Abnormal cardiac sensitivity in patients with chest pain and normal coronary arteries

Cardiovascular Diagnosis Section, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.

The causes of chest pain in patients found to have angiographically normal coronary arteries during cardiac catheterization remain controversial. Cardiac sensitivity to catheter manipulation, pacing at various stimulus intensities and intracoronary injection of contrast medium was examined in several groups of patients who underwent cardiac catheterization. Right heart (especially right ventricular) catheter manipulation and pacing and intracoronary contrast medium provoked chest pain typical of that previously experienced in 29 (81%) of 36 patients with chest pain and angiographically normal coronary arteries and 15 (46%) of 33 symptomatic patients with hypertrophic cardiomyopathy. In contrast, only 2 (6%) of 33 symptomatic patients with coronary artery disease experienced their typical chest pain with these sensitivity tests (p less than 0.001). None of 10 patients with valvular heart disease but without a chest pain syndrome experienced any sensation with these tests. Cutaneous pain threshold testing demonstrated that patients with chest pain and normal coronary arteries had a higher pain threshold to thermal stimulation compared with patients who had coronary artery disease or hypertrophic cardiomyopathy. No relation existed between cardiac sensitivity and cutaneous sensitivity testing. Thus, patients who have chest pain despite angiographically normal coronary arteries may have abnormal cardiac sensitivity to a variety of stimuli. This increased sensitivity may be of causal importance to their chest pain syndrome or may contribute to their perception of ischemia-induced pain. The same phenomenon was also commonly seen in symptomatic patients with hypertrophic cardiomyopathy. Whether this phenomenon represents abnormal activation of pain receptors within the heart or abnormal processing of visceral afferent neural impulses in the peripheral or central nervous system is unknown.

This article has been cited by other articles:

				G. A. Lanza, A. Buffon, A. Sestito, L. Natale, G. A. Sgueglia, L. Galiuto, F. Infusino, L. Mariani, A. Centola, and F. Crea Relation between stress-induced myocardial perfusion defects on cardiovascular magnetic resonance and coronary microvascular dysfunction in patients with cardiac syndrome X. J. Am. Coll. Cardiol., January 29, 2008; 51(4): 466 - 472. [Abstract] [Full Text] [PDF]

				I. A.C. Vermeltfoort, O. Bondarenko, P. G.H.M. Raijmakers, D. A.M. Odekerken, A. F.M. Kuijper, A. Zwijnenburg, M. J.E. van der Vis-Melsen, J. W.R. Twisk, A. M. Beek, G. J.J. Teule, et al. Is subendocardial ischaemia present in patients with chest pain and normal coronary angiograms? A cardiovascular MR study Eur. Heart J., July 1, 2007; 28(13): 1554 - 1558. [Abstract] [Full Text] [PDF]

				G. Angelo Sgueglia, A. Sestito, A. Spinelli, B. Cioni, F. Infusino, F. Papacci, F. Bellocci, M. Meglio, F. Crea, and G. Antonio Lanza Long-term follow-up of patients with cardiac syndrome X treated by spinal cord stimulation Heart, May 1, 2007; 93(5): 591 - 597. [Abstract] [Full Text] [PDF]

				G A Lanza Cardiac syndrome X: a critical overview and future perspectives Heart, February 1, 2007; 93(2): 159 - 166. [Abstract] [Full Text] [PDF]

				J. Madaric, J. Bartunek, K. Verhamme, M. Penicka, E. Van Schuerbeeck, P. Nellens, G. R. Heyndrickx, W. Wijns, M. Vanderheyden, and B. De Bruyne Hyperdynamic Myocardial Response to Beta-Adrenergic Stimulation in Patients With Chest Pain and Normal Coronary Arteries J. Am. Coll. Cardiol., October 4, 2005; 46(7): 1270 - 1275. [Abstract] [Full Text] [PDF]

				G. A. Lanza, A. Sestito, G. A. Sgueglia, F. Infusino, F. Papacci, M. Visocchi, C. Ierardi, M. Meglio, F. Bellocci, and F. Crea Effect of spinal cord stimulation on spontaneous and stress-induced angina and 'ischemia-like' ST-segment depression in patients with cardiac syndrome X Eur. Heart J., May 2, 2005; 26(10): 983 - 989. [Abstract] [Full Text] [PDF]

				J. F. Beltrame Advances in understanding the mechanisms of angina pectoris in cardiac syndrome X Eur. Heart J., May 2, 2005; 26(10): 946 - 948. [Full Text] [PDF]

				M. Valeriani, A. Sestito, D. L. Pera, L. D. Armas, F. Infusino, T. Maiese, G. A. Sgueglia, P. A. Tonali, F. Crea, D. Restuccia, et al. Abnormal cortical pain processing in patients with cardiac syndrome X Eur. Heart J., May 2, 2005; 26(10): 975 - 982. [Abstract] [Full Text] [PDF]

				R. Bugiardini and C. N. Bairey Merz Angina With "Normal" Coronary Arteries: A Changing Philosophy JAMA, January 26, 2005; 293(4): 477 - 484. [Abstract] [Full Text] [PDF]

				R. F. Redberg, R. O. Cannon III, N. Bairey Merz, A. Lerman, S. E. Reis, D. S. Sheps, and Endorsed by the American College of Cardiology Fou Women's Ischemic Syndrome Evaluation: Current Status and Future Research Directions: Report of the National Heart, Lung and Blood Institute Workshop: October 2-4, 2002: Section 2: Stable Ischemia: Pathophysiology and Gender Differences Circulation, February 17, 2004; 109 (6): e47 - e49. [Full Text] [PDF]

				C. Pizzi, O. Manfrini, F. Fontana, and R. Bugiardini Angiotensin-Converting Enzyme Inhibitors and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase in Cardiac Syndrome X: Role of Superoxide Dismutase Activity Circulation, January 6, 2004; 109(1): 53 - 58. [Abstract] [Full Text] [PDF]

				G A Lanza and F Crea The complex link between brain and heart in cardiac syndrome X Heart, October 1, 2002; 88(4): 328 - 330. [Full Text] [PDF]

				S D Rosen, E Paulesu, R J S Wise, and P G Camici Central neural contribution to the perception of chest pain in cardiac syndrome X Heart, June 1, 2002; 87(6): 513 - 519. [Abstract] [Full Text] [PDF]

				J. C. Kaski Overview of gender aspects of cardiac syndrome X Cardiovasc Res, February 15, 2002; 53(3): 620 - 626. [Abstract] [Full Text] [PDF]

				S. D Rosen The pathophysiology of cardiac syndrome X -- a tale of paradigm shifts Cardiovasc Res, November 1, 2001; 52(2): 174 - 177. [Full Text] [PDF]

				B. E. Eriksson, R. Tyni-Lenne, J. Svedenhag, R. Hallin, K. Jensen-Urstad, M. Jensen-Urstad, K. Bergman, and C. Sylven Physical training in Syndrome X: Physical training counteracts deconditioning and pain in Syndrome X J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1619 - 1625. [Abstract] [Full Text] [PDF]

				M. Bottcher, H. E. Botker, H. Sonne, T. T. Nielsen, and J. Czernin Endothelium-Dependent and -Independent Perfusion Reserve and the Effect of L-arginine on Myocardial Perfusion in Patients With Syndrome X Circulation, April 13, 1999; 99(14): 1795 - 1801. [Abstract] [Full Text] [PDF]

				M. F Bellamy, J. Goodfellow, A. C Tweddel, F. D.J Dunstan, M. J Lewis, and A. H Henderson Syndrome X and endothelial dysfunction Cardiovasc Res, November 1, 1998; 40(2): 410 - 417. [Abstract] [Full Text] [PDF]

				A. M. Lansing Syndrome X: relief by transmyocardial revascularization J. Thorac. Cardiovasc. Surg., July 1, 1998; 116(1): 174 - 176. [Full Text]

				Wen Lieng Lee, J.-W. Chen, Chi Woon Kong, Jiann Jong Wang, C.-T. Ting, Wan Leong Chan, S.-P. Wang, and M.-S. Chang Changes in Cardiac Autonomic Activities in Patients with Syndrome X: A Study of Spectral Analysis of Heart Rate Variability Angiology, October 1, 1996; 47(10): 929 - 939. [Abstract] [PDF]

				O. Frobert, P. Funch-Jensen, and J. P. Bagger Diagnostic Value of Esophageal Studies in Patients with Angina-like Chest Pain and Normal Coronary Angiograms Ann Intern Med, June 1, 1996; 124(11): 959 - 969. [Abstract] [Full Text]

				R. K. Goyal Changing Focus on Unexplained Esophageal Chest Pain Ann Intern Med, June 1, 1996; 124(11): 1008 - 1011. [Full Text]

				R. O. Cannon, A. A. Quyyumi, R. Mincemoyer, A. M. Stine, R. H. Gracely, W. B. Smith, M. F. Geraci, B. C. Black, T. W. Uhde, M. A. Waclawiw, et al. Imipramine in Patients with Chest Pain Despite Normal Coronary Angiograms N. Engl. J. Med., May 19, 1994; 330(20): 1411 - 1417. [Abstract] [Full Text]