Background: Exercise testing remains the most accessible and widely used technique for the detection of coronary artery disease (CAD) and for the assessment of its severity. Clinical usefulness of the simple exercise test is limited by poor sensitivity and imperfect specificity. Many patients referred for diagnostic stress testing cannot achieve an adequate increase in heart rate due to lack of motivation, poor physical condition, or medications. Atropine increases the heart rate and therefore myocardial oxygen consumption, and might improve the diagnostic accuracy of exercise testing, either reducing the number of non-diagnostic examinations, or increasing the positivity of the test in patients with non severe coronary disease.
Methods: One-hundred-seventy-two consecutive patients (144 males and 28 females, age 58 +/- 8 years) with suspected coronary artery disease underwent exercise testing and coronary angiography. Exercise testing was considered positive in the presence of ST segment depression > or = 0.10 mV horizontal or downsloping, > or = 0.15 mV upsloping, or in the presence of ST elevation without Q waves. The test was considered negative in the absence of significant ST depression or elevation if the exercise heart rate was > 85% of age-predicted maximum, non-diagnostic if the heart rate was < 85%. In 148 patients (86%) coronary angiography showed CAD (> 70% luminal reduction in at least one major vessel), in 24 patients (14%) non significant CAD or angiographically normal coronary arteries (NoCAD). Exercise testing was positive in 134 patients (78%: 85% in CAD, 33% in NoCAD), negative in 13 patients (8%: 3% in CAD, 38% in NoCAD), non-diagnostic in 25 patients (14%; 12% in CAD, 29% in NoCAD). The sensitivity was 85%, specificity was 38%, and diagnostic accuracy 78%. In the 25 patients with non-diagnostic test (18 CAD, 7 NoCAD) the exercise was repeated 30-90 minutes later, immediately after i.v. injection of 1-2 mg of atropine, and was stopped at the same workload of the index test.
Results: The atropine-exercise test was well tolerated and accomplished in all cases. The maximal heart rate (139 +/- 11 vs 121 +/- 11) and the double product (25,308 +/- 4082 vs 22,166 +/- 3569) were significantly greater after atropine. The increase of the maximal heart rate improved the detection of the electrocardiographic signs of exercise-induced myocardial ischemia only in CAD patients. In the 18 CAD patients the atropine-exercise test was positive in 8, negative in 5, non-diagnostic in 5. In the 7 NoCAD patients the atropine-exercise test was positive in 1, negative in 6. The test remained non-diagnostic only in 3% of patients. The sensitivity of the test with atropine was 91%, specificity was 63%, and diagnostic accuracy 87%.
Conclusions: The addition of atropine to exercise testing, which causes further chronotropic stress to the myocardium, is well tolerated and safe, and improves the diagnostic accuracy of the test for the detection of coronary artery disease in patients who cannot achieve an adequate exercise heart rate. The combination with atropine increases the utility and the cost-effectiveness of exercise testing.