A North-South Partnership in Congenital Heart Disease (CHD)

先天性心脏病（CHD）是最常见的出生畸形，影响了近1%的活产儿童。这也是流产的一个主要原因。在西方国家，心脏直视手术甚至可以矫正严重的心脏畸形，这改变了冠心病患者的前景。在20世纪50年代，只有大约10%患有严重心脏畸形的儿童活到成年；现在这个比率超过了90%。相比之下，非洲国家在管理患有冠心病的儿童和成人方面面临巨大挑战，这与缺乏资源和缺乏非洲特定的证据基础有关。几乎所有关于冠心病病因、治疗和结果的研究都是在西方国家进行的。我们甚至不知道一些基本的信息，如非洲人群中冠心病的发病率是否与西方人群相同，以及所遇到的冠心病的范围是否相似。在某些非洲环境中，可能存在导致冠心病发展的特定风险因素，如果了解这些因素，可以对其进行修改以降低发生冠心病的风险，但迄今为止，非洲对可能导致冠心病的因素的研究很少或根本没有。在治疗方面，在任何非洲国家都不容易获得心脏直视手术，而且在选择最有可能从手术中受益的患者、最大限度地提高他们对手术的适应性以及术后随访复杂病例方面资源有限。这导致在如何在不太可能迅速改变的严重资源限制下为非洲CHD人群提供最佳结果的知识方面存在重大差距。该基金项目将在非洲大陆领先的教育机构南非开普敦大学建立可持续的CHD研究基础设施；并创建一个可以应用于其他南非中心和合作的非洲国家的模式。我们将邀请南非最大的开普敦冠心病病房的成人和儿童患者参与该项目。我们将建立一个全面的数据库，包括患者及其家属的临床信息，我们将要求血液或唾液样本，使我们能够调查遗传因素（基因）在导致冠心病中的作用。我们的目标是在两年的资助期内招募至少1200名患者。曼彻斯特大学的英国合作小组在研究基因在冠心病中的作用方面处于世界领先地位，所以我们将在非洲人群中测试我们已经证明在西方人群中很重要的基因的重要性，作为我们的第一个实验。如果基金会项目表明在非洲冠心病患者中招募并进行基因研究是可行的，我们将在未来的实验中很好地寻找特别是非洲冠心病的遗传原因。我们还将使用功能强大的计算机对冠心病患者的异常血流进行建模研究，看看我们是否能识别出对预测患者预后有用的模式。患者数据库还将为非洲研究人员提供一个独特的资源，以解决基因之外的冠心病病因的关键问题；特定心脏畸形的发生率；以及非洲患者的治疗结果。我们将请求同意与所有入组患者保持联系，这将使我们能够在两年的基金会奖励后研究冠心病在患者整个生命过程中的影响。该资源将帮助非洲研究人员确定最重要和最可行的研究主题，以便在他们所服务的人群中进行未来的研究。该登记处的研究成果将为解决西方国家和非洲国家之间冠心病的极端不同结果提供明确的指示。冠心病现在是一种高度可治疗的疾病。

Congenital heart disease (CHD) is the commonest birth malformation, affecting nearly 1% of liveborn children. It is also a major cause of miscarriage. In Western countries, the availability of open-heart surgery to correct even severe heart malformations has transformed the outlook for CHD patients. In the 1950s, only around 10% of children with a serious heart malformation lived to adulthood; the rate now is over 90%. By contrast, African countries face enormous challenges in managing children and adults with CHD, related both to lack of resources and lack of an African specific evidence base. Almost all research carried out into the causes, treatment and outcomes of CHD has been done in Western countries. We do not even know for certain such basic information as whether the rate at which CHD occurs is the same in African populations as it is in Western populations, and whether the range of CHD conditions encountered is similar. There may be particular risk factors for the development of CHD in certain African environments that, if they were known about, could be modified to reduce the risk of CHD occurring - but there is little or no African based research thus far into factors that may cause CHD. Regarding treatment, open heart surgery is not readily available in any African country, and there is limited resource to select the patients most likely to benefit from an operation, maximise their fitness for a procedure, and follow up complex cases following surgery. This results in major gaps in knowledge regarding how best to provide optimal outcomes for African CHD populations, within severe resource constraints that are unlikely to change rapidly. This foundation project will establish a sustainable CHD research infrastructure at the University of Cape Town, South Africa, the leading educational institution on the African continent; and create a model that could be applied in other South African centres and collaborating African countries. We will invite adult and child patients who attend the CHD units in Cape Town, which are among the largest in South Africa, to participate in the project. We will establish a comprehensive database containing clinical information about the patients and their families, and we will request samples of blood or saliva to enable us to investigate the role of inherited factors (genes) in causing CHD. We aim to enrol at least 1200 patients in the two year period of the grant. The UK partner group at The University of Manchester is among the world leaders in studying the role of genes in CHD, so we will test in this African population the importance of genes we have already shown to be important in Western populations, as our first experiment. If the foundation project shows that it is feasible to enrol and conduct genetic studies in African CHD patients, we will be very well placed to search for particularly African genetic causes of CHD in future experiments. We will also carry out studies modelling the abnormal blood flow that occurs in CHD patients using powerful computers, to see if we can identify patterns that are useful in predicting outcomes for patients.The patient database will also provide a unique resource for African researchers to address key questions about the causation of CHD beyond genetics; the rates at which particular heart malformations occur; and the outcomes for patients in an African context. We will request consent to keep in contact with all enrolled patients, which will enable us to study the effects of CHD throughout patients' lifecourse following the two-year Foundation Award. The resource will help African researchers to define the most important and feasible research topics for future study in the population they are serving. The research emerging from this registry will provide clear signposts on steps that can be taken to address the extremely different outcomes of CHD, which is now a highly treatable condition, between Western and African countries.