Cardiac Performance by Quantitative Echocardiography

描述(由申请人提供)： 这是一个竞争的K24更新应用程序的重要项目，“心脏表现定量超声心动图。候选人在同行评议的出版物中的生产力，在外部资助方面的成功，以及在以患者为导向的研究中积极的指导活动，都是这个奖项的直接结果。这位候选人最近被提升为终身医学教授，并指导了7名临床研究实习生，结果出版了12篇同行评议的出版物，其中实习生是第一作者，候选人是资深作者；其他8本已提交或正在筹备中。所有受训人员都成功地获得了候选人作为导师的竞争性支持，包括来自美国超声心动图学会的同行评议团契奖和结果奖助金。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测试了一些关键假设，即新的负荷非依赖性超声心动图左心室(LV)功能测量方法可以识别使用辅助装置(LVAD)的心力衰竭(HF)患者，这些患者的左室功能恢复，以及心脏炎症和肿瘤坏死因子-α的表达是可逆性LV功能障碍的标志。我们在36名LVAD患者身上的令人兴奋的初步数据显示，在10名患者中，LV恢复并成功移除。与常规的临床评估(包括运动耗氧量和右心导管术)相比，这项建议将测试我们新的预负荷调整最大功率的成像方法。我们还将把左心功能恢复与心肌炎症标志物和肿瘤坏死因子-α的表达联系起来，以增加机械性洞察力。项目2的重点是心脏再同步治疗(CRT)，使许多心衰患者受益，但根据QRS标准，仍有25%-35%的患者无反应。项目2测试了关键假设：1)新的机械不同步的成像标志物可以可靠地预测患者对CRT的反应；2)成像引导的LV导联放置在最后机械激活的位置将导致比常规LV导联放置更有利的临床结果。我们的新方法包括组织多普勒和散斑跟踪，以评估纵向和径向力学。我们对42名患者的数据预测了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导联位置比常规导联位置有更大的改善。这项建议将在320名CRT患者中测试我们的成像不同步标志物的预测价值，并包括一项图像引导的LV导联位置与常规护理的随机试验。主要结果变量(Packer综合心力衰竭评分，6分钟。步行试验和射血分数)将在6个月时进行评估。一年。这些研究将为正确使用这些广泛的治疗方法提供有价值的见解，并为学员的指导提供丰富的机会。

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.