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

调查心源性休克结果的基因组决定因素的前瞻性观察研究 (GOlDilOCS)

• 批准号: MR/W03011X/1
• 负责人: Alastair Proudfoot
• 金额: $ 27.83万
• 依托单位: Barts Health NHS Trust
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW03011X%2F1
• 关键词: Prospective; observational; study; investigating; genomic

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.

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。这种类型的休克发生时，心脏突然无法泵足够的血液在身体周围，以满足重要器官，如大脑，肺，肝脏和肾脏的需要，从而损害他们的正常功能的能力。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如何应对心源性休克引起的血液供应不足，并找出这种反应如何以及为什么从一个病人到另一个病人。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获得正确的治疗，提高心源性休克的生存率。我们还希望确定药物治疗的新靶点，旨在改变身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。尽管我们在如何为急性心脏病患者提供护理方面有所改进，但在过去二十年中，心源性休克的死亡率仍然高得令人无法接受，在30%至50%之间。目前的治疗使用药物和机械泵暂时恢复或取代心脏的功能，为心脏恢复“争取时间”。大多数死亡的患者是由于其他重要器官的衰竭，尽管心脏功能通常有所恢复。我们认为，在许多情况下，死亡是由免疫系统对初始损伤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，慢性疾病，反复住院和入院，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，通过测量这种情况下患者血液中的基因活性和炎症介质的水平。使用这些数据，我们将：- 更好地了解人们发生心源性休克并死于心源性休克的原因-确定患者在疾病严重程度和对当前治疗的反应方面存在差异的原因-找出哪些患者可能从当前和新的治疗中获益最多，以及原因-与从事心源性休克新疗法临床试验的医生合作，利用本研究获得的知识改进这样的审判工作将在哪里进行？这项工作将在玛丽女王大学伦敦、牛津大学和威康桑格研究所进行，使用的血液样本来自英国和德国的患者。 这项工作将于何时进行？我们将在2022年至2025年之间完成这项工作。

项目成果

Cardiogenic shock: all hail the RCT, long live the registry

心源性休克：RCT 欢呼，登记万岁

• DOI: 10.1186/s13054-024-04835-0
• 发表时间: 2024
• 期刊: Critical Care
• 影响因子: 15.1
• 作者: Warren A

In perspective: the patient at the heart of research in acute cardiovascular care.

透视：患者是急性心血管护理研究的核心。

• DOI: 10.1093/ehjacc/zuad027
• 发表时间: 2023
• 期刊: European heart journal. Acute cardiovascular care
• 作者: Thomson RJ

EPidemiology Of Cardiogenic sHock in Scotland (EPOCHS): A multicentre, prospective observational study of the prevalence, management and outcomes of cardiogenic shock in Scotland

苏格兰心源性休克流行病学 (EPOCHS)：一项关于苏格兰心源性休克患病率、治疗和结果的多中心前瞻性观察研究

• DOI: 10.1177/17511437231217877
• 发表时间: 2023
• 期刊: Journal of the Intensive Care Society
• 影响因子: 2.7
• 作者: Warren A