Understanding children’s heart disease in Africa

University researchers are working to understand the causes and impact of congenital heart disease (CHD) in African populations.

Understanding the problem 

Congenital heart disease (CHD) is a significant contributor to childhood mortality, accounting for one-third of all birth defects globally. CHD occurs when something goes wrong with the formation of a baby’s heart in early pregnancy, resulting in babies born with ‘holes in the heart’, blood vessels wrongly connected, or parts of the heart not properly formed.  

The outcomes for babies born with CHD are influenced by several important factors, including diagnostic capacity and access to healthcare.  

In low-income countries, which often face reduced diagnostic capabilities and limited healthcare access, CHD diagnosis can be late and treatment options reduced. Those with the condition are often not seen until CHD is at an advanced stage – when treatment is harder and outcomes become less positive. 

In 2019, the largest ever systematic review of this topic was carried out by a collaborative team of researchers from Manchester and the University of Cape Town. It provided evidence of a particularly severe unmet CHD diagnostic and research need in the African continent. 

Addressing the CHD knowledge gap  

Due to limited research in this area, it was important to understand whether CHD occurs at the same rate in African populations as in White European populations; if the range of conditions encountered is similar; and if there are different factors that influence CHD outcomes for children. 

Our researchers also needed to learn more about why CHD occurs in African people. After showing the importance of genetic factors in European populations, variations in the genomes of African volunteer patients were studied to see if the same genes are involved. With more genetic variation in African people than in those from other parts of the world, studying CHD genetics in the continent provides important insights, such as for patients of African heritage living elsewhere. 

The collaborative Manchester and Cape Town team created PROTEA (Partnerships in Congenital Heart Disease in Africa) to address these knowledge gaps and build research capacity and expertise in South Africa and Namibia. 

Creating better diagnostics  

Researchers worked with colleagues from the Red Cross War Memorial Children’s Hospital in Cape Town to use Computational Fluid Dynamics (CFD) to develop a patient-specific CFD pipeline that can be utilised in low-or middle-income countries.

CFD provides important diagnostic data and can be used to assess potential procedures and the associated risk of complications. In high-income countries, CFD is used routinely, but often relies on high-resolution Magnetic Resonance Imaging (MRI). 

Access to MRI is often limited or not possible in low-or middle-income countries, so researchers used more available technologies such as CT scans and Doppler echocardiography. 

The pipeline makes use of cloud computing where computational resources are otherwise unavailable. If adopted, this pipeline will enable countries with limited healthcare resources to benefit from the patient-specific diagnostic information and the insights which CFD provides.

Genomics of congenital heart disease in Africa 

Researchers collected DNA from mouth swabs provided by volunteer African patients and families. These were analysed by sequencing all the parts of the genome that code for proteins (around 30 million ‘letters’ of genetic code) and checked whether any segments of the genome had a different number of copies than the usual two (one from mother and one from father). 

After using these techniques on European populations, research had previously shown the impact of individual genetic ‘spelling mistakes’ and of differences in gene copy number on CHD risk, researchers recapitulated the findings in the African patient population and could identify credible genetic causes in around 20% of the patients. Many of the genes discovered were new.

Continuing the research and evaluating its impact 

Working with CHD volunteer families, research continues to investigate the genetic and molecular determinants within the region and creating new knowledge about the genetics of CHD. Having shown that we can generate high quality genetic data in Africa, with African patients, we are now looking to increase the number of patients in our study to give it greater power to detect important genetic influences. 

This work is also enabling the training of students and young scientists in South Africa in state-of-the-art genomic medicine and bioinformatics, delivering high-value skills and building capacity for CHD research in the area. 

The project has resulted in the first Zebra fish facility focused on cardiovascular disease on the African continent. The laboratory work is all done within South Africa to enhance local infrastructure.   

PROTEA has also created an open-source database to improve the quality, detail and accessibility of clinical record-keeping to support patient care planning. For example, patients who need to be fast tracked for procedures can be easily identified and contacted through information held in the database.  

The database became operational in Namibia in early 2021 and is being used to facilitate research and clinical care at Windhoek Central Hospital. Plans are now in place to roll this out to two further African countries.  

Meet the experts

Professor Bernard Keavney – BHF Professor of Cardiovascular Medicine at The University of Manchester and Consultant Cardiologist at Manchester University NHS Foundation Trust. 

Other investigators

• Professor Alistair Revell (The University of Manchester) 
• Professor Mark Engel (The University of Cape Town and South African Medical Research Council) 
• Professor Liesl Zühlke (Red Cross War Memorial Children’s Hospital, University of Cape Town, and South African Medical Research Council) 
• Associate Professor Malebogo Ngoepe (The University of Cape Town) 

Related publications

• Global birth prevalence of congenital heart defects 1970–2017: updated systematic review and meta-analysis of 260 studies.
• PROTEA, a southern African multicenter congenital heart disease registry and biorepository: rationale, design, and initial results.
• A patient-specific CFD pipeline using Doppler echocardiography for application in coarctation of the aorta in a limited resource clinical context. 

Related projects 

• DGEMBE (Developing GEnomic Medicine BEtween Africa and the UK)