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，影响近1%的活产儿童。这也是流产的主要原因。在西方国家，即使是严重的心脏畸形，也可以进行心内直视手术，这改变了CHD患者的前景。在20世纪50年代，只有大约10%的患有严重心脏畸形的儿童活到成年;现在这个比例超过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着巨大的挑战，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的病因、治疗和结局的研究都是在西方国家进行的。我们甚至不知道某些基本信息，如非洲人群中CHD的发生率是否与西方人群相同，以及CHD疾病的范围是否相似。在某些非洲环境中可能存在冠心病发展的特殊风险因素，如果已知这些因素，可以对其进行修改以降低冠心病发生的风险-但迄今为止很少或没有基于非洲的研究可能导致冠心病。关于治疗，在任何非洲国家都不容易进行心脏直视手术，而且资源有限，无法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度，并在手术后对复杂病例进行随访。这导致在不太可能迅速改变的严重资源限制范围内，如何最好地为非洲冠心病人群提供最佳结局的知识存在重大差距。该基金会项目将在非洲大陆领先的教育机构南非开普敦大学建立一个可持续的冠心病研究基础设施;并创建一个可在南非其他中心和非洲合作国家应用的模式。我们将邀请在开普敦的CHD单位就诊的成人和儿童患者参加该项目，该单位是南非最大的CHD单位之一。我们将建立一个包含患者及其家属临床信息的综合数据库，我们将要求血液或唾液样本，以便我们能够调查遗传因素（基因）在导致CHD中的作用。我们的目标是在两年的补助期内至少招募1200名患者。曼彻斯特大学的英国合作小组是研究基因在CHD中作用的世界领导者之一，因此我们将在这个非洲人群中测试我们已经证明在西方人群中重要的基因的重要性，作为我们的第一个实验。如果该基金会项目表明，在非洲CHD患者中招募和进行遗传研究是可行的，我们将在未来的实验中特别有能力寻找CHD的非洲遗传原因。我们还将利用强大的计算机对冠心病患者发生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，以解决有关冠心病病因的关键问题，而不仅仅是遗传学;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选患者保持联系，这将使我们能够在两年基金会奖励后研究CHD对患者整个生命过程的影响。该资源将帮助非洲研究人员确定最重要和最可行的研究课题，供今后在他们所服务的人口中进行研究。这项登记研究将提供明确的路标，说明可以采取哪些措施来解决西方国家和非洲国家之间冠心病（现在是一种高度可治疗的疾病）的极端不同结果。

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.