Skip to main content
Log in

Cardiac Syndrome X

Diagnosis, Pathogenesis and Management

  • Review Article
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Patients with cardiac syndrome X (typical chest pain and normal coronary arteriograms) represent a heterogeneous syndrome, which encompasses different pathogenic mechanisms. Although symptoms in most patients with cardiac syndrome X are non-cardiac, a sizable proportion of them have angina pectoris due to transient myocardial ischemia. Thus radionuclide myocardial perfusion defects, coronary sinus oxygen saturation abnormalities and pH changes, myocardial lactate production and stress-induced alterations of cardiac high energy phosphate suggest an ischemic origin of symptoms in at least a proportion of patients with cardiac syndrome X. Microvascular abnormalities, caused by endothelial dysfunction, appear to be responsible for myocardial ischemia in patients with cardiac syndrome X. Endothelial dysfunction is likely to be multifactorial in these patients and it is conceivable that risk factors such as hypertension, hypercholesterolemia, diabetes mellitus and smoking can contribute to its development. Most patients with cardiac syndrome X are postmenopausal women and estrogen deficiency has been therefore proposed as a pathogenic factor in female patients. Additional factors such as abnormal pain perception may contribute to the pathogenesis of chest pain in patients with angina pectoris and normal coronary angiograms. Although prognosis is good regarding survival, patients with cardiac syndrome X have an impaired quality of life. Management of this syndrome represents a major challenge to the treating physician. Understanding the mechanism underlying the condition is of vital importance for patient management. Thus diagnostic tests should aim at identifying the cause of the symptoms in the individual patient, i.e. myocardial ischemia, increased pain perception, abnormalities of adrenergic tone, non-cardiac mechanisms, etc. Moreover, it is important to bear in mind that treatment of cardiac syndrome X should be mainly directed towards improving quality of life, as prognosis is usually good in these patients. Conventional antianginal agents such nitrates, calcium channel antagonists, β-adrenoceptor antagonists and nicorandil are effective particularly in patients in whom chest pain and ECG changes are clearly suggestive of myocardial ischemia and in those with objective documentation of ischemia. Angiotensin-converting enzyme inhibitors have been shown to be useful in syndrome X patients with increased adrenergic tone, borderline systemic hypertension, and those with documented endothelial dysfunction. Analgesic interventions of different sorts have been proposed based on the hypothesis that somatic and visceral perception of pain is altered in cardiac syndrome X patients. Pharmacological agents such as imipramine and aminophylline, and neural electrical stimulation techniques have been assessed in recent years with encouraging results. Psychological treatment, particularly cognitive therapy, appears to be useful in defined patient subsets. Relaxation techniques such as transcendental meditation have been successfully used in small studies and shown to improve not only chest pain but also exercise-induced ST segment changes. Reports indicate that these techniques improve quality of life.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Table I
Fig. 2
Table II
Table III

Similar content being viewed by others

References

  1. Kaski JC. Cardiac syndrome X and microvascular angina. In: Kaski JC, editor. Chest pain with normal coronary angiograms: pathogenesis, diagnosis and management. London: Kluwer Academic Publishers, 1999: 1–12

    Chapter  Google Scholar 

  2. Crenshaw JH, el Zeky F, Vander ZR, et al. The effect of noncritical coronary artery disease on long-term survival. Am J Med Sci 1995; 310(1): 7–13

    Article  PubMed  CAS  Google Scholar 

  3. Juelsgaard P, Ronnow Sand NP. Somatic and social prognosis of patients with angina pectoris and normal coronary arteriography: a follow-up study. Int J Cardiol 1993; 39(1): 49–57

    Article  PubMed  CAS  Google Scholar 

  4. Ockene IS, Shay MJ, Alpert JS, et al. Unexplained chest pain in patients with normal coronary arteriograms: a follow-up study of functional status. N Engl J Med 1980; 303(22): 1249–52

    Article  PubMed  CAS  Google Scholar 

  5. Potts SG, Bass CM. Psychosocial outcome and use of medical resources in patients with chest pain and normal or near-normal coronary arteries: a long-term follow-up study. Q J Med 1993; 86(9): 583–93

    PubMed  CAS  Google Scholar 

  6. Potts SG, Bass CM. Psychological morbidity in patients with chest pain and normal or near-normal coronary arteries: a long-term follow-up study. Psychol Med 1995; 25(2): 339–47

    Article  PubMed  CAS  Google Scholar 

  7. Proudfit WL, Shirey EK, Sones Jr FM. Selective cine coronary arteriography: correlation with clinical findings in 1000 patients. Circulation 1966; 33(6): 901–10

    Article  PubMed  CAS  Google Scholar 

  8. Kemp HG, Elliott WC, Gorlin R. The anginal syndrome with normal coronary arteriography. Trans Assoc Am Physicians 1967; 80: 59–70

    PubMed  CAS  Google Scholar 

  9. Likoff W, Segal BL, Kasparian H. Paradox of normal selective coronary arteriograms in patients considered to have unmistakable coronary heart disease. N Engl J Med 1967; 276(19): 1063–6

    Article  PubMed  CAS  Google Scholar 

  10. Arbogast R, Bourassa MG. Myocardial function during atrial pacing in patients with angina pectoris and normal coronary arteriograms: comparison with patients having significant coronary artery disease. Am J Cardiol 1973; 32(3): 257–63

    Article  PubMed  CAS  Google Scholar 

  11. Kemp Jr HG. Left ventricular function in patients with the anginal syndrome and normal coronary arteriograms. Am J Cardiol 1973; 32(3): 375–6

    Article  PubMed  Google Scholar 

  12. Kaski JC, Rosano GM, Collins P, et al. Cardiac syndrome X: clinical characteristics and left ventricular function: long-term follow-up study. J Am Coll Cardiol 1995; 25(4): 807–14

    Article  PubMed  CAS  Google Scholar 

  13. Galassi AR, Kaski JC, Crea F, et al. Heart rate response during exercise testing and ambulatory ECG monitoring in patients with syndrome X. Am Heart J 1991; 122(2): 458–63

    Article  PubMed  CAS  Google Scholar 

  14. Gavrielides S, Kaski JC, Galassi AR, et al. Recovery-phase patterns of ST segment depression in the heart rate domain cannot distinguish between anginal patients with coronary artery disease and patients with syndrome X. Am Heart J 1991; 122(6): 1593–8

    Article  PubMed  CAS  Google Scholar 

  15. Pupita G, Kaski JC, Galassi AR, et al. Similar time course of ST depression during and after exercise in patients with coronary artery disease and syndrome X. Am Heart J 1990; 120(4): 848–54

    Article  PubMed  CAS  Google Scholar 

  16. Hsu NW, Chen JW, Jen SL, et al. Differentiating syndrome X from coronary artery disease by treadmill exercise test in patients with chest pain and exercise-induced myocardial ischaemia. Angiology 1998; 49(1): 13–24

    Article  PubMed  CAS  Google Scholar 

  17. Kaski JC, Crea F, Nihoyannopoulos P, et al. Transient myocardial ischaemia during daily life in patients with syndrome X. Am J Cardiol 1986; 58(13): 1242–7

    Article  PubMed  CAS  Google Scholar 

  18. Cannon III RO, Camici PG, Epstein SE. Pathophysiological dilemma of syndrome X. Circulation 1992; 85(3): 883–92

    Article  PubMed  Google Scholar 

  19. Opherk D, Zebe H, Schuler G, et al. Reduced coronary reserve and abnormal exercise left ventricular reserve in patients with syndrome X. Arch Mal Coeur Vaiss 1983; 76: 231–5

    PubMed  Google Scholar 

  20. Egashira K, Inou T, Hirooka Y, et al. Evidence of impaired endothelium-dependent coronary vasodilatation in patients with angina pectoris and normal coronary angiograms. N Engl J Med 1993; 328(23): 1659–64

    Article  PubMed  CAS  Google Scholar 

  21. Hasdai D, Gibbons RJ, Holmes Jr DR, et al. Coronary endothelial dysfunction in humans is associated with myocardial perfusion defects. Circulation 1997; 96(10): 3390–5

    Article  PubMed  CAS  Google Scholar 

  22. Chauhan A, Mullins PA, Taylor G, et al. Both endothelium-dependent and endothelium-independent function is impaired in patients with angina pectoris and normal coronary angiograms. Eur Heart J 1997; 18(1): 60–8

    Article  PubMed  CAS  Google Scholar 

  23. Cox ID, Botker HE, Bagger JP, et al. Elevated endothelin concentrations are associated with reduced coronary vasomotor responses in patients with chest pain and normal coronary arteriograms. J Am Coll Cardiol 1999; 34(2): 455–60

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  25. Motz W, Vogt M, Rabenau O, et al. Evidence of endothelial dysfunction in coronary resistance vessels in patients with angina pectoris and normal coronary angiograms. Am J Cardiol 1991; 68(10): 996–1003

    Article  PubMed  CAS  Google Scholar 

  26. Cannon III RO, Watson RM, Rosing DR, et al. Angina caused by reduced vasodilator reserve of the small coronary arteries. J Am Coll Cardiol 1983; 1(6): 1359–73

    Article  PubMed  Google Scholar 

  27. Greenberg MA, Grose RM, Neuburger N, et al. Impaired coronary vasodilator responsiveness as a cause of lactate production during pacing-induced ischaemia in patients with angina pectoris and normal coronary arteries. J Am Coll Cardiol 1987; 9(4): 743–51

    Article  PubMed  CAS  Google Scholar 

  28. Geltman EM, Henes CG, Senneff MJ, et al. Increased myocardial perfusion at rest and diminished perfusion reserve in patients with angina and angiographically normal coronary arteries. J Am Coll Cardiol 1990; 16(3): 586–95

    Article  PubMed  CAS  Google Scholar 

  29. Buus NH, Bottcher M, Bottker HE, et al. Reduced vasodilator capacity in syndrome X related to structure and function of resistance arteries. Am J Cardiol 1999; 83(2): 149–54

    Article  PubMed  CAS  Google Scholar 

  30. Quyyumi AA, Cannon III RO, Panza JA, et al. Endothelial dysfunction in patients with chest pain and normal coronary arteries. Circulation 1992; 86(6): 1864–71

    Article  PubMed  CAS  Google Scholar 

  31. Legrand V, Hodgson JM, Bates ER, et al. Abnormal coronary flow reserve and abnormal radionuclide exercise test results in patients with normal coronary angiograms. J Am Coll Cardiol 1985; 6(6): 1245–53

    Article  PubMed  CAS  Google Scholar 

  32. Camici PG, Gistri R, Lorenzoni R, et al. Coronary reserve and exercise ECG in patients with chest pain and normal coronary angiograms. Circulation 1992; 86(1): 179–86

    Article  PubMed  CAS  Google Scholar 

  33. Sanderson JE, Woo KS, Chung HK, et al. Endothelium-dependent dilation of the coronary arteries in syndrome X: effects of the cold pressor test. Cardiology 1997; 88(5): 414–7

    Article  PubMed  CAS  Google Scholar 

  34. Kaski JC, Elliott PM, Salomone O, et al. Concentration of circulating plasma endothelin in patients with angina and normal coronary angiograms. Br Heart J 1995; 74: 620–4

    Article  PubMed  CAS  Google Scholar 

  35. Kaski JC, Cox ID, Crook JR, et al. Differential plasma endothelin levels in subgroups of patients with angina and angiographically normal coronary arteries. Am Heart J 1998; 136(3): 412–7

    Article  PubMed  CAS  Google Scholar 

  36. Rosano GM, Ponikowski P, Adamopoulos S, et al. Abnormal autonomic control of the cardiovascular system in syndrome X. Am J Cardiol 1994; 73(16): 1174–9

    Article  PubMed  CAS  Google Scholar 

  37. Frobert O, Molgaard H, Botker HE, et al. Autonomie balance in patients with angina and a normal coronary angiogram. Eur Heart J 1995; 16(10): 1356–60

    PubMed  CAS  Google Scholar 

  38. Montorsi P, Fabbiocchi F, Loaldi A, et al. Coronary adrenergic hyperreactivity in patients with syndrome X and abnormal electrocardiogram at rest. Am J Cardiol 1991; 68(17): 1698–703

    Article  PubMed  CAS  Google Scholar 

  39. Gulli G, Cemin R, Pancera P, et al. Evidence of parasympathetic impairment in some patients with cardiac syndrome X. Cardiovasc Res 2001; 52(2): 208–16

    Article  PubMed  CAS  Google Scholar 

  40. Adamopoulos S, Rosano GM, Ponikowski P, et al. Impaired baroreflex sensitivity and sympathovagal balance in syndrome X. Am J Cardiol 1998; 82(7): 862–8

    Article  PubMed  CAS  Google Scholar 

  41. Shapiro LM, Crake T, Poole-Wilson PA. Is altered cardiac sensation responsible for chest pain in patients with normal coronary arteries?: clinical observation during cardiac catheterisation. Br Med J (Clin Res Ed) 1988; 296(6616): 170–1

    Article  CAS  Google Scholar 

  42. Pasceri V, Lanza GA, Buffon A, et al. Role of abnormal pain sensitivity and behavioral factors in determining chest pain in syndrome X. J Am Coll Cardiol 1998; 31(1): 62–6

    Article  PubMed  CAS  Google Scholar 

  43. Chauhan A, Mullins PA, Thuraisingham SI, et al. Abnormal cardiac pain perception in syndrome X. J Am Coll Cardiol 1994; 24(2): 329–35

    Article  PubMed  CAS  Google Scholar 

  44. Cannon III RO, Quyyumi AA, Schenke WH, et al. Abnormal cardiac sensitivity in patients with chest pain and normal coronary arteries. J Am Coll Cardiol 1990; 16(6): 1359–66

    Article  PubMed  Google Scholar 

  45. Turiel M, Galassi AR, Glazier JJ. Pain threshold and tolerance in women with syndrome x and women with stable angina pectoris. Am J Cardiol 1987; 60(7): 503–7

    Article  PubMed  CAS  Google Scholar 

  46. Lagerqvist B, Sylven C, Waidenstrom A. Lower threshold for adenosine-induced chest pain in patients with angina and normal coronary angiograms. Br Heart J 1992; 68(3): 282–5

    Article  PubMed  CAS  Google Scholar 

  47. Rosen SD, Uren NG, Kaski JC, et al. Coronary vasodilator reserve, pain perception, and sex in patients with syndrome X. Circulation 1994; 90(1): 50–60

    Article  PubMed  CAS  Google Scholar 

  48. Rosen SD, Paulesu E, Wise RJ, et al. Central neural contribution to the perception of chest pain in cardiac syndrome X. Heart 2002; 87(6): 513–9

    Article  PubMed  CAS  Google Scholar 

  49. Cox ID, Salomone O, Brown SJ, et al. Serumendothelin levels and pain perception in patients with cardiac syndrome X and in healthy controls. Am J Cardiol 1997; 80(5): 637–40

    Article  PubMed  CAS  Google Scholar 

  50. Botker HE, Sonne HS, Frobert O, et al. Enhanced exercise-induced hyperkalemia in patients with syndrome X. J Am Coll Cardiol 1999; 33(4): 1056–61

    Article  PubMed  CAS  Google Scholar 

  51. Poole-Wilson PA. Potassium and the heart. Clin Endocrinol Metab 1984; 13(2): 249–68

    Article  PubMed  CAS  Google Scholar 

  52. Murakami H, Urabe K, Nishimura M. Inappropriate microvascular constriction produced transient ST-segment elevation in patients with syndrome X. J Am Coll Cardiol 1998; 32(5): 1287–94

    Article  PubMed  CAS  Google Scholar 

  53. Mohri M, Koyanagi M, Egashira K, et al. Angina pectoris caused by coronary microvascular spasm. Lancet 1998; 351(9110): 1165–9

    Article  PubMed  CAS  Google Scholar 

  54. Rosano GM, Peters NS, Lefroy D, et al. 17-beta-Estradiol therapy lessens angina in postmenopausal women with syndrome X. J Am Coll Cardiol 1996; 28(6): 1500–5

    Article  PubMed  CAS  Google Scholar 

  55. Rosano GM, Lindsay DC, Poole-Wilson PA. Syndrome X: an hypothesis for cardiac pain without ischaemia. Cardiologia 1991; 36(11): 885–95

    PubMed  CAS  Google Scholar 

  56. Rosano GM, Collins P, Kaski JC, et al. Syndrome X in women is associated with oestrogen deficiency. Eur Heart J 1995; 16(5): 610–4

    PubMed  CAS  Google Scholar 

  57. Roque M, Heras M, Roig E, et al. Short-term effects of transdermal oestrogen replacement therapy on coronary vascular reactivity in postmenopausal women with angina pectoris and normal results on coronary angiograms. J Am Coll Cardiol 1998; 31(1): 139–43

    Article  PubMed  CAS  Google Scholar 

  58. Koren W, Koldanov R, Peleg E, et al. Enhanced red cell sodium-hydrogen exchange in microvascular angina. Eur Heart J 1997; 18(8): 1296–9

    Article  PubMed  CAS  Google Scholar 

  59. Gaspardone A, Ferri C, Crea F, et al. Enhanced activity of sodium-lithium countertransport in patients with cardiac syndrome X: a potential link between cardiac and metabolic syndrome X. J Am Coll Cardiol 1998; 32(7): 2031–4

    Article  PubMed  CAS  Google Scholar 

  60. Lanza GA, Andreotti F, Sestito A, et al. Platelet aggregability in cardiac syndrome X. Eur Heart J 2001; 22(20): 1924–30

    Article  PubMed  CAS  Google Scholar 

  61. Cosin-Sales J, Pizzi C, Brown S, et al. C-Reactive protein, clinical presentation and ischemic activity in patients with chest pain and normal coronary angiograms. J Am Coll Cardiol 2003; 41(9): 1468–74

    Article  PubMed  CAS  Google Scholar 

  62. Antonios TF, Kaski JC, Hasan KM, et al. Rarefaction of skin capillaries in patients with anginal chest pain and normal coronary arteriograms. Eur Heart J 2001; 22(13): 1144–8

    Article  PubMed  CAS  Google Scholar 

  63. Cannon III RO, Epstein SE. “Microvascular angina” as a cause of chest pain with angiographically normal coronary arteries. Am J Cardiol 1988; 61(15): 1338–43

    Article  PubMed  Google Scholar 

  64. Chauhan A, Mullins PA, Petch MC, et al. Syndrome X: an abnormality of epicardial or microvascular coronary circulation? J Am Coll Cardiol 1994; 23(3): 830–1

    Article  PubMed  CAS  Google Scholar 

  65. Maseri A. Abnormal coronary vasomotion in ischemic heart disease. J Cardiovasc Pharmacol 1992; 20 Suppl. 7: S30–1

    Article  PubMed  Google Scholar 

  66. Panting JR, Gatehouse PD, Yang GZ, et al. 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 

  67. Shiraishi A, Ikeda H, Haramaki N, et al. Abnormal myocardial blood flow distribution in patients with angina pectoris and normal coronary arteriograms. Jpn Circ J 2000; 64(8): 566–71

    Article  PubMed  CAS  Google Scholar 

  68. Zeiher AM, Krause T, Schachinger V, et al. Impaired endothelium-dependent vasodilation of coronary resistance vessels is associated with exercise-induced myocardial ischaemia. Circulation 1995; 91(9): 2345–52

    Article  PubMed  CAS  Google Scholar 

  69. Cox ID, Schwartzman RA, Atienza F, et al. Angiographie progression in patients with angina pectoris and normal or near normal coronary angiograms who are restudied due to unstable symptoms. Eur Heart J 1998; 19(7): 1027–33

    Article  PubMed  CAS  Google Scholar 

  70. Kolasinska-Kloch W, Lesniak W, Kiec-Wilk B, et al. Biochemical parameters of endothelial dysfunction in cardiological syndrome X. Scand J Clin Lab Invest 2002; 62(1): 7–13

    Article  PubMed  CAS  Google Scholar 

  71. Lekakis JP, Papmichael CM, Vemmos CN, et al. Peripheral vascular endothelial dysfunction in patients with angina pectoris and normal coronary arteriograms. J Am Coll Cardiol 1998; 31(3): 541–6

    Article  PubMed  CAS  Google Scholar 

  72. Chauhan A, Foote J, Petch MC, et al. Hyperinsulinemia, coronary artery disease and syndrome X. J Am Coll Cardiol 1994; 23(2): 364–8

    Article  PubMed  CAS  Google Scholar 

  73. Newby DE, Flint LL, Fox KA, et al. Reduced responsiveness to endothelin-1 in peripheral resistance vessels of patients with syndrome X. J Am Coll Cardiol 1998; 31(7): 1585–90

    Article  PubMed  CAS  Google Scholar 

  74. Swan JW, Walton C, Godsland IF, et al. Insulin resistance syndrome as a feature of cardiological syndrome X in non-obese men. Br Heart J 1994; 71(1): 41–4

    Article  PubMed  CAS  Google Scholar 

  75. Kaski JC. Overview of gender aspects of cardiac syndrome X. Cardiovasc Res 2002; 53(3): 620–6

    Article  PubMed  CAS  Google Scholar 

  76. Hayward CS, Kelly RP, Collins P. The roles of gender, the menopause and hormone replacement on cardiovascular function. Cardiovasc Res 2000; 46(1): 28–49

    Article  PubMed  CAS  Google Scholar 

  77. Volterrani M, Rosano G, Coats A, et al. Oestrogen acutely increases peripheral blood flow in postmenopausal women. Am J Med 1995; 99(2): 119–22

    Article  PubMed  CAS  Google Scholar 

  78. Bottcher M, Botker HE, Sonne H, et al. Endothelium-dependent and -independent perfusion reserve and the effect of L-arginine on myocardial perfusion in patients with syndrome X. Circulation 1999; 99(14): 1795–801

    Article  PubMed  CAS  Google Scholar 

  79. Collins P, Rosano GM, Sarrel PM, et al. 17 beta-Estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary heart disease. Circulation 1995; 92(1): 24–30

    Article  PubMed  CAS  Google Scholar 

  80. Chester AH, Jiang C, Borland JA, et al. Oestrogen relaxes human epicardial coronary arteries through non-endothelium-dependent mechanisms. Coron Artery Dis 1995; 6(5): 417–22

    Article  PubMed  CAS  Google Scholar 

  81. Gilligan DM, Badar DM, Panza JA, et al. Acute vascular effects of oestrogen in postmenopausal women. Circulation 1994; 90(2): 786–91

    Article  PubMed  CAS  Google Scholar 

  82. Mendelsohn ME, Karas RH. The protective effects of oestrogen on the cardiovascular system. N Engl J Med 1999; 340(23): 1801–11

    Article  PubMed  CAS  Google Scholar 

  83. Rosano GM, Peters NS, Kaski JC, et al. 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  PubMed  CAS  Google Scholar 

  84. Fragasso G, Rossetti E, Dosio F, et al. High prevalence of the thallium-201 reverse redistribution phenomenon in patients with syndrome X. Eur Heart J 1996; 17(10): 1482–7

    Article  PubMed  CAS  Google Scholar 

  85. Kaski JC. Cardiac imaging in syndrome X: the problem of “reverse redistribution”. Eur Heart J 1996; 17(10): 1459–61

    Article  PubMed  CAS  Google Scholar 

  86. Galassi AR, Crea F, Araujo LI, et al. Comparison of regional myocardial blood flow in syndrome X and one-vessel coronary artery disease. Am J Cardiol 1993; 72(2): 134–9

    Article  PubMed  CAS  Google Scholar 

  87. Huang MH, Horackova M, Negoescu RM, et al. Polysensory response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia. Cardiovasc Res 1996; 32(3): 503–15

    PubMed  CAS  Google Scholar 

  88. Cox DA, Vita JA, Treasure CB, et al. Reflex increase in blood pressure during the intracoronary administration of adenosine in man. J Clin Invest 1989; 84(2): 592–6

    Article  PubMed  CAS  Google Scholar 

  89. Crake T, Canepa-Anson R, Shapiro L, et al. Continuous recording of coronary sinus oxygen saturation during atrial pacing in patients with coronary artery disease or with syndrome X. Br Heart J 1988; 59(1): 31–8

    Article  PubMed  CAS  Google Scholar 

  90. Rosano GM, Kaski JC, Arie S, et al. Failure to demonstrate myocardial ischaemia in patients with angina and normal coronary arteries: evaluation by continuous coronary sinus pH monitoring and lactate metabolism. Eur Heart J 1996; 17(8): 1175–80

    Article  PubMed  CAS  Google Scholar 

  91. Buchthal SD, den Hollander JA, Merz CN, et al. Abnormal myocardial phosphorus-31 nuclear magnetic resonance spectroscopy in women with chest pain but normal coronary angiograms. N Engl J Med 2000; 342(12): 829–35

    Article  PubMed  CAS  Google Scholar 

  92. Buffon A, Rigattieri S, Santini SA, et al. Myocardial ischaemia-reperfusion damage after pacing-induced tachycardia in patients with cardiac syndrome X. Am J Physiol Heart Circ Physiol 2000; 279(6): H2627–33

    PubMed  CAS  Google Scholar 

  93. Camici PG, Marraccini P, Lorenzoni R, et al. Coronary hemodynamics and myocardial metabolism in patients with syndrome X: response to pacing stress. J Am Coll Cardiol 1991; 17(7): 1461–70

    Article  PubMed  CAS  Google Scholar 

  94. Nihoyannopoulos P, Kaski JC, Crake T, et al. Absence of myocardial dysfunction during stress in patients with syndrome X. J Am Coll Cardiol 1991; 18(6): 1463–70

    Article  PubMed  CAS  Google Scholar 

  95. Panza JA, Laurienzo JM, Curiel RV, et al. Investigation of the mechanism of chest pain in patients with angiographie ally normal coronary arteries using tran-sesophageal dobutamine stress echocardiography. J Am Coll Cardiol 1997; 29(2): 293–301

    Article  PubMed  CAS  Google Scholar 

  96. 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(3): 821–6

    Article  PubMed  CAS  Google Scholar 

  97. Lagerqvist B, Sylven C, Hedenstrom H, et al. Intravenous adenosine but not its first metabolite inosine provokes chest pain in healthy volunteers. J Cardiovasc Pharmacol 1990; 16(1): 173–6

    Article  PubMed  CAS  Google Scholar 

  98. Lagerqvist B, Sylven C, Beermann B, et al. Intracoronary adenosine causes angina pectoris like pain: an inquiry into the nature of visceral pain. Cardiovasc Res 1990; 24(8): 609–13

    Article  PubMed  CAS  Google Scholar 

  99. Botker HE, Moller N, Schmitz O, et al. Myocardial insulin resistance in patients with syndrome X. J Clin Invest 1997; 100(8): 1919–27

    Article  PubMed  CAS  Google Scholar 

  100. Rosen SD, Paulesu E, Frith CD, et al. Central nervous pathways mediating angina pectoris. Lancet 1994; 344(8916): 147–50

    Article  PubMed  CAS  Google Scholar 

  101. Rosen SD, Paulesu E, Nihoyannopoulos: silent ischemia as a central problem: regional brain activation compared in silent and painful myocardial ischemia. Ann Intern Med 1996; 124(11): 939–49

    PubMed  CAS  Google Scholar 

  102. Mammana C, Salomone OA, Kautzner J, et al. Heart rate-independent prolongation of QTc interval in women with syndrome X. Clin Cardiol 1997; 20(4): 357–60

    Article  PubMed  CAS  Google Scholar 

  103. Rosen SD, Dritsas A, Bourdillon PJ, et al. Analysis of the electrocardiographic QT interval in patients with syndrome X. Am J Cardiol 1994; 73(13): 971–2

    Article  PubMed  CAS  Google Scholar 

  104. Batchvarov V, Kaski JC, Parchure N, et al. Comparison between ventricular gradient and a new descriptor of the wavefront direction of ventricular activation and recovery. Clin Cardiol 2002; 25(5): 230–6

    Article  PubMed  Google Scholar 

  105. Camici PG, Marraccini P, Gistri R, et al. Adrenergically mediated coronary vasoconstriction in patients with syndrome X. Cardiovasc Drugs Ther 1994; 8(2): 221–6

    Article  PubMed  CAS  Google Scholar 

  106. Lee WL, Chen JW, Kong CW, et al. Changes in cardiac autonomic activities in patients with syndrome X: a study of spectral analysis of heart rate variability. Angiology 1996; 47(10): 929–39

    Article  PubMed  CAS  Google Scholar 

  107. Kelly RA, Balligand JL, Smith TW. Nitric oxide and cardiac function. Circ Res 1996; 79(3): 363–80

    Article  PubMed  CAS  Google Scholar 

  108. Lanza GA. Abnormal cardiac nerve function in syndrome X. Herz 1999; 24(2): 97–106

    Article  PubMed  CAS  Google Scholar 

  109. Foussas SG, Adamopoulou EN, Kafaltis NA, et al. Clinical characteristics and follow-up of patients with chest pain and normal coronary arteries. Angiology 1998; 49(5): 349–54

    Article  PubMed  CAS  Google Scholar 

  110. Lichtlen PR, Bargheer K, Wenzlaff P. Long-term prognosis of patients with angina-like chest pain and normal coronary angiographic findings. J Am Coll Cardiol 1995; 25(5): 1013–8

    Article  PubMed  CAS  Google Scholar 

  111. Pasternak RC, Thibault GE, Savoia M, et al. Chest pain with angiographically insignificant coronary arterial obstruction: clinical presentation and long-term follow-up. Am J Med 1980; 68(6): 813–7

    Article  PubMed  CAS  Google Scholar 

  112. Kemp HG, Kronmal RA, Vlietstra RE, et al. Seven year survival of patients with normal or near normal coronary arteriograms: a CASS registry study. J Am Coll Cardiol 1986; 7(3): 479–83

    Article  PubMed  CAS  Google Scholar 

  113. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000; 101(16): 1899–906

    Article  PubMed  CAS  Google Scholar 

  114. Suwaidi JA, Hamasaki S, Higano ST, et al. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 2000; 101(9): 948–54

    Article  PubMed  CAS  Google Scholar 

  115. Opherk D, Schuler G, Wetterauer K, et al. Four-year follow-up study in patients with angina pectoris and normal coronary arteriograms (“syndrome X”). Circulation 1989; 80(6): 1610–6

    Article  PubMed  CAS  Google Scholar 

  116. Suzuki H, Takeyama Y, Koba S, et al. Small vessel pathology and coronary hemodynamics in patients with microvascular angina. Int J Cardiol 1994; 43(2): 139–50

    Article  PubMed  CAS  Google Scholar 

  117. Al Suwaidi J, Velianou JL, Gertz MA, et al. Systemic amyloidosis presenting with angina pectoris. Ann Intern Med 1999; 131(11): 838–41

    PubMed  CAS  Google Scholar 

  118. Kaski JC, Valenzuela Garcia LF. Therapeutic options for the management of patients with cardiac syndrome X. Eur Heart J 2001; 22(4): 283–93

    Article  PubMed  CAS  Google Scholar 

  119. Braunwald E, Antman E, Beasley J, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction-summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol 2002; 40(7): 1366–74

    Article  PubMed  Google Scholar 

  120. Lanza G A, Manzoli A, Bia E, et al. Acute effects of nitrates on exercise testing in patients with syndrome X: clinical and pathophysiological implications. Circulation 1994; 90(6): 2695–700

    Article  PubMed  CAS  Google Scholar 

  121. Radice M, Giudici V, Albertini A, et al. Usefulness of changes in exercise tolerance induced by nitroglycerin in identifying patients with syndrome X. Am Heart J 1994; 127(3): 531–5

    Article  PubMed  CAS  Google Scholar 

  122. Hongo M, Takenaka H, Uchikawa S, et al. Coronary microvascular response to intracoronary administration of nicorandil. Am J Cardiol 1995; 75(4): 246–50

    Article  PubMed  CAS  Google Scholar 

  123. Yamabe H, Namura H, Yano T, et al. Effect of nicorandil on abnormal coronary flow reserve assessed by exercise 201T1 scintigraphy in patients with angina pectoris and nearly normal coronary arteriograms. Cardiovasc Drugs Ther 1995; 9(6): 755–61

    Article  PubMed  CAS  Google Scholar 

  124. Chen JW, Lee WL, Hsu NW, etal. Effects of short-term treatment of nicorandil on exercise-induced myocardial ischaemia and abnormal cardiac autonomie activity in microvascular angina. Am J Cardiol 1997; 80(1): 32–8

    Article  PubMed  CAS  Google Scholar 

  125. Nalbantgil S, Altnt LA, Imaz HYL, et al. The effect of trimetazidine in the treatment of microvascular angina. Int J Angiol 1999; 8(1): 40–3

    Article  PubMed  Google Scholar 

  126. Cannon III RO, Watson RM, Rosing DR, et al. 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(4): 242–6

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  128. Kemp Jr HG, Vokonas PS, Cohn PF, et al. The anginal syndrome associated with normal coronary arteriograms: report of a six year experience. Am J Med 1973; 54(6): 735–42

    Article  PubMed  Google Scholar 

  129. Fragasso G, Chierchia SL, Pizzetti G, et al. Impaired left ventricular filling dynamics in patients with angina and angiographie ally normal coronary arteries: effect of beta adrenergic blockade. Heart 1997; 77(1): 32–9

    PubMed  CAS  Google Scholar 

  130. Romeo F, Gaspardone A, Ciavolella M, et al. Verapamil versus acebutolol for syndrome X. Am J Cardiol 1988; 62(4): 312–3

    Article  PubMed  CAS  Google Scholar 

  131. Lanza GA, Colonna G, Pasceri V, et al. Atenolol versus amlodipine versus isosorbide-5-mono nitrate on anginal symptoms in syndrome X. Am J Cardiol 1999; 84(7): 854–6, A8

    Article  PubMed  CAS  Google Scholar 

  132. Galassi AR, Kaski JC, Pupita G, et al. Lack of evidence for alpha-adrenergic receptor-mediated mechanisms in the genesis of ischaemia in syndrome X. Am J Cardiol 1989; 64(5): 264–9

    Article  PubMed  CAS  Google Scholar 

  133. Rosen SD, Lorenzoni R, Kaski JC, et al. Effect of alphal -adrenoceptor blockade on coronary vasodilator reserve in cardiac syndrome X. J Cardiovasc Pharmacol 1999; 34(4): 554–60

    Article  PubMed  CAS  Google Scholar 

  134. Botker HE, Sonne HS, Schmitz O, et al. Effects of doxazosin on exercise-induced angina pectoris, ST-segment depression, and insulin sensitivity in patients with syndrome X. Am J Cardiol 1998; 82(11): 1352–6

    Article  PubMed  CAS  Google Scholar 

  135. Griendling KK, Alexander RW. Oxidative stress and cardiovascular disease. Circulation 1997; 96(10): 3264–5

    PubMed  CAS  Google Scholar 

  136. Ganten D. Peptidergic control of cardiovascular function: the angiotensin paradigm. Eur Heart J 1990; 11 Suppl. B: 72–8

    PubMed  CAS  Google Scholar 

  137. Iwatsubo H, Nagano M, Sakai T, et al. Converting enzyme inhibitor improves forearm reactive hyperemia in essential hypertension. Hypertension 1997; 29 (1 Pt 2): 286–90

    Article  PubMed  CAS  Google Scholar 

  138. Mancini GB, Henry GC, Macaya C, et al. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease: the TREND (Trial on Reversing ENdothelial Dysfunction) Study. Circulation 1996; 94(3): 258–65

    Article  PubMed  CAS  Google Scholar 

  139. Perondi R, Saino A, Tio RA, et al. ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. Circulation 1992; 85(6): 2004–13

    Article  PubMed  CAS  Google Scholar 

  140. Boger RH, Bode-Boger SM, Thiele W, et al. Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease. Circulation 1997; 95(8): 2068–74

    Article  PubMed  CAS  Google Scholar 

  141. Boger RH, Bode-Boger SM, Szuba A, et al. Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 1998; 98(18): 1842–7

    Article  PubMed  CAS  Google Scholar 

  142. Miyazaki H, Matsuoka H, Cooke JP, et al. Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation 1999; 99(9): 1141–6

    Article  PubMed  CAS  Google Scholar 

  143. Kaski JC, Rosano G, Gavrielides S, et al. Effects of angiotensin-converting enzyme inhibition on exercise-induced angina and ST segment depression in patients with microvascular angina. J Am Coll Cardiol 1994; 23(3): 652–7

    Article  PubMed  CAS  Google Scholar 

  144. Nalbantgil I, Onder R, Altintig A, et al. Therapeutic benefits of cilazapril in patients with syndrome X. Cardiology 1998; 89(2): 130–3

    Article  PubMed  CAS  Google Scholar 

  145. Chen JW, Hsu NW, Wu TC, et al. Long-term angiotensin-converting enzyme inhibition reduces plasma asymmetric dimethyl argi ni ne and improves endothelial nitric oxide bioavailability and coronary microvascular function in patients with syndrome X. Am J Cardiol 2002; 90(9): 974–82

    Article  PubMed  CAS  Google Scholar 

  146. Kayikcioglu M, Payzin S, Yavuzgil O, et al. Benefits of statin treatment in cardiac syndrome-X. Eur Heart J 2003; 24(22): 1993–4

    Article  CAS  Google Scholar 

  147. Magni G. The use of antidepressants in the treatment of chronic pain. A review of the current evidence. Drugs 1991; 42(5): 730–48

    Article  PubMed  CAS  Google Scholar 

  148. Cannon RO, III, Quyyumi AA, et al. Imipramine in patients with chest pain despite normal coronary angiograms. N Engl J Med 1994; 330(20): 1411–7

    Article  PubMed  Google Scholar 

  149. Cox ID, Hann CM, Kaski JC. Low dose imipramine improves chest pain but not quality of life in patients with angina and normal coronary angiograms. Eur Heart J 1998; 19(2): 250–4

    Article  PubMed  CAS  Google Scholar 

  150. Maseri A, Crea F, Kaski JC, et al. Mechanisms of angina pectoris in syndrome X. J Am Coll Cardiol 1991; 17(2): 499–506

    Article  PubMed  CAS  Google Scholar 

  151. Elliott PM, Krzyzowska-Dickinson K, Calvino R, et al. Effect of oral aminophylline in patients with angina and normal coronary arteriograms (cardiac syndrome X). Heart 1997; 77(6): 523–6

    PubMed  CAS  Google Scholar 

  152. Emdin M, Picano E, Lattanzi F, et al. Improved exercise capacity with acute aminophylline administration in patients with syndrome X. J Am Coll Cardiol 1989; 14(6): 1450–3

    Article  PubMed  CAS  Google Scholar 

  153. Yoshio H, Shimizu M, Kita Y, et al. Effects of short-term aminophylline administration on cardiac functional reserve in patients with syndrome X. J Am Coll Cardiol 1995; 25(7): 1547–51

    Article  PubMed  CAS  Google Scholar 

  154. Radice M, Giudici V, Pusineri E, et al. Different effects of acute administration of aminophylline and nitroglycerin on exercise capacity in patients with syndrome X. Am J Cardiol 1996; 78(1): 88–92

    Article  PubMed  CAS  Google Scholar 

  155. Lanza GA, Gaspardone A, Pasceri V, et al. Effects of bamiphylline on exercise testing in patients with syndrome X. G Ital Cardiol 1997; 27(1): 50–4

    PubMed  CAS  Google Scholar 

  156. Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965; 150(699): 971–9

    Article  PubMed  CAS  Google Scholar 

  157. Mannheimer C, Carlsson CA, Emanuelsson H, et al. The effects of transcutaneous electrical nerve stimulation in patients with severe angina pectoris. Circulation 1985; 71(2): 308–16

    Article  PubMed  CAS  Google Scholar 

  158. Chauhan A, Mullins PA, Thuraisingham SI, et al. Effect of transcutaneous electrical nerve stimulation on coronary blood flow. Circulation 1994; 89(2): 694–702

    Article  PubMed  CAS  Google Scholar 

  159. Sanderson JE, Woo KS, Chung HK, et al. The effect of transcutaneous electrical nerve stimulation on coronary and systemic haemodynamics in syndrome X. Coron Artery Dis 1996; 7(7): 547–52

    Article  PubMed  CAS  Google Scholar 

  160. Eliasson T, Albertsson P, Hardhammar P, et al. Spinal cord stimulation in angina pectoris with normal coronary arteriograms. Coron Artery Dis 1993; 4(9): 819–27

    Article  PubMed  CAS  Google Scholar 

  161. Sarrel PM, Lindsay D, Rosano GM, et al. Angina and normal coronary arteries in women: gynecologic findings. Am J Obstet Gynecol 1992; 167(2): 467–71

    PubMed  CAS  Google Scholar 

  162. Albertsson PA, Emanuelsson H, Milsom I. Beneficial effect of treatment with transdermal estradiol-17-beta on exercise-induced angina and ST segment depression in syndrome X. Int J Cardiol 1996; 54(1): 13–20

    Article  PubMed  CAS  Google Scholar 

  163. Paoletti R, Wenger N K. Review of the international position on women’s health and menopause: a comprehensive approach. Circulation 2003; 107: 1336–9

    Article  PubMed  Google Scholar 

  164. Potts SG, Bass C. Chest pain with normal coronary arteries: Psychological aspects. In: Kaski JC, editor. Chest pain with normal coronary arteries: pathogenesis, diagnosis and management. Boston: Kluwer Academic Publishers, 1999: 13–32

    Chapter  Google Scholar 

  165. Klimes I, Mayou RA, Pearce MJ, et al. Psychological treatment for atypical non-cardiac chest pain: a controlled evaluation. Psychol Med 1990; 20(3): 605–11

    Article  PubMed  CAS  Google Scholar 

  166. Mayou RA, Bryant BM, Sanders D, et al. A controlled trial of cognitive behavioural therapy for non-cardiac chest pain. Psychol Med 1997; 27(5): 1021–31

    Article  PubMed  CAS  Google Scholar 

  167. Peski-Oosterbaan AS, Spinhoven P, Van der Does AJ, et al. Cognitive change following cognitive behavioural therapy for non-cardiac chest pain. Psychother Psychosom 1999; 68(4): 214–20

    Article  PubMed  Google Scholar 

  168. Sanders D, Bass C, Mayou RA, et al. Non-cardiac chest pain: why was a brief intervention apparently ineffective? Psychol Med 1997; 27(5): 1033–40

    Article  PubMed  CAS  Google Scholar 

  169. Cunningham C, Brown S, Kaski JC. Effects of transcendental meditation on symptoms and electrocardiographic changes in patients with cardiac syndrome X. Am J Cardiol 2000; 85(5): 653–5, A10

    Article  PubMed  CAS  Google Scholar 

  170. Eriksson BE, Tyni-Lenne R, Svedenhag J, et al. Physical training in syndrome X: physical training counteracts deconditioning and pain in syndrome X. J Am Coll Cardiol 2000; 36: 1619–25

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

G. Aldama and J. Cosin-Sales are recipients of research scholarships from the Spanish Society of Cardiology. The authors have provided no information on conflicts of interest directly relevant to the content of this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Juan Carlos Kaski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaski, J.C., Aldama, G. & Cosin-Sales, J. Cardiac Syndrome X. Am J Cardiovasc Drugs 4, 179–194 (2004). https://doi.org/10.2165/00129784-200404030-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00129784-200404030-00005

Keywords

Navigation