The atropine factor in pharmacologic stress echocardiography. Echo Persantine (EPIC) and Echo Dobutamine International Cooperative (EDIC) Study Groups.

OBJECTIVES: This study sought to compare, head to head, the two most popular pharmacologic stress echocardiographic tests--dipyridamole and dobutamine--with state of the art protocols in a large multicenter prospective study. BACKGROUND: In the continuing quest for ideal diagnostic accuracy, pharmacologic stress echocardiography has quickly moved over the years from low to high dose regimens and is currently performed with atropine coadministration. METHODS: Dobutamine (up to 40 microgram/kg body weight per min) plus atropine (up to 1 mg over 4 h) and dipyridamole (up to 0.84 mg/kg per min over 10 h) plus atropine (up to 1 mg over 4 h) stress echocardiography was performed on different days, in random order and within 1 week in 360 patients with chest pain syndrome. Thirteen different echocardiographic laboratories, all fulfilling quality control criteria for stress echocardiographic reading, contributed to the study. RESULTS: No major complications occurred during either test. The test was interrupted before achievement of predetermined end points for limiting side effects in 37 dobutamine-atropine and 7 dipyridamole-atropine stress echocardiographic studies (feasibility 90% vs. 98%, p < 0.01). Diagnostic accuracy was assessed in a subset of 110 patients with no obvious rest dyssynergy (akinesia or dyskinesia) who underwent coronary angiography independently of test results and within 1 week of testing. Significant coronary artery disease (> or = 50% diameter reduction in at least one major coronary vessel by quantitative coronary angiography) was found in 92 patients. Sensitivity for detection of coronary artery disease was 84% (77 of 92) for dobutamine-atropine and 82% (75 of 92) for dipyridamole-atropine stress echocardiography (p = NS), with a specificity of 89% (16 of 18) for dobutamine-atropine and 94% (17 of 18) for dipyridamole-atropine stress echocardiography (p = NS). A significant correlation was present between peak wall motion score index during dipyridamole-atropine and dobutamine-atropine stress echocardiography (r = 0.83, p < 0.0001). CONCLUSIONS: Dobutamine-atropine and dipyridamole-atropine stress echocardiography are safe and feasible, although submaximal studies are more frequent with dobutamine. The two stresses have comparable accuracy in the detection of angiographically assessed coronary artery disease, although dobutamine is marginally more sensitive and dipyridamole marginally more specific. Stratification of the ischemic response in the space domain is also comparable with the two stresses.

Stress echocardiographic results predict risk of reinfarction early after uncomplicated acute myocardial infarction: large-scale multicenter study. Echo Persantine International Cooperative (EPIC) Study Group.

OBJECTIVES: This study sought to assess the value of dipyridamole echocardiography in predicting reinfarction in patients evaluated early after uncomplicated acute myocardial infarction. BACKGROUND: The identification of future nonfatal reinfarction seems an elusive target for physiologic testing. However, a large sample population is needed to detect minor differences in phenomena with a low event rate. METHODS: We assessed the value of dipyridamole echocardiography in predicting reinfarction in 1,080 patients (mean [+/- SD] age 56 +/- 9 years; 926 men, 154 women) evaluated early (10 +/- 5 days) after uncomplicated acute myocardial infarction and followed up for 14 +/- 10 months. RESULTS: Submaximal studies due to limiting side effects occurred in 14 patients (1.3%); these test results were included in the analysis. Results of dipyridamole echocardiography were positive in 475 patients (44%). During follow-up, there were 50 reinfarctions: 45 nonfatal, 5 fatal (followed by cardiac death < or = 4 days after reinfarction). Reinfarction (either nonfatal or fatal) occurred in 30 patients with positive and 20 with negative results (6.3% vs. 3.3%, p < 0.01). Nonfatal reinfarction occurred in 25 patients with positive and 20 with negative results (5% vs. 3.3%, p < 0.05). Reinfarction was fatal in 5 of 30 patients with positive and in none of 20 with negative results (16.6% vs. 0%, p = 0.07). The relative risk of reinfarction was 1.9. CONCLUSIONS: Dipyridamole echocardiographic positivity identifies patients evaluated early after uncomplicated acute myocardial infarction at higher risk of reinfarction, especially fatal reinfarction.

Prognostic value of dipyridamole echocardiography early after uncomplicated myocardial infarction: a large-scale, multicenter trial. The EPIC Study Group.

PURPOSE: To determine the prognostic capability of the dipyridamole echocardiography test (DET) early after an acute myocardial infarction. PATIENTS AND METHODS: On the basis of 11 different echocardiographic laboratories, all with established experience in stress echocardiography and fulfilling quality-control requirements for stress echocardiographic readings, 925 patients were evaluated after a mean of 10 days from an acute myocardial infarction and followed up for a mean of 14 months. RESULTS: During the follow-up, there were 34 deaths and 37 nonfatal myocardial infarctions; 104 patients developed class III or IV angina and 149 had coronary revascularization procedures (bypass or angioplasty). Considering all spontaneous events (angina, reinfarction, and death), the most important univariate predictor was the presence of an inducible wall motion abnormality after dipyridamole administration (chi 2 = 45.8). With a Cox analysis, echocardiographic positivity, age, and male gender were found to have an independent and additive value. Considering survival (and, therefore, death as the only event), age was the most meaningful parameter, followed by the wall motion score index during dipyridamole administration (chi 2 = 12.1). Among other parameters, the resting wall motion score index was a significant predictor of death. In a multivariate analysis, the prognostic contributions of age (relative risk estimate = 1.08) and wall motion score index during dipyridamole administration (relative risk estimate = 4.1) were independent and additive. In particular, considering death only, the event rate was 2% in patients with negative DET results, 4% in patients with positive high-dose DET results, and 7% in patients with positive low-dose DET results. CONCLUSIONS: DET is feasible and safe early after uncomplicated myocardial infarction and allows effective risk stratification on the basis of the presence, severity, extent, and timing of the induced dyssynergy.

Usefulness of dipyridamole-echocardiographic test to identify jeopardized myocardium after thrombolysis. Limited clinical predictivity of dipyridamole-echocardiographic test in convalescing acute myocardial infarction: correlation with coronary angiography.

A dipyridamole-echocardiographic test (DET) was carried out to find out how safe and useful it was in predicting clinical outcome and in identifying patients at risk. The test was performed in 107 asymptomatic patients early (5 to 8 days) after a first acute uncomplicated myocardial infarction managed with thrombolytic therapy. All patients were followed up for a mean of 15 months and 94 underwent coronary angiography. The test was considered positive if transient asynergy of contraction was newly detected either in the infarct and adjacent areas or in the remote zones; two subsets were studied, according to the dose of dipyridamole (0.56 or 0.84 mg.kg-1) needed to induce ischaemia. The test was accomplished satisfactorily in 96% of patients. Intra-inter-observer agreements were 88% and 91% respectively. The test also proved safe at the high infusion dose. During the follow-up period, two patients died, one experienced re-infarction and 12 (12%) developed recurrence of angina. DET was abnormal in 32 patients (adjacent and remote asynergy in 28 and four patients respectively): 18 had a critical and two a non-critical stenosis in the infarct-related vessel, and nine had an occluded artery with collateral distal flow. Multivessel disease was present in 11 patients considered positive, four in the remote and seven in the adjacent zones. However, 20 patients with negative DET results had multivessel disease. Of the positive DET patients, seven had angina. There were eight total events in the 71 negative DET patients, five of whom had multivessel disease. Abnormality was more pronounced in positive DET patients, but did not influence the outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

[Prognostic value of the dipyridamole-echocardiography test immediately after a non-complicated myocardial infarct: a large scale multicenter study. Echo Persantine Italian Cooperative Study]. / Valore prognostico del test eco-dipiridamolo subito dopo infarto miocardico recente non complicato: studio multicentrico su larga scala. Ricercatori Dello Studio EPIC.

BACKGROUND: Any new diagnostic test should follow a pathway similar to that of a new drug, from initial studies in highly selected populations under strictly controlled conditions, up to large scale multicenter trials more likely to represent the true performance of the test in the clinical arena. AIM OF THE STUDY: To evaluate the capability of prognostic stratification of high dose (up to 0.84 mg/kg over 10') dipyridamole-echocardiography test (DET) early after an acute myocardial infarction in a "phase IV" study, based upon 11 different echocardiographic laboratories, all with established experience in stress echo and fulfilling quality control requirements for stress echo readings. STUDY POPULATION: Nine-hundred twenty five patients were evaluated after a mean of 10 days from an acute myocardial infarction and followed up for a mean of 14 months. RESULTS: During DET, one major adverse reaction occurred, consisting of a prolonged ischemia resistant to aminophylline and nitrates, and progressing to small uncomplicated reinfarction. In 11 patients the lower dipyridamole dose (0.56 mg/kg over 4') gave limiting side effects. Patients were followed up for 14 +/- 9.9 months (range = 1.53). During the follow-up, there were 34 deaths and 37 non-fatal myocardial infarctions; 104 patients developed class III or IV angina, and 149 had coronary revascularization procedures (bypass or angioplasty). Considering all spontaneous events (angina, reinfarction and death), the most important univariate predictor was the result of DET (chi-square = 45.8). With a Cox analysis, echocardiographic positivity, age and sex were found to have an independent and additive value. Considering survival (and therefore death as the only event) age was the most meaningful parameter, followed by the Wall Motion Score Index during dipyridamole (chi-square = 12.1); among other parameters, the resting Wall Motion Score Index was a significant predictor of death. By Cox analysis, age (relative risk estimate = 1.02) and Wall Motion Score Index during dipyridamole (relative risk estimate = 14) showed an independent and additional prognostic value. In particular, considering death only, the event rate was of 2% in patients with negative DET, 4% in patients with high dose positive DET and 7% in patients with low dose positive DET. CONCLUSIONS: Dipyridamole echocardiography is feasible and safe early after uncomplicated myocardial infarction and allows an effective risk stratification on the basis of the presence, severity, extent and timing of the induced dyssynergy. In particular, the risk of death doubles in patients with high dose positivity and almost quadruples in patients with low dose positivity.

Dipyridamole-echocardiography in coronary artery disease.

Regional wall motion impairment incurred by means of dipyridamole-induced ischemia, is regarded with higher sensitivity and specificity than the conventional findings in the ECG. Based on the latter considerations, a new test, the dipyridamole echocardiogram has been introduced in which the development of regional wall motion impairment is designated as the positive diagnostic criterion. Dipyridamole is a vasodilator of coronary arterioles. During the course of the examination, three consecutively occurring mechanisms are considered responsible for the appearance of dipyridamole-induced ischemia in the presence of coronary stenosis. The ischemia is initially attributed to a steal-effect, then to reflex-induced rise in rate-pressure product and, lastly, to a vasospastic component. In 680 patients with thoracic pain, on use of 0.84 mg/kg over ten minutes, there was a sensitivity of 74% in detection of angiographically-documented coronary artery disease, defined as greater than 70% stenosis in at least one major coronary artery, and a specificity of 95%. The onset of regional wall motion impairment after dipyridamole infusion was correlated with the severity of the disease, the localization of the wall motion impairment enabled delineation of the localization of the stenosis in the coronary vascular system. By means of the dipyridamole echocardiogram, the effectiveness of therapeutic measures such as PTCA, ACVB, medical antianginal treatment and thrombolysis can be assessed. Lastly, the dipyridamole echocardiogram provides important information with regard to prognosis.