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Clinical Quiz Answer

A 'Sensitive Heart' in a Tennis Player

John D. Cantwell, MD; Charles W. Wickliffe, MD



Return to case presentation.

The patient was diagnosed as having syndrome X (figure 2), based on his history of angina pectoris, ST-segment depression on exercise testing, evidence of ischemia on laboratory testing, and the presence of a normal coronary angiogram.

[Figure 2]

He was placed on 60 mg isosorbide mononitrate once daily and 180 mg diltiazem hydrochloride once daily. The patient did not tolerate nitroglycerin patches because of headaches. He still has mild exertional chest pain, but feels better and is able to enjoy routine activities. Should his pain intensify, we will consider a trial of imipramine hydrochloride or a proton-pump inhibitor.


In 1967, Kemp et al (1) and Likoff et al (2) described a number of patients who had angina-like pain, ST-segment depression on exercise testing, and normal coronary arteries on angiography. Six years later, Kemp (3) applied the term "syndrome X" to this symptom cluster, indicating the uncertain cause.

The literature on syndrome X can be confusing because definitions vary. Some authors apply the term to patients who have angina pectoris and less than 50% occlusion of epicardial coronary arteries, while others insist on a normal coronary arteriogram. The term syndrome X has also been applied to a metabolic disorder, the "deadly quartet" of obesity, hyperlipidemia, hypertension, and insulin resistance. There might be some overlap, as insulin resistance has been reported in the cardiac syndrome X (4).

Endothelial function of epicardial coronary arteries and in the cardiac microvasculature has been investigated as a possible cause of the disorder (5). Endothelium-dependent vasodilation can be studied by injecting acetylcholine, whereas endothelium-independent response to vasodilators is assessed using substances such as adenosine or papaverine. Some investigators have shown attenuation of both endothelial responses in syndrome X (6,7), but the dysfunction has not been correlated with ST-segment depression on exercise testing or associated with segmental myocardial wall motion abnormalities seen during typical myocardial ischemia.

Other hypotheses have included enhanced cardiac pain perception (8) (an overly sensitive heart caused by heightened visceral pain sensitivity), exercise-induced abnormalities in potassium and catecholamine metabolism (9), esophageal hypersensitivity (9), sensitivity to adenosine (10), a reduced pain threshold (11), and lowered central endogenous opioid activity (12).

Whatever the mechanism, the symptoms can be difficult to treat. Nitroglycerin may or may not help. The same applies to beta-blockers and to calcium-channel antagonists. Cannon et al (13) found that imipramine (useful in other types of chronic pain syndromes) can possibly exert an "analgesic effect on the sensitive heart." Estrogen patches might be tried in postmenopausal women (14). Proton-pump inhibitors and histamine H2-receptor antagonists might help if gastroesophageal dysfunction is involved (15).

Though patient prognosis is good in syndrome X, the condition can significantly impair quality of life (16). Many patients will remain symptomatic and require ongoing medical treatment.


  1. Kemp HG, Elliott WC, Gorlin R: The anginal syndrome with normal coronary arteriography. Trans Assoc Am Physicians 1967;80:59-70
  2. 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):1063-1066
  3. Kemp HG Jr: Left ventricular function in patients with the anginal syndrome and normal coronary arteriograms. Am J Cardiol 1973;32(3):375-376
  4. Munnings F: Syndrome X: a deadly combination of diseases. Phys Sportsmed 1994;22(8):63-66
  5. Hoffmann E, Assennato P, Donatelli M, et al: Plasma endothelin-1 levels in patients with angina pectoris and normal coronary angiograms. Am Heart J 1998;135(4):684-688
  6. Zeiher AM, Krause T, Schachinger V, et al: Impaired endothelium-dependent vasodilation of coronary resistance vessels is associated with exercise-induced myocardial ischemia. Circulation 1995;91(9):2345-2352
  7. Cannon RO III, Curiel RV, Prasad A, et al: Comparison of coronary endothelial dynamics with electrocardiographic and left ventricular contractile responses to stress in the absence of coronary artery disease. Am J Cardiol 1998;82(6):710-714
  8. Cannon RO III: The sensitive heart: a syndrome of abnormal cardiac pain perception. JAMA 1995;273(11):883-887
  9. Botker HE, Sonne HS, Frobert O, et al: Enhanced exercise-induced hyperkalemia in patients with syndrome X. J Am Coll Cardiol 1999;33(4):1056-1061
  10. Assey ME: The puzzle of normal coronary arteries in the patient with chest pain: what to do? Clin Cardiol 1993;16(3):170-180
  11. 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):62-66
  12. Fedele F, Agati L, Pugliese M, et al: Role of the central endogenous opiate system in patients with syndrome X. Am Heart J 1998;136(6):1003-1009
  13. Cannon RO III, Quyyumi AA, Mincemoyer R, et al: Imipramine in patients with chest pain despite normal coronary angiograms. N Engl J Med 1994;330(20):1411-1417
  14. 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):1500-1505
  15. Borjesson M, Albertsson P, Dellborg M, et al: Esophageal dysfunction in syndrome X. Am J Cardiol 1998;82(10):1187-1191
  16. Atienza F, Velasco JA, Brown S, et al: Assessment of quality of life in patients with chest pain and normal coronary arteriogram (syndrome X) using a specific questionnaire. Clin Cardiol 1999;22(4):283-290

Dr Cantwell is a cardiologist at Cardiology of Georgia, PC, and Dr Wickliffe is cardiologist and chief of staff at Piedmont Hospital, both in Atlanta. Address correspondence to John D. Cantwell, MD, Cardiology of Georgia, PC, 95 Collier Rd NW, Suite 2075, Atlanta, GA 30309.