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Clinical and genetic characterisation of inherited forms of heart muscle disease and the impact on service provision and patient care

Summary of the impact

Over the past decade our research findings have impacted on the diagnosis and treatment of patients with inherited cardiomyopathies. Our work on risk stratification in patients with hypertrophic cardiomyopathy forms the basis for international guidelines on the use of implantable cardioverter defibrillators. Our research in patients with arrhythmogenic right ventricular cardiomyopathy has led to the development of a new international standard for the diagnosis of disease in patients and relatives. We have contributed to national and European guidelines on genetic testing in these conditions. We have also been influential in changing national policies, service design, and provision of care for inherited heart muscle disease.

Submitting Institution

University College London

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Biological Sciences: Genetics
Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Neurosciences

Practice-changing clinical trials expand the treatment options for heart disease

Summary of the impact

Randomised placebo-controlled trials (RCTs) are the most robust way to demonstrate the effectiveness of medical therapies. The University of Glasgow's Robertson Centre for Biostatistics (RCB) is internationally renowned for its biostatistical input and leading roles on landmark RCTs of cardiovascular therapies. The findings of the BEAUTIFUL and SHIFT studies underpinned European and UK regulatory approval for a novel use of the heart-rate-lowering drug ivabradine, potentially preventing thousands of hospital admissions for heart failure every year. The IONA trial supported UK approval of generic versions of another heart drug (nicorandil), thereby enhancing cost-effectiveness for the NHS. The BEAUTIFUL, SHIFT, DOT-HF and CAPRICORN trials provided the evidence base for US, European and UK guideline recommendations, steering best practice for treatment of patients with heart disease worldwide.

Submitting Institution

University of Glasgow

Unit of Assessment

Public Health, Health Services and Primary Care

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services

Lower risks to patients, advances in international practice and substantial resource savings result from ‘beating heart’ off-pump coronary artery bypass surgery

Summary of the impact

University of Bristol researchers at the Bristol Heart Institute (BHI) have pioneered the development and clinical take-up of the novel technique of off-pump coronary artery bypass (OPCAB) surgery. Over ten clinical trials and several large cohort analyses have assessed the impact of this technique on elective and high-risk patients. The results have shown that it is as safe as the conventional coronary artery bypass grafting (CABG) technique that uses a cardiopulmonary bypass pump and cardioplegic arrest. Most importantly, however, OPCAB significantly reduces the risk of post-operative complications, and reduces morbidity and mortality. It also uses less hospital resources, reducing time in intensive care and length of hospital stay. In 2011 (the last year for which data are available), 20% of CABG operations in the UK were carried out with the OPCAB technique and it has had significant take-up overseas (for example, 18% of CABG operations in the US and 21% in the EU in 2010). NICE has recommended the safety and efficacy of OPCAB surgery.

Submitting Institution

University of Bristol

Unit of Assessment

Clinical Medicine

Summary Impact Type

Technological

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services

A: The GRACE risk score: a reference standard for the management of acute coronary syndrome

Summary of the impact

Impact: Health and welfare; the GRACE risk score (derived using data from 102,000 patients with acute coronary syndrome (ACS) in 30 countries) identifies high-risk ACS patients more effectively than do alternative methods.

Significance: GRACE is now a reference standard and has resulted in international guideline changes. It is estimated to save 30-80 lives for every 10,000 patients presenting with non-ST elevation ACS.

Beneficiaries: Patients with ACS; the NHS and healthcare delivery organisations.

Attribution: All work was led by Fox (UoE) with co-chair Gore (University of Massachusetts) and was developed from Edinburgh-based studies.

Reach: Worldwide: guidelines adopted in more than 55 countries; >10,000 downloads of app.

Submitting Institution

University of Edinburgh

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Public Health and Health Services

L: Pharmacological and interventional therapies for acute coronary syndromes improve patient outcome

Summary of the impact

Impact: Health and welfare, policy and clinical practice; randomised trial evidence has changed the management and outcome of acute coronary syndromes (ACS) globally.

Significance: Advanced anti-platelet and revascularisation therapies have become standards of care worldwide. There have been large (10-50%) reductions in the death rate from coronary heart disease across Europe. Clopidogrel was the second best-selling drug in the USA in 2011.

Beneficiaries: Patients with ACS, clinical practitioners, NHS and healthcare delivery organisations, policy-makers, pharmaceutical companies.

Attribution: Building on prior studies, Fox (UoE) and colleagues led multicentre randomised controlled trials; international trials were co-chaired by Fox with international investigators.

Reach: Global; guideline changes in Europe and USA; applies to the up to 5% of the population who have ACS.

Submitting Institution

University of Edinburgh

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology

Improving clinical care for lymphangioleiomyomatosis

Summary of the impact

Research at the University of Nottingham has defined the clinical phenotype and management of lymphangioleiomyomatosis, a rare and often fatal multisystem disease affecting 1 in 200,000 women worldwide. The group has led the development and evaluation of new therapies and diagnostic strategies which are now part of routine clinical care. The research has underpinned the transformation of this previously under recognised and untreatable disease into a condition recognised by respiratory physicians, with international clinical guidelines, patient registries, clinical trials, specific treatments and a UK specialist clinical service.

Submitting Institution

University of Nottingham

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services

Reducing mortality following acute myocardial infarction (AMI)

Summary of the impact

Patients with evidence of heart failure following acute myocardial infarction (AMI) have a particularly poor prognosis, with substantially increased risk of death and subsequent cardiovascular events. The Acute Infarct Ramipril Efficacy (AIRE) Randomised Controlled Trial (RCT) was an international trial designed and led by the University of Leeds. AIRE demonstrated, for the first time, that early treatment of patients with clinical evidence of heart failure following AMI with the angiotensin converting enzyme inhibitor (ACEI) ramipril significantly improved survival and quality of life compared with placebo treated patients. The strategy of early initiation of ACEI is now a cornerstone in the management of patients suffering from AMI, leading to a global improvement in post-AMI outcomes.

Submitting Institution

University of Leeds

Unit of Assessment

Public Health, Health Services and Primary Care

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences

D: Preventing deaths from pesticide self-poisoning in rural Asia – pralidoxime is hazardous and banning organophosphorus insecticides is beneficial

Summary of the impact

Impact: Health and welfare; public health studies in Sri Lanka and clinical trials in a cohort of 35,000 pesticide self-poisoning patients have led to the withdrawal of high-dose pralidoxime as a WHO-recommended treatment and bans of three toxic pesticides in Sri Lanka.

Significance: Resultant changes in clinical practice and pesticide regulation have saved 3000 lives in the last four years in Sri Lanka alone; in the rest of Asia many times this as local guidelines and practice have changed.

Beneficiaries: Patients and communities, healthcare providers, policy-makers.

Attribution: Studies designed and led, with international collaborators, by Michael Eddleston, UoE.

Reach: International, particularly Asia, changes in WHO and international guidelines on pesticide use.

Submitting Institution

University of Edinburgh

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Pharmacology and Pharmaceutical Sciences, Public Health and Health Services

BNP as a Diagnostic and Risk Stratifying Test in Cardiology

Summary of the impact

Our research on brain/B-type naturietic peptide (BNP) has helped to diagnose both types of heart failure (systolic and diastolic heart failure) and to identify high-risk aortic stenosis patients for surgery. We were first to demonstrate the value of BNP as a biomarker for left ventricular systolic dysfunction, isolated diastolic dysfunction and for aortic stenosis. BNP testing is now recommended in Guidelines as a screening test for patients with suspected heart failure (Class I recommendation) and in the current European Society of Cardiology consensus statement for diagnosis of diastolic heart failure. The European Society of Cardiology Guidelines have also introduced BNP testing in the management of patients with aortic stenosis (Class IIb recommendation).

Submitting Institution

University of Dundee

Unit of Assessment

Clinical Medicine

Summary Impact Type

Technological

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences

Molecular genetic characterisation of the causes of familial hypercholesterolaemia has led to improved diagnosis, prevention and treatment.

Summary of the impact

Basic molecular genetic research undertaken over the last 20 years by UCL Cardiovascular Genetics has had a significant impact on the identification and treatment of patients with familial hypercholesterolaemia (FH). We have developed DNA testing methods in the three genes currently known to cause FH and have established DNA diagnostic protocols which are now in wide use throughout the UK. As a direct consequence of our work, we estimate that up to 3,000 FH patients in the UK have had their diagnosis of FH confirmed by a DNA test. Our work led to the National Institute of Health and Clinical Excellence (NICE) in 2008 strongly recommending DNA and cascade testing and early treatment with high intensity statins, and furthermore, the inclusion of FH checks in the NHS's Vascular Checks programme.

Submitting Institution

University College London

Unit of Assessment

Clinical Medicine

Summary Impact Type

Health

Research Subject Area(s)

Medical and Health Sciences: Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services

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