Usefulness of Blunted Heart Rate Reserve as an Imaging-Independent Prognostic Predictor During Dipyridamole Stress Echocardiography

Abstract

A blunted heart rate (HR) response during dipyridamole myocardial perfusion imaging has been associated with a poor outcome. To assess the value of HR response in patients who underwent high-dose dipyridamole stress echocardiography (SE), we retrospectively selected a sample of 3,059 patients (none with pacemakers or atrial fibrillation; mean age 66 ± 11 years). All underwent high-dose (0.84 mg/kg) dipyridamole SE for evaluation of known or suspected coronary artery disease and/or heart failure in 2 laboratories of Pisa-IFC and Lucca. HR (with 12-lead ECG) was obtained each minute and recorded at rest and peak stress. HR reserve (HRR) was calculated as the peak/rest HR ratio. All patients were followed up. Patients were randomly divided into the modeling and validation group of equal size. During a median follow-up time of 1,004 days, 321 hard events occurred: 231 deaths and 90 nonfatal myocardial infarctions. HRR ≤ 1.22 identified by receiver operating characteristic analysis in the modeling group was an independent predictor of infarction-free survival in the modeling (hazard ratio 1.83, 95% confidence interval [CI] 1.30 to 2.60, p = 0.001), in the validation (hazard ratio 1.47, 95% CI 1.08 to 2.01, p = 0.02), and in the overall group (hazard ratio 1.60, 95% CI 1.27 to 2.02, p <0.0001), either off- or on-β blockers. Five-year event rate increased from 8% to 24 % from the highest (≥1.41) to the lowest (≤1.14) HRR quartile. In conclusion, blunted HRR is a useful nonimaging predictor of adverse events during high-dose dipyridamole SE, independent of inducible ischemia, and beta-blocker therapy.