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

点击翻译按钮获取中文摘要

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.