Enabling advances in diagnosis, patient stratification and treatment for dilated cardiomyopathy patients and families (DCM Next)

扩张型心肌病(DCM)是一种以心室变薄和拉伸为特征的心肌疾病，使心脏更难泵血(收缩功能障碍)。据估计，这种疾病的患病率高达1/250，主要影响年轻人。它与严重的发病率和死亡率有关，包括心力衰竭和心脏性猝死，终末期扩张型心肌病是心脏移植的主要适应症。目前扩张型心肌病的疾病负担主要归因于两个重要的科学知识空白：第一，我们对扩张型心肌病的病因学和遗传结构的了解仍然有限，阻碍了基因检测在临床患者管理中的应用。其次，DCM患者的治疗选择有限。现有的治疗方法是通用的和针对症状的。除了侵入性心脏移植外，目前还没有根治性的治疗方法，也没有获得批准的治疗方法来研究潜在的分子疾病机制。为了为这些未得到满足的医疗需求提供解决方案，迫切需要对扩张型心肌病的遗传结构和所涉及的基因和遗传变异有更全面的了解。DCM Next财团结合了世界领先的跨学科专业知识和8名研究人员的资源，这些研究人员涉及DCM、深度临床表型、心脏基因组学、心脏转录学、人工智能、硅胶药物靶标发现和功能研究等领域。他们将独特地利用他们无与伦比的11,750名DCM先证者和亲属，拥有广泛的临床和组学数据。通过前沿的基因组和心脏转录组研究，该项目旨在(1)革新基因测试和患者分层，以便更准确地预测疾病的发生、发展和重大不良心脏事件的风险；(2)通过确定和验证参与DCM发病机制的靶点，加快新疗法的开发。

Dilated Cardiomyopathy (DCM) is a heart muscle disorder characterised by thinning and stretching of the heart ventricles, making it harder for the heart to pump blood (systolic dysfunction). This disorder, with an estimated prevalence of up to 1/250, predominantly affects younger adults. It is associated with significant morbidity and mortality, including heart failure and sudden cardiac death, with end-stage DCM being the leading indication for heart transplantation. The current disease burden in DCM is largely attributable to two important gaps in scientific knowledge: Firstly, our understanding of the aetiology and genetic architecture of DCM remains limited, hindering the utility of genetic testing in clinical patient management. Secondly, there are limited therapeutic options for DCM patients. Existing therapies are generic and target symptoms. No curative treatments exist, apart from invasive heart transplantation and there are no approved therapiestargeting underlying molecular disease mechanisms. A fuller understanding of the genetic architecture of DCM and knowledge of the genes and genetic variants involved are critically needed to provide solutions for these unmet medical needs. The DCM NEXT consortium combines world-leading interdisciplinary expertise and resources of 8 investigators in the fields of DCM, deep clinical phenotyping, cardiogenomics, cardiac transcriptomics, artificial intelligence, in silico drug target discovery and functional studies. They will uniquely leverage their unparalleled cohort of 11,750 DCM probands and relatives with extensive clinical and omics data. Through cutting-edge genomic and cardiac transcriptomic studies, the project aims to (1) revolutionise genetic testing and patient stratification for more precise prediction of disease onset, progression and risk of major adverse cardiac events; and (2) accelerate development of novel therapies by identifying and validating targets involved in pathogenesis of DCM.