Electromechanical interactions in the heart: a computational study
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The motivation for this research was to fill gaps in the current understanding of the electromechanical interactions in the heart, with the expectation that this improved understanding will lead to better treatment for cardiac diseases, specifically cardiac arrhythmias and dyssynchronous heart failure (DHF). This research was conducted using a computer modeling approach, making it possible to analyze the electrical and mechanical activity in the whole heart at a high spatiotemporal resolution. First, it was investigated how the recruitment of stretch-activated channel (SAC) affects scroll wave stability. Second, the predominant mechanism underlying stroke work improvement in the acute response of cardiac resynchronization therapy (CRT) was determined. Third, the feasibility of optimizing CRT pacing locations to achieve maximal hemodynamics improvement while simultaneously minimizing ATP consumption heterogeneity throughout the left ventricle in the DHF ventricles was demonstrated. Regarding the effects of mechano-electric feedback on arrhythmias, It was found that recruitment of SAC affects scroll wave stability differently depending on SAC reversal potential and channel conductance; the mechanisms are also different. Regarding CRT therapy for DHF patients, the predominant mechanism underlying stroke work improvement in the acute response of CRT was found to be efficient preloading of the ventricles by a properly timed atrial contraction instead of resynchronization of ventricular contraction. Reduction of mitral regurgitation by CRT led to stroke work worsening. Lastly, an ATP based method to optimize CRT pacing sites was suggested for DHF ventricles. This research provides insights into the electromechanical interactions in the heart, and will contribute to the development of better treatment for cardiac diseases, specifically cardiac arrhythmias and DHF.