Our Impact

Cardiogenomics – Decoding inherited cardiovascular diseases to deliver new pathways of patient care

UCLH BRC cardiovascular theme has transformed understanding of inherited cardiovascular disorders that affect 600,000 people in the UK, improving outcomes in affected families. Research is embedded in the UK’s largest inherited cardiac disease services, which evaluate over 8000 patients each year, creating databases of detailed genetic sequences of patients’ and relatives’ DNA, linked to clinical data to help interpret test results and support family screening. This has enabled new genetic discoveries1 and identified mutations placing patients at high risk of sudden death.

Now, three in five patients with inherited heart muscle disease receive a genetic diagnosis, enabling clinicians to more precisely target expensive, but lifesaving defibrillator treatment. At the same time, 53% of healthy relatives are discharged from lifelong screening.

With international collaborators, the UCLH team developed risk calculators for adults and children with hypertrophic cardiomyopathy and laminopathies. These are incorporated in European guidelines on defibrillator treatment, helping to prevent thousands of sudden cardiac deaths.

The UCLH team has also identified and maintained databases of mutations causing Familial Hypercholesterolaemia (FH), a condition leading to premature heart attacks prevented by early treatment with cholesterol-lowering statin drugs.

It was the first to show that FH is twice as common as previously thought, affecting 1 in 250 people, that only 7% of those affected have been identified and treated, and that patients with many weak genetic variants may masquerade as FH patients2. Establishment by UCLH in 2012 of the UK Paediatric FH Register has demonstrated the safety and normal growth rate of children with FH treated with statins.

UCLH genetic discoveries are included in the National Genetic Testing portfolio, and UCLH research findings have informed the Chief Medical Officer (CMO) 2016 report on Genomic Medicine3, are incorporated in 2017 NICE guidance (CG71) on eligibility for FH cascade testing in families and had a direct influence on the 2019 NHS Long Term plan which has an ambition to identify 25% of undetected FH patients within the next 5 years.

Locally, the findings have supported the 24 lipid clinics within the greater London region and led to implementation of an FH screening tool through the North Thames Genomic Alliance and local GP services, with sequencing results now being added to health records.

  1. Lopes LR., European Heart Journal, 2021;
  2. Talmud, P., Lancet, 2013;
  3. Humphries S., CMO Report 2016, Genomics

Faster and better heart imaging for improved patient care

Our cardiologists, physicists, and computer scientists have advanced cardiac magnetic resonance imaging (MRI) producing static and moving images of the heart in greater detail than ever before. Strategic links with industry including, Siemens and Phillips, mean technological advances developed at UCLH are available to patients world-wide. Having been incorporated into 14 international clinical guidelines, these techniques are revolutionising patient care not just locally, but globally.

Cardiac MRI has also become a standard test for assessing response to new drugs pushing the frontiers of treatment. The UCLH team has made cardiac MRI faster (improving tolerability and patient experience), better (measuring structure and function, and now the biological changes leading to disease, to develop and evaluate targeted treatment) and more streamlined (using computer systems for image processing and interpretation).

Clinicians can now accurately identify early changes to heart muscle caused by inherited or lifestyle diseases, so that earlier treatment can prevent irreversible damage. This has delivered benefits in the treatment of common and rare conditions (e.g., heart failure and familial heart muscle diseases) and led to insights into how the heart changes with age, athletic training, and pregnancy. It has also revealed new unanticipated causes of disease such as deposition of abnormal proteins (amyloidosis) in the heart with age, from cancer or genetic diseases2.

Combined with electrical mapping, cardiac MRI is pinpointing sites of dangerous heart rhythms more accurately, so ablation treatment is now delivered more effectively. Heart patients often receive lifesaving pacemakers. However, until recently, if they developed conditions, such as cancer or stroke, they were denied MRI scans because of safety concerns over electronic devices in magnetic scanners, delaying care.

The UCLH team, in partnership with Barts Heart Centre, developed safe protocols3 now in national guidance that give all heart patients access, increasing MRI scans four-fold for affected patients. By harnessing the power of artificial intelligence, UCLH- led innovations have accelerated the rate at which high quality MRI images are produced, processed, and interpreted3. This means cardiac MRI can now be used routinely in the youngest children and infants, becoming a pivotal test in modern congenital heart disease care. It also means cardiac MRI will become a routine, daily test, reducing NHS cost and increasing throughput, freeing clinicians for direct patient care.

1. Knott KD, Circulation, 2020;
2. Scully PR, European Heart Journal, 2020;
3. Bhuva A, European Heart Journal, 2021

Transforming national and international clinical practice for the treatment of resistant hypertension

UCLH BRC has led research to understand causes of resistant hypertension and assess the safety of a commonly used treatment, spironolactone. This has transformed clinical practice for patients globally and could reduce deaths from uncontrolled high blood pressure by 25%. Hypertension, or high blood pressure (BP), is a common cause of heart disease, kidney disease and stroke, affecting over a billion people worldwide and accounting for 10million deaths each year. In most cases, BP is controlled by lifestyle and drug therapy. However, one in ten people have “resistant” hypertension. Their BP is poorly controlled despite a combination of three different BP-lowering medicines. Over 100million people globally are affected by resistant hypertension and yet the underlying causes were poorly understood, with no rational basis for treatment recommendations.

Research led by UCLH BRC director, Professor Bryan Williams, in collaboration with Queen Mary’s and Dundee University and the British Hypertension Society PATHWAY study group, identified the underlying causes of resistant hypertension, transforming care of patients worldwide. In the landmark PATHWAY2 trial1, 2 the team showed resistant hypertension is mainly due to excessive sodium (salt) retention, in many cases caused by high levels of the salt-retaining hormone, aldosterone, and proved that repurposing a cheap diuretic drug, spironolactone – an aldosterone antagonist – could control BP in these patients.

Patients with chronic kidney disease (CKD) are at especially high risk from resistant hypertension and were excluded from the PATHWAY 2 trial because of a higher risk of developing dangerously high blood potassium levels with spironolactone treatment. The UCLH BRC team in collaboration with a consortium of clinical academics from Europe and US, conducted a Phase II trial in patients with advanced CKD and uncontrolled resistant hypertension, across 62 centres in 10 countries3. They demonstrated for the first time that spironolactone can be used effectively and safely to reduce blood pressure in patients with advanced CKD when combined with a novel potassium binding agent (patiromer).

PATHWAY research is cited as key evidence in all international guidelines and has transformed clinical practice around the world, providing an effective, accessible, low-cost treatment to reduce the burden of cardiovascular disease. Once fully implemented, the new treatments should reduce disease and death due to uncontrolled blood pressure by up to 25% globally.

1. Williams B, Lancet, 2015;
2. Williams B, Lancet Diabetes, 2018;
3. Agarwal R, Lancet, 2019

Woman in lab