Vasospastic angina: pathophysiology and clinical significance
https://doi.org/10.15829/1728-8800-2020-1-2391
Abstract
The review discusses an analysis of the literature on various aspects of the pathogenesis, diagnosis and treatment of vasospastic angina (VA). Data on the prevalence of coronary artery spasm (CAS) in various populations, as well as risk factors and triggers, are presented. We considered pathophysiological mechanisms of CAS, including hyperreactivity of coronary smooth muscle cells, endothelial dysfunction, nonspecific inflammation, oxidative stress, magnesium deficiency, autonomic imbalance, etc. The relationship of CAS with coronary atherosclerosis and thrombosis is emphasized. Modern recommendations for the diagnosis and treatment of VA are presented. Invasive verification of CAS is performed by pharmacological provocation tests with certain contraindications. Calcium antagonists and their combination with long-acting nitrates play a key role in the treatment of VA. Medications with a prospect for use in VA are Rho-kinase inhibitors, ATP-sensitive potassium channel activators, alpha-1 blockers. The management of patients with refractory VA and the prospects for endovascular treatment are discussed. It was noted that patients with multi-vessel VA are more likely to develop life-threatening arrhythmias and sudden death.
Supporting agencies: This study was conducted under the grants of the Russian Foundation for Basic Research № 18-29-03131, № 19-29-01077
About the Authors
B. I. Geltser
Far Eastern Federal University
Russian Federation
Russian Federation
Vladivostok
M. M. Tsivanyuk
Far Eastern Federal University; Vladivostok clinical hospital №1
Russian Federation
Russian Federation
V. N. Kotelnikov
Far Eastern Federal University
Russian Federation
Russian Federation
Vladivostok
R. S. Karpov
Tomsk National Research Medical Center
Russian Federation
Russian Federation
References
1. Prinzmetal M, Kennamer R, Merlis R, et al. Angina pectoris. I. A variant form of angina pectoris. Am J Med. 1959;27:375-88. doi:10.1016/0002-9343(59)90003-8.
2. Yasue H, Mizuno Y, Harada E. Coronary artery spasm — Clinical features, pathogenesis, 9.and treatment. Proc Jpn Acad. 2019;Ser.B95:53-66. doi:10.2183/pjab.95.005.
3. JCS Joint Working Group. Guidelines for diagnosis and treatment of patients with vasospastic angina (Coronary Spastic Angina) (JCS 2013). Circ. J. 2014;78:2779-10. 801. doi:10.1253/circj.CJ-66-0098.
4. Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease. The Task force on the management of stable coronary artery disease of the european society of Cardiology. Eur. Heart J. 2013;34(38):2949-3003. doi:10.1093/eurheartj/eht296.
5. Picard F, Sayah N, Spagnoli V, et al. Vasospastic angina: A literature review of 12. current evidence. Archives of cardiovascular disease. 2019;112:44-55. doi:101016/j.acvd.2018.08.002.
6. Lanza GA, Careri G, Crea F. Mechanisms of coronary artery spasm. Circulation. 2011;124(16):1774-82. doi:10.1161/circulationaha.111.037283.
7. Hung MY, Hsu KH, Hung MJ, et al. Interactions among gender, age, hypertension and 13. C-reactive protein in coronary vasospasm. Eur J Clin Invest. 2010;40(12):1094-103. doi:10.1111/j.1365-2362.2010.02360.x.
8. Ong P, Athanasiadis A, Borgulya G, et al. High prevalence of a pathological response 14. to acetylcholine testing in patients with stable angina pectoris and unobstructed coronary arteries. The ACOVA Study (Abnormal COronary VAsomotion in patients with stable angina and unobstructed coronary arteries). JACC. 2012;59:655-62. doi:10.1016/j.jacc.2011.11.015.
9. Montone R.A, Niccoli G, Fracassi F, et al. Patients with acute myocardial infarction and non-obstructive coronary arteries: safety and prognostic relevance of invasive coronary provocative tests. Eur Heart J. 2018;39:91-8. doi:10.1093/eurheartj/ehx667.
10. Nakayama N, Kaikita K, Fukunaga T, et al. Clinical features and prognosis of patients with coronary spasm-induced nonST-segment elevation acute coronary syndrome. J Am Heart Assoc. 2014;3:e000795. doi:10.1161/jaha.114.000795.
11. Cho SW, Park TK, Gwag HB, et al. Clinical Outcomes of Vasospastic Angina Patients Presenting With Acute Coronary Syndrome. J Am Heart Assoc. 2016;5:e004336 doi:10.1161/jaha.116.004336.
12. Ulbasheva EA, Namitokov AM, Kandinsky MV, et al. Clinical patterns of vasospastic angina. Complex Issues of Cardiovascular Diseases. 2018;7(4):121-7 (In Russ.) doi:10.17802/2306-1278-2018-7-4-121-127.
13. Patel RS, Kamil SH, Bachu R, et al. Marijuana use and acute myocardial infarction: A systematic review of published cases in the literature. Trends Cardiovasc Med. 2019; pii: S1050-1738(19)30112-4. doi:10.1016/j.tcm.2019.08.003.
14. Singh S, Brocker C, Koppaka V, et al. Aldehyde dehydrogenases in cellular responses to oxidative / electrophilic stress. Free Radic Biol Med. 2013;56:89-101. doi:10.1016/j.freeradbiomed.2012.11.010.
15. Chen CH, Ferreira JC, Gross ER, et al. Targeting aldehyde dehydrogenase 2: New therapeutic opportunities. Physiol Rev. 2014;94:1-34. doi: 10.1152/physrev.00017.2013.
16. Mizuno Y, Hokimoto S, Harada E, et al. Variant aldehyde dehydrogenase 2 (ALDH2*2) is a risk factor for coronary spasm and ST-segment elevation myocardial infarction. J Am Heart Assoc. 2016;5:e003247. doi:10.1161/jaha.116.003247.
17. Mizuno Y, Hokimoto S, Harada E, et al. Variant aldehyde dehydrogenase 2 (ALDH2*2) in east asians interactively exacerbates tobacco smoking risk for coronary spasm — Possible role of reactive aldehydes. Circ. J. 2016;81:96-102. doi: 10.1253/circj.cj-16-0969.
18. Kitani Y, Nakagawa N, Sakamoto N, et al. Unexpectedly High Prevalence of Coronary Spastic Angina in Patients With Anderson-Fabry Disease. Circ J. 2019;83:481-4. doi:101253/circj.cj-18-0734.
19. Arai R, Kano H, Suzuki S, et al. Myocardial bridging is an independent predictor of positive spasm provocation testing by intracoronary ergonovine injections: a retrospective observational study. Heart Vessels. 2019Sep27. doi:10.1007/s00380-019-01518-7.
20. Mizuno Y, Harada E, Morita S, et al. East Asian variant of aldehyde dehydrogenase 2 is associated with coronary spastic angina: Possible roles of reactive aldehydes and implications of alcohol flushing syndrome. Circulation. 2015;131:1665-73. doi:10.1161/circulationaha.114.013120.
21. Shimokawa H, Sunamura S, Satoh K. RhoA/Rho-Kinase in the Cardiovascular System. Circ Res. 2016;118:352-66. doi:10.1161/circresaha.115.306532.
22. Yasue H, Mizuno Y, Harada E, et al. Effects of a 3-hydroxy-3-methylglutaryl coenzyme 40. A reductase inhibitor, fluvastatin, on coronary spasm after withdrawal of calcium-channel blockers. JACC. 2008;51;1742-8. doi:10.1016/j.jacc.2007.12.049.
23. Bussemaker E, Pistrosch F, Forster S, et al. Rho kinase contributes to basal vascular tone in humans: Role of endothelium-derived nitric oxide. Am J Physiol Heart Circ 41. Physiol. 2007;293:541-7. doi:10.1152/ajpheart.00770.2006.
24. Maslov LN, Voronkov NS, Sementsov AS, et al. Reperfusion injury of the heart. The main links of pathogenesis. Russian Journal of Physiology. 2018;104(8):881-903. (In Russ.) doi:10.7868/S0869813918070018.
25. Rodrigo R, Gonzalez J, Paoletto F. The role of oxidative stress in the pathophysiology 43. of hypertension. Hypertens Res. 2011;34:431-40. doi:10.1038/hr.2010.264.
26. Krylatov AV, Maslov LN, Voronkov NS, et al. Reactive oxygen species as intracellular signaling molecules in the cardiovascular system. Curr Cardiol Rev. 2018;14(4):290-300. doi:10.2174/1573403X14666180702152436.
27. Kiani AA, Nazarabad VH, Ahmadi K, et al. Polymorphisms of Endothelial Nitric Oxide Synthase and Hypoxia-Inducible Factor 1 Alpha Genes Play a Role in Susceptibility 45. to Coronary Artery Disease. Biomedical Research and Therapy. 2018; 5(9):2688-96. doi:10.15419/bmrat.v5i9.480.
28. Maylian DE, Kolomiets VV. Magnesium deficiency in pathogenesis of cardiovascular 46. diseases: recent developments. Russian Journal of Cardiology. 2017;(6):167-72. (In Russ.) doi: 10.15829/1560-4071-2017-6-167-172.
29. Morita S, Mizuno Y, Harada E, et al. Differences and interactions between 48. risk factors for coronary spasm and atherosclerosis — Smoking, aging, inflammation, and blood pressure. Intern. Med. 2014;53:2663-70. doi :10.2169/ internalmedicine.53.2705.
30. Nishimiya K, Matsumoto Y, Shindo T, et al. Association of adventitial vasa vasorum andinflammation with coronary hyperconstriction after drug-eluting stent implantation in pigs in vivo. Circ J. 2015;79:1787-98. doi:10.1253/circj.cj-15-0149.
31. Ohyama K, Matsumoto Y, Takanami K, et al. Coronary adventitial and perivascular adipose tissue inflammation in patients with vasospastic angina. JACC. 2018;71:414-25. doi:10.1016/j.jacc.2017.11.046.
32. Libby P, Bornfeldt KE, Tall AR. Atherosclerosis: Successes, surprises, and future challenges. Circ Res. 2016;118:531-4. doi:10.1161/circresaha.116.308334.
33. Katoh D, Mizuno Y, Harada E, et al. High incidence of provoked coronary spasm in the presence of a stent after myocardial infarction: Therapeutic and prognostic implications. Coron Artery Dis. 2012;23:141-5. doi:10.1097/mca.0b013e32835115ee.
34. Hokimoto S, Mizuno Y, Sueta D, et al. High incidence of CAS after percutaneous coronary interventions: Comparison between new generation drug-eluting stent and bare-metal stent. Int J Cardiol. 2015;182:171-3. doi:10.1016/j.ijcard.2014.12.151.
35. Hata R, Oka N, Kubo S, et al. Impact of stent type and presence of vasospastic angina on long-term prognosis. Circ J. 2018;82:469-76. doi:10.1253/circj.CJ-17-0298.
36. Beltrame JF, Crea F, Kaski JC, et al. International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017;38:2565-8. doi:10.1093/eurheartj/ehv351.
37. Knuuti J, Wijns W, Saraste A, et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: The Task Force for the Diagnosis and Management of Chronic Coronary Syndromes of the European Society of Cardiology (ESC). Eur Heart J. 2019. pii: ehz425:42. doi:10.1093/eurheartj/ehz425.
38. Matsumura M, Oshita C, Fujii Y, et al. Vasospastic Angina Diagnosed by the Spasm Provocation Test with the Combined Use of the Acetylcholine and Ergonovine Provocation Tests. Intern Med. 2019;58( 16):2377-81. doi: 10.2169/ internalmedicine.2710-19.
39. Yasue H, Mizuno Y, Harada E. Association of East Asian Variant Aldehyde Dehydrogenase 2 Genotype (ALDH2*2*) with Coronary Spasm and Acute Myocardial Infarction. Adv Exp Med Biol. 2019;1193:121-34. doi:10.1007/978-981-13-6260-6_7.
40. Morikawa Y, Mizuno Y, Harada E, et al. Aerobic interval exercise training in the afternoon reduces attacks of coronary spastic angina in conjunction with improvement in endothelial function, oxidative stress, and inflammation. Coron Artery Dis. 2013;24:177-82. doi:10.1097/MCA.0b013e32835cbef5.
41. Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:267-315. doi:10.1093/eurheartj/ehv320.
42. Hung MJ, Hu P, Hung MY. Coronary Artery Spasm: Review and Update. Int J Med Sci. 2014;11(11):1161-71. doi:10.7150/ijms.9623.
43. Kim MC, Ahn Y, Park KH, et al. Clinical outcomes of low-dose aspirin administration in patients with variant angina pectoris. Int J Cardiol. 2013;167:2333-4. doi:10.1016/j.ijcard.2016.06.195.
44. Ishii M, Kaikita K, Sato K, et al. Impact of statin therapy on clinical outcome in patients with coronary spasm. J Am Heart Assoc. 2016;5:e003426. doi:10.1161/jaha.116.003426.
45. Horinaka S, Yabe A, Yagi H, et al. Effects of nicorandil on cardiovascular events in patients with coronary artery disease in the Japanese Coronary Artery Disease (JCAD) study. Circ J. 2010;74(3):503-9. doi:10.1253/circj.cj-09-0649.
46. Sakata Y, Nakatani D, Shimizu M, et al. Oral treatment with nicorandil at discharge is associated with reduced mortality after acute myocardial infarction. J Cardiol. 2012;59(1):14-21. doi:10.1016/j.jjcc.2011.08.001.
47. Eschalier R, Souteyrand G, Jean F, et al. Should an implanted defibrillator be considered in patients with vasospastic angina? Arch Cardiovasc Dis. 2014;107:42-7. doi:10.1016/j.acvd.2013.10.006.
48. Sueda S, Kohno H, Miyoshi T, et al. Spasm provocation tests performed under medical therapy: a new approach for treating patients with refractory coronary spastic angina on emergency admission. Intern Med. 2014;53:1739-47. doi:10.2169/internalmedicine.53.2429.
49. Takagi Y, Yasuda S, Tsunoda R, et al. Clinical characteristics and long-term prognosis of vasospastic angina patients who survived out-of-hospital cardiac arrest: Multicenter registry study of the Japanese Coronary Spasm Association. Circ Arrhythm Electrophysiol. 2014;295-302. doi:10.1161/circep.110.959809.
50. Ahn JM, Lee KH, Yoo SY, et al. Prognosis of variant angina manifesting as aborted sudden cardiac death. JACC. 2016;68:137-45. doi:10.1016/j.jacc.2016.04.050.
Review
For citations:
Geltser B.I., Tsivanyuk M.M., Kotelnikov V.N., Karpov R.S. Vasospastic angina: pathophysiology and clinical significance. Cardiovascular Therapy and Prevention. 2020;19(1):99-105. (In Russ.) https://doi.org/10.15829/1728-8800-2020-1-2391
Views:
3977
Email this article 
