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

扩张型心肌病（DCM）是一种心肌疾病，其特征是心室变薄和伸展，使心脏更难泵血（收缩功能障碍）。这种疾病的估计患病率高达1/250，主要影响年轻人。它与显著的发病率和死亡率相关，包括心力衰竭和心源性猝死，终末期DCM是心脏移植的主要适应症。目前DCM的疾病负担主要归因于科学知识的两个重要空白：首先，我们对DCM的病因学和遗传结构的理解仍然有限，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目标症状。除了侵入性心脏移植外，目前还没有治愈性治疗方法，也没有批准的针对潜在分子疾病机制的治疗方法。迫切需要更全面地了解DCM的遗传结构以及所涉及的基因和遗传变异的知识，以便为这些未满足的医疗需求提供解决方案。DCM NEXT联盟结合了DCM、深度临床表型、心脏基因组学、心脏转录组学、人工智能、计算机药物靶点发现和功能研究领域的8名研究人员的世界领先的跨学科专业知识和资源。他们将独特地利用其无与伦比的11，750名DCM先证者和亲属的队列，提供广泛的临床和组学数据。通过尖端的基因组学和心脏转录组学研究，该项目旨在（1）彻底改变基因检测和患者分层，以更准确地预测疾病发作，进展和主要不良心脏事件的风险;（2）通过识别和验证DCM发病机制中涉及的靶点，加速新型疗法的开发。

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.