Skip to main content
SpringerLink
Log in

Vasospastic Angina

  • Chapter
  • First Online:
Book cover Microcirculation

  • 575 Accesses

Abstract

Vasospastic angina is a form of ischemic heart disease caused by episodes of coronary artery increased focal vasomotor tone occurring typically at rest. Clinically episodes will manifest as angina at rest associated with ST-segment changes on the electrocardiogram (ECG) and promptly relieved by calcium channel antagonist (CCB) or short-acting nitrates. In recent years studies have demonstrated that coronary spasm can occur during physical or emotional stress and episodes could be associated with ST-segment depression on the ECG. Diffuse coronary artery spasm, characterizing vasotonic angina, is a manifestation of endothelial dysfunction involving the entire coronary tree and the coronary microcirculation is the major culprit. These patients will present with symptoms of stable and unstable angina and ST-segment depression on the ECG.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Osler W. The lumleian lectures on angina pectoris. Lancet. 1910;175(4517):839–44.

    Article  Google Scholar 

  2. Prinzmetal M, Kennamer R, Merliss R, Wada T, Bor N. Angina pectoris. I. A variant form of angina pectoris; preliminary report. Am J Med. 1959;27:375–88.

    Article  CAS  PubMed  Google Scholar 

  3. Maseri A, Severi S, Nes MD, L’Abbate A, Chierchia S, Marzilli M, Ballestra AM, Parodi O, Biagini A, Distante A. “Variant” angina: one aspect of a continuous spectrum of vasospastic myocardial ischemia. Pathogenetic mechanisms, estimated incidence and clinical and coronary arteriographic findings in 138 patients. Am J Cardiol. 1978;42(6):1019–35.

    Article  CAS  PubMed  Google Scholar 

  4. Bugiardini R, Pozzati A, Ottani F, Morgagni GL, Puddu P. Vasotonic angina: a spectrum of ischemic syndromes involving functional abnormalities of the epicardial and microvascular coronary circulation. J Am Coll Cardiol. 1993;22(2):417–25.

    Article  CAS  PubMed  Google Scholar 

  5. JCS Joint Working Group. Guidelines for diagnosis and treatment of patients with vasospastic angina (coronary spastic angina) (JCS 2008): digest version. Circ J. 2010;74(8):1745–62.

    Article  Google Scholar 

  6. Bugiardini R, Manfrini O, Pizzi C, Fontana F, Morgagni G. Endothelial function predicts future development of coronary artery disease: a study of women with chest pain and normal coronary angiograms. Circulation. 2004;109(21):2518–23.

    Article  PubMed  Google Scholar 

  7. Bugiardini R, Borghi A, Biagetti L, Puddu P. Comparison of verapamil versus propranolol therapy in syndrome X. Am J Cardiol. 1989;63(5):286–90.

    Article  CAS  PubMed  Google Scholar 

  8. MacAlpin RN. Relation of coronary arterial spasm to sites of organic stenosis. Am J Cardiol. 1980;46(1):143–53.

    Article  CAS  PubMed  Google Scholar 

  9. Manfrini O, Pizzi C, Trerè D, Fontana F, Bugiardini R. Parasympathetic failure and risk of subsequent coronary events in unstable angina and non-ST-segment elevation myocardial infarction. Eur Heart J. 2003;24(17):1560–6.

    Article  PubMed  Google Scholar 

  10. Cenko E, Bugiardini R. Vasotonic angina as a cause of myocardial ischemia in women. Cardiovasc Drugs Ther. 2015;29(4):339–45.

    Article  CAS  PubMed  Google Scholar 

  11. Khuddus MA, Pepine CJ, Handberg EM, Bairey Merz CN, Sopko G, Bavry AA, Denardo SJ, McGorray SP, Smith KM, Sharaf BL, Nicholls SJ, Nissen SE, Anderson RD. An intravascular ultrasound analysis in women experiencing chest pain in the absence of obstructive coronary artery disease: a substudy from the National Heart, lung and blood institute-sponsored Women’s ischemia syndrome evaluation (WISE). J Interv Cardiol. 2010;23(6):511–9.

    Article  PubMed  Google Scholar 

  12. Manfrini O, Bazzocchi G, Luati A, Borghi A, Monari P, Bugiardini R. Coronary spasm reflects inputs from adjacent esophageal system. Am J Physiol Heart Circ Physiol. 2006;290(5):H2085–91.

    Article  CAS  PubMed  Google Scholar 

  13. Bertrand ME, Lablanche JM, Rousseau MF, Warembourg HH, Stankowtak C, Soots G. Surgical treatment of variant angina: use of plexectomy with aortocoronary bypass. Circulation. 1980;61(5):877–82.

    Article  CAS  PubMed  Google Scholar 

  14. Betriu A, Pomar JL, Bourassa MG, Grondin CM. Influence of partial sympathetic denervation on the results of myocardial revascularization in variant angina. Am J Cardiol. 1983;51(5):661–7.

    Article  CAS  PubMed  Google Scholar 

  15. Miller D, Waters DD, Warnica W, Szlachcic J, Kreeft J, Théroux P. Is variant angina the coronary manifestation of a generalized vasospastic disorder? N Engl J Med. 1981;304(13):763–6.

    Article  CAS  PubMed  Google Scholar 

  16. Vanmolkot FH, Van Bortel LM, de Hoon JN. Altered arterial function in migraine of recent onset. Neurology. 2007;68(19):1563–70.

    Article  PubMed  Google Scholar 

  17. Halcox JP, Schenke WH, Zalos G, Mincemoyer R, Prasad A, Waclawiw MA, Nour KR, Quyyumi AA. Prognostic value of coronary vascular endothelial dysfunction. Circulation. 2002;106(6):653–8.

    Article  PubMed  Google Scholar 

  18. Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation. 2000;101(9):948–54.

    Article  CAS  PubMed  Google Scholar 

  19. Manfrini O, Cenko E, Verna E, Salerno Uriarte JA, Bugiardini R. Endothelial dysfunction versus early atherosclerosis: a study with high resolution imaging. Int J Cardiol. 2013;168(2):1714–6.

    Article  PubMed  Google Scholar 

  20. Vita JA, Treasure CB, Nabel EG, McLenachan JM, Fish RD, Yeung AC, Vekshtein VI, Selwyn AP, Ganz P. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation. 1990;81(2):491–7.

    Article  CAS  PubMed  Google Scholar 

  21. Pries AR, Badimon L, Bugiardini R, Camici PG, Dorobantu M, Duncker DJ, Escaned J, Koller A, Piek JJ, de Wit C. Coronary vascular regulation, remodelling, and collateralization: mechanisms and clinical implications on behalf of the working group on coronary pathophysiology and microcirculation. Eur Heart J. 2015;36(45):3134–46.

    Article  CAS  PubMed  Google Scholar 

  22. Bugiardini R, Cenko E. A short history of vasospastic angina. J Am Coll Cardiol. 2017;70(19):2359–62.

    Article  PubMed  Google Scholar 

  23. Zeiher AM, Drexler H, Wollschlaeger H, Saurbier B, Just H. Coronary vasomotion in response to sympathetic stimulation in humans: importance of the functional integrity of the endothelium. J Am Coll Cardiol. 1989;14(5):1181–90.

    Article  CAS  PubMed  Google Scholar 

  24. Bugiardini R, Badimon L, Collins P, Erbel R, Fox K, Hamm C, Pinto F, Rosengren A, Stefanadis C, Wallentin L, Van de Werf F. Angina, “normal” coronary angiography, and vascular dysfunction: risk assessment strategies. PLoS Med. 2007;4(2):e12.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Badimon L, Bugiardini R, Cenko E, Cubedo J, Dorobantu M, Duncker DJ, Estruch R, Milicic D, Tousoulis D, Vasiljevic Z, Vilahur G, De Wit C, Koller A. Position paper of the European Society of Cardiology-working group of coronary pathophysiology andmicrocirculation: obesity and heart disease. Eur Heart J. 2017;38(25):1951–8.

    Article  CAS  PubMed  Google Scholar 

  26. Ong P, Athanasiadis A, Borgulya G, Mahrholdt H, Kaski JC, Sechtem U. High prevalence of a pathological response 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). J Am Coll Cardiol. 2012;59(7):655–62.

    Article  CAS  PubMed  Google Scholar 

  27. Crea F, Davies G, Chierchia S, Romeo F, Bugiardini R, Kaski JC, Freedman B, Maseri A. Different susceptibility to myocardial ischemia provoked by hyperventilation and cold pressor test in exertional and variant angina pectoris. Am J Cardiol. 1985;56(1):18–22.

    Article  CAS  PubMed  Google Scholar 

  28. Vrints CJ, Bult H, Hitter E, Herman AG, Snoeck JP. Impaired endothelium-dependent cholinergic coronary vasodilation in patients with angina and normal coronary arteriograms. J Am Coll Cardiol. 1992;19(1):21–31.

    Article  CAS  PubMed  Google Scholar 

  29. Bugiardini R, Bairey Merz CN. Angina with “normal” coronary arteries: a changing philosophy. JAMA. 2005;293(4):477–84.

    Article  CAS  PubMed  Google Scholar 

  30. Rosano GM, Peters NS, Kaski JC, Mavrogeni SI, Collins P, Underwood RS, Poole-Wilson PA. Abnormal uptake and washout of thallium-201 in patients with syndrome X and normal-appearing scans. Am J Cardiol. 1995;75(5):400–2.

    Article  CAS  PubMed  Google Scholar 

  31. Panting JR, Gatehouse PD, Yang GZ, Grothues F, Firmin DN, Collins P, Pennell DJ. Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. N Engl J Med. 2002;346(25):1948–53.

    Article  PubMed  Google Scholar 

  32. Bugiardini R, Borghi A, Sassone B, Pozzati A, Puddu P. Prognostic significance of silent myocardial ischemia in variant angina pectoris. Am J Cardiol. 1991;68(17):1581–6.

    Article  CAS  PubMed  Google Scholar 

  33. Araki H, Koiwaya Y, Nakagaki O, Nakamura M. Diurnal distribution of ST-segment elevation and related arrhythmias in patients with variant angina: a study by ambulatory ECG monitoring. Circulation. 1983;67(5):995–1000.

    Article  CAS  PubMed  Google Scholar 

  34. Pozzati A, Pancaldi LG, Di Pasquale G, Pinelli G, Bugiardini R. Transient sympathovagal imbalance triggers “ischemic” sudden death in patients undergoing electrocardiographic Holter monitoring. J Am Coll Cardiol. 1996;27(4):847–52.

    Article  CAS  PubMed  Google Scholar 

  35. Waters DD, Szlachcic J, Bourassa MG, Scholl JM, Théroux P. Exercise testing in patients with variant angina: results, correlation with clinical and angiographic features and prognostic significance. Circulation. 1982;65(2):265–74.

    Article  CAS  PubMed  Google Scholar 

  36. de Servi S, Falcone C, Gavazzi A, Mussini A, Bramucci E, Curti MT, Vecchio C, Specchia G, Bobba P. The exercise test in variant angina: results in 114 patients. Circulation. 1981;64(4):684–8.

    Article  PubMed  Google Scholar 

  37. Minoda K, Yasue H, Kugiyama K, Okumura K, Motomura K, Shimomura O, Takahashi M. Comparison of the distribution of myocardial blood flow between exercise-induced and hyperventilation-induced attacks of coronary spasm: a study with thallium-201 myocardial scintigraphy. Am Heart J. 1994;127(6):1474–80.

    Article  CAS  PubMed  Google Scholar 

  38. Bairey Merz CN, Shaw LJ, Reis SE, Bittner V, Kelsey SF, Olson M, Johnson BD, Pepine CJ, Mankad S, Sharaf BL, Rogers WJ, Pohost GM, Lerman A, Quyyumi AA, Sopko G, Investigators W. Insights from the NHLBI-sponsored Women’s ischemia syndrome evaluation (WISE) study: part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. J Am Coll Cardiol. 2006;47(3 Suppl):S21–9.

    Article  PubMed  Google Scholar 

  39. Shaw LJ, Merz CN, Pepine CJ, Reis SE, Bittner V, Kip KE, Kelsey SF, Olson M, Johnson BD, Mankad S, Sharaf BL, Rogers WJ, Pohost GM, Sopko G. Investigators WsISEW. The economic burden of angina in women with suspected ischemic heart disease: results from the National Institutes of Health--National Heart, Lung, and Blood Institute--sponsored Women’s ischemia syndrome evaluation. Circulation. 2006;114(9):894–904.

    Article  PubMed  Google Scholar 

  40. Bugiardini R, Manfrini O, De Ferrari GM. Unanswered questions for management of acute coronary syndrome: risk stratification of patients with minimal disease or normal findings on coronary angiography. Arch Intern Med. 2006;166(13):1391–5.

    Article  PubMed  Google Scholar 

  41. Vaccarino V, Badimon L, Corti R, de Wit C, Dorobantu M, Manfrini O, Koller A, Pries A, Cenko E, Bugiardini R. Presentation, management, and outcomes of ischaemic heart disease in women. Nat Rev Cardiol. 2013;10(9):508–18.

    Article  PubMed  Google Scholar 

  42. Britten MB, Zeiher AM, Schächinger V. Microvascular dysfunction in angiographically normal or mildly diseased coronary arteries predicts adverse cardiovascular long-term outcome. Coron Artery Dis. 2004;15(5):259–64.

    Article  PubMed  Google Scholar 

  43. Vaccarino V, Badimon L, Corti R, de Wit C, Dorobantu M, Hall A, Koller A, Marzilli M, Pries A, Bugiardini R. Ischaemic heart disease in women: are there sex differences in pathophysiology and risk factors? Position paper from the working group on coronary pathophysiology and microcirculation of the European society of cardiology. Cardiovasc Res. 2011;90(1):9–17.

    Article  CAS  PubMed  Google Scholar 

  44. Braun LT. Calcium channel blockers for the treatment of coronary artery spasm: rationale, effects, and nursing responsibilities. Heart Lung. 1983;12(3):226–32.

    CAS  PubMed  Google Scholar 

  45. Yasue H, Takizawa A, Nagao M, Nishida S, Horie M, Kubota J, Omote S, Takaoka K, Okumura K. Long-term prognosis for patients with variant angina and influential factors. Circulation. 1988;78(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  46. Lombardi M, Morales MA, Michelassi C, Moscarelli E, Distante A, L’Abbate A. Efficacy of isosorbide-5-mononitrate versus nifedipine in preventing spontaneous and ergonovine-induced myocardial ischaemia. A double-blind, placebo-controlled study. Eur Heart J. 1993;14(6):845–51.

    Article  CAS  PubMed  Google Scholar 

  47. Robertson RM, Wood AJ, Vaughn WK, Robertson D. Exacerbation of vasotonic angina pectoris by propranolol. Circulation. 1982;65(2):281–5.

    Article  CAS  PubMed  Google Scholar 

  48. Cannon CPBE. Unstable angina and non-ST elevation myocardial infarction. 8th ed. Philadelphia: Saunders Elsevier; 2008.

    Google Scholar 

  49. Satake K, Lee JD, Shimizu H, Ueda T, Nakamura T. Relation between severity of magnesium deficiency and frequency of anginal attacks in men with variant angina. J Am Coll Cardiol. 1996;28(4):897–902.

    Article  CAS  PubMed  Google Scholar 

  50. Teragawa H, Kato M, Yamagata T, Matsuura H, Kajiyama G. The preventive effect of magnesium on coronary spasm in patients with vasospastic angina. Chest. 2000;118(6):1690–5.

    Article  CAS  PubMed  Google Scholar 

  51. Pizzi C, Manfrini O, Fontana F, Bugiardini R. Angiotensin-converting enzyme inhibitors and 3-hydroxy-3-methylglutaryl coenzyme a reductase in cardiac syndrome X: role of superoxide dismutase activity. Circulation. 2004;109(1):53–8.

    Article  CAS  PubMed  Google Scholar 

  52. Manfrini O, Pizzi C, Morgagni G, Fontana F, Bugiardini R. Effect of pravastatin on myocardial perfusion after percutaneous transluminal coronary angioplasty. Am J Cardiol. 2004;93(11):1391–3, A6.

    Article  CAS  PubMed  Google Scholar 

  53. Yasue H, Mizuno Y, Harada E, Itoh T, Nakagawa H, Nakayama M, Ogawa H, Tayama S, Honda T, Hokimoto S, Ohshima S, Hokamura Y, Kugiyama K, Horie M, Yoshimura M, Harada M, Uemura S, Saito Y. Investigators SSaCAST. Effects of a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, fluvastatin, on coronary spasm after withdrawal of calcium-channel blockers. J Am Coll Cardiol. 2008;51(18):1742–8.

    Article  CAS  PubMed  Google Scholar 

  54. Miwa K, Kambara H, Kawai C. Effect of aspirin in large doses on attacks of variant angina. Am Heart J. 1983;105(2):351–5.

    Article  CAS  PubMed  Google Scholar 

  55. Sueda S, Suzuki J, Watanabe K, Mineoi K, Kondou T, Yano K, Ochi T, Ochi N, Kawada H, Hayashi Y, Uraoka A. Comparative results of coronary intervention in patients with variant angina versus those with non-variant angina. Jpn Heart J. 2001;42(6):657–67.

    Article  CAS  PubMed  Google Scholar 

  56. Tanabe Y, Itoh E, Suzuki K, Ito M, Hosaka Y, Nakagawa I, Kumakura M. Limited role of coronary angioplasty and stenting in coronary spastic angina with organic stenosis. J Am Coll Cardiol. 2002;39(7):1120–6.

    Article  PubMed  Google Scholar 

  57. Corcos T, David PR, Bourassa MG, Val PG, Robert J, Mata LA, Waters DD. Percutaneous transluminal coronary angioplasty for the treatment of variant angina. J Am Coll Cardiol. 1985;5(5):1046–54.

    Article  CAS  PubMed  Google Scholar 

  58. Gaspardone A, Tomai F, Versaci F, Ghini AS, Polisca P, Crea F, Chiariello L, Gioffrè PA. Coronary artery stent placement in patients with variant angina refractory to medical treatment. Am J Cardiol. 1999;84(1):96–8, A8.

    Article  CAS  PubMed  Google Scholar 

  59. Matsue Y, Suzuki M, Nishizaki M, Hojo R, Hashimoto Y, Sakurada H. Clinical implications of an implantable cardioverter-defibrillator in patients with vasospastic angina and lethal ventricular arrhythmia. J Am Coll Cardiol. 2012;60(10):908–13.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, BO, Italy

    Edina Cenko & Raffaele Bugiardini

Authors
  1. Edina Cenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raffaele Bugiardini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raffaele Bugiardini .

Editor information

Editors and Affiliations

  1. Department of Cardiology, Carol Davila University of Medicine, Bucharest, Romania

    Maria Dorobantu

  2. Cardiovascular Program-ICCC, IR- Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain

    Lina Badimon

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Cenko, E., Bugiardini, R. (2020). Vasospastic Angina. In: Dorobantu, M., Badimon, L. (eds) Microcirculation. Springer, Cham. https://doi.org/10.1007/978-3-030-28199-1_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-28199-1_10

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-28198-4

  • Online ISBN: 978-3-030-28199-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation