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 angina pectoris in patients with coronary artery disease than in patients with syndrome X, but it is not known whether their effect on exercise 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 > or = 1 mm on the control exercise test. Compared with the control test, the main differences in the two groups observed during the exercise test after administration of ISDN were (1) heart rate at 1-mm ST-segment depression was higher (126 +/- 25 versus 104 +/- 15 beats 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-pressure product at 1-mm ST-segment depression, the time to 1-mm ST-segment 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 seconds, P < .01; 494 +/- 279 versus 622 +/- 194 seconds, P = .013, respectively); (3) a normalization of the ECG (no ST-segment depression) was obtained 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 no patient of group X (P < .01). CONCLUSIONS: In patients presenting with anginal chest pain, the effects of sublingual nitrates on exercise testing appear to be clinically useful to distinguish patients with coronary artery stenoses from patients with syndrome X. Indeed, worsening of 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 prearteriolar nitric oxide production is unlikely to play a key role in the pathophysiology of the syndrome.

[Neurovegetative changes before and during episodes of silent ischemia in variant angina]. / Modificazioni neurovegetative prima e durante episodi di ischemia silente nell'angina variante.

In order to evaluate whether variations in autonomic nervous tone have a significant role in the induction of coronary arterial spasm in variant angina, we analyzed the changes in heart rate variability (HRV) related to spontaneous episodes of ST-segment elevation, recorded during 24-hour ambulatory ECG monitoring, in 13 patients with variant angina (9 men and 4 women, aged 63 +/- 12 years). In order to obtain an accurate analysis of HRV changes, we only included ischemic episodes characterized by silent ST-segment elevation, lasting at least 3 min and without any ST change in the previous 30 min. HRV indexes in the time domain (RR interval, standard deviation of RR intervals [SD], pNN50, r-MSSD) and in the frequency domain (LF = 0.04-0.15 Hz, HF = 0.15-0.40 HZ, LF/HF ratio) were calculated on 2 min intervals, centered at 15 min before (15B), 5 min before ed 1 min before (1B) the appearance of ST elevation, as well as at peak of ST-segment elevation. Of 161 ischemic episodes found on 24-hour Holter recordings, 60 (37%) fulfilled the inclusion criteria for analysis (4.6 +/- 3.5 episodes/patient, range 1-12). The duration of the selected episodes was 6 +/- 2.5 min and ST elevation was 2.2 +/- 1.0 mm. Heart rate (HR) did not have any change before ST elevation, whereas it showed a small, but significant increase at peak ST (73 +/- 12 versus 67 +/- 11 b/min at 15B, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)