Some thoughts on the continuing dilemma of angina pectoris

Abstract

electrocardiographic abnormalities. 5 Many reports followed documenting ischaemia by different methods in such patients but, in contrast to ischaemia associated with obstructive CAD, left ventricular wall motion appeared to be preserved. This finding led to speculation about long-term outcomes of such patients. Indeed multiple early reports suggested that outcomes were similar to those of selected subjects without angina and obstructive CAD. Unfortunately, this conclusion was widely embraced and led to dismissal of such patients from subspecialty care and also from general medical care. During our attempts to identify reasons for higher ischaemic heart disease (IHD) event rates among women vs. men, it became clear that there was a strong bias against evaluation of women with chest pain and other findings suggesting IHD. The public message about this gender inequity then prompted referral of more women with these findings to coronary angiography. We began to see increasing numbers of such women who were not only disabled by persistent angina, but had serious adverse outcomes. These concerns led to the WISE study in 1996, and about two-thirds of the initial consecutive cohort of women with chest pain and other findings suggesting IHD were found to have no obstructive CAD: their adverse outcomes confirmed that this was not a benign syndrome, as initially believed. 2 Also important was the application of coronary artery reactivity testing for endothelial and microvascular function (Figure 1). Among women with normal coronary arteries and non-obstructive CAD, WISE study data showed that most had endothelial and/or microvascular dysfunction. The latter was defined by low coronary flow reserve and independently predicted adverse cardiovascular events (e.g. first occurrence of death, myocardial infarction, stroke, or hospitalization for heart failure) after 5.4 years followup. 3 These serious events are consistent with the cardiovascular disease continuum expected for a disorder involving the microvasculature. Furthermore, they consume a large amount of healthcare resources. Cardiac magnetic resonance imaging provided superior resolution to evaluate perfusion, and these patients were found to have a relative failure of subendocardial perfusion to increase with adenosine, which could explain the absence of major changes in left ventricular wall motion. 6