Abstract 3840: In Patients With Coronary Artery Disease, DPP-4 Inhibition Improves the Myocardial Response to Dobutamine Stress and Mitigates Stunning
Introduction Glucagon-like peptide-1 (GLP-1) has been shown to promote the uptake of glucose by the myocardium. The degradation of the active amide GLP-1 (7–36) by the enzyme DPP-4 is inhibited by sitagliptin. We assessed the hypothesis that sitagliptin would protect the heart from ischemic left ventricular (LV) dysfunction during dobutamine stress echocardiography (DSE) in patients with stable angina and coronary artery disease.
Methods Fourteen patients (age 64±7 yrs) with coronary artery disease and good LV function awaiting elective revascularisation were studied. Two DSE scans were conducted in a randomised order following the oral intake of 75g glucose to promote GLP-1 secretion. Patients received a single dose of sitagliptin 100mg two hours prior to oral glucose before one of the scans and the other acted as a control. Blood samples were taken for glucose, insulin and GLP-1 (7–36). Tissue Doppler imaging was acquired in three apical views at rest, peak stress and 30 minutes into recovery. Myocardial segments considered to be ischemic were assigned to the perfusion territories of vessels with >50% stenoses.
Results There was no difference in the rate pressure products between the sitagliptin and control scans (19448±3229 vs 19855±3761; p=0.54). Sitagliptin inhibited DPP-4 resulting in a higher plasma level of GLP-1 (7–36) than control at peak stress (16.5±10.7 vs 9.7±8.7 pg/ml; p=0.003) and in recovery (12.4±5.5 vs 9.0±5.5 pg/ml; p=0.01). Global and regional wall LV function were increased by sitagliptin at peak stress and in recovery compared to control (Table⇓). The improvement in function at peak stress was greater in ischemic (Vs: 9.81±4.27 vs 8.79±3.95 cm/s; p=0.007) than non-ischemic segments (Vs: 11.52±4.82 vs 11.22±4.55 cm/s; p=0.11).
Conclusion The inhibition of DPP-4 augmented plasma levels of GLP-1 (7–36) which improved global and regional wall LV function during dobutamine stress and mitigated post ischemic stunning in the recovery period.