New methods for quantifying the synchrony of contraction and relaxation in the heart

Synchronous contraction and relaxation of the myocardium is required to optimize cardiac function. Regional timing of contraction and relaxation is dyssynchronous in many patients with heart failure. Cardiac resynchronization therapy (CRT) is a highly successful treatment for dyssynchronous heart failure. Patients are currently selected for CRT using surface electrocardiogram QRS duration as a measure of dyssynchrony. However, up to 30% of patients selected for CRT show no improvement. This poor response rate may in part be explained by the poor correlation between mechanical dyssynchrony and QRS duration. Thus, better methods to quantify mechanical dyssynchrony in the heart may improve the poor CRT response rate. The overall goal of this project was to develop better methods to diagnose dyssynchrony in the left ventricle (LV). We developed two new methods with different approaches. The first method improved upon existing tissue-Doppler based echocardiographic diagnosis of dyssynchrony by utilizing a cross-correlation (XC) function to quantify dyssynchrony during post-processing as opposed to the quantitatively simplistic time-to-peak analysis that is currently utilized. The second method utilized standard cine cardiac magnetic resonance (CMR) images to quantify the dyssynchrony in the flow of blood within the LV, which may represent a more direct, physiologically relevant measure of dyssynchrony. Specific aim 1 demonstrated that the new XC delay parameters can be quantified accurately with a stationary region of interest and therefore require significantly less post-processing time to calculate compared to the time-to-peak dyssynchrony parameters. Specific aim 2 showed that XC delays are superior to existing time-to-peak dyssynchrony parameters at discriminating patients with LV dyssynchrony from those with normal function. The time-to-peak parameters showed dyssynchrony in approximately half of the normal, healthy volunteers while the XC delay parameters had nearly perfect diagnostic accuracy. The results of specific aim 3 showed that XC delays could diagnose acute, pacing-induced dyssynchrony in young, healthy children with 79% accuracy while the time-to-peak parameters showed accuracies of 71%, 57% and 57%. Specific aim 4 showed that CMR-based quantification of LV internal flow can be used to discriminate patients with dyssynchronous heart failure from normal controls with 95% accuracy.Ph.D