Minimally Invasive Ventricular Polymeric Injection for Treatment of Heart Failure

描述（由申请人提供）：心力衰竭（HF）是一种世界性流行病，在发达国家的医疗保健总成本中占相当大的比例。患有这种复杂疾病的人数正在以惊人的速度增加-这一趋势很可能 在未来的许多年里继续下去。我们提出的研究的总体目标是优化HF的治疗，包括在衰竭心肌中经皮注射水凝胶（Algisyl-LVR）。考虑到心血管系统的复杂性，需要跨实验和计算领域的多学科专业知识来充分研究这种新型HF治疗。三个具体目标包括以下内容：首先，我们将验证用Algisyl-LVR +冠状动脉旁路移植术或Algisyl-LVR单独治疗的衰竭左心室的数学（有限元）模型。有限元模型将具有基于磁共振成像的逼真3D几何形状，并通过体内心肌应变与左心室和右心室压力测量进行验证。此外，离体3D肌纤维取向和直接力测量在皮肤纤维制备。其次，我们将使用经验证的有限元模型和我们用于自动优化治疗HF的医疗器械的方法来设计最佳Algisyl-LVR注射模式，并在患有收缩期HF的猪中进行测试。最后，我们将使用目标2中确定的最佳注射模式输送Algisyl-LVR percent，并在患有收缩期HF的猪中进行测试。所提出的方法和方法在模拟动物特异性装置治疗方面是创新的，其对于HF流行病的治疗具有非常重要的前景。

DESCRIPTION (provided by applicant): Heart failure (HF) is a worldwide epidemic that contributes considerably to the overall cost of health care in developed nations. The number of people afflicted with this complex disease is increasing at an alarming pace-a trend that is likely to continue for many years to come. The overall goal of our proposed research is to optimize a therapy for HF that involves percutaneous injection of a hydrogel (Algisyl-LVR) in the failing myocardium. Given the cardiovascular system's complexity, a multi-disciplinary expertise across experimental and computational domains is required to fully investigate this novel HF therapy. The three specific aims include the following: First, we will validate mathematical (finite element models of failing left ventricles that have been treated with Algisyl-LVR + coronary artery bypass grafting or Algisyl-LVR alone. The finite element models will have realistic 3D geometries based on magnetic resonance imaging and validated with in-vivo myocardial strain versus left and right ventricular pressure measurements. Additionally, ex-vivo 3D myofiber orientation and direct force measurements in skinned fiber preparations will be made. Second, we will use the validated finite element models and our method for automatically optimizing medical devices for treating HF to design the optimal Algisyl-LVR injection pattern and test it in swine with systolic HF. Lastly, we will deliver Algisyl-LVR percutaneously, using the optimal injection pattern determined in Aim 2, and test it in swine with systolic HF. The proposed approach and methodologies are innovative in simulation of animal-specific device therapy that holds very significant promise for treatment of the epidemic of HF.