Coronary Slow-Flow Syndrome: A Review on Natural History of Disease and Best Practices
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Abstract
Coronary slow flow (CSF) poses significant clinical challenges, marked by delayed coronary blood flow despite angiographically normal epicardial arteries. With a prevalence of 1% to 7%, the underlying pathogenesis and clinical manifestations of this condition remain incompletely understood. This review examines the natural history of CSF, including its pathophysiological mechanisms, ranging from inflammatory cascades to microvascular dysfunction. Diagnostic approaches, such as corrected TIMI frame count, scintigraphy, and ECG analysis, provide valuable insights into its complex presentation. Further, the review outlines management strategies, focusing on pharmacological interventions like calcium channel blockers and anti-inflammatory agents. Understanding CSF’s natural history is crucial for implementing effective preventive measures, spanning primary to tertiary prevention. Still, further research is essential to fully elucidate its pathophysiology and optimize therapeutic strategies for improving patient outcomes in this complex disorder.
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2. Henein MY, Vancheri F. Defining coronary slow flow. Sage Publications Sage CA: Los Angeles, CA; 2021. p. 805-7.
3. Mangieri E, Macchiarelli G, Ciavolella M, Barillà F, Avella A, Martinotti A, et al. Slow coronary flow: clinical and histopathological features in patients with otherwise normal epicardial coronary arteries. Catheterization and cardiovascular diagnosis. 1996;37(4):375-81.
4. Tambe A, Demany M, Zimmerman HA, Mascarenhas E. Angina pectoris and slow flow velocity of dye in coronary arteries—a new angiographic finding. American heart journal. 1972;84(1):66-71.
5. Beltrame JF, Limaye SB, Horowitz JD. The coronary slow flow phenomenon–a new coronary microvascular disorder. Cardiology. 2002;97(4):197-202.
6. Gibson CM, Cannon CP, Daley WL, Dodge Jr JT, Alexander B, Marble SJ, et al. TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation. 1996;93(5):879-88.
7. Saya S, Hennebry TA, Lozano P, Lazzara R, Schechter E. Coronary slow flow phenomenon and risk for sudden cardiac death due to ventricular arrhythmias: a case report and review of literature. Clinical Cardiology: An International Indexed and Peer‐Reviewed Journal for Advances in the Treatment of Cardiovascular Disease. 2008;31(8):352-5.
8. Kunadian V, Chieffo A, Camici PG, Berry C, Escaned J, Maas AHEM, et al. An EAPCI Expert Consensus Document on Ischaemia with Non-Obstructive Coronary Arteries in Collaboration with European Society of Cardiology Working Group on Coronary Pathophysiology & Microcirculation Endorsed by Coronary Vasomotor Disorders International Study Group. European Heart Journal. 2020;41(37):3504-20.
9. Ong P, Camici PG, Beltrame JF, Crea F, Shimokawa H, Sechtem U, et al. International standardization of diagnostic criteria for microvascular angina. International Journal of Cardiology. 2018;250:16-20.
10. Dutta U, Sinha A, Demir OM, Ellis H, Rahman H, Perera D. Coronary Slow Flow Is Not Diagnostic of Microvascular Dysfunction in Patients With Angina and Unobstructed Coronary Arteries. Journal of the American Heart Association. 2023;12(1):e027664.
11. Sanati H, Kiani R, Shakerian F, Firouzi A, Zahedmehr A, Peighambari M, et al. Coronary slow flow phenomenon clinical findings and predictors. Research in cardiovascular medicine. 2016;5(1).
12. Hawkins BM, Stavrakis S, Rousan TA, Abu-Fadel M, Schechter E. Coronary Slow Flow–Prevalence and Clinical Correlations–. Circulation Journal. 2012;76(4):936-42.
13. Wang Y, Zhao H-w, Wang C-f, Zhang X-j, Tao J, Cui C-s, et al. Incidence, Predictors, and Prognosis of Coronary Slow-Flow and No-Reflow Phenomenon in Patients with Chronic Total Occlusion Who Underwent Percutaneous Coronary Intervention. Therapeutics and Clinical Risk Management. 2020;16:95-101.
14. Chaudhry MA, Smith M, Hanna EB, Lazzara R. Diverse Spectrum of Presentation of Coronary Slow Flow Phenomenon: A Concise Review of the Literature. Cardiology Research and Practice. 2012;2012:383181.
15. Cesar L, Ramires J, CV SJ, Meneghetti J, Antonelli R, Da-Luz P, et al. Slow coronary run-off in patients with angina pectoris: clinical significance and thallium-201 scintigraphic study. Brazilian journal of medical and biological research= Revista brasileira de pesquisas medicas e biologicas. 1996;29(5):605-13.
16. Demirkol MO, Yaymac B, Mutlu B. Dipyridamole myocardial perfusion single photon emission computed tomography in patients with slow coronary flow. Coronary artery disease. 2002;13(4):223-9.
17. Karahan MZ, Aktan A, Güzel T, Günlü S, Kılıç R. The effect of coronary slow flow on ventricular repolarization parameters. Journal of Electrocardiology. 2023;78:39-43.
18. Mayer M, Allan T, Harkin KL, Loftspring E, Saffari SE, Reynolds HR, et al. Angiographic coronary slow Flow is not a valid surrogate for invasively diagnosed coronary microvascular dysfunction. Cardiovascular Interventions. 2024;17(7):920-9.
19. Maddali V, Nagula P, Ravi S, P K. Predictors of coronary slow flow phenomenon in patients with angina and normal epicardial coronaries. European Heart Journal. 2021;42(Supplement_1):ehab724. 1082.
20. Elsanan MAHA, Tahoon IHHH, Mohamed GI, ZeinElabdeen SG, Shehata IE. Relationship between inflammatory markers and coronary slow flow in type 2 diabetic patients. BMC Cardiovascular Disorders. 2023;23(1):244.
21. Karauzum K, Karauzum I, Hanci K, Gokcek D, Gunay B, Bakhshian H, et al. The Systemic Immune-Inflammation Index May Predict the Coronary Slow Flow Better Than High-Sensitivity C-Reactive Protein in Patients Undergoing Elective Coronary Angiography. Cardiology Research and Practice. 2022;2022.
22. Brunetti ND, Salvemini G, Cuculo A, Ruggiero A, De Gennaro L, Gaglione A, et al. Coronary artery ectasia is related to coronary slow flow and inflammatory activation. Atherosclerosis. 2014;233(2):636-40.
23. Tang O, Wu J, Qin F. Relationship between methylenetetrahydrofolate reductase gene polymorphism and the coronary slow flow phenomenon. Coronary Artery Disease. 2014;25(8):653-7.
24. Shi G-L, Cai X-X, Su Y-M, Chen C, Deng X-T, Pan H-Y, et al. Interleukin-10 promotor-592A/C polymorphism is associated with slow coronary flow in Han Chinese. International Journal of Clinical and Experimental Pathology. 2015;8(4):4091.
25. Liu C-L, Xue Z-Q, Gao S-P, Chen C, Chen X-H, Pan M, et al. The Relationship between Interleukin-6 Promotor Polymorphisms and Slow Coronary Flow Phenomenon. Clinical Laboratory. 2016;62(5):947-53.
26. Elamragy AA, Abdelhalim AA, Arafa ME, Baghdady YM. Anxiety and depression relationship with coronary slow flow. Plos one. 2019;14(9):e0221918.
27. Yavuz F, Alici H, Alici D, Inanc IH, Ercan S, Davutoglu V. The controversy about the association between depression and coronary slow flow phenomenon. International Journal of Cardiology. 2015;186:109-10.
28. Simsek H, Sahin M, Gunes Y, Akdag S, Akil M, Akyol A, et al. A novel echocardiographic method as an indicator of endothelial dysfunction in patients with coronary slow flow. Eur Rev Med Pharmacol Sci. 2013;17(5):689-93.
29. Tanriverdi H, Evrengul H, Tanriverdi S, Kuru O, Seleci D, Enli Y, et al. Carotid intima–media thickness in coronary slow flow: relationship with plasma homocysteine levels. Coronary artery disease. 2006;17(4):331-7.
30. Zhu X, Shen H, Gao F, Wu S, Ma Q, Jia S, et al. Clinical profile and outcome in patients with coronary slow flow phenomenon. Cardiology research and practice. 2019;2019.
31. Zhu Q, Wang S, Huang X, Zhao C, Wang Y, Li X, et al. Understanding the pathogenesis of coronary slow flow: Recent advances. Trends in Cardiovascular Medicine. 2022.
32. Aksoy S, Öz D, Öz M, Agirbasli M. Predictors of Long-Term Mortality in Patients with Stable Angina Pectoris and Coronary Slow Flow. Medicina. 2023;59(4):763.
33. Aparicio A, Cuevas J, Morís C, Martín M. Slow coronary blood flow: pathogenesis and clinical implications. European Cardiology Review. 2022;17.
34. Algoet M, Janssens S, Himmelreich U, Gsell W, Pusovnik M, Van den Eynde J, et al. Myocardial ischemia-reperfusion injury and the influence of inflammation. Trends in cardiovascular medicine. 2022.
35. Takahashi M, Arai T, Kimura T, Hojo R, Hiraoka M, Fukamizu S. Relationship between coronary blood flow and improvement of cardiac function after catheter ablation for persistent atrial fibrillation. Journal of Interventional Cardiac Electrophysiology. 2023:1-8.
36. Zivanic A, Stankovic I, Ilic I, Putnikovic B, Neskovic A. Prognosis of patients with previous myocardial infarction, coronary slow flow, and normal coronary angiogram. Herz. 2019:1-7.
37. Rasmi Y, Bagheri M, Faramarz-Gaznagh S, Nemati M, Khadem-Ansari MH, Saboory E, et al. Transcriptional activity of tumor necrosis factor-alpha gene in peripheral blood mononuclear cells in patients with coronary slow flow. ARYA atherosclerosis. 2017;13(4):196.
38. Liu B, Liu Y, Ma L, Liu J, Li J, Huang K, et al. The Immediate And Long-Term Effects of Shexiang Tongxin Dropping Pill On Coronary Slow Flow: Study Protocol For A Randomized Double-Blind Placebo-Controlled Trial. 2021.
39. Zengin A, Karaca M, Aruğaslan E, Yıldırım E, Karataş MB, Çanga Y, et al. Performance of neutrophil to lymphocyte ratio for the prediction of long-term morbidity and mortality in coronary slow flow phenomenon patients presented with non-ST segment elevation acute coronary syndrome. Journal of Cardiovascular and Thoracic Research. 2021;13(2):125.
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| Files | ||
| Issue | Vol 20 No 1 (2025) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/jthc.v20i1.19222 | |
| Keywords | ||
| Angiography Coronary Arterial Diseases Coronary Slow Flow Natural History of Disease TIMI Frame Count | ||
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How to Cite
1.
Iqhrammullah M, Rampengan D. Coronary Slow-Flow Syndrome: A Review on Natural History of Disease and Best Practices. Res Heart Yield Transl Med. 2025;20(1):55-68.
