Postgrad Med J: first published as 10.1136/pgmj.67.783.4 on 1 January 1991. Downloaded from Postgrad Med J (1991) 67, 4 - 8 ) The Fellowship of Postgraduate Medicine, 1991 Leading Article Angina and myocardial infarction with normal coronary arteries M.E. Bourke and D.L.H. Patterson Cardiac Department, Whittington Hospital, Highgate Hill, London N19 SNF, UK. Introduction Coronary ischaemic syndromes, including chest imbalance between myocardial oxygen supply and pain suggestive of angina pectoris, and document- demand might be abnormal haemoglobin oxygen ed myocardial infarction, in the presence of angio- dissociation, as in carbon monoxide poisoning.6 graphically normal coronary arteries, have been Classic angina pectoris usually indicates myocar- the subject of much attention. In contrast to dial ischaemia, secondary to obstructive coronary atheromatous coronary artery disease the patho- artery disease. It can arise when myocardial physiology ofsuch conditions is poorly understood ischaemia is due not to reduction ofcoronary blood and the mechanisms underlying myocardial ischae- flow, but to other mechanisms such as increased mia in these circumstances have been the cause ofa cardiac work as in aortic stenosis; altered blood great deal of conjecture and controversy. oxygen content in severe anaemia; rheological abnormalities of the blood in hypergammaglobin- aemia or, as described in this issue of the Journal, by copyright. Myocardial infarction due to thyrotoxicosis.'5 In Europe, approximately 10% ofpatients refer- A small percentage of patients presenting with red to cardiac units for assessment ofchest pain are acute myocardial infarction are found to have found on diagnostic cardiac catheterization to have angiographically normal epicardial coronary arter- no angiographic evidence of significant coronary ies. The prevalence is high in certain subsets of artery disease.'6 It is important to appreciate that myocardial infarction patients, such as the very coronary angiograms only visualize coronary young,' especially those infarcting during or fol- arteries of greater than 400 gAm diameter. The lowing severe physical exercise,2 and in young majority will have a non-cardiac cause for their http://pmj.bmj.com/ women during pregnancy or using oral contracep- symptoms and in many cases careful reassessment tives and smoking.3 Documented myocardial and investigation will reveal a musculoskeletal, infarction in the presence of normal coronary oesophageal or psychological cause.'7 It may be arteries has been reported in thyrotoxicosis; both difficult to determine whether anxiety-related true and factitious,4 temporally related to cocaine symptoms are a cause or consequence of the use,5 after acute exposure to carbon monoxide,6 current chest pain. In a small minority of patients and in patients with viral myocarditis.7 This issue of there will still be a clinical suspicion that symptoms the Journal contains a case report on a multisystem are due to myocardial ischaemia. on September 23, 2021 by guest. Protected vasculitis leading to myocardial infarction without evidence of coronary artery involvement.8 Amongst suggested mechanisms are defects in Coronary vasospasm clotting factors and platelet activity,9"10 coronary artery spasm," thrombosis with rapid spontaneous In 1959 Prinzmetal et al. introduced the concept of lysis,'2 coronary emboli' and small vessel disease.'3 epicardial artery spasm causing the specific clinical In cases of chronic Chagas' heart disease, where syndrome, 'variant angina', which is characterized there is parasympathetic ganglion destruction it is by angina at rest with elevated ST segments on postulated that transitory sympathetic overdrive electrocardiogram (ECG).'8 Now it is thought that causes myocardial infarction.' In these cases the this mechanism may play a role in other aspects of coronary arteries are not only free ofatheroma but ischaemic heart disease. Spasm can be detected in indeed are larger in comparison to hypertensive angiographically normal segments, or may be and normal patients. Another cause of an extreme superimposed on an atherosclerotic lesion - 'dynamic coronary stenosis'. Unfortunately the Correspondence: D.L.H. Patterson, M.D., F.R.C.P. literature has become confused because the term Received: 6 September 1990 coronary spasm is often applied to any situation of Postgrad Med J: first published as 10.1136/pgmj.67.783.4 on 1 January 1991. Downloaded from NORMAL CORONARY ARTERIES AND ISCHAEMIC SYNDROMES 5 increased coronary vasomotor tone. It should be symptoms. Many patients have a poor response to confined to a situation of focal coronary constric- long acting nitrate therapy, and a good response to tion sufficient to cause transient coronary occlu- calcium antagonists. The incidence ofsudden death sion, which gives rise to attacks ofischaemic pain at in patients with documented coronary artery rest. spasm is unknown. Since episodes of complete Although various neural'9 and humoral202' heart block and ventricular tachycardia are known mechanisms have been proposed, the genesis of to occur during coronary artery spasm, it may be coronary spasm is as yet undefined. Maseri and his that some patients have died as a result of these co-workers postulate a focal hyperreactivity to a rhythm disturbances. Overall the prognosis of a variety of coronary vasoconstrictive stimuli acting patient with severe coronary atherosclerosis and on different receptors.22 It has been observed that in coronary artery spasm depends upon the degree of variant angina, coronary spasm usually occurs at atherosclerosis.29,30 the site ofatheromatous plaques,23 but the fact that such plaques are common and classical variant Syndrome X angina rare, suggests that some additional factor other than the presence of plaque is required. In a The term Syndrome X was first used by Kemp3' in large study of patients with chronic coronary 1973 in an editorial discussion of a paper by ischaemic syndromes other than variant angina, Arbogast and Bourassa,32 who performed pacing Bertrand et al.24 showed that when stenosis existed studies in patients with chest pain and normal there was no correlation between the degree of coronary arteries and showed ST depression dur- underlying stenosis and the occurrence of spasm. ing atrial pacing. No mention was made ofexercise- Bertrand could demonstrate ergonovine-induced induced ST segment changes in these patients. The angina in only 4% of those with chronic stable authors designated their patient cohort as group X. angina and 6% with old myocardial infarction. In The phrase was later popularized by Opherk et al.33 contrast 20% ofpatients with recent infarction and The term has been widely used, but with a lack of 30% ofthose experiencing angina at rest developed agreed hard diagnostic criteria. This has resulted in by copyright. focal coronary occlusion in response to ergono- a confusing picture as each study has used it own vine. It may be that in these acute situations there is terms of reference, making comparisons very a focal hyperreactivity to coronary vasoconstrictor difficult. agents. Less than 1% of those who present to a cardiac Recent studies have shown that vasoactive com- unit with possible angina, and in whom a non- pounds affect segments of the human coronary cardiac cause has been excluded, will fulfil the circulation differentially.22 This has implications in diagnostic criteria of a tight, albeit empirical, the pathophysiology of both focal coronary artery definition of Syndrome X:34 (a) typical angina on spasm and of 'Syndrome X', which has been effort; (b) positive exercise test; (c) no demonstrable http://pmj.bmj.com/ suggested to be due to a more diffuse disturbance of coronary stenosis; (d) no other obvious cause, such coronary blood flow. Intracoronary injection of as hypertension, valve disease or overt cardio- organic nitrates causes marked dilatation ofepicar- myopathy. Even applying these strict criteria will dial vessels, suggesting a resting coronary motor not give an infallible diagnosis, since, for instance tone. In contrast these doses have little affect on exercise testing has its limitations. total coronary blood flow, implying little effect on An alternative approach to the diagnosis is to use intramural resistance vessels. Adenosine displays a conceptual definition, i.e. inducible ischaemia in the opposite pattern, with a marked distal dilating the absence of large coronary artery stenosis or on September 23, 2021 by guest. Protected effect but relatively minor actions on the epicardial haemodynamic overload. This approach intro- vessels. duces practical problems because ofthe difficulty in Studies ofthe effects ofintracoronary infusion of demonstrating ischaemia unequivocally. various endogenous vasoactive substances, includ- Several studies have used the demonstration of ing calcitonin gene related peptide,25 neuropeptide stimulation ofanaerobic metabolism as evidence of y,26 acetylcholine27 and substance P,28 point to a ischaemia. This is a specific but not sensitive heterogeneity of responses within the human cor- marker. In studies of patients with postulated onary circulation, and may allow some pharma- Syndrome X, 12-100% demonstrated myocardial cological intervention of coronary blood flow lactate production in response to pacing or dipyrid- regulation. It is difficult to validate their relevance amole infusion.34'35 to the pathophysiology of conditions under con- A fall in coronary sinus oxygen saturation in sideration here. response