This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Heart failure is a major cause of morbidity/mortality and affects nearly 5 million people in the United States. Cardiac resynchronization therapy (CRT) has great potential clinical benefit for a number of these patients, but application is limited by difficulty identifying appropriate patients and technical limitations regarding left ventricular lead placement. This project applies a novel cardiac magnetic resonance (CMR) pulse sequence for strain known as cine DENSE (displacement encoding with stimulated echoes) to the evaluation of patients undergoing CRT. Of note, cine DENSE has been largely developed here at the University of Virginia and, as shown in the preliminary data, yields very high quality regional strain data even in patients with dilated and thinned left ventricles. In this study, we will test the hypothesis that CMR with DENSE assessment of circumferential mechanical dyssynchrony and scar imaging is significantly more accurate than echocardiography in predicting CRT response, with nonresponse the likely result when the left ventricular lead is positioned in or near significant scar. The specific aims are: 1) to assess the clinical use of CMR-based evaluation of mechanical dyssynchrony using cine DENSE for accurate prediction of CRT response, as measured by standard response indices;and 2) to establish the optimal relationship between left ventricular lead position and the underlying myocardial substrate using CMR scar imaging and three-dimensional scar maps. To address these aims, we are performing a prospective study with baseline clinical assessment, cardiac imaging, cardiopulmonary exercise testing, and neurohormonal assessment, followed by the clinical CRT procedure. These baseline assessments will then be repeated 6 months after CRT, with long-term 3-year follow-up. Statistical methods used in the data analysis will include Fisher's exact test, McNemar's test, logistic regression, and survival analysis. We believe the findings of this work will be of major public health importance to many patients with heart failure.