Correspondence

Chest Pain and Normal Coronary Arteries

N Engl J Med 2000; 343:511-512August 17, 2000

Article

To the Editor:

Buchthal et al. (March 23 issue)1 report an abnormal, reversible decrease in the myocardial phosphocreatine:ATP ratio during mild handgrip exercise, a finding suggestive of ischemia, in 7 of 35 women with angina and no angiographically significant coronary stenoses and in 4 of 11 patients with critical stenoses. This observation was made possible by the application of myocardial phosphorus-31 nuclear magnetic resonance spectroscopy, which appears to have sufficient sensitivity to detect metabolic ischemic alterations in the anterior cardiac wall in the absence of ischemic ST-segment changes. However, the finding of a positive response in only 20 percent of the cases may be due not only to the mild stimulus used, as acknowledged by the authors, but also to heterogeneity among the patients. Given this possibility, together with the lack of recognizable differences between the women with a positive response and those without a positive response, this study joins the list of controversial reports on angina caused by coronary microvascular dysfunction.2

In their multicenter study, the authors selected patients on the basis of sex, absence of angiographically significant coronary stenoses, and a history of angina sufficient to represent an indication for angiography according to local practice. However, only some of the patients who meet these very broad inclusion criteria report a typical history of effort-induced angina and consistently have angina with diagnostic, transient ST-segment depression during exercise stress testing.3 In addition, in this select subgroup of patients, in whom there is at least some evidence that the symptoms have cardiac origin, an ischemic mechanism is still uncertain, because no contraction abnormalities develop during angina and ST-segment depression.2 A possible explanation for this paradox could be a patchy distribution of small foci of ischemia distal to the most constricted microvessels that is sufficient to cause transient ST-segment depression and, when confluent, myocardial perfusion abnormalities, but not extensive enough to cause contractile dysfunction.4

The use of nuclear magnetic resonance spectroscopy in the evaluation of patients who have diagnostic ST-segment depression during effort-induced angina, in association with anterior myocardial perfusion defects, would identify those whose chest pain has a noncardiac origin and those with alterations involving the inferior cardiac wall, and might put an end to this controversy. However, since microvascular constriction may not only have multiple causes3 but also be episodic rather than persistent,5 nuclear magnetic resonance spectroscopy should be applied during tests that cause transient diagnostic electrocardiographic changes.

Attilio Maseri, M.D.
Catholic University of the Sacred Heart, 00168 Rome, Italy

5 References

1. 1

   Buchthal SD, den Hollander JA, Merz CNB, et al. Abnormal myocardial phosphorus-31 nuclear magnetic resonance spectroscopy in women with chest pain but normal coronary angiograms. N Engl J Med 2000;342:829-835
   Full Text | Web of Science | Medline

2. 2

   Cannon RO III, Balaban RS. Chest pain in women with normal coronary angiograms. N Engl J Med 2000;342:885-887
   Full Text | Web of Science | Medline

3. 3

   Syndrome X and microvascular angina. In: Maseri A. Ischemic heart disease: a national basis for clinical practise and clinical research. New York: Churchill Livingstone, 1995:507-32.
   

4. 4

   Maseri A, Crea F, Kaski JC, Crake T. Mechanisms of angina pectoris in syndrome X. J Am Coll Cardiol 1991;17:499-506
   CrossRef | Web of Science | Medline

5. 5

   Lanza GA, Manzoli A, Pasceri V, et al. Ischemic-like ST-segment changes during Holter monitoring in patients with angina pectoris and normal coronary arteries but negative exercise testing. Am J Cardiol 1997;79:1-6
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: The points raised by Maseri are important. We agree that a greater level of stress than that provided by handgrip alone would be useful to enhance the sensitivity of the phosphocreatine:ATP ratio. We are exploring pharmacologic methods to use in conjunction with handgrip exercise to increase workload safely. However, we must be cautious, since even in healthy persons, oxygen availability at high workloads may not be adequate to maintain normal phosphocreatine:ATP levels. Lamb et al.1 reported that myocardial phosphocreatine:ATP ratios decreased by an average of 14±13 percent in healthy persons subjected to a pharmacologically induced increase of 200 percent in the rate–pressure product and that there was no electrocardiographic evidence of ischemia during a threefold increase of the rate–pressure product with bicycle exercise. These results suggest that the metabolic response to stress occurs before the development of electrocardiographic abnormalities.

Regarding the speculation that “a patchy distribution of small foci” might be responsible for the reduced sensitivity, it may be part of the explanation in some of our patients who had less than a statistically significant reduction in phosphocreatine:ATP levels during stress. The question of whether the decrease is regional or global is under investigation with use of magnetic resonance systems with higher field strength to improve spatial sensitivity.2,3

Steven D. Buchthal, Ph.D.
Gerald M. Pohost, M.D.
University of Alabama at Birmingham, Birmingham, AL 35205

3 References

1. 1

   Lamb HJ, Beyerbacht HP, Ouwerkerk R, et al. Metabolic response of normal human myocardium to high-dose atropine-dobutamine stress studied by 31P-MRS. Circulation 1997;96:2969-2977
   Web of Science | Medline

2. 2

   Buchthal SD, den Hollander JA, Pohost GM. Fast low-angle 31P MRSI of the human heart at 4.1 tesla. Proc ISMRM 1999;7:279-279
   

3. 3

   Buchthal SD, den Hollander JA, Evanochko WT, Pohost GM. Isometric handgrip exercise testing of cardiac metabolism at 4.1 tesla using fast, low-angle phosphorus NMR spectroscopic imaging (31P-MRSI). J Cardiovasc Magn Reson 1999;1:348-348