QT Dynamics and Variability Wojciech Zareba, M.D., Ph.D. ∗ and Antoni Bayes de Luna, M.D.† From ∗ The Heart Research Follow-up Program, Cardiology Unit, University of Rochester Medical Center, Rochester, NY, and †Cardiology Unit, Autonomous University of Barcelona, Barcelona, Spain Repolarization dynamics and variability are of increasing interest as Holter-derived parameters re- flecting changes in myocardial vulnerability and contributing to increased risk of arrhythmic events and sudden death. Repolarization dynamics is usually defined as phenomenon describing and quan- tifying QT adaptation to changing heart rate. The analysis of QT–R-R slopes in long ECG recordings is one of the ways to evaluate repolarization dynamics. Increased QT–R-R slopes are frequently ob- served in patients at risk for cardiac death and arrhythmic events: postinfarction patients, long QT syndrome patients, patients with nonischemic cardiomyopathy as well as in patients taking drugs affecting repolarization. QT variability reflects beat-to-beat changes in repolarization duration and morphology and such changes can be quantified using a number of algorithms currently in various phases of development and validation. Increased QT variability is observed in several conditions with increased risk of arrhythmias. Recent data from MADIT II indicate that increased QT variability is a powerful predictor of arrhythmic events in postinfarction patients with left ventricular dysfunction. More studies are needed to determine further the potential clinical usefulness for diagnosing patients and for risk stratification purposes using both QT dynamics and QT variability methods, and compare these methods with exercise-induced T wave alternans. A.N.E. 2005;10(2):256–262 QT dynamics; QT variability; repolarization; risk stratification The QT interval measured in the ECG is a repre- sentation of global repolarization duration in the ventricular myocardium. Repolarization is a com- plex electrical process governed by a multitude of transmembrane ion currents having different tim- ing, distinct kinetics, and operating in different lay- ers of myocardium. Last decade witnessed major breakthrough in understanding of electrophysiolog- ical background of repolarization process, mainly due to identification of genes for the long QT syn- drome. 1 Various genetic forms of LQTS revealed in- volvement of the ion currents in repolarization pro- cess: I Ks potassium current and min-K component of this current, I Kr potassium current and MiRP1 component of this current, and SCN5A sodium cur- rent. Function of these channels is heart rate de- pendent and therefore, repolarization as a whole process is also heart rate dependent. Heart rate dependency of repolarization process represents a form of repolarization dynamics ap- preciated already in 1920s by several researchers including Bazett 2 and Fridericia 3 who described the QT–R-R relationship and established heart rate cor- Address for reprints: Wojciech Zareba, M.D., Ph.D., Heart Research Follow-up Program, University of Rochester Medical Center, Box 653 Rochester, NY 14642. Fax: (585) 273-5283; E-mail: wojciech zareba@urmc.rochester.edu rection formulae that are in use to date. Dynamic behavior of repolarization might also be manifested by beat-to-beat changes in repolarization duration and morphology. T wave alternans, described for the first time nearly a 100 years ago, 4 is the prime example of repolarization dynamics and in its mi- crovolt form is being increasingly used as a risk marker of arrhythmic events. 5–7 The 2:1 behavior of repolarization changes, typical for T wave alter- nans, is rarely observed at heart rates below 90–100 bpm. However, non-2:1 changes in repolarization morphology and duration are observed more of- ten and this so-called repolarization variability (also known as QT variability or T wave lability), is con- sidered as yet another emerging marker of cardiac events. 8–10 QT–R-R relationship and QT variability are de- scribed in this review together, because they seem to represent somewhat related phenomena reflect- ing increased vulnerability of myocardium. In- creased vulnerability of myocardium together with altered myocardial substrate and changes in au- tonomic control of the heart constitute conditions 256