Contemporary approach to prevention and therapy of the no-reflow phenomenon
Abstract
No-reflow phenomenon is defined as a state of inadequate (incomplete) myocardial perfusion through a certain segment of the coronary circulation, in the absence of mechanical obstruction of the epicardial coronary artery, i.e. without the presence of significant residual stenosis, spasm, occlusive dissection or intracoronary thrombosis. The development of the no-reflow phenomenon in patients with acute myocardial infarction with ST elevation increases the risk of early clinical complications and mortality many times over. Early intrahospital complications are manifested in the form of hemodynamic instability, acute heart failure including cardiogenic shock, myocardial rupture, and arise as a result of the extension of the area of myocardial necrosis, malignant cardiac arrhythmias, conduction disorders and acute pulmonary edema. The aim of this review is to present the modern aspects of prevention and therapeutic possibilities in patients with the developed no-reflow phenomenon. Prevention involves the application of various strategies before the complete reopening of the occluded infarcted coronary artery, with the aim of preparing the coronary microcirculation for reperfusion. Preventive measures should be directed towards different pathophysiological mechanisms of the no-reflow phenomenon in order to be effective, from the reduction of the total ischemic time, to the application of various pharmacological and non-pharmacological measures. Application of therapeutic measures is necessary in case of unsuccessful prevention and development of no-reflow phenomenon. In this context, therapeutic agents should be effective during current and progressive myocardial circulation damage, and the modern method of primary percutaneous coronary intervention provides the possibility of delivering high local doses of pharmacological agents directly to the infarcted coronary artery, unlike traditional treatment using fibrinolytic therapy.
References
2.Ooi E, Tavella R, Arstall M, et al. Incidence and outcomes of the no-reflow phenomenon during percutaneous coronary intervention: Insights from the CADOSA registry. Heart, Lung and Circulation. 2015; 24; S279.
3.Choo EH, Kim PJ, Chang K, et al. The impact of no-reflow phenomena after primary percutaneous coronary intervention: a time-dependent analysis of mortality. Coron Artery Dis. 2014; 25: 392-8.
4.Bøtker HE, Kharbanda R, Schmidt MR, et al. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial. Lancet. 2010; 375: 727-34.
5.Ibanez B, James S, Agewall S, et al. ESC Scientific Document Group. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018; 39: 119-77.
6.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: 2154-9.
7.Sadeghian M, Mousavi SH, Aamaraee Z, Shafiee A. Administration of intracoronary adenosine before stenting for the prevention of no-reflow in patients with ST-elevation myocardial infarction. Scand Cardiovasc J. 2022; 56: 23-7.
8.Kostic J, Djordjevic-Dikic A, Dobric M, et al. The effects of nicorandil on microvascular function in patients with ST segment elevation myocardial infarction undergoing primary PCI. Cardiovasc Ultrasound. 2015;13:26.
9.Geng N, Ren L, Xu L, Zou D, Pang W. Clinical outcomes of nicorandil administration in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials. BMC Cardiovasc Disord. 2021; 21: 488.
10.Amit G, Cafri C, Yaroslavtsev S, et al. 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. 2006; 152: 887.e9-14.
11.Zhao YJ, Fu XH, Ma XX, et al. Intracoronary fixed dose of nitroprusside via thrombus aspiration catheter for the prevention of the no-reflow phenomenon following primary percutaneous coronary intervention in acute myocardial infarction. Exp Ther Med. 2013; 6: 479-4.
12.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: 143-52.
13.Carrick D, Oldroyd KG, McEntegart M, et al. A randomized trial of deferred stenting versus immediate stenting to prevent no- or slow-reflow in acute ST-segment elevation myocardial infarction (DEFER-STEMI). J Am Coll Cardiol. 2014; 63: 2088-98.
14.Kelbæk H, Høfsten DE, Køber L, et al. Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction (DANAMI 3-DEFER): an open-label, randomised controlled trial. Lancet. 2016; 387: 2199-206.
15.Cassese S, Belle L, Ndrepepa G, et al. Deferred vs Immediate Stenting in Primary Percutaneous Coronary Intervention: A Collaborative Meta-analysis of Randomized Trials With Cardiac Magnetic Resonance Imaging Data. Can J Cardiol. 2018; 34: 1573-80.
16.Desch S, Wöhrle J, Hambrecht R, et al. Intracoronary versus intravenous abciximab bolus in patients with ST-segment elevation myocardial infarction: 1-year results of the randomized AIDA STEMI trial. J Am Coll Cardiol. 2013; 62: 1214-5.
17.Alyamani M, Campbell S, Navarese E, Welsh RC, Bainey KR. Safety and Efficacy of Intracoronary Thrombolysis as Adjunctive Therapy to Primary PCI in STEMI: A Systematic Review and Meta-analysis. Can J Cardiol. 2021; 37:339-46.
18.Malmberg K, Rydén L, Efendic S, et al. Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. J Am Coll Cardiol. 1995; 26: 57-65.
19.Iwakura K. Modulation of individual susceptibility to the no-reflow phenomenon after acute myocardial infarction. Curr Pharm Des. 2013; 19: 4519-28.
20.Atar D, Petzelbauer P, Schwitter J, et al. Effect of intravenous FX06 as an adjunct to primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction results of the F.I.R.E. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury) trial. J Am Coll Cardiol. 2009; 53: 720-9.
21.Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018; 39: 119-77.
22.Rezkalla SH, Stankowski RV, Hanna J, Kloner RA. Management of No-Reflow Phenomenon in the Catheterization Laboratory. JACC Cardiovasc Interv. 2017; 10: 215-23.
23.Kumar D, Ahmed I, Bardooli F, et al. Techniques to Treat Slow-Flow/No-Reflow During Primary Percutaneous Coronary Intervention. Cardiovasc Revasc Med. 2023; 47: 1-4.
24.Sinha SK, Kumar P, Sharma AK, et al. Perforated balloon technique mediated intracoronary delivery of nicorandil to treat coronary no-reflow phenomenon: a novel pharmacological solution to precarious situation. Am J Cardiovasc Dis. 2021; 11: 544-54.
25.Xu L, Wang L, Li K, et al. Nicorandil prior to primary percutaneous coronary intervention improves clinical outcomes in patients with acute myocardial infarction: a meta-analysis of randomized controlled trials. Drug Des Devel Ther. 2019; 13: 1389-1400.
26.Navarese EP, Frediani L, Kandzari DE, et al. Efficacy and safety of intracoronary epinephrine versus conventional treatments alone in STEMI patients with refractory coronary no-reflow during primary PCI: The RESTORE observational study. Catheter Cardiovasc Interv. 2021; 97: 602-11.
27.Darwish A, Frere AF, Abdelsamie M, Awady WE, Gouda M. Intracoronary epinephrine versus adenosine in the management of refractory no-reflow phenomenon: a single-center retrospective cohort study. Ann Saudi Med. 2022; 42: 75-82.
28.Grancini L, Diana D, Centola A, et al. The SALINE Technique for the Treatment of the No-Reflow Phenomenon during Percutaneous Coronary Intervention in STEMI. Journal of Clinical Medicine. 2023; 12: 2405.
29.Nazir SA, Khan JN, Mahmoud IZ, et al. The REFLO-STEMI (REperfusion Facilitated by LOcal adjunctive therapy in ST-Elevation Myocardial Infarction) trial: a randomised controlled trial comparing intracoronary administration of adenosine or sodium nitroprusside with control for attenuation of microvascular obstruction during primary percutaneous coronary intervention. Southampton (UK): NIHR Journals Library; 2016 Dec. PMID: 27929619.
30.Annibali G, Scrocca I, Aranzulla TC, Meliga E, Maiellaro F, Musumeci G. “No-Reflow” Phenomenon: A Contemporary Review. J Clin Med 2022, 11, 2233.