Cardiac Performance by Quantitative Echocardiography

描述（由申请人提供）： 这是一个竞争性的K24更新申请的重要项目，"心脏性能的定量超声心动图。“候选人在同行评审的出版物中的生产力，在校外资助中的成功，以及在以患者为导向的研究中的积极指导活动，都是这个奖项的直接结果。 该候选人最近被晋升为终身医学教授，并指导了7名实习生进行临床研究，产生了12篇同行评审的出版物，实习生为第一作者，候选人为资深作者;其他8篇已提交或正在编写中。所有学员都成功地获得了候选人作为导师的竞争性支持，包括美国超声心动图学会的同行评审奖学金和成果奖。所有人都已经或将继续担任全职学术教职。这一更新将继续并加强这些活动。项目1测试了以下关键假设：新型负荷无关性超声心动图左心室（LV）功能测量可以识别LV恢复的辅助装置（LVAD）心力衰竭（HF）患者，并且心肌炎和TNF-α表达是可逆性LV功能障碍的标志物。我们对36例LVAD患者的令人兴奋的初步数据表明，10例患者的LV恢复和LVAD成功移除。该提案将测试我们的新的成像方法的预负荷调整的最大功率，与常规的临床评估，包括运动耗氧量和右心导管插入术。我们还将把左心室恢复与心肌炎症标志物和TNF-α表达联系起来，以增加对机制的了解。项目2的重点是心脏起搏治疗（CRT），使许多HF患者受益，但使用QRS标准仍有25 - 35%为无应答者。项目2测试了关键假设：1）机械不同步的新型成像标记物可以可靠地预测患者对CRT的反应，2）在最近一次机械激活部位的成像引导LV电极导线置入将导致比常规LV电极导线置入更有利的临床结局。我们的新方法包括组织多普勒和斑点跟踪，以评估纵向和径向力学。我们对42例患者的数据预测了CRT的急性反应（高达95%的敏感性和100%的特异性），然而，预测长期结果尚不清楚。我们还表明，与最新机械激活部位一致的LV电极导线放置比常规电极导线定位有更大的改善。该提案将在320例CRT患者中测试我们的成像不同步标记物的预测价值，并包括图像引导LV电极导线位置与常规护理的随机试验。将在6个月时评估主要结局变量（Packer复合HF评分、6分钟步行试验和射血分数）。和1年。这些研究将为正确利用这些广泛的疗法提供宝贵的见解，并为指导学员提供丰富的机会。

DESCRIPTION (provided by applicant): This is a competing K24 renewal application for the important project, "Cardiac Performance by Quantitative Echocardiography." The candidate's productivity in peer-reviewed publications, success in extramural funding, and vigorous mentoring activities in patient-oriented research have been a direct result of this award. The candidate been recently been promoted to tenured Professor of Medicine and has mentored 7 trainees in clinical research resulting in 12 peer-reviewed publications with the trainee as 1st author and the candidate as senior author; 8 others are submitted or in preparation. All trainees successfully obtained competitive support with the candidate as mentor, including a peer-reviewed Fellowship Award and Outcomes Grant from the American Society of Echocardiography. All have or will be going on to full-time academic faculty positions. This renewal will continue and intensify these activities. Project 1 tests the key hypotheses that novel load-independent echocardiographic left ventricular (LV) functional measures can identify heart failure (HF) patients on assist device (LVAD) who have LV recovery, and that mvocardial inflammation and expression of TNF-alpha are markers for reversible LV dysfunction. Our exciting preliminary data on 36 LVAD patients demonstrate identification of LV recovery and successful LVAD removal in 10. This proposal will test our novel imaging approach of preload-adjusted maximal power, in comparison to a routine clinical assessment that includes exercise oxygen consumption and right heart catheterization. We will also correlate LV recovery with markers of myocardial inflammation and TNF-alpha expression to add mechanistic insight. Project 2 focuses on cardiac resynchronization therapy (CRT) that benefits many HF patients, but 25-35% are still non-responders using QRS criteria. Project 2 tests the key hypotheses: 1) that novel imaging markers of mechanical dyssynchrony can reliably predict patient response to CRT and 2) that imaging-guided LV lead placement at the site of latest mechanical activation will result in a more favorable clinical outcome than routine LV lead placement. Our novel approaches include tissue Doppler and speckle tracking to assess longitudinal and radial mechanics. Our data on 42 patients predict acute response to CRT (up to 95% sensitivity and 100% specificity), however, predicting long-term outcome is unclear. We have also shown that LV lead placement concordant with site of latest mechanical activation results in greater improvements than routine lead positioning. This proposal will test the predictive value of our imaging dyssynchrony markers in 320 CRT patients and includes a randomized trial of image-guided LV lead position vs. routine care. Primary outcome variables (Packer composite HF score, 6 min. walk test, and ejection fraction) will be assessed at 6 mo. and 1 year. These studies will provide valuable insight to the correct utilization of these extensive therapies and provide abundant opportunities for mentoring of trainees.