Opposing effects of propranolol and diltiazem on the angina threshold during an exercise test in patients with syndrome X

: Patients with angina pectoris, exercise induced myocardial ischemia, normal coronary arteries and no evidence of epicardial spasm, i.e. patients with syndrome x, have been suggested to haven inadequate increase in coronary blood flow during tachycardia, possibly due to a functional disorder of small coronary vessels. To evaluate the best medical management of this syndrome we studied 13 patients who showed the above set of findings. Patients were given propranolol (160 mg daily), diltiazem (360 mg daily) and placebo for 2 weeks, using a randomized single blind protocol. Upright bicycle ergometer testing was performed at the end of each period of treatment. Compared to placebo, diltiazem significantly (p less than 0.001) prolonged exercise duration (x +/- SD: 365 +/- 86 vs 303 +/- 89 sec) and time to onset of angina (358 +/- 88 vs 276 +/- 90 sec). Angina appeared in 7 patients with diltiazem vs 13 patients with placebo and occurred at a higher rate pressure product (26.3 +/- 3.5 vs 24.1 +/- 2.8 X 10(-3); p less than 0.02). Conversely, following propranolol exercise duration and time to onset of angina were unchanged and angina appeared in all patients at a lower rate pressure product (18.3 +/- 2.9 vs 24.4 +/- 3.6 X 10(-3); p less than 0.001). The most likely explanations for these findings are: propranolol counteracts beta 2-adrenergic receptors, thus further reducing coronary reserve. This may lower the anginal threshold; Diltiazem reduces smooth muscle tone in small coronary vessels. This may result in increased coronary reserve and exercise duration.