflow' after percutaneous coronary intervention". Circulation. 89 (6): 2514–8. PMID 8205658. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW (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)". Journal of the American College of Cardiology. 45 (11): 1775–80. doi:10.1016/j.jacc.2005.02.061. PMID 15936605. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Sdringola S, Assali A, Ghani M, Yepes A, Rosales O, Schroth GW, Fujise K, Anderson HV, Smalling RW (2000). <394::AID-CCD4>3.0.CO;2-G "Adenosine use during aortocoronary vein graft interventions reverses but does not prevent the slow-no reflow phenomenon". Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 51 (4): 394–9. PMID 11108667. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Stoel MG, Marques KM, de Cock CC, Bronzwaer JG, von Birgelen C, Zijlstra F (2008). "High dose adenosine for suboptimal myocardial reperfusion after primary PCI: A randomized placebo-controlled pilot study". Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 71 (3): 283–9. doi:10.1002/ccd.21334. PMID 17985384. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Werner GS, Lang K, Kuehnert H, Figulla HR (2002). "Intracoronary verapamil for reversal of no-reflow during coronary angioplasty for acute myocardial infarction". Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 57 (4): 444–51. doi:10.1002/ccd.10375. PMID 12455077. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help) - ↑ Weyrens FJ, Mooney J, Lesser J, Mooney MR (1995). "Intracoronary diltiazem for microvascular spasm after interventional therapy". The American Journal of Cardiology. 75 (12): 849–50. PMID 7717298. Retrieved 2011-12-15. Unknown parameter
|month=ignored (help)
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