Study of Treatment's Echocardiographic Mechanisms (CLOVERS-STEM)

项目摘要/摘要 当宿主对感染的反应-包括免疫和应激反应-导致 器官功能障碍，中枢性心血管功能障碍。由此导致的败血症相关性低血压是致命的； 目前还不知道如何最好地治疗它。两种主要的治疗方法-静脉输液和儿茶酚胺 血管加压剂的输注-两者都有毒性，包括对心脏的直接影响，从而导致 通常被称为感染性心肌病。 NIH/NHLBI资助的一项大型临床试验，早期复苏败血症的晶体类药物或血管升压药 (三叶草)，将患者随机分为治疗脓毒症相关性低血压的竞争策略：Liberal 液体(血管升压剂之前的≥5L液体)或早期血管升压药(不含额外的直接血管升压药 流体)。三叶草是一个理想的实验室，可以用来了解管理策略对 感染性心肌病的演变及右室和左室的相对贡献 感染性心肌病(LV)对预后的损害以及基线超声心动图的意义 对某些人群的治疗效果的研究结果。治疗的超声心动图研究 机制(三叶草-STEM)是一项在三叶草中进行的前瞻性观察辅助研究。学习 受试者(N=210)在登记时和24小时后接受斑点跟踪超声心动图检查。三 综合AIMS使用稳健的超声心动图方法评估感染性心肌病的演变 以及对治疗的不同敏感性。 目的1评估早期血管升压剂治疗是否会导致24小时的左心室功能受损 全球纵向应变。目的2评估早期血管升压剂治疗是否会导致右室功能受损，如 测量右室与左室舒张末期面积的比值和右室游离壁的纵向应变。这两个目标将 同时探讨左、右室功能受损对临床终点的影响。AIM 3使用经过验证的 持续替代结局--第3天多器官功能障碍的变化--以探讨可能的可能性 基于基线超声心动图结果的治疗效果的异质性。该项目在以下方面有所创新 多个方面，以极大地促进我们对全球发病率和死亡率的一个主要原因的理解。

Project Summary/Abstract Sepsis results when the host response to infection—comprising both immune and stress responses—leads to organ dysfunction, centrally cardiovascular dysfunction. The resulting sepsis-associated hypotension is lethal; how best to treat it is currently unknown. The two main treatments—intravenous fluid and catecholamine vasopressor infusions—both have toxicities, including direct effects on the heart, thus contributing to what is often termed septic cardiomyopathy. A large NIH/NHLBI-funded clinical trial, Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS), randomizes patients to competing strategies for treating sepsis-associated hypotension: liberal fluids (≥5L fluids before vasopressors) or early vasopressors (immediate vasopressors without additional fluids). CLOVERS represents an ideal laboratory for understanding the effects of management strategies on the evolution of septic cardiomyopathy, the relative contributions of right ventricular (RV) and left ventricular (LV) impairment to outcomes from septic cardiomyopathy, and the implications of baseline echocardiographic findings for the effect of treatments in certain groups of people. The Study of Treatment’s Echocardiographic Mechanisms (CLOVERS-STEM) is a prospective observational ancillary study within CLOVERS. Study subjects (N=210) will undergo speckle-tracked echocardiograms at enrollment and 24 hours later. Three integrated aims employ robust echocardiographic measures to assess the evolution of septic cardiomyopathy and differential susceptibility to treatment. Aim 1 assesses whether the early vasopressor treatment leads to LV impairment at 24 hours, as measured by global longitudinal strain. Aim 2 assesses whether the early vasopressor treatment leads to RV impairment, as measured by the ratio of RV to LV end-diastolic areas and RV free wall longitudinal strain. These two aims will also explore the contributions of LV and RV impairment to clinical endpoints. Aim 3 uses a validated continuous surrogate outcome—the change in multiple organ dysfunction on day 3—to explore possible heterogeneity of treatment effect based on the baseline echocardiographic results. This project innovates in multiple respects to dramatically advance our understanding of a major cause of global morbidity and mortality.