Clinical aspects of cardiac resynchronization therapy

This thesis addresses clinical aspects of cardiac resynchronization therapy (CRT). Prediction and assessment of (volumetric) response were investigated as well as clinical outcome. We analyzed the additional value of echocardiographic parameters of mechanical dyssynchrony as predictors of CRT response besides the generally used electrocardiographic parameters like left bundle branch block (LBBB) and QRS duration and assessed whether latest electrically activated segments also start contracting the latest. Furthermore, we evaluated whether echocardiographic response is accompanied by improved health status and exercise capacity. We also explored whether echocardiographic volumetric response differs at different points in time (i.e. after six and 14 months), and which parameter is best to use as a surrogate outcome marker. Furthermore, it was investigated whether these predictors and surrogate outcome measures are equally applicable for patients with ischemic and non-ischemic cardiomyopathy (ICM and NICM, respectively). Chapter 3 describes the additional value of echocardiographic parameters of mechanical dyssynchrony concerning the prediction of reverse remodeling. Two models, with and without echocardiographic parameters of mechanical dyssynchrony, were tested in a CRT population on their capacity to predict reverse remodeling 6 months after device implantation. In addition, model performance was tested separately for patients with non-ischemic cardiomyopathy and ischemic cardiomyopathy. In chapter 4 we evaluate whether electrically latest activated regions of the LV are also latest mechanically activated as both electrical delays and mechanical delays have been used in previous studies to guide LV lead positioning. To assess electrical activation delays electrical mappings were performed in the coronary sinus and its large side branches. Mechanical activation delays were evaluated by 2D speckle tracking analyses and time to peak strain was assessed. Definition of response is still under debate. In chapter 5 several surrogate markers of CRT response, among them change in LVESV, are investigated and their relationship to long-term outcome is assessed. In addition, we evaluate whether these surrogate outcome measures are equally appropriate for patients with ischemic and non-ischemic cardiomyopathy. In chapter 6 we evaluate whether echocardiographic responders also show significant improved exercise capacity six months after CRT implantation. All included patients performed an exercise test pre- and 6 months post implantation and echocardiographic studies were performed at the same time points. In chapter 7 we investigate whether echocardiographic responders are also health status responders after 6 months of CRT. We defined health status response by the Kansas City Cardiomyopathy Questionnaire (KCCQ), which is a self-report questionnaire that has been validated and shown to be sensitive to clinical change in HF patients. [52] Echocardiographic response was defined as LVESV decrease of at least 15 %. In chapter 8 we measure echocardiographic response, by LVESV decrease, at 6 and 14 months after device implantation and assess which percentage of patients show a cross-over to another response group (either from non- to responder or the other way around) between 6 and 14 months, focusing on patients being responder at 6 months and nonresponder at 14 months. Furthermore, we assess whether response rates at either six or 14 months better correspond to long-term health outcomes.