Cardiac resynchronization therapy (CRT) is a clinically proven therapy for patients with arrhythmia (irregular heartbeats) and heart failure (decreased cardiac function). It works through surgical implantation of a device that regulates the electrical signal firing sequence to restore the normal or required heart rhythm. However, about 30% of the patients do not respond to CRT, and these patients often have prior incidences of heart attacks (blockage of coronary arteries, aka, myocardial infarction) which left tissues scars in their heart muscles. The way the scars affect patient responsiveness to CRT is complicated by the process of heart remodeling, a process in which the normal heart muscles compensate for the damaged heart muscle cells with visible changes in the size, shape and function of the heart.
In a recent study published in the journal Medical Imaging Analysis (1), Kerckhoffs and colleagues analyzed the mechanism of CRT resistance in heart failure patients with left bundle branch block (LBBB), a condition caused by the poor conduction of electrical signals in the left bundle branch of the atrioventricular bundle (bundle of His) of the heart. This also leaves the Purkinje fibers in the left ventricular wall with no signal to distribute, and a delayed contraction in the left ventricle (LV) usually observed in the electrocardiogram (ECG). Using Continuity (2,3), the authors took advantage of computational models established in earlier studies (4,5), and simulated LBBB, acute simultaneous biventricular pacing (BiV) in hearts with chronic scars of different sizes, and measured a number of regional and global function indicators of the heart (Figure 1).
The simulation produced functional indicators that are in agreement with experimental and clinical findings (Figure 2). It also indicated that the failing heart could benefit from BiV and the non-scared regions functions independently of scar sizes during biventricular pacing. This somewhat surprising finding indicates that the paced failing heart could function “normally” despite tissue heterogeneity. The transmural (across the heart wall) heterogeneity has been previously hypothesized to be important for a uniform contraction in the normal heart (4), and detailed mechanical models have been proposed (6). However, the simplifications made in these models and the variations observed in clinical studies suggest that patient specific modeling is critical to further understanding of the heterogeneity of patient responses to CRT, and for better heart pacing strategies.
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Links:
Continuity: http://www.continuity.ucsd.edu
NBCR: http://www.nbcr.net
NBCR Tools: http://tools.nbcr.net
NCRR: http://www.ncrr.nih.gov |
Figure 1. Computational models of heart failure with increasingly realistic geometry and model complexity for accurate simulations.
Figure 2. Continuity 6 allows simulations to be conducted for geometrically realistic models of canine heart with LBBB or biventricular pacing in normal and heart failure conditions. Crosses indicate pacer locations. The color indicates the activation time of cardiac action potential propagation.
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References:
1. Kerckhoffs, R. C., McCulloch, A. D., Omens, J. H. & Mulligan, L. J. (2008). Effects of biventricular pacing and scar size in a computational model of the failing heart with left bundle branch block. Med Image Anal.
2. Rogers, J. M. & McCulloch, A. D. (1994). A collocation--Galerkin finite element model of cardiac action potential propagation. IEEE Trans Biomed Eng 41, 743-57.
3. Usyk, T. P. & McCulloch, A. D. (2003). Relationship between regional shortening and asynchronous electrical activation in a three-dimensional model of ventricular electromechanics. J Cardiovasc Electrophysiol 14, S196-202.
4. Kerckhoffs, R. C. P., Bovendeerd, P. H. M., Kotte, J. C. S., Prinzen, F. W., Smits, K. & Arts, T. (2003). Homogeneity of cardiac contraction despite physiological asynchrony of depolarization: A model study. Annals of Biomedical Engineering 31, 536-547.
5. Kerckhoffs, R. C. P., Lumens, J., Vernooy, K., Omens, J. H., Mulligan, L. J., Delhaas, T., Arts, T., McCulloch, A. D. & Prinzen, F. W. (2008). Cardiac resynchronization: Insight from experimental and computational models. Progress in Biophysics and Molecular Biology 97, 543-561.
6. Campbell, S. G., Flaim, S. N., Leem, C. H. & McCulloch, A. D. (2008). Mechanisms of transmurally varying myocyte electromechanics in an integrated computational model. Philos Transact A Math Phys Eng Sci 366, 3361-80.
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