Identifying coronary artery flow reduction and ischemia using quasistationary QT/RR-interval hysteresis measurements

Because myocardial ischemia induces QT/RR hysteresis, a correlation was hypothesized to exist between the extent of myocardial flow reduction and the magnitude of QT/RR hysteresis. Graded reductions in regional myocardial perfusion in the distribution of the left anterior descending coronary artery in open-chest pigs were used to model 1-vessel coronary artery disease. At each reduced level of left anterior descending coronary artery flow, the heart was electrically paced at progressively higher and lower rates between an initial control and maximum heart rate values. Digitized surface and intramyocardial electrograms and aortic pressure were used to measure QT/RR hysteresis, QT-interval adaptation, ST- and TQ-segment depression, and cardiac contractility. Intraexperimental blood samples were analyzed to assess inflammatory response (interleukin 6), oxidative stress (protein carbonyls), and myocyte injury (creatine kinase). Higher values of QT/RR hysteresis correlated with the severity of ischemia as assessed by TQ-segment depression in intramyocardial electrograms (P = .002). Lower flow rates were strongly associated with higher values of QT/RR hysteresis and slower QT-interval adaptation (P or= .02). Significant increases in systemic measures of inflammation, oxidative stress, and cardiac myocyte injury and major decrease in cardiac contractility preceded the most severe stages of flow reduction (30% and 20% of normal flow). We determined QT/RR hysteresis index thresholds corresponding to these mechanical and immunochemical responses. QT/RR hysteresis is a strong indicator of reduced myocardial perfusion and may provide information for noninvasive assessment of mechanical and immunochemical changes associated with early stages of coronary artery disease.