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

项目总结/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。由此产生的败血症相关的低血压是致命的; 如何最好地治疗它目前是未知的。两个主要的治疗-静脉输液和儿茶酚胺 血管加压素输注-两者都有毒性，包括对心脏的直接影响，从而导致 通常被称为脓毒性心肌病。 一项由NIH/NHLBI资助的大型临床试验，晶体自由或血管加压药在脓毒症中的早期复苏 （CLOVERS），将患者随机分配至治疗脓毒症相关低血压的竞争策略：自由 液体（血管加压药前≥ 5 L液体）或早期血管加压药（立即血管加压药，无额外 流体）。CLOVERS代表了一个理想的实验室，用于了解管理策略对 脓毒性心肌病的演变，右心室（RV）和左心室的相对贡献 (LV)脓毒性心肌病预后的损害，以及基线超声心动图检查的意义 在某些人群中的治疗效果的发现。超声心动图治疗的研究 机制（CLOVERS-STEM）是CLOVERS中的一项前瞻性观察性辅助研究。研究 受试者（N=210）将在入组时和24小时后进行斑点追踪超声心动图。三 综合性aims采用强有力的超声心动图测量来评估脓毒性心肌病的演变 和对治疗的不同敏感性。 目的1评估早期血管加压药治疗是否导致24小时的LV损伤，如通过以下指标测量的 整体纵向应变目的2评估早期血管加压药治疗是否导致RV损伤， 通过RV与LV舒张末期面积的比值和RV游离壁纵向应变测量。这两个目标将 还探讨了LV和RV损伤对临床终点的贡献。Aim 3使用经过验证的 连续替代结果-第3天多器官功能障碍的变化-以探索可能的 基于基线超声心动图结果的治疗效果异质性。该项目创新于 从多个方面极大地促进了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.