Abstract
Patients suffering from heart failure and left bundle branch block show electrical ventricular dyssynchrony causing an abnormal blood pumping. Cardiac resynchronization therapy (CRT) is recommended for these patients. Patients with positive therapy response normally present QRS shortening and an increased left ventricle (LV) ejection fraction. However, around one third do not respond favorably. Therefore, optimal location of pacing leads, timing delays between leads and/or choosing related biomarkers is crucial to achieve the best possible degree of ventricular synchrony during CRT application. In this study, computational modeling is used to predict the optimal location and delay of pacing leads to improve CRT response. We use a 3D electrophysiological computational model of the heart and torso to get insight into the changes in the activation patterns obtained when the heart is paced from different regions and for different atrioventricular and interventricular delays. The model represents a heart with left bundle branch block and heart failure, and allows a detailed and accurate analysis of the electrical changes observed simultaneously in the myocardium and in the QRS complex computed in the precordial leads. Computational simulations were performed using a modified version of the O'Hara et al. action potential model, the most recent mathematical model developed for human ventricular electrophysiology. The optimal location for the pacing leads was determined by QRS maximal reduction. Additionally, the influence of Purkinje system on CRT response was assessed and correlation analysis between several parameters of the QRS was made. Simulation results showed that the right ventricle (RV) upper septum near the outflow tract is an alternative location to the RV apical lead. Furthermore, LV endocardial pacing provided better results as compared to epicardial stimulation. Finally, the time to reach the 90% of the QRS area was a good predictor of the instant at which 90% of the ventricular tissue was activated. Thus, the time to reach the 90% of the QRS area is suggested as an additional index to assess CRT effectiveness to improve biventricular synchrony.
Highlights
Heart failure (HF) constitutes a major public health problem worldwide and much attention has been paid to the understanding of the arrhythmogenic mechanisms in the failing heart induced by the structural, electrical, and metabolic remodeling
Under HF + left bundle branch block (LBBB) conditions, activation began in the right ventricle (RV) endocardium and reached the left ventricle (LV) endocardium in the apical septal region after 46 ms from the onset of the RV depolarization
The major findings of this study can be summarized as follows: (i) the optimal leads location based on shortest QRS criterion was the RV upper septum and the LV mid posterior region minimizing total activation time (TAT); (ii) for the optimal lead location, the delay configuration leading to the shortest QRS duration (QRSd) was atrioventricular delay (AVD) = 140 ms, interventricular delay (VVD) = 30 ms
Summary
Heart failure (HF) constitutes a major public health problem worldwide and much attention has been paid to the understanding of the arrhythmogenic mechanisms in the failing heart induced by the structural, electrical, and metabolic remodeling. Lack of synchrony in heart contraction is worsened when the failing heart is affected by left bundle branch block (LBBB). These patients present electrical and mechanical ventricular dyssynchrony causing pump dysfunction, reduced functional capacity, and myocardial remodeling. LBBB is associated with delayed contraction of the left ventricle (LV), reduced ventricular performance and widening of the QRS complex. Recent studies have concluded that patients with LBBB are more likely to respond to CRT than those with right bundle branch block (RBBB) or nonspecific interventricular conduction delays (IVCDs) (Zareba et al, 2011)
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