Rick Schreurs

11 General introduction pressures. Implantable cardioverter defibrillators (ICD) are indicated in patients with reduced LV ejection fraction or life-threatening arrhythmias to prevent sudden cardiac death. In therapy resistant end-stage heart failure left ventricular assist devices or heart transplantation should be considered [6]. Cardiac resynchronization therapy Patients with electrical conduction disorders may also benefit from cardiac resynchronization therapy (CRT) using biventricular pacemakers [8-10]. CRT is a pacemaker therapy that aims to correct the dyssynchronous electrical activation and consequently improve cardiac pump function. CRT emerged during the 1990s and became FDA approved in 2001. Generally, CRT is performed through simultaneous (biventricular) pacing of both ventricles by one pacemaker lead in the RV apex and one lead in an epicardial vein on the posterolateral wall of the LV, accompanied by a RA lead to sense or pace atrial electrical activation [11]. CRT has proven to be more successful than pharmacological treatment, especially in patients with reduced LV ejection (<35%) and LBBB with increased QRS duration (>130ms). It acutely improves cardiac output and LV systolic pressure [12] and at the long term leads to reverse remodeling (reduction of ventricular dimensions) and increased LV ejection fraction [13]. Patients benefit through decreased mortality and hospitalization rate and an increase in quality of life [14]. Indications for CRT According to the guidelines of the European Society of Cardiologists, CRT is currently recommended for symptomatic heart failure patients with a QRS duration ≥130ms and LBBB morphology on the electrocardiogram and with LV ejection fraction ≤35% despite optimal medical therapy [6, 8]. In patients with non-LBBB morphology it should be considered when QRS duration ≥150ms and may be considered in QRS 130-149ms. Furthermore, CRT is recommended over RV-only pacing in patients with heart failure with reduced ejection fraction who have an indication for ventricular pacing due to a high degree AV block. Patients with reduced ejection fraction who clinically worsen after initiating RV- only pacing may be considered for an upgrade to CRT [6]. The abovementioned indications of CRT focus on reducing interventricular dyssynchrony. Interesting, a few years before CRT merged, a few small studies indicated that also patients with heart failure and a prolonged PR-interval (first-degree AV-block) suggested significant functional and symptomatic improvement with restored AV coupling [15-17]. In this case RV pacing was used to normalize AV-delay and to restore AV coupling. With the rise of CRT, this possible application of pacemaker therapy lost attention, until a few years ago sub-analyses of clinical trials investigating the benefit of CRT revitalized the interest in this topic [18]. In sub-studies of the MADIT-CRT and COMPANION trial, only non-LBBB patients with prolonged PR-interval showed a significant clinical improvement to CRT, which was not present in non-LBBB patients with normal AV conduction [19, 20]. A sub-study of the ReThinQ trial investigated the benefit of CRT in patients with QRS duration <130ms, and 1