Cardiac Resynchronization Therapy - Refocus on the Electrical Substrate -

Abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp s its name suggests, cardiac resynchronization therapy (CRT) aims to treat the electrical substrate in symptomatic heart failure (HF) patients with reduced LV ejection fraction (EF) and wide QRS complex. A recent metaanalysis pooled more than 3,000 CRT patients from 6 trials and reported a reduction in all-cause mortality of 29% and a reduction in the number of new hospitalizations for worsening HF of 37%. 1 Nevertheless, a QRS duration >120 ms has proven to be a moderate predictor of CRT efficacy, as 30-50% of implanted patients do not respond to the therapy. This has sparked major efforts into identifying patients who benefit from CRT by investigating mechanical dyssynchrony. However, the relatively slow improvement in CRT efficacy in recent years has renewed interest in the electrical substrate. It has become increasingly clear that left bundle branch block (LBBB) is the hallmark conduction disease that is treatable by CRT, as evidenced by efficacy of CRT in canine hearts with isolated LBBB and in CRT patients with LBBB compared to CRT patients with other conduction disorders. 2, 3 In this review we will explore current knowledge concerning the electrical substrate in CRT candidates and apply this to current CRT practice. We will then discuss why the electrical substrate is both essential and sufficient for successful CRT. We will show that this is true if the electrical substrate is defined more accurately than just by duration of the QRS complex. LBBBA century has passed since Eppinger and Tothberger first described LBBB by associating distinctive electrophysiological changes with the destruction of only a small region in the interventricular septum in the canine heart. 4 The typical QRSmorphology changes seen in the esophageal-to-rectal lead in the dogs were directly extrapolated to leads II and III in human patients. This misinterpretation caused LBBB to be erroneously diagnosed as right bundle branch block (RBBB) and vice versa in the first quarter of the past century.It was only until decades after the rectification that the anatomy of the left bundle branch (LBB) and the significance of its dysfunction were investigated in detail. In 1972, Demoulin et al reported their histopathological findings in human patients without known cardiac disease, showing that the LBB emerges from the His bundle between the non-coronary and right-coronary aortic cusps and runs as a 6-10-mm wide ribbon-like structure inferiorly and slightly anteriorly over the septal subendocardium. 5 With considerable variation, the fibers of the LBB quickly separate to form fasciculi in anterior, posterior and often septal main radiations (Figure 1). The LBB enables fast activation of the left ventricle (LV) because it ends in a rich peripheral Purkinje network that couples with individual (sub)endocardial myocardial cells. 6 Extensive electrical mapping in isolated human hearts with an intact LBB showed up to 3 LV endocardial breakthrough si...

Why QRS Duration Should Be Replaced by Better Measures of Electrical Activation to Improve Patient Selection for Cardiac Resynchronization Therapy

“…Endocardial non-contact mapping has also identified two different patterns of electrical wave front propagation in the LV of these patients. The first entity, observed in approximately two thirds of patients, is characterized by a U-shaped pattern of activation that turns around the LV apex and inferior wall in order to activate the lateral wall [ 39 , 41 , 43 ], which is similar to the activation pattern that has been observed during endocardial non-contact mapping in canine hearts where proximal ablation of the left bundle-branch has been performed [ 44 ]. The second entity is characterized by homogeneous propagation of electrical activation throughout the left ventricle [ 41 , 43 ].…”

Electrical and Mechanical Ventricular Activation During Left Bundle Branch Block and Resynchronization

“…5Typical examples of 3D electrical activation in canine hearts with chronic LBBB and transmural myocardial infarction during CRT with epicardial LV pacing ( left panel ) and endocardial LV pacing ( right panel ). Reproduced with permission [1]…”

“…Large clinical trials have shown that CRT benefits most patients but approximately one third of patients to not show clinical or echocardiographic response. Furthermore, further analysis of these studies show that the amount of responders was considerably higher in patients with LBBB as compared with patients without this conduction disease [1]. These aspects have revamped major interest in LBBB.…”

Animal Models of Dyssynchrony

“…In healthy canine hearts, isolated LBBB induces electrical and mechanical dyssynchrony that eventually will lead to loss of LV pump function and ventricular remodeling. In these hearts, CRT largely reversed global and regional function and structural abnormalities, indicating that LBBB as electrical substrate is sufficient for acute and long-term response to CRT [39]. Recently, multiple clinical trials have indeed shown high CRT efficacy in heart failure patients who were not severely symptomatic (NYHA class I and II) [2, 40–43].…”