Department of Perioperative Medicine, Bart's Heart Centre, St. Bartholomew's Hospital, London, UK.
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
Crit Care. 2023 Nov 27;27(1):460. doi: 10.1186/s13054-023-04752-8.
Recent clinical and research efforts in cardiogenic shock (CS) have largely focussed on the restoration of the low cardiac output state that is the conditio sine qua non of the clinical syndrome. This approach has failed to translate into improved outcomes, and mortality has remained static at 30-50%. There is an unmet need to better delineate the pathobiology of CS to understand the observed heterogeneity of presentation and treatment effect and to identify novel therapeutic targets. Despite data in other critical illness syndromes, specifically sepsis, the role of dysregulated inflammation and immunity is hitherto poorly described in CS. High-dimensional molecular profiling, particularly through leukocyte transcriptomics, may afford opportunity to better characterise subgroups of patients with shared mechanisms of immune dysregulation. In this state-of-the-art review, we outline the rationale for considering molecular subtypes of CS. We describe how high-dimensional molecular technologies can be used to identify these subtypes, and whether they share biological features with sepsis and other critical illness states. Finally, we propose how the identification of molecular subtypes of patients may enrich future clinical trial design and identification of novel therapies for CS.
近期，针对心源性休克（CS）的临床和研究工作主要集中在恢复低心输出量状态上，因为这是临床综合征的必要条件。但这种方法并未转化为改善预后的效果，死亡率仍保持在 30-50%的稳定水平。人们迫切需要更好地阐明 CS 的病理生理学，以了解观察到的临床表现和治疗效果的异质性，并确定新的治疗靶点。尽管在其他危重病综合征（特别是脓毒症）中已有数据，但 CS 中炎症和免疫失调的作用迄今描述甚少。高维分子谱分析，特别是通过白细胞转录组学，可能为更好地描述具有共同免疫失调机制的患者亚群提供机会。在这篇最新综述中，我们概述了考虑 CS 分子亚型的基本原理。我们描述了如何使用高维分子技术来识别这些亚型，以及它们是否与脓毒症和其他危重病状态具有生物学特征。最后，我们提出了如何通过鉴定患者的分子亚型来丰富未来 CS 的临床试验设计和新型疗法的开发。
