No Reflow in Acute Coronary Syndromes: An Old Foe or a New Frontier?

Garzon, Stefano

doi:10.36660/abc.20210118

Keywords
Myocardial Ischemic; Cardiovascular Diseases/mortality; Percutaneous Coronary Interventions; Myocardial Infarction; Coronary Artery Disease; Risk Factors; Vascular Resistance

Palavras-chave
Isquemia Miocárdica; Doenças Cardiovasculares/mortalidade; Intervenção Coronária Percutânea; Infarto do Miocárdio; Doença da Artéria Coronária; Fatores de Risco; Resistência Vascular

Keywords
Myocardial Ischemic; Cardiovascular Diseases/mortality; Percutaneous Coronary Interventions; Myocardial Infarction; Coronary Artery Disease; Risk Factors; Vascular Resistance

Palavras-chave
Isquemia Miocárdica; Doenças Cardiovasculares/mortalidade; Intervenção Coronária Percutânea; Infarto do Miocárdio; Doença da Artéria Coronária; Fatores de Risco; Resistência Vascular

According to the World Health Organization (WHO), ischemic heart disease is the leading cause of death worldwide, accounting for 16% of the world's deaths in 2019.¹ However, due to continuous evolution in medical treatment and revascularization techniques, a steady decline in death rates in acute coronary syndromes (ACS) has been observed in recent years.²

Currently, percutaneous coronary intervention (PCI) is the gold-standard treatment for ST-elevation myocardial infarction (STEMI)³ and a mainstay therapeutic option for non-STEMI ACS⁴ and stable coronary artery disease.⁵ Nonetheless, and particularly in STEMI patients, PCI can be very challenging at times. One of the most dreaded events during PCI in STEMI is the phenomenon commonly referred as “no-reflow”, an impaired myocardial perfusion secondary to microvascular obstruction without angiographic evidence of coronary obstruction(6). Initially described in animal models,⁶^,⁷ it was also recognized in humans in the following decades,⁸^,⁹ being first described after PCI for STEMI by Feld in 1992.¹⁰ Its occurrence is related to poorer short- and long-term outcomes following PCI,¹¹^,¹² and it is present in more than 20% of patients undergoing primary PCI for STEMI.¹³

In a recent publication,¹⁴ Rezkalla et al. thoroughly reviewed the management of no-reflow, identifying many risk factors, which include longer time to reperfusion, high-pressure balloon dilation, longer stents, and also clinical characteristics of the patient, many of which overlap with those of coronary artery disease and ACS. If no-reflow is anticipated, pharmacological and technical measures can be taken in an attempt to prevent it, potentially minimizing its occurrence and alerting the operator to promptly act in case it occurs.

According to this idea, the article “The Comparison between Two Risk Scores as for the Prediction of Coronary Microvascular Obstruction during Primary Percutaneous Intervention,”¹⁵ published in the current edition of this journal, explores the ability of two risk scores in predicting the occurrence of no-reflow. It compares the SAK score, which uses purely clinical parameters (symptom onset to balloon inflation time, ACT level on admission, Killip classification, age, neutrophil/lymphocyte ratio, and glucose levels), with the ATI score, whose parameters are an invasive measure of microvascular resistance (IMR) obtained via coronary microcatheter, age and thrombus score in the culprit artery. In this study, both scores performed well, with the SAK score presenting an AUC of 0.855. In this study, no-reflow was more commonly associated with older patients with longer reperfusion times, higher glucose levels, higher serum creatinine levels, higher leucocyte counts, Killip III classification and increased myocardial necrosis biomarkers, which is in accordance with current medical literature. However, other factors, such as hypertension, dyslipidemia, diabetes, and smoking were not related to the occurrence of the phenomenon, suggesting that its physiopathology is not yet fully understood. Also, there are no data regarding how no-reflow was treated and whether the treatment resulted in improvement of microvascular resistance and possibly better outcomes.

In a study recently published,¹⁶ Viana et al. compared the SYNTAX and GRACE scores in predicting cardiovascular mortality and recurring non-fatal coronary events after ACS. Both were effective in predicting cardiovascular death (C-statistic 0.80 vs. 0.89, p=0.19, for the SYNTAX and GRACE scores, respectively), but the anatomical SYNTAX score was the only one capable of predicting recurring non-fatal coronary events (C-statistic 0.64 vs. 0.50, p=0.027), suggesting that intra-procedural complications and outcomes, such as no-reflow, are not accounted for when using purely clinical ACS risk scores.

Understanding the full complexity of ACS still seems to be out of our reach at the moment. However, realizing that prognosis and outcomes of such patients result from numerous clinical and intra-procedural factors might be the beacon to help us navigate these troubled and not-yet-fully-charted waters.

Short editorial related to the article: The Comparison between Two Risk Scores as for the Prediction of Coronary Microvascular Obstruction during Primary Percutaneous Intervention

References

¹ World Health Organization.(WHO). World Health Statistics. Monitoring Health For The SDGs Sustainable Development Goals. Geneva;2020.
² Fox KAA, Steg PG, Eagle KA, Goodman SG, Anderson FA, Granger CB, et al. Decline in rates of death and heart failure in acute coronary syndromes, 1999-2006. J Am Med Assoc. 2007;297(17):1892-900.
³ Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2018;39(2):119-77.
⁴ Collet J-P, Thiele H, Barbato E, Barthélémy O, Bauersachs J, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42(14):1289-367.
⁵ Sousa-Uva M, Neumann FJ, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur J Cardiothoracic Surg. 2019; 55(1):4-90.
⁶ Kloner RA, Ganote CE, Jennings RB. The “no reflow” phenomenon after temporary coronary occlusion in the dog. J Clin Invest. 1974;54(6):1496-508.
⁷ Krug A, Du Mesnil de Rochemont, Korb G. Blood supply of the myocardium after temporary coronary occlusion. Circ Res. 1966;19(1):57-62.
⁸ Schofer J, Montz R, Mathey DG. Scintigraphic evidence of the “No reflow” phenomenon in human beings after coronary thrombolysis. J Am Coll Cardiol. 1985;5(3):593-8.
⁹ Bates ER, Krell MJ, Dean EN, O’Neill WW, Vogel RA. Demonstration of the “no-reflow” phenomenon by digital coronary arteriography. Am J Cardiol. 1986;57(1):177-8.
¹⁰ Feld H, Lichstein E, Schachter J, Shani J. Early and late angiographic findings of the “no-reflow” phenomenon following direct angioplasty as primary treatment for acute myocardial infarction. Am Heart J. 1992;123(3):782-4.
¹¹ Morishima I, Sone T, Okumura K, Tsuboi H, Kondo J, Mukawa H, 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(4):1202-9.
¹² Harrison RW, Aggarwal A, Ou FS, Klein LW, Rumsfeld JS, Roe MT, et al. Incidence and outcomes of no-reflow phenomenon during percutaneous coronary intervention among patients with acute myocardial infarction. Am J Cardiol. 2013;111(2):178-84.
¹³ Jaffe R, Charron T, Puley G, Dick A, Strauss BH. Microvascular obstruction and the no-reflow phenomenon after percutaneous coronary intervention. Circulation. 2008;117(24):3152-6.
¹⁴ Rezkalla SH, Stankowski R V., Hanna J, Kloner RA. Management of No-Reflow Phenomenon in the Catheterization Laboratory. JACC: Cardiovasc Intervent. 2017;10(3):215-23.
¹⁵ Xiao Y, Chen H, Liu D, Wang Y, Wang W, Zhang Q, et al. The Comparison between Two Risk Scores as for the Prediction of Coronary Microvascular Obstruction during Primary ercutaneous Intervention. Arq Bras Cardiol. 2021; 116(5):959-967.
¹⁶ Viana MS, Correia VCA, Ferreira FM, Lacerda YF, Bagano GO, Fonseca LL, et al. Competência Prognóstica Distinta entre Modelo Clínico e Anatômico em Síndromes Coronarianas Agudas: Comparação por Tipo de Desfecho. Arq Bras Cardiol. 2020;115(2):219-25.

Publication Dates

Publication in this collection
17 May 2021
Date of issue
May 2021

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] ¹ World Health Organization.(WHO). World Health Statistics. Monitoring Health For The SDGs Sustainable Development Goals. Geneva;2020.

[2] ² Fox KAA, Steg PG, Eagle KA, Goodman SG, Anderson FA, Granger CB, et al. Decline in rates of death and heart failure in acute coronary syndromes, 1999-2006. J Am Med Assoc. 2007;297(17):1892-900.

[3] ³ Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2018;39(2):119-77.

[4] ⁴ Collet J-P, Thiele H, Barbato E, Barthélémy O, Bauersachs J, et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42(14):1289-367.

[5] ⁵ Sousa-Uva M, Neumann FJ, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur J Cardiothoracic Surg. 2019; 55(1):4-90.

[6] ⁶ Kloner RA, Ganote CE, Jennings RB. The “no reflow” phenomenon after temporary coronary occlusion in the dog. J Clin Invest. 1974;54(6):1496-508.

[7] ⁷ Krug A, Du Mesnil de Rochemont, Korb G. Blood supply of the myocardium after temporary coronary occlusion. Circ Res. 1966;19(1):57-62.

[8] ⁸ Schofer J, Montz R, Mathey DG. Scintigraphic evidence of the “No reflow” phenomenon in human beings after coronary thrombolysis. J Am Coll Cardiol. 1985;5(3):593-8.

[9] ⁹ Bates ER, Krell MJ, Dean EN, O’Neill WW, Vogel RA. Demonstration of the “no-reflow” phenomenon by digital coronary arteriography. Am J Cardiol. 1986;57(1):177-8.

[10] ¹⁰ Feld H, Lichstein E, Schachter J, Shani J. Early and late angiographic findings of the “no-reflow” phenomenon following direct angioplasty as primary treatment for acute myocardial infarction. Am Heart J. 1992;123(3):782-4.

[11] ¹¹ Morishima I, Sone T, Okumura K, Tsuboi H, Kondo J, Mukawa H, 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(4):1202-9.

[12] ¹² Harrison RW, Aggarwal A, Ou FS, Klein LW, Rumsfeld JS, Roe MT, et al. Incidence and outcomes of no-reflow phenomenon during percutaneous coronary intervention among patients with acute myocardial infarction. Am J Cardiol. 2013;111(2):178-84.

[13] ¹³ Jaffe R, Charron T, Puley G, Dick A, Strauss BH. Microvascular obstruction and the no-reflow phenomenon after percutaneous coronary intervention. Circulation. 2008;117(24):3152-6.

[14] ¹⁴ Rezkalla SH, Stankowski R V., Hanna J, Kloner RA. Management of No-Reflow Phenomenon in the Catheterization Laboratory. JACC: Cardiovasc Intervent. 2017;10(3):215-23.

[15] ¹⁵ Xiao Y, Chen H, Liu D, Wang Y, Wang W, Zhang Q, et al. The Comparison between Two Risk Scores as for the Prediction of Coronary Microvascular Obstruction during Primary ercutaneous Intervention. Arq Bras Cardiol. 2021; 116(5):959-967.

[16] ¹⁶ Viana MS, Correia VCA, Ferreira FM, Lacerda YF, Bagano GO, Fonseca LL, et al. Competência Prognóstica Distinta entre Modelo Clínico e Anatômico em Síndromes Coronarianas Agudas: Comparação por Tipo de Desfecho. Arq Bras Cardiol. 2020;115(2):219-25.