CARDIAC PERFORMANCE BY QUANTITATIVE ECHOCARDIOGRAPHY

描述(申请人--S摘要) 候选人是一位42岁的终身副教授，他已经11岁了 在团契培训结束后一年。他是一名老牌的独立调查员 世卫组织完全致力于终生从事研究和 对实习生的指导。他杰出的制度环境是 支持高质量的协作和持续的研究。这是职业生涯中期 以患者为中心的研究提案中的研究员奖将使 假说驱动的人类研究的两个主要领域的扩展：1) 细胞因子对患者左心功能的影响 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 最近获得了国家助学金，题为“炎症的影响” 心脏手术后左心功能的介体 申请人为私家侦探。这笔为期3年的赠款将支持作为 此K24应用程序的要求。一个明确的目标是检验这一假设 炎症介质在心脏抑制中起重要作用 在冠脉搭桥手术后。尤其是细胞因子的表达 肿瘤坏死因子-α将在冠状静脉窦进行系统和局部研究。 样本。将对72名患者在搭桥前后使用 经食道回波自动边界检测和高保真压力 以一种主要的负荷无关的方式量化LV性能的导管 利用压力-体积关系。腺苷的抗细胞因子作用将是 通过随机将患者分为接受常规心脏停搏或 腺苷心脏涂膜液。这项K24奖励将允许申请者扩大 这项研究工作和指导研究人员通过直接参与 这个项目和相关项目。该提案的第二个分支将测试 假设收缩储备是一项重要的预后决定因素 严重心力衰竭的患者。多巴酚丁胺超声心动图 无创性评价心肌β-肾上腺素能的功能 100例射血分数偏低的心力衰竭患者的受体复合体 超过35%。定量的自动边界检测和组织多普勒将 使用。收缩储备将被检测为S患者预后的标志 用途：预负荷调节最大功率，组织多普勒测量纵向 短轴缩短率、右室面积变化。这个 多巴酚丁胺不能增强心室收缩能力将 被测试为预测心脏病发病率或死亡率的标志物 年。将跟踪患者的不良事件，将其定义为要求 因心力衰竭住院，持续静脉变力或 机械循环支持。这一信息有望戏剧性地 对这些患者的临床管理的影响，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.