The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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Microvascular angina: angina that predominantly affects women

  • Park, Jin Joo (Cardiovascular Center, Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Park, Sung-Ji (Division of Cardiology, Department of Internal Medicine, Cardiovascular Imaging Center, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Choi, Dong-Ju (Cardiovascular Center, Department of Internal Medicine, Seoul National University Bundang Hospital)
  • Received : 2015.02.02
  • Accepted : 2015.02.07
  • Published : 2015.03.01
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Abstract

In women receiving evaluation for suspected ischemic symptoms, a "normal" diagnosis is five times more common than it is in men. These women are often labeled as having cardiac syndrome X, also known as microvascular angina (MVA). MVA is defined as angina pectoris caused by abnormalities of the small coronary arteries, and is characterized by effort chest pain and evidence of myocardial ischemia with a non-invasive stress test, although the coronary arteries can appear normal or near normal by angiography. MVA patients are often neglected due to the assumption of a good prognosis. However, MVA has important prognostic implications and a proper diagnosis is necessary in order to relieve the patients' symptoms and improve clinical outcomes. The coronary microvasculature cannot be directly imaged using coronary angiography, due to the small diameter of the vessels; therefore, the coronary microvascular must be assessed functionally. Treatment of MVA initially includes standard anti-ischemic drugs (${\beta}$-blockers, calcium antagonists, and nitrates), although control of symptoms is often insufficient. In this review, we discuss the pathophysiology, diagnosis, and treatment of MVA.

Keywords

References

  1. Mieres JH, Shaw LJ, Arai A, et al. Role of noninvasive testing in the clinical evaluation of women with suspected coronary artery disease: consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association. Circulation 2005;111:682-696. https://doi.org/10.1161/01.CIR.0000155233.67287.60
  2. Sullivan AK, Holdright DR, Wright CA, Sparrow JL, Cunningham D, Fox KM. Chest pain in women: clinical, investigative, and prognostic features. BMJ 1994;308:883-886. https://doi.org/10.1136/bmj.308.6933.883
  3. Task Force Members, Montalescot G, Sechtem U, 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;34:2949-3003. https://doi.org/10.1093/eurheartj/eht296
  4. Kaski JC, Rosano GM, Collins P, Nihoyannopoulos P, Maseri A, Poole-Wilson PA. Cardiac syndrome X: clinical characteristics and left ventricular function: longterm follow-up study. J Am Coll Cardiol 1995;25:807-814. https://doi.org/10.1016/0735-1097(94)00507-M
  5. Panza JA. Myocardial ischemia and the pains of the heart. N Engl J Med 2002;346:1934-1935. https://doi.org/10.1056/NEJMp020047
  6. Lanza GA. Cardiac syndrome X: a critical overview and future perspectives. Heart 2007;93:159-166.
  7. Hochman JS, Tamis JE, Thompson TD, et al. Sex, clinical presentation, and outcome in patients with acute coronary syndromes: global use of strategies to open occluded coronary arteries in acute coronary syndromes IIb investigators. N Engl J Med 1999;341:226-232. https://doi.org/10.1056/NEJM199907223410402
  8. Glaser R, Herrmann HC, Murphy SA, et al. Benefit of an early invasive management strategy in women with acute coronary syndromes. JAMA 2002;288:3124-3129. https://doi.org/10.1001/jama.288.24.3124
  9. Krumholz HM, Douglas PS, Lauer MS, Pasternak RC. Selection of patients for coronary angiography and coronary revascularization early after myocardial infarction: is there evidence for a gender bias? Ann Intern Med 1992;116:785-790. https://doi.org/10.7326/0003-4819-116-10-785
  10. Diver DJ, Bier JD, Ferreira PE, et al. Clinical and arteriographic characterization of patients with unstable angina without critical coronary arterial narrowing (from the TIMI-IIIA Trial). Am J Cardiol 1994;74:531-537. https://doi.org/10.1016/0002-9149(94)90739-0
  11. Bugiardini R, Bairey Merz CN. Angina with “normal” coronary arteries: a changing philosophy. JAMA 2005;293:477-484. https://doi.org/10.1001/jama.293.4.477
  12. Jespersen L, Hvelplund A, Abildstrom SZ, et al. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J 2012;33:734-744. https://doi.org/10.1093/eurheartj/ehr331
  13. van de Hoef TP, Bax M, Damman P, et al. Impaired coronary autoregulation is associated with long-term fatal events in patients with stable coronary artery disease. Circ Cardiovasc Interv 2013;6:329-335. https://doi.org/10.1161/CIRCINTERVENTIONS.113.000378
  14. Radico F, Cicchitti V, Zimarino M, De Caterina R. Angina pectoris and myocardial ischemia in the absence of obstructive coronary artery disease: practical considerations for diagnostic tests. JACC Cardiovasc Interv 2014;7:453-463.
  15. Mohri M, Koyanagi M, Egashira K, et al. Angina pectoris caused by coronary microvascular spasm. Lancet 1998;351:1165-1169. https://doi.org/10.1016/S0140-6736(97)07329-7
  16. Lanza GA, Crea F. Primary coronary microvascular dysfunction: clinical presentation, pathophysiology, and management. Circulation 2010;121:2317-2325. https://doi.org/10.1161/CIRCULATIONAHA.109.900191
  17. Quyyumi AA. Endothelial function in health and disease: new insights into the genesis of cardiovascular disease. Am J Med 1998;105(1A):32S-39S.
  18. Cannon RO 3rd, Epstein SE. "Microvascular angina" as a cause of chest pain with angiographically normal coronary arteries. Am J Cardiol 1988;61:1338-1343. https://doi.org/10.1016/0002-9149(88)91180-0
  19. Rosen SD, Paulesu E, Wise RJ, Camici PG. Central neural contribution to the perception of chest pain in cardiac syndrome X. Heart 2002;87:513-519. https://doi.org/10.1136/heart.87.6.513
  20. Lanza GA, Giordano A, Pristipino C, et al. Abnormal cardiac adrenergic nerve function in patients with syndrome X detected by [123I]metaiodobenzylguanidine myocardial scintigraphy. Circulation 1997;96:821-826. https://doi.org/10.1161/01.CIR.96.3.821
  21. Gulli G, Cemin R, Pancera P, Menegatti G, Vassanelli C, Cevese A. Evidence of parasympathetic impairment in some patients with cardiac syndrome X. Cardiovasc Res 2001;52:208-216. https://doi.org/10.1016/S0008-6363(01)00369-8
  22. 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;59:655-662. https://doi.org/10.1016/j.jacc.2011.11.015
  23. Pijls NH, De Bruyne B, Peels K, et al. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med 1996;334:1703-1708. https://doi.org/10.1056/NEJM199606273342604
  24. Tonino PA, De Bruyne B, Pijls NH, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213-224. https://doi.org/10.1056/NEJMoa0807611
  25. De Bruyne B, Pijls NH, Kalesan B, et al. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Engl J Med 2012;367:991-1001. https://doi.org/10.1056/NEJMoa1205361
  26. De Bruyne B, Fearon WF, Pijls NH, et al. Fractional flow reserve-guided PCI for stable coronary artery disease. N Engl J Med 2014;371:1208-1217. https://doi.org/10.1056/NEJMoa1408758
  27. Henry PD, Yokoyama M. Supersensitivity of atherosclerotic rabbit aorta to ergonovine: mediation by a serotonergic mechanism. J Clin Invest 1980;66:306-313. https://doi.org/10.1172/JCI109858
  28. Auch-Schwelk W, Paetsch I, Krackhardt F, Grafe M, Hetzer R, Fleck E. Modulation of contractions to ergonovine and methylergonovine by nitric oxide and thromboxane A2 in the human coronary artery. J Cardiovasc Pharmacol 2000;36:631-639. https://doi.org/10.1097/00005344-200011000-00013
  29. Hackett D, Larkin S, Chierchia S, Davies G, Kaski JC, Maseri A. Induction of coronary artery spasm by a direct local action of ergonovine. Circulation 1987;75:577-582. https://doi.org/10.1161/01.CIR.75.3.577
  30. Kaufmann PA, Camici PG. Myocardial blood flow measurement by PET: technical aspects and clinical applications. J Nucl Med 2005;46:75-88.
  31. Yilmaz A, Athanasiadis A, Mahrholdt H, et al. Diagnostic value of perfusion cardiovascular magnetic resonance in patients with angina pectoris but normal coronary angiograms assessed by intracoronary acetylcholine testing. Heart 2010;96:372-379. https://doi.org/10.1136/hrt.2009.174367
  32. Kalinowski L, Dobrucki LW, Szczepanska-Konkel M, et al. Third-generation beta-blockers stimulate nitric oxide release from endothelial cells through ATP efflux: a novel mechanism for antihypertensive action. Circulation 2003;107:2747-2752. https://doi.org/10.1161/01.CIR.0000066912.58385.DE
  33. Bertrand ME, Lablanche JM, Tilmant PY. Treatment of Prinzmetal’s variant angina: role of medical treatment with nifedipine and surgical coronary revascularization combined with plexectomy. Am J Cardiol 1981;47:174-178. https://doi.org/10.1016/0002-9149(81)90306-4
  34. Lanza GA, Parrinello R, Figliozzi S. Management of microvascular angina pectoris. Am J Cardiovasc Drugs 2014;14:31-40. https://doi.org/10.1007/s40256-013-0052-1
  35. Cannon RO 3rd, Watson RM, Rosing DR, Epstein SE. Efficacy of calcium channel blocker therapy for angina pectoris resulting from small-vessel coronary artery disease and abnormal vasodilator reserve. Am J Cardiol 1985;56:242-246. https://doi.org/10.1016/0002-9149(85)90842-2
  36. Ozcelik F, Altun A, Ozbay G. Antianginal and anti-ischemic effects of nisoldipine and ramipril in patients with syndrome X. Clin Cardiol 1999;22:361-365. https://doi.org/10.1002/clc.4960220513
  37. Li L, Gu Y, Liu T, et al. A randomized, single-center double-blinded trial on the effects of diltiazem sustained-release capsules in patients with coronary slow f low phenomenon at 6-month follow-up. PLoS One 2012;7:e38851. https://doi.org/10.1371/journal.pone.0038851
  38. Montorsi P, Cozzi S, Loaldi A, et al. Acute coronary vasomotor effects of nifedipine and therapeutic correlates in syndrome X. Am J Cardiol 1990;66:302-307. https://doi.org/10.1016/0002-9149(90)90840-W
  39. Lindqvist M, Kahan T, Melcher A, Ekholm M, Hjemdahl P. Long-term calcium antagonist treatment of human hypertension with mibefradil or amlodipine increases sympathetic nerve activity. J Hypertens 2007;25:169-175. https://doi.org/10.1097/HJH.0b013e3280104dba
  40. Harrison DG, Bates JN. The nitrovasodilators: new ideas about old drugs. Circulation 1993;87:1461-1467. https://doi.org/10.1161/01.CIR.87.5.1461
  41. Lanza GA, Colonna G, Pasceri V, Maseri A. Atenolol versus amlodipine versus isosorbide-5-mononitrate on anginal symptoms in syndrome X. Am J Cardiol 1999;84:854-856. https://doi.org/10.1016/S0002-9149(99)00450-6
  42. Lamendola P, Nerla R, Pitocco D, et al. Effect of ranolazine on arterial endothelial function in patients with type 2 diabetes mellitus. Atherosclerosis 2013;226:157-160. https://doi.org/10.1016/j.atherosclerosis.2012.10.051
  43. Villano A, Di Franco A, Nerla R, et al. Effects of ivabradine and ranolazine in patients with microvascular angina pectoris. Am J Cardiol 2013;112:8-13. https://doi.org/10.1016/j.amjcard.2013.02.045
  44. Mehta PK, Goykhman P, Thomson LE, et al. Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. JACC Cardiovasc Imaging 2011;4:514-522.
  45. Kaski JC, Valenzuela Garcia LF. Therapeutic options for the management of patients with cardiac syndrome X. Eur Heart J 2001;22:283-293. https://doi.org/10.1053/euhj.2000.2152
  46. Hongo M, Takenaka H, Uchikawa S, Nakatsuka T, Watanabe N, Sekiguchi M. Coronary microvascular response to intracoronary administration of nicorandil. Am J Cardiol 1995;75:246-250. https://doi.org/10.1016/0002-9149(95)80029-R
  47. Chen JW, Lee WL, Hsu NW, et al. Effects of short-term treatment of nicorandil on exercise-induced myocardial ischemia and abnormal cardiac autonomic activity in microvascular angina. Am J Cardiol 1997;80:32-38. https://doi.org/10.1016/S0002-9149(97)00279-8
  48. Yamabe H, Namura H, Yano T, et al. Effect of nicorandil on abnormal coronary flow reserve assessed by exercise 201Tl scintigraphy in patients with angina pectoris and nearly normal coronary arteriograms. Cardiovasc Drugs Ther 1995;9:755-761. https://doi.org/10.1007/BF00879868
  49. Nalbantgil S, Altinti, gbreve, Yilmaz H, Nalbantgil II, Onder R. The effect of trimetazidine in the treatment of microvascular angina. Int J Angiol 1999;8:40-43. https://doi.org/10.1007/BF01616842
  50. Leonardo F, Fragasso G, Rossetti E, et al. Comparison of trimetazidine with atenolol in patients with syndrome X: effects on diastolic function and exercise tolerance. Cardiologia 1999;44:1065-1069.
  51. Perez NG, Piaggio MR, Ennis IL, et al. Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction. Hypertension 2007;49:1095-1103. https://doi.org/10.1161/HYPERTENSIONAHA.107.087759
  52. Radovits T, Bomicke T, Kokeny G, et al. The phosphodiesterase-5 inhibitor vardenafil improves cardiovascular dysfunction in experimental diabetes mellitus. Br J Pharmacol 2009;156:909-919. https://doi.org/10.1111/j.1476-5381.2008.00098.x
  53. Park SJ, Park JJ, Choi DJ, et al. Understanding of chest pain in microvascular disease proved by cardiac magnetic resonance image (UMPIRE): study protocol for a randomized controlled trial. Trials 2014;15:333. https://doi.org/10.1186/1745-6215-15-333

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