Predicting the Local Onset of Alternans in the Heart

Abstract

Beat-to-beat variations in cardiac action potential durations (APD) are a phenomenon known as alternans. Alternans has been linked to ventricular fibrillation, and thus predicting the onset of alternans can be clinically beneficial. Theoretically, the slope of a restitution curve, i.e. the dependence of the APD on preceding diastolic intervals should predict the onset of alternans. Nevertheless, many studies have reported varying slope values at the onset of alternans leaving this hypothesis unconfirmed. Recently, the restitution portrait, which measures several restitution curves simultaneously, predicted the onset of alternans in isolated myocytes. However, the behavior of the whole heart is temporally and spatially more complex, and it is unclear whether the restitution portrait can predict the onset of alternans in the heart. The aim of this project was twofold. The first aim was to develop a user-friendly software to analyze the correlation between alternans formation and the restitution properties of optically mapped tissue. A three tier program, named OptiMAP, was developed in PV-WAVE. The first tier allowed for averaging, filtering, and map construction of cardiac action potential responses from optical mapping movies. The second tier reviews the results from the first and allows for final data refinement and omitting of outliers. Lastly, the third tier analyzes the correlation of the initial onset of alternans and the restitution properties of the tissue in question. The second aim was to use OptiMAP to investigate the spatiotemporal formation of alternans in isolated rabbit hearts and to determine whether the restitution portrait slopes could predict the initial, spatially local onset of alternans. Optical mapping was used in juncture with a voltage-sensitive dye to visualize the onset of alternans. All rabbit experiment data were analyzed using OptiMAP to investigate the evolution of restitution slope values over different pacing frequencies until the onset of alternans. Slope values were averaged separately between two spatial regions of the heart that did or did not exhibit alternans. It was demonstrated that the restitution portrait slope, accurately predicted the local onset of alternans in the heart, although its value was significantly different from the theoretically predicted value of one.