An electrocardiographic sign of ischemic preconditioning.
Ischemic preconditioning is a form of intrinsic cardioprotection where an episode of sublethal ischemia protects against subsequent episodes of ischemia. Identifying a clinical biomarker of preconditioning could have important clinical implications, and prior work has focused on the electrocardiographic ST segment. However, the electrophysiology biomarker of preconditioning is increased action potential duration (APD) shortening with subsequent ischemic episodes, and APD shortening should primarily alter the T wave, not the ST segment. We translated findings from simulations to canine to patient models of preconditioning to test the hypothesis that the combination of increased [delta (Δ)] T wave amplitude with decreased ST segment elevation characterizes preconditioning. In simulations, decreased APD caused increased T wave amplitude with minimal ST segment elevation. In contrast, decreased action potential amplitude increased ST segment elevation significantly. In a canine model of preconditioning (9 mongrel dogs undergoing 4 ischemia-reperfusion episodes), ST segment amplitude increased more than T wave amplitude during the first ischemic episode [ΔT/ΔST slope = 0.81, 95% confidence interval (CI) 0.46-1.15]; however, during subsequent ischemic episodes the T wave increased significantly more than the ST segment (ΔT/ΔST slope = 2.43, CI 2.07-2.80) (P < 0.001 for interaction of occlusions 2 vs. 1). A similar result was observed in patients (9 patients undergoing 2 consecutive prolonged occlusions during elective percutaneous coronary intervention), with an increase in slope of ΔT/ΔST of 0.13 (CI -0.15 to 0.42) in the first occlusion to 1.02 (CI 0.31-1.73) in the second occlusion (P = 0.02). This integrated analysis of the T wave and ST segment goes beyond the standard approach to only analyze ST elevation, and detects cellular electrophysiology changes of preconditioning.
Department of Cardiology, Catharina Hospital Eindhoven, The Netherlands;
Loek P B
LP
Meijs
Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, United States Food and Drug Administration, Silver Spring, Maryland;
Loriano
L
Galeotti
University of Zaragoza and CIBER-BBN, Spain;
Esther P
EP
Pueyo
University of Zaragoza and CIBER-BBN, Spain;
Daniel
D
Romero
Duke University Medical Center, Durham, North Carolina;
Robert B
RB
Jennings
Department of Cardiology, Lund University, Lund, Sweden/Center for Integrative Electrocardiology at Lund University, Lund, Sweden/Thoracic Center, Blekingesjukhuset, Karlskrona, Sweden; and.
Michael
M
Ringborn
Charleston Area Medical Center, Charleston, West Virginia.
Stafford G
SG
Warren
Duke University Medical Center, Durham, North Carolina;
Galen S
GS
Wagner
Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, United States Food and Drug Administration, Silver Spring, Maryland; david.strauss@fda.hhs.gov.
David G
DG
Strauss
D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D004285:Dogs; D004562:Electrocardiography / Q000379:methods*; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008955:Models, Cardiovascular; D015428:Myocardial Reperfusion Injury / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
acute myocardial infarction; electrocardiology; electrophysiology; quantitative modeling