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.
The influence of each ischemic component (hypoxia, hyperkalemia, and acidosis) on arrhythmogenesis is controversial and difficult to study experimentally. In the present study, we investigate how the different ischemic components affect the vulnerable window (VW) for reentry using computational simulations. Simulations were performed in a 3D biventricular model that includes a realistic ischemic region and the His-Purkinje conduction system. At the cellular level, we used a modified version of the O'Hara action potential model adapted to simulate acute ischemia. Three different levels of ischemia were simulated: mild, moderate, and severe. The effects on the width of the VW of each ischemic parameter were analyzed. The model allowed us to obtain a realistic reentrant pattern corresponding to ventricular tachycardia in all simulations. Results suggest that the ischemic level plays an important role in the generation of reentries. Furthermore, hypoxia has the most significant effect on the width of the VW. The presence of Purkinje system is key to the generation of reentries.
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