KSEF RDE: Co-occurrence of Depolarization Alternans in T Wave Alternans Positive ECGs

There is a need for better non-invasive tools for predicting the odds of lethal ventricular arrhythmic events in an individual. Several predictors have been and continue to be investigated, notably; ejection fraction, heart rate variability and turbulence, and T wave alternans (TWA). While much effort has been and continues to be devoted to this problem, none of the currently available tools work very well. Among those available, TWA (which is measured as micro-volt TWA) appears to be the most promising predictor. Large clinical studies have shown TWA to have high negative predictive value but with a modest positive predictive value. A key reason hindering this development is that the causal mechanisms of these types of ventricular arrhythmia are not clearly understood. Our working hypothesis is that TWA has poor specificity because it only includes repolarization dynamics of cardiac myocytes. We have recently reported that alternans in the depolarization phase of action potentials during repolarization alternans plays a critical role in stability of activation. Mathematical models show that these alternans lead to alternans of the R wave amplitude in the ECG. A link between amplitude alternans and arrhythmia has also been recently reported by another group. These independent studies support the hypothesis that inclusion of information from depolarization dynamics is likely to advance our understanding of the mechanisms that underlie this complex phenomenon, these advances will ultimately lead to better clinical predictors. Our aim in the proposed study is to collect preliminary data in support of a subsequent larger study. Specifically, in the proposed study we will i) develop and refine algorithms to simultaneously quantify R wave amplitude alternans and TWA, and ii) determine the incidence of co-existence of depolarization (i.e. R wave amplitude) and repolarization (i.e. TWA) alternans in a population of patients at higher risk for developing arrhythmic events.