Prognostic significance of ischemic electrocardiographic changes during adenosine infusion in patients with normal myocardial perfusion imaging

Background. The development of ST-segment depression during adenosine myocardial perfusion imaging (MPI) has been shown to be an independent predictor of subsequent cardiac events and worse outcome, particularly in association with ischemic defects. However, the prognostic significance of ST-segment depression with adenosine in patients with normal MPI is not known. Methods and Results. We performed a retrospective analysis of 3231 patients undergoing adenosine MPI. Patients with baseline electrocardiographic (ECG) abnormalities were excluded. Overall, 228 patients (7%) had ischemic ECG changes develop during adenosine infusion. Of these, 66 (29% [2% of all patients]) had normal MPI (+ECG group). An age- and sex-matched group of 200 patients with normal MPI without ECG changes served as control subjects (-ECG group). During a mean follow-up of 29 -h 12 months, patients in the +ECG group had significantly more adverse cardiac events than those in the -ECG group (nonfatal myocardial infarction, 7.6% vs 0.5%, respectively, P = .004; subsequent revascularization, 13.6% vs 2.5%, respectively, P = .0015). Although cardiac death alone did not differ between the 2 groups (+ECG, 3.0%, vs -ECG, 1.0%; P = .25), cumulative survival free from cardiac death and nonfatal myocardial infarction was worse in patients with ST-segment depression during adenosine infusion and normal MPI (+ECG, 10.6%, vs -ECG, 1.5%; log-rank chi(2) = 11.82; P = .0006). Conclusions. Patients with normal myocardial perfusion images in whom ST-segment depression develops during adenosine administration appear to be at increased risk for future cardiac events compared with similar patients without ECG evidence of ischemia. Ischemic ECG changes during adenosine MPI should warrant further evaluation, even when perfusion images are reassuring.