Tuesday, February 6, 2007

Cardiac syndrome X: Diagnosis

Cardiac syndrome X: Diagnosis

G A Lanza
Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Rome, Italy

The classic definition of cardiac syndrome X (CSX) is angina-like pain on effort, ST segment depression on exercise stress test and totally normal coronary arteries at angiography in the absence of any other cardiac or systemic diseases (for example, hypertension or diabetes) known to influence vascular function.
Although the origin of the syndrome is still debated, several studies have suggested that CSX is mainly caused by coronary microvascular dysfunction, and indeed the term is often used as a synonym for microvascular angina.

DIAGNOSIS
According to the proposed definition (see above), the diagnosis of CSX would require, together with the presence of typical angina and normal (or near normal) coronary arteries at angiography, some findings compatible with myocardial ischaemia or coronary microvascular dysfunction, or both.
A major diagnostic challenge for the cardiologist, however, is whether patients with CSX can be distinguished with sufficient reliability from those with obstructive CAD on the basis of a careful assessment of clinical findings and non-invasive investigation, which would avoid subjecting the patient to the small but definite risk associated with coronary angiography and would also have favourable effects on costs and use of medical resources.
General data are of limited diagnostic help in individual patients. Compared with those with obstructive CAD, patients with CSX are more commonly women, in whom angina often appears after menopause (either spontaneous or surgical); however, female patients with CAD are also more likely to have angina symptoms after menopause.
The characteristics of chest pain also do not often permit distinguishing between the two groups of patients. However, the presence of some findings strongly orient the diagnosis towards CSX. These, in particular, are a prolonged (> 15–20 min) dull persistence of chest discomfort after resolution of typical chest pain induced by exercise and a lack of response, or a slow or incomplete response, to administration of short-acting nitrates to relieve pain, both features occurring in about 50% of patients.
Among diagnostic stress tests, the careful analysis of abnormal exercise and stress scintigraphic results also does not usually help to identify patients with CSX. In contrast, the induction of typical, often severe angina during echocardiographic stress test (for example, with dipyridamole or dobutamine) in the presence of ST segment depression, but in the absence of LV contractile abnormalities, strongly suggests CSX, although LV dysfunction can also be undetectable in patients with mild forms of CAD.
Repeating exercise testing after giving sublingual nitrates may also help to identify patients with CSX. Indeed, preventive administration of short-acting nitrates usually improves exercise-induced ST segment changes and symptoms in patients with CAD, whereas short-acting nitrates may paradoxically induce earlier ST segment changes during the test in some patients with CSX.
Lastly, although unpractical for clinical use, assessing platelet reactivity in response to ADP/collagen after exercise may provide a further clue to CSX diagnosis in patients with angina. Indeed, by using the platelet function analyser-100 method, we have recently found that a lengthening by =" type="#_x0000_t75">10 s of the aggregation time after exercise (implying a reduction of platelet reactivity) was detectable only in patients with CSX, whereas a reduction =" type="#_x0000_t75">10 s (implying an increase of platelet reactivity) was detectable only in patients with CAD.
Thus, careful clinical and non-invasive diagnostic assessment of patients with effort angina can find strong clues to the diagnosis of CSX, which may lead to a sufficiently reliable diagnosis of probable CSX, in particular when more suggestive findings are detected together in individual patients.
In the presence of probable CSX, when a definitive diagnosis is required, the preferred test to document the presence of normal coronary arteries should perhaps now be considered to be multislice spiral computed tomography coronary angiography, which has a high negative predictive value for significant CAD (> 95%) and would avoid the small but definite risk of invasive coronary angiography to the patient.

Heart 2007;93:159-166
© 2007 by BMJ Publishing Group Ltd & British Cardiovascular Society

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