@article {Simula.simula.66,
	title = {Ventricular Dilation and Electrical Dyssynchrony Synergistically Increase Regional Mechanical Non-Uniformity But Not Mechanical Dyssynchrony; a Computational Model},
	journal = {Circulation: Heart Failure},
	volume = {3},
	number = {4},
	year = {2010},
	month = {May},
	pages = {528-536},
	abstract = {Background Heart failure (HF) in combination with mechanical dyssynchrony is associated with a high mortality rate. To quantify contractile dysfunction in patients with HF, investigators have proposed several indices of mechanical dyssynchrony, including percentile range of time to peak shortening (WTpeak), circumferential uniformity ratio estimate (CURE), and internal stretch fraction (ISF). The goal of this study was to compare the sensitivity of these indices to 4 major abnormalities responsible for cardiac dysfunction in dyssynchronous HF: dilation, negative inotropy, negative lusitropy, and dyssynchronous activation. Methods and Results All combinations of these 4 major abnormalities were included in 3D computational models of ventricular electromechanics. Compared with a nonfailing heart model, ventricles were dilated, inotropy was reduced, twitch duration was prolonged, and activation sequence was changed from normal to left bundle branch block. In the nonfailing heart, CURE, ISF, and WTpeak were 0.97\pm0.004, 0.010\pm0.002, and 78\pm1 milliseconds, respectively. With dilation alone, CURE decreased 2.0\pm0.07\%, ISF increased 58\pm47\%, and WTpeak increased 31\pm3\%. With dyssynchronous activation alone, CURE decreased 15\pm0.6\%, ISF increased 14-fold (\pm3), and WTpeak increased 121\pm4\%. With the combination of dilation and dyssynchronous activation, CURE decreased 23\pm0.8\%, ISF increased 20-fold (\pm5), and WTpeak increased 147\pm5\%. Conclusions Dilation and left bundle branch block combined synergistically decreased regional cardiac function. CURE and ISF were sensitive to this combination, but WTpeak was not. CURE and ISF also reflected the relative nonuniform distribution of regional work better than WTpeak. These findings might explain why CURE and ISF are better predictors of reverse remodeling in cardiac resynchronization therapy.},
	author = {J. H. {Omens} and Andrew D. {McCulloch} and L. J. {Mulligan}}
}
@article {Simula.sc.1198,
	title = {Effect of Transmurally Heterogeneous Myocyte Excitation-contraction Coupling on Canine Left Ventricular Electromechanics},
	journal = {Experimental Physiology},
	volume = {94},
	number = {5},
	year = {2009},
	pages = {541-552},
	publisher = {BioMedCentral},
	doi = {10.1113/expphysiol.2008.044057},
	author = {S. G. {Campbell} and Howard, E. and Aguado-Sierra, Jazmin and B. A. {Coppola} and J. H. {Omens} and L. J. {Mulligan} and Andrew D. {McCulloch}}
}
@article {Simula.sc.934,
	title = {Cardiac Resynchronization: Insight From Experimental and Computational Models},
	journal = {Progress in Biophysics and Molecular Biology},
	volume = {97},
	number = {2-3},
	year = {2008},
	month = {June-July},
	pages = {543-561},
	abstract = {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.},
	doi = {10.1016/j.pbiomolbio.2008.02.024},
	author = {Lumens, J. and Vernooy, K. and J. H. {Omens} and L. J. {Mulligan} and Delhaas, T. and Arts, Thomas and Andrew D. {McCulloch} and F. W. {Prinzen}}
}
