Functional Optimization of Cardiac Resynchronization Therapy in Heart Failure

心力衰竭心脏再同步治疗的功能优化

• 批准号: 7771136
• 负责人: BRUCE D JOHNSON
• 金额: $ 23.24万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7771136
• 关键词: Address; Algorithms; Area; Award; Breathing; Cardiac; Cardiopulmonary; Cardiovascular system; Data; Development; Devices; Exercise; Exercise stress test; Gases; Goals; Health; Health Status; Heart; Heart Atrium; Heart Rate; Heart failure; Implant; Left Ventricular Ejection Fraction; Link; Lung; Measures; Medical; Medicine; Metabolic; Methods; Modeling; North America; Parents; Patient Selection; Patients; Pattern; Pharmacotherapy; Physical activity; Population; Procedures; Pulmonary Gas Exchange; Randomized Controlled Clinical Trials; Refractory; Relative (related person); Research; Research Project Grants; Selection Criteria; Series; Stress; Surface; Symptoms; System; Techniques; Testing; United States National Institutes of Health; Venous; Ventricular; Walking; base; clinical practice; cost; design; implantable device; implantation; improved; novel strategies; programs; public health relevance; response

DESCRIPTION (provided by applicant): Cardiac resynchronization therapy (CRT) by bi-ventricular pacing has been an important treatment advance for patients with advanced heart failure (HF). It is estimated that there were >150,000 CRT devices implanted in North America in 2007 at an initial cost of ~1-3 billion dollars, with much higher post implantation costs. However, nearly 30% of subjects are considered non or poor responders. While this may be due to problems with patient selection, this may also suggest problems of optimization of atrioventricular (AV) and interventricular (V-V) intervals of the CRT devices. Current selection criteria for CRT are limited to LVEF <35%, QRS duration >120 ms, and refractory NYHA class III-IV symptoms despite optimized pharmacotherapy. However, it is clear that more individualized and physiologically based approaches are needed to improve response rates. Low level physical activity challenges (stresses) the heart through increased metabolic demands, altered systemic venous return, influences on cardiac pre and after load and in HF may enhance ventricular interdependence. The lungs lie in series with the heart, share a common surface area and are intimately linked hemodynamically as well as neuro-mechanically and thus measures of breathing pattern and gas exchange particularly during a mild cardiac load provide a dynamic window of integrated cardiopulmonary function. It is the premise of this proposal that low level, non-invasive cardiopulmonary exercise provides a novel approach for determining which HF patients may be most likely to benefit from CRT and individualizing and optimizing CRT interval settings. This will be addressed in two specific aims. Aim 1 will test and refine an algorithm based on non-invasive measures of breathing pattern, gas exchange and heart rate, obtained during low intensity exercise that predicts HF patient responsiveness to CRT device therapy. Aim 2 will test the ability of a similar algorithm, based on non-invasive cardiopulmonary gas exchange measures, to optimize atrial- ventricular synchrony and ventricular activation in HF patients receiving CRT device therapy relative to standard approaches for setting CRT intervals. This approach fills a significant need in this growing field, has the potential to reduce cost and individualize the approach to treatment. This proposal is designed to obtain initial exploratory data in order to test the techniques and further develop gas exchange algorithms/models to optimize the clinical practice of CRT. PUBLIC HEALTH RELEVANCE: The long term goal of our research program has been to understand the functional relationships between the cardiovascular and pulmonary systems, particularly as it relates to the heart failure population. This R21 application takes advantage of important cardio-pulmonary relationships and focuses on a novel approach to using non invasive pulmonary gas exchange measures obtained during slow treadmill walking to optimize atrioventricular (AV) and interventricular (V-V) intervals of cardiac resynchronization therapy (CRT) devices. This is important as CRT has become an important adjunct to medical therapy in the heart failure population, however, 25-30% of patients implanted have a poor or refractory response. This may be due to patient selection or current methods of setting device intervals. The premise of this proposal is that an algorithm of non invasive pulmonary gas exchange measures will not only help guide which patients would respond most positively to treatment, but will help to improve the response. This approach has the potential to improve patient health, simplify device optimization procedures, support an individualized approach to medicine and substantially impact CRT costs.

描述（由申请人提供）：通过双心室起搏进行的心脏起搏治疗（CRT）是晚期心力衰竭（HF）患者的重要治疗进展。据估计，2007年在北美植入了> 150，000个CRT设备，初始成本约为10 - 30亿美元，植入后成本高得多。然而，近30%的受试者被认为是无应答者或应答差者。虽然这可能是由于患者选择的问题，但这也可能表明CRT设备的房室（AV）和室间（V-V）间期的优化问题。目前CRT的选择标准仅限于LVEF <35%，QRS持续时间>120 ms，尽管优化了药物治疗，但仍有难治性NYHA III-IV级症状。然而，显然需要采取更加个性化和基于生理的方法来提高响应率。低水平的体力活动通过增加代谢需求、改变全身静脉回流、影响负荷前后的心脏以及HF可能增强心室相互依赖性来挑战（压迫）心脏。肺与心脏串联，共享共同的表面积，并且在血流动力学以及神经机械学上密切相关，因此呼吸模式和气体交换的测量，特别是在轻度心脏负荷期间，提供了综合心肺功能的动态窗口。该建议的前提是，低水平、无创心肺运动提供了一种新方法，用于确定哪些HF患者最有可能从CRT中获益，并个性化和优化CRT间期设置。这将在两个具体目标中解决。目标1将测试和完善基于低强度运动期间获得的呼吸模式、气体交换和心率的无创测量的算法，该算法预测HF患者对CRT器械治疗的反应性。目标2将测试基于无创心肺气体交换测量的类似算法相对于设置CRT间期的标准方法优化接受CRT器械治疗的HF患者的房室同步性和心室激动的能力。这种方法填补了这一日益增长的领域的重大需求，有可能降低成本和个性化的治疗方法。本提案旨在获得初始探索性数据，以测试技术并进一步开发气体交换算法/模型，从而优化CRT的临床实践。 公共卫生关系：我们研究项目的长期目标是了解心血管和肺系统之间的功能关系，特别是与心力衰竭人群相关的功能关系。该R21应用利用了重要的心肺关系，并侧重于一种新方法，该方法使用在缓慢跑步机行走期间获得的无创肺气体交换测量值来优化心脏起搏治疗（CRT）器械的房室（AV）和室间（V-V）间期。这一点很重要，因为CRT已成为心力衰竭人群药物治疗的重要辅助手段，然而，25-30%的植入患者反应较差或难治性。这可能是由于患者选择或当前设置器械间期的方法。该建议的前提是，无创肺气体交换测量的算法不仅有助于指导哪些患者对治疗反应最积极，而且有助于改善反应。这种方法有可能改善患者健康，简化设备优化程序，支持个性化的医学方法，并大大影响CRT成本。