A Method for Automatically Optimizing Medical Devices for Treating Heart Failure: Designing Polymeric Injection Patterns
ABSTRACT 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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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 · 8.31 Impact Factor
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