Cardiac resynchronization: insight from experimental and computational models.

Cardiac resynchronization therapy (CRT) is a promising therapy for heart failure patients with a conduction disturbance, such as left bundle branch block. The aim of CRT is to resynchronize contraction between and within ventricles. However, about 30% of patients do not respond to this therapy. Therefore, a better understanding is needed for the relation between electrical and mechanical activation. In this paper, we focus on to what extent animal experiments and mathematical models can help in order to understand the pathophysiology of asynchrony to further improve CRT.

Electromechanics of paced left ventricle simulated by straightforward mathematical model: comparison with experiments.

Intraventricular synchrony of cardiac activation is important for efficient pump function. Ventricular pacing restores the beating frequency but induces more asynchronous depolarization and more inhomogeneous contraction than in the normal heart. We investigated whether the increased inhomogeneity in the left ventricle can be described by a relatively simple mathematical model of cardiac electromechanics, containing normal mechanical and impulse conduction properties. Simulations of a normal heartbeat and of pacing at the right ventricular apex (RVA) were performed. All properties in the two simulations were equal, except for the depolarization sequence. Simulation results of RVA pacing on local depolarization time and systolic midwall circumferential strain were compared with those measured in dogs, using an epicardial sock electrode and MRI tagging, respectively. We used the same methods for data processing for simulation and experiment. Model and experiment agreed in the following aspects. 1) Ventricular pacing decreased systolic pressure and ejection fraction relative to natural sinus rhythm. 2) Shortening during ejection and stroke work declined in early depolarized regions and increased in late depolarized regions. 3) The relation between epicardial depolarization time and systolic midwall circumferential strain was linear and similar for the simulation (slope = -3.80 +/- 0.28 s(-1), R2 = 0.87) and the experiments [slopes for 3 animals -2.62 +/- 0.43 s(-1) (R2 = 0.59), -2.97 +/- 0.38 s(-1) (R2 = 0.69), and -4.44 +/- 0.51 s(-1) (R2 = 0.76)]. We conclude that our model of electromechanics is suitable to simulate ventricular pacing and that the apparently complex events observed during pacing are caused by well-known basic physiological processes.

Homogeneity of cardiac contraction despite physiological asynchrony of depolarization: a model study.

The use of mathematical models combining wave propagation and wall mechanics may provide new insights in the interpretation of cardiac deformation toward various forms of cardiac pathology. In the present study we investigated whether combining accepted mechanisms on propagation of the depolarization wave, time variant mechanical properties of cardiac tissue after depolarization, and hemodynamic load of the left ventricle (LV) by the aortic impedance in a three-dimensional finite element model results in a physiological pattern of cardiac contraction. We assumed that the delay between depolarization for all myocytes and the onset of crossbridge formation was constant. Two simulations were performed, one in which contraction was initiated according to the regular depolarization pattern (NORM simulation), and another in which contraction was initiated after synchronous depolarization (SYNC simulation). In the NORM simulation propagation of depolarization was physiological, but wall strain was unphysiologically inhomogeneous. When simulating LV mechanics with unphysiological synchronous depolarization (SYNC) myofiber strain was more homogeneous and more physiologic. Apparently, the assumption of a constant delay between depolarization and onset of crossbridge formation results in an unrealistic contraction pattern. The present finding may indicate that electromechanical delay times are heterogeneously distributed, such that a contraction in a normal heart is more synchronous than depolarization.