ACUTE EFFECTS OF NITRATES ON EXERCISE TESTING IN PATIENTS WITH SYNDROME-X - CLINICAL AND PATHOPHYSIOLOGICAL IMPLICATIONS

Background Sublingual nitrates are much more effective in relieving an gina pectoris in patients with coronary artery disease than in patient s with syndrome X, but it is not known whether their effect on exercis e tolerance is also different in these two groups of patients. Methods and Results Treadmill exercise testing was performed before and after administration of sublingual isosorbide dinitrate (ISDN, 5 mg) in 18 patients with syndrome X (effort angina and normal coronaries, group X ) and in 33 patients with documented coronary artery disease (group C) . As a selection criterion, all patients had ST-segment depression gre ater than or equal to 1 mm on the control exercise test. Compared with the control test, the main differences in the two groups observed dur ing the exercise test after administration of ISDN were (1) heart tate at 1-mm ST-segment depression was higher (126+/-25 versus 104+/-15 be ats per minute [bpm], P<.01) in group C,whereas it was not different ( 125+/-15 versus 126+/-16 beats per minute) in group X; (2) the rate-pr essure product at 1-mm ST-segment depression, the time to 1-mm ST-segm ent depression, and the exercise duration were significantly improved in group C (P<.01 for all) but were worsened in group X (18 047+/-4159 versus 20 535+/-4507 bpm mm Hg, P=.014; 268+/-312 versus 429+/-214 se conds, P<.01; 494+/-279 versus 622+/-194 seconds, P=.013, respectively ); (3) a normalization of the ECG (no ST-segment depression) was obtai ned in 10 patients (30%) of group C but in only 1 (5%) of group X (P<. 01); (4) angina was prevented in 10 of 19 patients of group C but in n o patient of group X (P<.01). Conclusions In patients presenting with anginal chest pain, the effects of sublingual nitrates on exercise tes ting appear to be clinically useful to distinguish patients with coron ary artery stenoses from patients with syndrome X. Indeed, worsening o f exercise tolerance is highly predictive of normal coronary arteries. Furthermore, the failure of nitrates to improve exercise tolerance in patients with syndrome X suggests that a deficiency in coronary prear teriolar nitric oxide production is unlikely to play a key role in the pathophysiology of the syndrome.