Cardiac resynchronization therapy: refinements in patient selection and technology

Abstract

More than twenty years of research has established the role of cardiac resynchronization therapy (CRT) in patients with medically refractory systolic heart failure with abnormal QRS complex morphology and duration. In this patient population, CRT bestows a mortality benefit, a reduction in heart failure hospitalizations and an improved functional status. The first CRT implantation took place back in March 1993 in the University Medical Center of Utrecht. Its introduction has been no less than revolutionary for patients with advanced heart failure whose only previous option was cardiac transplantation. Nowadays CRT is also a realistic and cost-effective treatment option for patients with mild heart failure. One could probably say that CRT has been one of the most exciting recent advancements in heart failure treatment. Despite that CRT has become one of the pillars of heart failure management, it continues to face a relatively high non-responder rate of 30-40%, depending on the definition for non-response used. Accordingly, there is still room for improvement of the therapy. The determination to increase CRT response rates is the inspiration of all the scientific research performed worldwide to improve the therapy. By taking advantage of some of the latest developments in device technology, cardiac imaging, and electrophysiology, this dissertation addresses several treatment-refinement strategies aimed to improve response to CRT. Roughly these can be divided into strategies to i) improve patient selection, ii) improve CRT delivery, and to iii) optimize CRT configurations. In the first part of this dissertation, the electromechanical substrate amendable by CRT is addressed. In doing so, several electrical (obtained with vectorcardiography) and mechanical (obtained with echocardiographic strain imaging) parameters are proposed which may be used for the improvement of patient selection in clinical practice. After selection of the right patient for CRT, a next key step for ensuring the best possible patient outcome is optimization of the CRT implantation procedure. Placing the left ventricular (LV) lead at an optimal position is one of the most challenging technical aspects of a CRT device implantation. Improving and facilitating CRT delivery, therefore, is the next strategy evaluated for the refinement of CRT in this dissertation. After LV lead placement, multiple device settings are programmable to increase the effect of CRT. The third and final part of this dissertation, therefore, examines optimization of device programming using pressure-volume loop analyses and evaluates the role of multipoint pacing over conventional biventricular pacing in patients with a strict left bundle branch block. By addressing these strategies, this thesis aims to provide more insight into the possibilities to better diagnose and treat patients with dyssynchronous heart failure.