Advertisement

Variant Angina and Aborted Sudden Cardiac Death

  • Amartya Kundu
  • Aditya Vaze
  • Partha Sardar
  • Ahmed Nagy
  • Wilbert S. Aronow
  • Naomi F. Botkin
Ischemic Heart Disease (D Mukherjee, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Ischemic Heart Disease

Abstract

Purpose of Review

Variant angina, which is characterized by recurrent chest pain and transient ECG changes along with angiographic evidence of coronary artery spasm, generally has a favorable prognosis. However, episodes of ischemia caused by vasospasm may lead to potentially life-threatening ventricular arrhythmias and cardiac arrest, even in patients with no history of prior cardiac disease. This review describes the epidemiology, pathogenesis, clinical spectrum, and management of variant angina, as well as outcomes in patients who present with aborted sudden cardiac death (ASCD).

Recent Findings

Contrary to prior opinions, evidence from recent observational studies indicate that patients with variant angina presenting with ASCD face a worse prognosis than those without this type of presentation. Predictors of ASCD include age, hypertension, hyperlipidemia, family history of sudden cardiac death, multi-vessel spasm, and left anterior descending artery spasm. Medical therapy alone with calcium channel blockers and nitrates may not be sufficiently protective in these patients and there is lack of concrete data on the optimal management strategy. Current guidelines recommend implantable cardiac defibrillator (ICD) therapy in patients who are survivors of cardiac arrest caused by ventricular fibrillation or unstable ventricular tachycardia after reversible causes are excluded, and should strongly be considered in these patients.

Summary

Although medical therapy is absolutely imperative for patients with variant angina and a history of ASCD, ICD therapy in these patients is justified. Further large-scale studies are required to determine whether ICD therapy can improve survival in this high-risk group of patients.

Keywords

Variant angina Coronary vasospasm Sudden death Cardiac arrest 

Notes

Compliance with Ethical Standards

Conflict of Interest

Amartya Kundu, Aditya Vaze, Partha Sardar, Ahmed Nagy, Wilbert S. Aronow, and Naomi F. Botkin declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Prinzmetal M, Kennamer R, Wada T, Bor N. Angina pectoris. I. A variant form of angina pectoris; preliminary report. Am J Med. 1959;27:375–88.CrossRefPubMedGoogle Scholar
  2. 2.
    Silverman ME. William Heberden and some account of a disorder of the breast. Clin Cardiol. 1987;10:211–3.CrossRefPubMedGoogle Scholar
  3. 3.
    Curry RC Jr, Pepine CJ, Sabom MB, Conti CR. Similarities of ergonovine-induced and spontaneous attacks of variant angina. Circulation. 1979;59:307–12.CrossRefPubMedGoogle Scholar
  4. 4.
    Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, et al. International standardization of diagnostic criteria for vasospastic angina. Eur Heart J. 2017;38:2565–8.PubMedGoogle Scholar
  5. 5.
    Myerburg RJ, Kessler KM, Mallon SM, Cox MM, de Marchena E, Interian A, et al. Life-threatening ventricular arrhythmias in patients with silent myocardial ischemia due to coronary artery spasm. N Engl J Med. 1992;326:1451–5.CrossRefPubMedGoogle Scholar
  6. 6.
    Beltrame JF, Sasayama S, Maseri A. Racial heterogeneity in coronary artery vasomotor reactivity: differences between Japanese and Caucasian patients. J Am Coll Cardiol. 1999;33:1442–52.CrossRefPubMedGoogle Scholar
  7. 7.
    JCS Joint Working Group. Japanese Circulation Society of guidelines for diagnosis and treatment of patients with vasospastic angina (coronary spastic angina) (JCS 2008): digest version. Cir J. 2010;74:1745–62.CrossRefGoogle Scholar
  8. 8.
    Sueda S, Kohno H, Fukuda H, Ochi N, Kawada H, Hayashi, et al. Frequency of provoked coronary spasms in patients undergoing coronary arteriography using a spasm provocation test via intracoronary administration of ergonovine. Angiology. 2004;55:403–11.CrossRefPubMedGoogle Scholar
  9. 9.
    Hung MY, Hsu KH, Hung MJ, Cheng CW, Cherng WJ. Interactions among gender, age, hypertension and C-reactive protein in coronary vasospasm. Eur J Clin Investig. 2010;40:1094–103.CrossRefGoogle Scholar
  10. 10.
    Bertrand ME, LaBlanche JM, Tilmant PY, Thieuleux FA, Delforge MR, Carre AG, et al. Frequency of provoked coronary arterial spasm in 1089 consecutive patients undergoing coronary arteriography. Circulation. 1982;65:1299–306.CrossRefPubMedGoogle Scholar
  11. 11.
    Hung MJ, Cherng WJ, Cheng CW, Li LF. Comparison of serum levels of inflammatory markers in patients with coronary vasospasm without significant fixed coronary artery disease versus patients with stable angina pectoris and acute coronary syndromes with significant fixed coronary artery disease. Am J Cardiol. 2006;97:1429–34.CrossRefPubMedGoogle Scholar
  12. 12.
    Hung MJ, Cheng CW, Yang NI, Hung MY, Cherng WJ. Coronary vasospasm- induced acute coronary syndrome complicated by life-threatening cardiac arrhythmias in patients without hemodynamically significant coronary artery disease. Int J Cardiol. 2007;117:37–44.CrossRefPubMedGoogle Scholar
  13. 13.
    Ong P, Athanasiadis A, Hill S, Vogelsberg H, Voehringer M, Coronary SU. Artery spasm as a frequent cause of acute coronary syndrome: the CASPAR (coronary artery spasm in patients with acute coronary syndrome) study. J Am Coll Cardiol. 2008;52:523–7.CrossRefPubMedGoogle Scholar
  14. 14.
    • Takagi Y, Yasuda S, Tsunoda R, Ogata Y, Seki A, Sumiyoshi, 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. 2011;4:295–302. This is a large observational study reporting poor outcomes in patients with variant angina who survived out of hospital cardiac arrest. CrossRefPubMedGoogle Scholar
  15. 15.
    Maseri A, L'Abbate A, Baroldi G, Chierchia S, Marzilli M, Ballestra AM, et al. Coronary vasospasm as a possible cause of myocardial infarction. A conclusion derived from the study of "preinfarction" angina. N Engl J Med. 1978;299:1271–7.CrossRefPubMedGoogle Scholar
  16. 16.
    Yasue H, Kugiyama K. Coronary spasm: clinical features and pathogenesis. Intern Med. 1997;36:760–5.CrossRefPubMedGoogle Scholar
  17. 17.
    Nakamura M, Takeshita A, Nose Y. Clinical characteristics associated with myocardial infarction, arrhythmias, and sudden death in patients with vasospastic angina. Circulation. 1987;75:1110–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Kishida H, Otsu F, Suzuki K, Hata N, Kusama Y, Suzuki T, et al. Prominent negative U wave in variant angina pectoris. Jpn Heart J. 1985;26(6):885–96.CrossRefPubMedGoogle Scholar
  19. 19.
    Ozaki Y, Keane D, Serruys PW. Fluctuation of spastic location in patients with vasospastic angina: a quantitative angiographic study. J Am Coll Cardiol. 1995;26:1606–14.CrossRefPubMedGoogle Scholar
  20. 20.
    Maseri A, Severi S, Nes MD, L'Abbate A, Chierchia S, Marzilli M, et al. "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: 1019–1035.Google Scholar
  21. 21.
    Waters DD, Szlachcic J, Theroux P, Dauwe F, Mizgala HF. Ergonovine testing to detect spontaneous remissions of variant angina during long-term treatment with calcium antagonist drugs. Am J Cardiol. 1981;47:179–84.CrossRefPubMedGoogle Scholar
  22. 22.
    Whittle JL, Feldman RL, Pepine CJ, Curry RC, Conti CR. Variability of electrocardiographic responses to repeated ergonovine provocation in variant angina patients with coronary artery spasm. Am Heart J. 1982;103:161–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Hung MJ, Hu P, Hung MY. Coronary artery spasm: review and update. Int J Med Sci. 2014;11:1161–71.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Yasue H, Nakagawa H, Itoh T, Harada E, Mizuno Y. Coronary artery spasm--clinical features, diagnosis, pathogenesis, and treatment. J Cardiol. 2008;51:2–17.CrossRefPubMedGoogle Scholar
  25. 25.
    Nishizaki M, Arita M, Sakurada H, Suzuki M, Ashikaga T, Yamawake N, et al. Induction of polymorphic ventricular tachycardia by programmed ventricular stimulation in vasospastic angina pectoris. Am J Cardiol. 1996;77:355–60.CrossRefPubMedGoogle Scholar
  26. 26.
    Suzuki M, Nishizaki M, Arita M, Ashikaga T, Yamawake N, Kakuta T, et al. Increased QT dispersion in patients with vasospastic angina. Circulation. 1998;98:435–40.CrossRefPubMedGoogle Scholar
  27. 27.
    Seniuk W, Mularek-Kubzdela T, Grygier M, Grajek S, Cieśliński A. Cardiac arrest related to coronary spasm in patients with variant angina: a three-case study. J Intern Med. 2002;252:368–76.CrossRefPubMedGoogle Scholar
  28. 28.
    Hung MJ, Wang CH, Kuo LT, Cherng WJ. Coronary artery spasm-induced paroxysmal atrial fibrillation-a case report. Angiology. 2001;52:559–62.CrossRefPubMedGoogle Scholar
  29. 29.
    Nishizaki M, Arita M, Sakurada H, Suzuki M, Ashikaga T, Yamawake N, et al. Polymorphic ventricular tachycardia in patients with vasospastic angina—clinical and electrocardiographic characteristics and long-term outcome. Jpn Circ J. 2001;65:519–25.CrossRefPubMedGoogle Scholar
  30. 30.
    Parchure N, Batchvarov V, Malik M, Camm AJ, Kaski JC. Increased QT dispersion in patients with Prinzmetal’s variant angina and cardiac arrest. Cardiovasc Res. 2001;50:379–85.CrossRefPubMedGoogle Scholar
  31. 31.
    Inamura Y, Nishizaki M, Shimizu M, Fujii H, Yamawake N, Suzuki M, et al. Early repolarization and positive T-wave alternans as risk markers for life-threatening arrhythmias in patients with vasospastic angina. Int J Cardiol. 2015;196:7–13.CrossRefPubMedGoogle Scholar
  32. 32.
    Kaski JC, Maseri A, Vejar M, Crea F, Hackett D. Spontaneous coronary artery spasm in variant angina is caused by a local hyperreactivity to a generalized constrictor stimulus. J Am Coll Cardiol. 1989;14:1456–63.CrossRefPubMedGoogle Scholar
  33. 33.
    Kaski JC, Crea F, Meran D, Rodriguez L, Araujo L, Chierchia S, et al. Local coronary supersensitivity to diverse vasoconstrictive stimuli in patients with variant angina. Circulation. 1986;74:1255–65.CrossRefPubMedGoogle Scholar
  34. 34.
    Kugiyama K, Yasue H, Okumura K, Ogawa H, Fujimoto K, Nakao K, et al. Nitric oxide activity is deficient in spasm arteries of patients with coronary spastic angina. Circulation. 1996;94:266–71.CrossRefPubMedGoogle Scholar
  35. 35.
    Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Kugiyama K, Ogawa H, et al. T-786-->C mutation in the 5′-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation. 1999;99:2864–70.CrossRefPubMedGoogle Scholar
  36. 36.
    Kandabashi T, Shimokawa H, Miyata K, Kunihiro I, Kawano Y, Fukata Y, et al. Inhibition of myosin phosphatase by upregulated rho-kinase plays a key role for coronary artery spasm in a porcine model with interleukin-1beta. Circulation. 2000;101:1319–23.CrossRefPubMedGoogle Scholar
  37. 37.
    Kusama Y, Kodani E, Nakagomi A, Otsuka T, Atarashi H, Kishida H, et al. Variant angina and coronary artery spasm: the clinical spectrum, pathophysiology, and management. J Nippon Med Sch. 2011;78(1):4–12.CrossRefPubMedGoogle Scholar
  38. 38.
    Bory M, Pierron F, Panagides D, Bonnet JL, Yvorra S, Desfossez L. Coronary artery spasm in patients with normal or near normal coronary arteries. Long-term follow-up of 277 patients. Eur Heart J. 1996;17:1015–21.CrossRefPubMedGoogle Scholar
  39. 39.
    Ong P, Athanasiadis A, Borgulya G, Voehringer M, Sechtem U. 3-year follow-up of patients with coronary artery spasm as cause of acute coronary syndrome: the CASPAR (coronary artery spasm in patients with acute coronary syndrome) study follow-up. J Am Coll Cardiol. 2011;57:147–52.CrossRefPubMedGoogle Scholar
  40. 40.
    •• Ahn JM, Lee KH, Yoo SY, Cho YR, Suh J, Shin ES, et al. Prognosis of Variant Angina Manifesting as Aborted Sudden Cardiac Death. J Am Coll Cardiol. 2016;68:137–45. This is the largest observation study on variant angina patients comparing outcomes in those presenting with and without aborted sudden cardiac death. CrossRefPubMedGoogle Scholar
  41. 41.
    Chevalier P, Dacosta A, Defaye P, Chalvidan T, Bonnefoy E, Kirkorian G, et al. Arrhythmic cardiac arrest due to isolated coronary artery spasm: long-term outcome of seven resuscitated patients. J Am Coll Cardiol. 1998;31:57–61.CrossRefPubMedGoogle Scholar
  42. 42.
    Yamashina Y, Yagi T, Namekawa A, Ishida A, Mibiki Y, Sato H, et al. Favorable outcomes of patients with vasospastic angina associated with cardiac arrest. J Cardiol. 2014;63:41–5.CrossRefPubMedGoogle Scholar
  43. 43.
    Meune C, Joly LM, Chiche JD, Charpentier J, Leenhardt A, Rozenberg A, et al. Diagnosis and management of out off-hospital cardiac arrest secondary to coronary artery spasm. Resuscitation. 2013;58:145–52.CrossRefGoogle Scholar
  44. 44.
    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;60:908–13.CrossRefPubMedGoogle Scholar
  45. 45.
    • Meisel SR, Mazur A, Chetboun I, Epshtein M, Canetti M, Gallimidi J, et al. Usefulness of implantable cardioverter-defibrillators in refractory variant angina pectoris complicated by ventricular fibrillation in patients with angiographically normal coronary arteries. Am J Cardiol. 2002;89:1114–6. This was one of the first studies advocating ICD placement in patients with variant angina and cardiac arrest. CrossRefPubMedGoogle Scholar
  46. 46.
    Epstein AE, DiMarco JP, Ellenbogen KA, Estes M III, Freedman RA, Gettes LS, et al. ACC/AHA/HRS 2008 guidelines for devicebased therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (writing committee to revise the ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and Antiarrhythmia devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;51:e1–62.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Amartya Kundu
    • 1
  • Aditya Vaze
    • 2
  • Partha Sardar
    • 3
  • Ahmed Nagy
    • 2
  • Wilbert S. Aronow
    • 4
  • Naomi F. Botkin
    • 1
  1. 1.Department of Cardiovascular MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  3. 3.Department of CardiologyUniversity of Utah School of MedicineSalt Lake CityUSA
  4. 4.Department of CardiologyWestchester Medical CenterValhallaUSA

Personalised recommendations