Page 14 - Simplicity is Key in CRT

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CRT aims at reducing the dyssynchrony of the left ventricle by biventricular pacing [8]. The biventricular pacemaker typically uses leads in the right atrium, right ventricular (RV) apex and left ventricular (LV) postero-lateral epicardium. Atrial sensing triggers a sequence of pre-set delays and activations resulting in electrical stimulation at the LV and RV pacing electrodes, leading to a synchronous activation and coordinate contraction of the myocardium.
The very first observation of the benefit of biventricular pacing comes from the early ‘70s, when Gibson et al compared the behaviour of implanted aortic valve prostheses during RV, LV and biventricular pacing [12]. Since the 1990’s CRT has been shown to improve cardiac pump function in terms of LV systolic pressure build up and stroke volume [9]. On the long-term, reverse remodelling (reduction of the increased LV dimensions) has been observed as well as an increase in LVEF, which continues to increase even years after implantation of the device [10]. In terms of patient benefit, CRT leads to pronounced increase in quality of life, and reduction of HF hospitalizations and mortality [11].
Patient selection in CRT
The very first studies on CRT already used a wide QRS complex on the 12-lead electrocardiogram (ECG) as selection criterion [13]. Soon after the establishment of CRT as an HF therapy, studies showed increased QRS duration to be associated with outcome in CRT [15]. Subsequent studies showed the association of ECG markers of specific types of ventricular conduction delay (QRS morphology) with outcome of CRT. Especially differentiation between left bundle branch block (LBBB), right bundle branch block (RBBB), and non-specific intraventricular conduction delay (IVCD) seems relevant. While LBBB is consistently associated with the presence of delayed LV lateral wall activation, this is much less the case for RBBB and IVCD [16]. In substudies of the landmark CRT trials, an LBBB morphology was shown to be associated with significantly more benefit from CRT than other QRS morphologies [17-20]. Based on the aforementioned findings, QRS duration and QRS morphology are currently guideline recommended markers of the presence of dyssynchrony [1, 21].
The role of LBBB as an ECG marker has changed considerably over time. Initially, it was described as an (innocent) electrocardiographical phenomenon. Later LBBB was described as a marker of worse prognosis in heart failure. Only recently, since the demonstration of structural remodelling in canine LBBB models [22] and its reversal by CRT [23], LBBB is regarded as a possible cause of the development of heart failure. Strikingly and most important for research presented later in this thesis, there are multiple definitions of LBBB, each using their own criteria derived from the ECG. Most of these definitions of LBBB consist of elaborate and complex morphological features, which are highly sensitive to subjective interpretation.
In order to improve patient selection for CRT, many other parameters that can be deducted from the 12-lead ECG like QRS axis, QRS fragmentation and left ventricular activation time (LVAT), have been evaluated [24-26]. More recently, the development of ECG-imaging has made is possible to more precisely determine the ventricular activation pattern [27]. In addition, assessment of mechanical dyssynchrony using imaging techniques like echocardiography [28] and cardiac magnetic resonance imaging (CMR) [29] have been employed. However, none of the abovementioned parameters have made it to clinical practice, primarily because these analysis and techniques are more complicated and therefore less robust in clinical practice.