Abnormal heart rate response to adenosine infusion is associated with silent myocardial ischemia in asymptomatic patients with diabetes mellitus

Abstract

Background: Many patients with type 2 Diabetes Mellitus (T2DM) have cardiac autonomic neuropathy (CAN), which has been associated with poor outcome. CAN is also associated with blunted heart rate response (HRR) to dipyridamole infusion. Furthermore in the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study CAN was associated with moderate and large myocardial perfusion defects. Therefore, we hypothesized that blunted HRR during adenosine infusion is associated with myocardial perfusion abnormalities and silent myocardial ischemia. Methods: 442 asymptomatic patients with T2DM, without known coronary artery disease who were enrolled in DIAD study, had quantitative adenosine-Tc-99m-Sestamibi SPECT imaging. Heart rate response to adenosine infusion was assessed as the ratio between baseline HR and HR at end of adenosine infusion. Myocardial perfusion defects were quantified and categorized as small, moderate and large. Results: Mean age of patients was 60.5± 6.8 years; females 47%; males 53%; T2DM duration 8.1 ± 7.1 years. 7% of the patients had either moderate or large perfusion abnormalities. Patients in the lowest decile of HRR (< 1.10), the cut point used to define an abnormal response, were more likely to have moderate or large perfusion abnormalities (OR=3.0, 95% CI 1.2, 7.0; p = .01). The sensitivity of lower HRR to predict moderate to large myocardial perfusion defects was 24% and specificity was 90%. The negative predictive value was 94%. Conclusion: In asymptomatic patients with T2DM a blunted HRR to adenosine infusion is a simple marker with high negative predictive value and high specificity for moderate and large silent myocardial ischemia.