Ucl Institute of Cardiovascular Science

Researchers say they developed an electrocardiographic imaging (ECGI) vest that could help predict sudden cardiac death risk. A team at University College London (UCL) says detailed mapping of the heart’s electrical activity was previously rare. It either required catheter insertion or single-use devices that prove costly and time-consuming. Plus, those devices could involve radiation. This team designed a reusable, time-efficient ECGI vest — which requires just five minutes per patient — with the potential for use in standard care. Dr. Gaby Captur of the UCL Institute of Cardiovascular Science and Royal Free Hospital, London, developed the vest. Researchers published their work in a paper in the Journal of Cardiovascular Magnetic Resonance. “We identified a problem in cardiology,” Captur said. “Heart imaging has made remarkable progress in recent decades, but the electrics of the heart have eluded us. The standard technology to monitor the heart’s electrical activity, the 12-lead electrocardiogram (ECG), has barely changed in 50 years. We believe the vest we have developed could be a quick and cost-effective screening tool and that the rich electrical information it provides could help us better identify people’s risk of life-threatening heart rhythms in the future. In addition, it can be used to assess the impact of drugs, new cardiac devices, and lifestyle interventions on heart health.” More about the ECGI vest UCL’s vest features 256 sensors that can combine with detailed images of heart structures taken by MRI. It generates 3D digital models of the heart and waves of electrical activity flowing through it. The reusable vest uses dry electrodes that can be washed between uses. These offer an alternative to metallic electrodes that require a layer of gel between the electrode and skin. UCL says this marks the first use of such electrodes for ECGI. Dr. Matthew Webber, a co-developer of the vest, says the in-depth ECGI can help correlate features of the heart with their consequences. He says the vest could show the impact the features have on the heart’s electrical system. “It adds a missing part of the puzzle,” Webber says. The team at UCL believes that better stratification of risk could help clinicians identify those in need of an implantable cardioverter defibrillator (ICD). ECGI-obtained biomarkers still need to be confirmed or dismissed through longitudinal studies that follow people over time, the team says. In the latest evaluation, the team assessed the vest’s feasibility in 77 patients, finding it reliable and durable. It’s been used successfully in 800 patients to date, according to UCL. Current uses of the vest include mapping the hearts of those with diseases like hypertrophic cardiomyopathy and dilated cardiomyopathy. The team patented its vest in the U.S. already and has ongoing work with g.tec medical engineering GmbH. g.tec made the prototype and the companies are looking at how to manufacture it more widely.

A new study looked at 926 polygenic risk scores for 310 diseases. It found that, on average, only 11% of individuals who develop disease are identified, while at the same time 5% of people who do not develop the disease test positive. Unaffected people usually outnumber those affected which results in far more false than true positive predictions. Polygenic risk scores, which estimate a person's disease risk based on thousands or millions of common genetic variants, perform poorly in screening and prediction of common diseases such as heart disease, according to a new study led by UCL (University College London) researchers. It has been claimed that polygenic risk scores will transform the prediction and prevention of common diseases. Companies have already been established that sell polygenic risk score testing services. Polygenic risk score testing is also one of the aims of the nationwide Our Future Health project. The new study, published in BMJ Medicine, looked at 926 polygenic risk scores for 310 diseases. It found that, on average, only 11% of individuals who develop disease are identified, while at the same time 5% of people who do not develop the disease test positive. Unaffected people usually outnumber those affected which results in far more false than true positive predictions. Lead author Professor Aroon Hingorani (UCL Institute of Cardiovascular Science) said: "Strong claims have been made about the potential of polygenic risk scores in medicine, but our study shows that this is not justified. "We found that, when held to the same standards as employed for other tests in medicine, polygenic risk scores performed poorly for prediction and screening across a range of common diseases." For the new study, researchers looked at data available in an open-access database, the Polygenic Score Catalog, to determine what the detection rate and false positive rate of the scores would be if used in screening. For breast cancer and coronary artery disease, the risk scores identified only 10% and 12% of eventual cases respectively, using a cut-off that resulted in 5% of unaffected individuals testing positive. The researchers also investigated how polygenic risk scores would perform if used alongside conventional screening methods. They found that, if used alongside conventional risk factors, several thousand people would need to have a polygenic risk score done to guide statin prescriptions to prevent one additional heart attack or stroke. The researchers noted that using age alone as a guide to statin prescription would be simpler and more effective at preventing heart attacks and strokes without the need for genetic testing. They also found that adding polygenic risk scores as first stage screening to determine who should be prioritised for mammography would miss most women who later develop breast cancer and generate many false positives, adding to the burden on healthcare systems. Co-author Professor Sir Nicholas Wald (UCL Institute of Health Informatics) said: "It has been suggested that polygenic risk scores could be introduced early on to help prevent breast cancer and heart disease but, in the examples we looked at, we found that the scores contributed little, if any, health benefit while adding cost and complexity." In the paper, the researchers suggest regulation of commercial genetic tests based on polygenic risk scores to "protect the public from unrealistic expectations and already stretched public health systems from becoming overburdened by the management of false positive results." The researchers said consumers of commercial polygenic risk score tests should be informed of the detection rate and false positive rate of the polygenic risk scores as well as the absolute risk with and without a polygenic score result so they can better judge whether the test is useful. Co-author Dr Jasmine Gratton (UCL Institute of Cardiovascular Science) said: "Polygenic risk scores seem attractive because genotyping is now inexpensive, the same for all diseases and is performed only once because a person's genotype does not change. However, these features are irrelevant if the test is not useful." Professor Sir Nick Wald said: "Our results build on evidence that indicates that polygenic risk scores do not have a role in public health screening programmes." The researchers said the performance of polygenic risk scores was unlikely to change much as the variants with the strongest effect had already been identified. Polygenic risk scores should not be confused with genetic testing for certain single gene mutations such as BRCA1 and BRCA2 which have an important role in screening for breast and ovarian cancer. Discovering variants that are associated with a higher risk of disease is still crucial for drug development, the team emphasised, as the variants encode proteins that can be targeted with drugs that would be useful for everyone regardless of their genetic makeup. The study was supported by the British Heart Foundation, UK Research and Innovation (UKRI), National Institute for Health and Care Research (NIHR), and the NIHR Biomedical Research Centre at UCLH and UCL.

Combining two types of heart scan techniques could help doctors to detect the deadly heart condition hypertrophic cardiomyopathy (HCM) before symptoms and signs on conventional tests appear. Combining two types of heart scan techniques could help doctors to detect the deadly heart condition hypertrophic cardiomyopathy (HCM) before symptoms and signs on conventional tests appear, according to a new study led by UCL researchers. The research, funded by the British Heart Foundation and published in the journal Circulation, opens the prospect of treating the condition at the earliest stages. Being able to detect HCM earlier than ever before will also assist trials investigating gene therapies and drug treatments aimed at stopping the disease developing in those at risk. HCM is an inherited condition that affects around 1 in 500 people in the UK. It causes the muscular walls of the heart to become thicker than normal, affecting how well the heart can pump blood around the body. It is a leading cause of heart failure and sudden cardiac death. Researchers from UCL, Barts Heart Centre and University of Leeds studied the hearts of three groups: healthy people, people who already had HCM, and people with an HCM-causing genetic mutation but no overt signs of disease (no heart muscle thickening). To do this, they used two cutting-edge heart scanning techniques: cardiac diffusion tensor imaging (cDTI), a type of MRI scan that shows how individual heart muscle cells are organised and packed together (the heart's microstructure), and cardiac MRI perfusion (perfusion CMR), which detects problems with the small blood vessels supplying the heart muscle (microvascular disease). The scans showed that people with overt signs of HCM have very abnormal organisation of their heart muscle cells, and a high rate and severity of microvascular disease compared to healthy volunteers. Crucially, the scans were also able to identify abnormal microstructure (muscle cell disorganisation) and microvascular disease in the people who had a problematic gene but no symptoms or muscle thickening. They found that 28% had defects in their blood supply, compared to healthy volunteers. This meant that doctors were able to more accurately spot the early signs of HCM developing in patient's hearts. The first drug to slow HCM progression -- mavacamten -- has recently been approved for use in Europe and will allow doctors to reduce the severity of the disease once symptoms and muscle thickening have appeared. Genetic therapies are also in development which could prevent symptoms entirely by intercepting HCM development at an early stage. Perfusion CMR is already being used in some clinics to help differentiate people with HCM from other causes of muscle thickening. The researchers think that these revolutionary new therapies, combined with cDTI and perfusion CMR scans, give doctors the best ever chance of treating people at risk of HCM early enough that the condition never develops. Dr George Joy, who led the research with Professor James Moon and Dr Luis Lopes (all UCL Institute of Cardiovascular Science), said: "The ability to detect early signs of HCM could be crucial in trials testing treatments aimed at preventing early disease from progressing or correcting genetic mutations. The scans could also enable treatment to start earlier than we previously thought possible. "We now want to see if we can use the scans to identify which patients without symptoms or heart muscle thickening are most at risk of developing severe HCM and its life-changing complications. The information provided from scans could therefore help doctors make better decisions on how best to care for each patient." Dr Luis Lopes (UCL Institute of Cardiovascular Science), senior author of the study, said: "By linking advanced imaging to our cohort of HCM patients (and relatives) with extensive genetic testing, this study detected microstructural abnormalities in vivo in mutation carriers for the first time and was the first to compare these parameters in HCM patients with and without a causal mutation. "The findings allow us to understand more about the early subclinical manifestations of this serious condition but also provide additional clinical tools for screening, monitoring and hopefully in the near future for therapeutic decision-making."