Advanced CMR Tissue-Based Prediction of Right Ventricular Dysfunction and Revascularization Response

项目概要/摘要 Jiwon Kim博士的K23申请将使她能够成为一名独立的临床研究者， 使用新型成像策略改善心力衰竭和冠状动脉粥样硬化患者的风险分层 动脉疾病（CAD）。K23奖将使Kim博士在3个领域获得专业知识：（1）新的心脏MRI（CMR） 改善右心室（RV）组织表征的方法，（2）先进的超声心动图 在基于人群的研究中应用于RV的技术，（3）临床研究的原则， 开始独立设计和执行复杂的研究方案。为了实现这些目标，金博士 组建了一个多学科的指导小组。她的主要导师Weinsaft博士是首席研究员 与K23配对的R 01，在心肌CMR评估方面具有丰富的研究经验 组织特性。王博士是一位在高分辨率CMR脉冲方面有着良好记录的共同导师 层序发育Devereux博士是心脏超声领域的二级共同导师， 流行病学Kim博士的K23研究的目标是识别基于心肌组织的RV标志物 CAD患者的功能障碍。高达40%的CAD患者发生RV功能障碍， 独立增加死亡风险。改变的心肌组织特性是潜在的致病基质 用于RV功能障碍，但由于可视化RV中梗死的能力有限，尚未在此背景下进行研究 RV壁薄。新的高分辨率技术（3D导航CMR），包括那些有可能被 为RV量身定制的（RV心外膜脂肪导航器）可以改善RV组织表征。为了验证这些概念， 将对150例在血运重建前后接受应激CMR的CAD患者进行研究。应力CMR将 用于确定左心室和右心室组织特性（缺血和梗死）之间的关系 和RV功能（目标1）。为了优化RV心肌梗死（RV-MI）检测，将使用 标准2D CMR和新的3D CMR技术（RV心外膜脂肪导航器）（目标2）。为了验证这个概念， 血运重建可改善RV功能，RV-MI将作为不可逆RV功能障碍的标志物进行研究： RV-MI将用于预测冠状动脉血运重建后的RV功能改善（目的3A）。最后， 为了研究RV-MI对功能后果的影响，将研究RV-MI与以下方面的努力耐力的关系： 心肺运动试验（Aim 3B）。该培训和研究计划将利用现有的 多学科合作和机构资源，包括Weinsaft博士的R 01， 将绘制和康奈尔临床转化科学中心，通过该硕士学位将被 在临床研究中获得。最后，这项研究将告知未来的R 01应用程序，这将测试新的 高分辨率右室冠状动脉灌注方法及右室功能反应研究 存活但缺血的RV的血运重建。

PROJECT SUMMARY / ABSTRACT This K23 application for Dr. Jiwon Kim will enable her to develop as an independent clinical investigator focused on the use of novel imaging strategies to improve risk stratification among patients with heart failure and coronary artery disease (CAD). A K23 award will allow Dr. Kim to attain expertise in 3 areas: (1) new cardiac MRI (CMR) approaches for improved tissue characterization of the right ventricle (RV), (2) advanced echocardiography techniques to be applied for the RV in population based studies, (3) principles of clinical investigation needed to initiate independent design and execution of sophisticated research protocols. To pursue these goals, Dr. Kim has assembled a multidisciplinary mentoring team. Her primary mentor, Dr. Weinsaft, is the principal investigator of the R01 to which this K23 is paired and has extensive research experience in CMR assessment of myocardial tissue properties. Dr. Wang is a co-mentor with an established track record in high-resolution CMR pulse sequence development. Dr. Devereux is a secondary co-mentor with expertise in cardiac ultrasound and epidemiology. The goal of Dr. Kim's K23 research is to identify myocardial tissue-based markers of RV dysfunction among CAD patients. RV dysfunction occurs in up to 40% of patients with CAD and has been shown to independently increase risk of death. Altered myocardial tissue properties is a potential causative substrate for RV dysfunction but has not yet been studied in this context due to limited ability to visualize infarction in the thin RV wall. New high-resolution techniques (3D navigator CMR) including those that have the possibility to be tailored for the RV (RV epicardial fat navigator) may improve RV tissue characterization. To test these concepts, 150 patients with CAD undergoing stress CMR pre- and post- revascularization will be studied. Stress CMR will be used to determine relationships between left and right ventricular tissue properties (ischemia and infarction) and RV function (Aim 1). To optimize RV myocardial infarction (RV-MI) detection, the RV will be assessed using standard 2D CMR and new 3D CMR technologies (RV epicardial fat navigator) (Aim 2). To test the concept that revascularization may improve RV function, RV-MI will be studied as a marker for irreversible RV dysfunction: RV-MI will be used to predict RV functional improvement following coronary revascularization (Aim 3A). Lastly, to study the impact of RV-MI on functional consequences, RV-MI will be studied in relation to effort tolerance on cardiopulmonary exercise testing (Aim 3B). This training and research plan will leverage existing multidisciplinary collaborations and institutional resources including Dr. Weinsaft's R01 from which imaging data will be drawn and the Cornell Clinical Translational Science Center through which a Master's degree will be obtained in Clinical Investigation. Finally, this research will inform future R01 applications, which will test new high resolution approaches for RV coronary perfusion and study RV functional response to coronary revascularization in viable but ischemic RV.