Dobutamine atropine stress echocardiography (DASE) detects coronary artery disease (CAD) by increasing myocardial oxygen demand causing ischemia. The sensitivity of the test for detection of CAD is reduced in patients with submaximal stress. We hypothesized that increasing cardiac work load by adding isometric exercise would improve the detection of ischemia during DASE. We studied 31 patients, mean age 57+/-11 years, with angiographically documented CAD. Patients underwent DASE using incremental dobutamine doses from 5 to 40 microg/kg/min, followed by atropine if peak heart rate was <85% of predicted maximal. Hand grip was then performed for 2 minutes at 33% of maximal voluntary contraction, while dobutamine infusion was maintained at the peak dose. The addition of hand grip during dobutamine stress was associated with a significant increase in systolic blood pressure (143+/-21 vs 164+/-24 mm Hg, p = 0.001) and left ventricular end-systolic circumferential wall stress (72+/-30 x 10(3) dynes/cm2 vs 132+/-34 x 10(3) dynes/cm2, p = 0.004). Wall motion score index increased from 1.0 at rest to 1.15+/-0.18 with dobutamine (p = 0.0004 vs rest), and increased further to 1.29+/-0.22 with the addition of hand grip (p = 0.004 vs dobutamine). Ischemia was detected in 19 patients (62%) with dobutamine-atropine stress alone and in 25 (83%) after the addition of hand grip (p <0.05). The addition of hand grip during DASE is feasible, and improves the detection of myocardial ischemia.