A Method for Automatically Optimizing Medical Devices for Treating Heart Failure: Designing Polymeric Injection Patterns

CardioPolymers, Inc., Laguna Hills, CA 92653, USA.
Journal of Biomechanical Engineering (Impact Factor: 1.78). 12/2009; 131(12):121011. DOI: 10.1115/1.4000165
Source: PubMed


Heart failure continues to present a significant medical and economic burden throughout the developed world. Novel treatments involving the injection of polymeric materials into the myocardium of the failing left ventricle (LV) are currently being developed, which may reduce elevated myofiber stresses during the cardiac cycle and act to retard the progression of heart failure. A finite element (FE) simulation-based method was developed in this study that can automatically optimize the injection pattern of the polymeric "inclusions" according to a specific objective function, using commercially available software tools. The FE preprocessor TRUEGRID((R)) was used to create a parametric axisymmetric LV mesh matched to experimentally measured end-diastole and end-systole metrics from dogs with coronary microembolization-induced heart failure. Passive and active myocardial material properties were defined by a pseudo-elastic-strain energy function and a time-varying elastance model of active contraction, respectively, that were implemented in the FE software LS-DYNA. The companion optimization software LS-OPT was used to communicate directly with TRUEGRID((R)) to determine FE model parameters, such as defining the injection pattern and inclusion characteristics. The optimization resulted in an intuitive optimal injection pattern (i.e., the one with the greatest number of inclusions) when the objective function was weighted to minimize mean end-diastolic and end-systolic myofiber stress and ignore LV stroke volume. In contrast, the optimization resulted in a nonintuitive optimal pattern (i.e., 3 inclusions longitudinallyx6 inclusions circumferentially) when both myofiber stress and stroke volume were incorporated into the objective function with different weights.

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    • "Last, it must be pointed out that the total prescribed injection volume of 0.24 ml is relatively small when compared to other computational models of injection treatment which have larger injection volumes e.g. $ 5 ml (Wall et al., 2006; Wenk et al., 2009) and $ 9.4 ml (Kortsmit et al., 2012). We did not increase the injection volume because doing so would lead to a highly distorted mesh near the injections, which would cause numerical instability. "
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    ABSTRACT: Injection of biomaterials into diseased myocardium has been associated with decreased myofiber stress, restored left ventricular (LV) geometry and improved LV function. However, its exact mechanism(s) of action remained unclear. In this work, we present the first patient-specific computational model of biomaterial injection that accounts for the possibility of residual strain and stress introduced by this treatment. We show that the presence of residual stress can create more heterogeneous regional myofiber stress and strain fields. Our simulation results show that the treatment generates low stress and stretch areas between injection sites, and high stress and stretch areas between the injections and both the endocardium and epicardium. Globally, these local changes are translated into an increase in average myofiber stress and its standard deviation (from 6.9±4.6 to 11.2±48.8kPa and 30±15 to 35.1±50.9kPa at end-diastole and end-systole, respectively). We also show that the myofiber stress field is sensitive to the void-to-size ratio. For a constant void size, the myofiber stress field became less heterogeneous with decreasing injection volume. These results suggest that the residual stress and strain possibly generated by biomaterial injection treatment can have large effects on the regional myocardial stress and strain fields, which may be important in the remodeling process.
    Journal of Biomechanics 06/2014; 47(12). DOI:10.1016/j.jbiomech.2014.06.026 · 2.75 Impact Factor
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    • "Left ventricular (LV) FE models, which incorporate myocardial contractility, have been described and used to determine the influence of myocardial infarction on structure and function (Dang et al. 2005a, Guccione et al. 2001, Walker et al. 2005a). Additionally, the efficacy of various surgical procedures has been simulated (Dang et al. 2005b, Walker et al. 2005b), as well as the effect of cardiac support devices (Jhun et al. 2010, Wenk et al. 2009). Models that include volumetric growth (Kroon et al. 2009a) and myofiber remodeling (Kroon et al. 2009b) have also been implemented with the FE method, and coupled to lumped-parameter models of the circulatory system. "
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    ABSTRACT: Numerical modelling of the cardiovascular system is becoming an important tool for assessing the influence of heart disease and treatment therapies. In the current study, we present an approach for modelling the interaction between the heart and the circulatory system. This was accomplished by creating animal-specific biventricular finite element (FE) models, which characterise the mechanical response of the heart, and by coupling them to a lumped-parameter model that represents the systemic and pulmonic circulatory system. In order to minimise computation time, the coupling was enforced in a weak (one-way) manner, where the ventricular pressure–volume relationships were generated by the FE models and then passed into the circulatory system model to ensure volume conservation and physiological pressure changes. The models were first validated by tuning the parameters, such that the output of the models matched experimentally measured pressures and volumes. Then the models were used to examine cardiac function and the myofibre stress in a healthy canine heart and a canine heart with dilated cardiomyopathy. The results showed good agreement with experimental measurements. The stress in the case of cardiomyopathy was found to increase significantly, while the pump function was decreased, compared to the healthy case. The total runtime of the simulations is lesser than that of many fully coupled models presented in the literature. This will allow for a much quicker evaluation of possible treatment strategies for combating the effects of heart failure, especially in optimisation schemes that require numerous FE simulations.
    Computer Methods in Biomechanics and Biomedical Engineering 01/2012; iFirst article(8-2012). DOI:10.1080/10255842.2011.641121 · 1.77 Impact Factor
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    • "Though initial studies investigated the ability of these materials to increase retention of stem cells within the ventricular wall, improvements in function and attenuation of remodelling resulting from the biomaterial alone were observed [12] [13]. Recent finite element models [14] [15] have shown that injection of any non-contractile material within the ventricle wall can reduce the MI induced elevated myofiber stresses through wall thickening and that stiffer materials resulted in a greater stress reduction. A wide range of hydrogels from purely biological materials such as fibrin [12], collagen [16] and alginate [17] through to the fully synthetic such as polyethylene glycol (PEG) [18] and thermoresponsive N-isopropyl acrylamide hydrogels [19] have been shown to result in potentially therapeutic outcomes after delivery. "
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    ABSTRACT: Biomaterials are increasingly being investigated as a means of reducing stress within the ventricular wall of infarcted hearts and thus attenuating pathological remodelling and loss of function. In this context, we have examined the influence of timing of delivery on the efficacy of a polyethylene glycol hydrogel polymerised with an enzymatically degradable peptide sequence. Delivery of the hydrogel immediately after infarct induction resulted in no observable improvements, but a delay of one week in delivery resulted in significant increases in scar thickness and fractional shortening, as well as reduction in end-systolic diameter against saline controls and immediately injected hydrogel at both 2 and 4 weeks post-infarction (p < 0.05). Hydrogels injected at one week were degraded significantly slower than those injected immediately and this may have played a role in the differing outcomes. The hydrogel assumed markedly different morphologies at the two time points having either a fibrillar or bulky appearance after injection immediately or one week post-infarction respectively. We argue that the different morphologies result from infarction induced changes in the cardiac structure and influence the degradability of the injectates. The results indicate that timing of delivery is important and that very early time points may not be beneficial.
    Biomaterials 12/2011; 33(7):2060-6. DOI:10.1016/j.biomaterials.2011.11.031 · 8.56 Impact Factor
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