chest pain in cardiac syndrome X due to subendocardial ischaemia?

European Heart Journal Advance Access originally published online on May 24, 2007
European Heart Journal 2007 28(13):1539-1540; doi:10.1093/eurheartj/ehm167

PubMed Citation
Articles by Camici, P. G.


© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Is the chest pain in cardiac syndrome X due to subendocardial ischaemia?
Paolo G. Camici
MRC Clinical Sciences Centre and National Heart and Lung Institute, Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UK

Corresponding author. Tel: +44 20 8383 3186; fax: +44 20 8383 3742. E-mail address: paolo.camici@csc.mrc.ac.uk

This editorial refers to ‘Is subendocardial ischaemia present in patients with chest pain and normal coronary angiograms? A cardiovascular MR study’ by I.A.C. Vermeltfoort et al., on page 1554



Over the past 30 years, the issue of chest pain in patients with a normal coronary angiogram has received much attention.1 The interest in this condition, which has also been termed cardiac syndrome X when the pain is accompanied by ST-segment depression during exercise electrocardiography, has two main reasons:

(i) The first is clinical. Does the patient have heart disease? Can the condition be effectively treated? Is the patient's life expectancy shortened? (ii) The second one is relative to the pathophysiology of this condition. Is the chest pain in patients with syndrome X of ischaemic origin? And if the pain is due to myocardial ischaemia what are the mechanisms?

Clinically, in a significant proportion of patients with a history of chest pain, the coronary angiogram does not show significant narrowing of the vessel lumen. These patients usually have a poor response to conventional anti-ischaemic therapy, which may lead to the unnecessary performance of repeated coronary angiograms over the years because of recurrence of chest pain. With regard to their prognosis, a number of studies have consistently shown that these patients have a life expectancy similar to that of the general population,2 with the exception of those with conduction abnormalities such as left bundle branch block that may develop dilated cardiomyopathy during follow-up.3

From the pathophysiological point of view things are far from clear. The initial hypothesis that the chest pain is of ischaemic origin was based on the presence of ST-segment depression during spontaneous or stress-induced chest pain, as well as on the evidence of reversible stress-induced myocardial perfusion defects. Furthermore, some studies have provided evidence of reduced endothelium-dependent and independent coronary vasodilatation as well as metabolic evidence of myocardial ischaemia.4 Other studies, however, failed to find evidence of abnormal myocardial blood flow or coronary flow reserve (CFR) or metabolic or functional evidence of ischaemia during stress.4 It must be noted, however, that inclusion and exclusion criteria in the vast majority of these studies have not been especially strict. In particular, the category of ‘normal coronary arteriogram’ has been a broad one, often including cases of coronary artery disease (CAD) ranging from minimal disease to coronary stenoses up to 50% of luminal diameter. A more homogeneous set of patients would be defined if the following exclusion criteria are employed: absence of left bundle branch block either on the resting or exercise electrocardiogram; absence of even minimal irregularities on the arteriogram; no evidence of diabetes mellitus, arterial hypertension, hyperlipidaemia, valve disease (including mitral valve prolapse), epicardial arterial spasm, and cardiomyopathy.

These exclusion criteria are essential because, more recently, it has become clear that abnormalities in the function and structure of the coronary microcirculation, which may be severe enough to contribute to myocardial ischaemia, occur in many of the above conditions.4 Most commonly, myocardial ischaemia is demonstrated in patients with CAD in whom CFR is reduced in parallel with the severity of coronary stenoses.5 However, a reduced CFR can also be demonstrated in patients with angiographically normal epicardial arteries and, in this circumstance, suggests coronary microvascular dysfunction (CMD). The latter has been demonstrated in patients who are at higher risk of developing CAD and is thought to represent the functional counterpart of traditional coronary risk factors. CMD can also occur in patients with primary (e.g. hypertrophic) or secondary (e.g. hypertensive) cardiomyopathies and is most commonly due to adverse remodelling of intramural arterioles [for a detailed review of CMD see Camici and Crea4]. The term syndrome X (originally the Group x in the paper of Arbogast and Bourassa of 1973)6 was coined to stress the uncertainty over the pathophysiology of chest pain. Therefore, this term should not be used in patients, such as those with risk factors for CAD or cardiomyopathies, in whom myocardial ischaemia due to CMD is known to occur.

It is possible, however, that a subset of patients exists who have a reduced CFR and metabolic evidence of myocardial ischaemia in whom none of the known causes of CMD can be demonstrated. Maseri et al.7 have proposed that in these patients focal ischaemia in small myocardial regions scattered throughout the myocardium and caused by pre-arteriolar dysfunction might explain the paradox of angina and ST-segment depression. One argument used by the supporters of the ischaemic origin of pain in syndrome X, is that ischaemia could be confined to small areas of the heart particularly in the subendocardium.

http://eurheartj.oxfordjournals.org/cgi/content/full/28/13/1539