Safety of intravenous high-dose dipyridamole echocardiography

Clinical data on 10,451 high-dose (up to 0.84 mg/kg over 10 minutes) dipyridamole-echocardiography tests (DET) performed in 9,122 patients were prospectively collected from 33 echocardiographic laboratories, each contributing >100 tests. All patients were studied for documented or suspected coronary artery disease (1,117 early [<18 days] after acute myocardial infarction and 293 had unstable angina). Significant side effects including major adverse reactions and minor but limiting side effects occurred in 113 patients (1.2%). Major adverse reactions occurred in 7 cases (0.07%). In 6 of these cases, adverse reactions were associated with echocardiographically assessed ischemia and included 1 prolonged cardiac asystole (complicated by acute myocardial infarction and coma, with death after 23 days), 1 short-lasting cardiac asystole, 2 myocardial infarctions, 1 pulmonary edema and 1 sustained ventricular tachycardia. In all 6 cases, the cardiologist-echocardiographer performing the study had a limited experience (<100 tests) with DET, and at off-line reading in 5 cases, the obvious echo-positivity preceded the onset of complications by 1 to 5 minutes. The only ischemia-independent major side effect was a short-lasting cardiac asystole that was reversed by aminophylline and atropine. Significant side effects associated with echocardiographically assessed ischemia occurred in 89 additional cases (21 with and 68 without concomitant echocardiographically assessed myocardial ischemia). The most frequent of these side effects was hypotension or bradycardia, or both, which occurred in 40 patients with negative and 6 with positive DET. In all cases, side effects promptly subsided after aminophylline. In 1,857 cases, the high dose was not given for echo-positivity before the eighth minute. In 60 cases, the full high dose was not given despite the echocardiographic negativity for limiting side effect, yielding an overall feasibility of high-dose DET of 99%. Aminophylline was routinely administered also at the end of negative tests. Noticeable side effects occurred in 17 cases. In 13 patients (7 with negative and 6 with positive DET) transient ST-segment elevation occurred 1 to 4 minutes after the onset of aminophylline infusion, accompanied by regional dyssynergy. All 13 patients had variant angina. Thus, high-dose DET is reasonably safe and well-tolerated, even early after acute myocardial infarction and in patients with unstable angina, when selectively used in patients in whom the lower dose did not induce either echocardiographic signs of ischemia or limiting side effects.