Prospective observational study investigating genomic determinants of outcome from cardiogenic shock (GOlDilOCS)

正在做什么？我们将研究患有危及生命的心源性休克的患者。当心脏突然不能向全身泵出足够的血液来满足脑、肺、肝和肾等重要器官的需要时，就会发生这种休克，从而损害了它们正常运作的能力。心源性休克通常是突发和意外事件的结果，例如心脏病发作。我们的研究旨在了解身体对心源性休克引起的血液供应不足的反应，并找出这种反应如何以及为什么因人而异。我们的长期目标是通过更好地了解哪些患者将从特定治疗中受益，以及我们如何确保正确的患者在正确的时间得到正确的治疗，来提高心源性休克的生存率。我们也希望确定新的药物治疗靶点，旨在改变机体对心源性休克的反应。为什么需要这样做？在欧洲，每年有超过50000名患者被诊断为心源性休克。尽管我们对急性心脏病患者的护理有所改进，但在过去20年里，心源性休克的死亡率仍然高得令人无法接受，在30%到50%之间。目前的治疗方法是使用药物和机械泵来暂时恢复或取代心脏的功能，为心脏恢复“争取时间”。大多数患者的死亡是由于其他重要器官的衰竭，尽管心脏功能有所恢复。我们认为，在许多情况下，死亡是由免疫系统对最初的侮辱的功能失调反应引起的炎症的结果。在幸存者中，30%将遭受长期心脏损伤（心力衰竭）的影响，以及严重疾病的后果，包括极度虚弱、疲劳、抑郁、反复住院的慢性疾病、无法重返工作岗位和生活质量差。如何做到这一点？我们认为，对心源性休克的失调和不适当的免疫反应会导致广泛的炎症、器官衰竭和死亡。此外，我们认为患者对心源性休克反应的性质和驱动因素在个体之间是不同的。我们将采取一种新的方法来研究心源性休克，通过测量基因活性和炎症介质的水平，从这种情况下的患者血液。使用这些数据，我们将：——更好地理解为什么人们开发心原性休克和死于它——识别为什么病人疾病的严重程度之间存在差异,应对目前的疗法——哪些患者可能从当前和新疗法中获益,为什么——工作与医生进行临床试验的新心原性休克的治疗方法使用从这项研究中获得的知识来改善这些试验的设计工作将在哪里做了什么?这项工作将在伦敦玛丽女王大学、牛津大学和威康桑格研究所进行，使用来自英国和德国患者的血液样本。这项工作什么时候开始？我们将于2022年至2025年完成这项工作。

What is being done? We will study patients with a life-threatening condition called cardiogenic shock. This type of shock happens when the heart is suddenly unable to pump sufficient blood around the body to meet the needs of vital organs such as the brain, lungs, liver and kidney, thereby impairing their ability to function normally. Cardiogenic shock is often a consequence of a sudden and unexpected event, for example a heart attack Our study is aimed at understanding how the body responds to the inadequate blood supply caused by cardiogenic shock and to find out how and why this response varies from one patient to another. Our long-term goal is to improve survival from cardiogenic shock by developing a better understanding of which patients will benefit from specific treatments and how we can ensure that the right patients are getting the right treatment at the right time. We also hope to identify new targets for drug treatment aimed at modifying the body's response to cardiogenic shock. Why is this needed? Every year across Europe over 50000 patients are diagnosed with cardiogenic shock. Despite improvements in how we deliver care to patients with acute heart problems, death rates from cardiogenic shock have remained unacceptably high at between 30% and 50% for the last two decades. Current treatments use drugs and mechanical pumps to temporarily restore or replace the function of the heart, to "buy-time" for the heart to recover. Most of the patients who die, do so due to failure of other vital organs, often despite some recovery of heart function. We believe that in many cases death is a consequence of inflammation caused by a dysfunctional response of the immune system to the initial insult. Of those who survive, 30% will suffer the effects of long-term heart damage (heart failure), as well as the consequences of critical illness, including extreme weakness, fatigue, depression, chronic ill health with repeated hospital attendances and admissions, being unable to return to work and a poor quality of life. How will this be done? We believe that a dysregulated and inappropriate immune response to cardiogenic shock results in widespread inflammation, organ failure and often death. Further we think that the nature and drivers of the patient response to cardiogenic shock differ between individuals. We will take a novel approach to studying cardiogenic shock by measuring the levels of gene activity and mediators of inflammation in blood from patients with this condition. Using these data, we will: - better understand the reasons why people develop cardiogenic shock and die from it - identify why there is variation between patients in severity of disease and the response to current therapies - work out which patients are likely to benefit most from current and new treatments and why - work with doctors undertaking clinical trials of new treatments for cardiogenic shock to use the knowledge gained from this study to improve the design of such trials Where will the work be done? The work will be undertaken at Queen Mary University London, the University of Oxford and the Wellcome Sanger Institute using blood samples from patients in the UK and Germany. When will this work take place? We will complete this work between 2022 and 2025.