CARDIAC PERFORMANCE BY QUANTITATIVE ECHOCARDIOGRAPHY

描述（申请人？s摘要） 这位候选人是一位42岁的终身副教授， 一年后的奖学金培训。他是一名独立调查员 他完全致力于终身的研究事业， 指导受训人员。他杰出的制度环境是 支持高质量的合作和正在进行的研究。这个中年 研究者奖以患者为导向的研究提案将使 扩大假设驱动的人类研究的两个主要领域：1） 细胞因子对患者左心室功能的影响 接受心脏手术和2）评估收缩储备以预测 心力衰竭患者的预后。美国心脏协会已经 最近获得了一项名为“炎症反应的影响”的国家补助金， 心脏手术后左心室功能的介导因子” 申请人为PI。这项为期3年的赠款将支持基础设施， 这是K24应用程序的要求。一个具体的目的是检验假设 炎症介质在心脏抑制中起重要作用 冠状动脉搭桥手术后特别地，细胞因子的表达 TNF-α将在冠状窦中进行全身和局部研究 样品72例患者将在使用旁路手术前后进行研究 经食管回声自动边界检测和高保真压力 导管以主要负载独立方式量化LV性能 使用压力-体积关系。腺苷的抗细胞因子作用将是 通过将患者随机分为接受常规心脏停搏或 腺苷心绞痛这个K24奖项将允许申请人扩大 这项研究工作，并指导研究人员直接参与他们在 及相关项目。该提案的第二部分将测试 假设收缩储备是一个重要预后决定因素， 严重心力衰竭患者。多巴酚丁胺超声心动图将 非侵入性地评估心肌β-肾上腺素能功能 100例射血分数降低的心力衰竭患者受体复合物 超过35%。定量自动边界检测和组织多普勒将 采用收缩储备将作为患者的标志物进行检测？的预后 使用：预负荷调整的最大功率，组织多普勒测量纵向 缩短速度和右心室面积分数变化。的 不能响应多巴酚丁胺而增加心室收缩性将 作为预测心脏病发病率或死亡率的标志物进行测试， 年将对患者进行定义为要求的不良事件随访 因心力衰竭住院治疗，持续静脉注射强心剂或 机械循环支持这一信息有希望戏剧性地 对这些患者临床管理的影响，包括优先地位 用于移植或机械循环辅助装置植入。 这些正在进行的研究为指导研究员提供了充足的机会， 以病人为中心的研究。

DESCRIPTION (Applicant?s Abstract) The candidate is a 42-year-old tenured Associate Professor who is in his 11th year after fellowship training. He is an established independent investigator who is completely committed to a life-long career in research and the mentoring of trainees. His outstanding institutional environment is supportive of high quality collaboration and ongoing research. This Midcareer Investigator Award in Patient-Oriented Research proposal will enable the expansion of two principal areas of hypotheses-driven human research: 1) Effects of cytokines on left ventricular (LV) performance in patients undergoing cardiac surgery and 2) Assessment of contractile reserve to predict prognosis in heart failure patients. The American Heart Association has recently awarded a National Grant-In-Aid entitled "Effects of Inflammatory Mediators on Left Ventricular Performance Following Cardiac Surgery" to the applicant as PI. This 3-year grant will support the infrastructure that is a requirement of this K24 application. A specific aim is to test the hypothesis that inflammatory mediators play an important role in cardiac depression following coronary bypass surgery. In particular, expression of the cytokine TNF- alpha will be studied both systemically and locally in coronary sinus samples. Seventy-two patients will be studied before and after bypass using transesophageal echo automated border detection and high fidelity pressure catheters to quantify LV performance in a predominant load-independent manner using pressure-volume relations. The anti-cytokine role of adenosine will be explored by randomizing patients to receive either routine cardioplegeia or an adenosine cardiopledgia. This K24 award will allow the applicant to expand this research work and mentor research fellows by directly involving them in this and related projects. The second arm of this proposal will test the hypothesis that contractile reserve is an important prognostic determinant in patients with severe heart failure. Dobutamine echocardiography will noninvasively assess the functionality of the myocardial beta-adrenergic receptor complex in 100 heart failure patients with ejection fraction less than 35%. Quantitative automated border detection and tissue Doppler will be used. Contractile reserve will be tested as a marker for patient?s prognosis using: preload-adjusted maximal power, tissue Doppler measures of longitudinal shortening velocity, and right ventricular fractional area change. The inability to augment ventricular contractility in response to dobutamine will be tested as a marker predictive of cardiac morbidity or mortality within one year. Patients will be followed for adverse events defined as requirements for hospitalization for heart failure, continuous intravenous inotropic or mechanical circulatory support. This information has promise to dramatically impact on the clinical management of these patients, including priority status for transplantation or mechanical circulatory assist device implantation. These ongoing studies provide ample opportunities for mentoring of fellows in patient-oriented research.