Mitral Annular Remodeling for MR Therapy

MR 治疗的二尖瓣环重塑

• 批准号: 6959620
• 负责人: Kiyotaka Fukamachi
• 金额: $ 38.52万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6959620
• 关键词: blood flow measurement; cardiovascular disorder therapy; disease /disorder model; dogs; echocardiography; fluorocarbon polymers; heart circulation; hemodynamics; human therapy evaluation; injection /infusion; mitral valve insufficiency; model design /development; organosilicon compound; tachycardia; technology /technique development

DESCRIPTION (provided by applicant): Functional mitral regurgitation (MR) plays a pivotal role in the pathophysiology of the congestive heart failure (CHF), a major cause of cardiac morbidity and mortality. Surgical therapy for functional MR has been limited in patients with severe CHF by relatively high operative mortality rates due to the effects of cardiopulmonary bypass and sternotomy. Therefore, there is a need for a minimally invasive method to treat MR to reduce patient risk. The purpose of this proposed program is to develop a new procedure for MR treatment: mitral annular remodeling resulting from a non-absorbable substance injection into the posterior mitral annulus. This procedure may enable the septal-lateral dimension to be efficiently reduced thus reducing MR without employing cardiopulmonary bypass or implanting a device into the coronary sinus. If this mitral annular remodeling proves to be efficacious in reducing functional MR, further development of a new device that will allow for percutaneously injection of the substance through the coronary sinus will be undertaken in the future. Therefore, as a first step in this process, we propose to evaluate the effects of mitral annular remodeling resulting from a nonabsorbable substance injection using an epicardial approach. To achieve this goal, the Specific Aims of this proposed program are: (1) to assess the feasibility of a precise injection of a nonabsorbable substance into the posterior mitral annulus on a beating heart in healthy canines, (2) to evaluate acute effects of mitral annular remodeling on the geometry of the mitral apparatus and the degree of MR in a canine tachycardia-induced MR model, and (3) to evaluate long-term effects of mitral annular remodeling on MR, tissue reaction, coronary circulation, and LV function by comparison with a tachycardia-induced MR Control group. Successful completion of this research program will provide us with preliminary data that will support our future program in which the development of a new percutaneously delivered device will allow for injection of the substance through the coronary sinus. Therefore, this proposed research program is an important first step in this novel procedure's development as one potential therapeutic option for high-risk CHF patients with functional MR.

描述（由申请方提供）：功能性二尖瓣返流（MR）在充血性心力衰竭（CHF）的病理生理学中起关键作用，CHF是心脏病发病率和死亡率的主要原因。功能性二尖瓣返流的手术治疗在严重CHF患者中受到限制，因为心肺转流术和胸骨切开术的影响导致手术死亡率相对较高。因此，需要一种微创方法来治疗MR以降低患者风险。本申报项目旨在开发一种新的二尖瓣返流治疗手术：将不可吸收物质注入二尖瓣后环导致二尖瓣环重塑。该手术可以有效地减小间隔-外侧尺寸，从而减少MR，而无需采用心肺分流术或将器械植入冠状窦。如果这种二尖瓣环重塑被证明在减少功能性二尖瓣返流方面有效，则未来将进一步开发一种新器械，允许通过冠状窦持续注射该物质。因此，作为该过程的第一步，我们建议使用心外膜入路评价不可吸收物质注射引起的二尖瓣环重塑的影响。为实现这一目标，拟议方案的具体目标是：（1）评估在健康犬的跳动心脏上将不可吸收物质精确注射到二尖瓣后环中的可行性，（2）评估二尖瓣环重塑对二尖瓣器几何形状和犬心动过速诱导的MR模型中的MR程度的急性影响，和（3）通过与心动过速诱导的MR对照组进行比较，评价二尖瓣环重塑对MR、组织反应、冠状动脉循环和LV功能的长期影响。该研究项目的成功完成将为我们提供初步数据，以支持我们未来的项目，在该项目中，开发一种新的perceptide输送装置将允许通过冠状窦注射该物质。因此，这项拟议的研究计划是这种新型手术开发的重要第一步，该手术是功能性MR高风险CHF患者的一种潜在治疗选择。