Work Sponsored by CORDA
Dudley Pennell
By Dudley Pennell, Professor of Cardiology
The Cardiovascular Magnetic Resonance (CMR) Unit at Royal Brompton Hospital is the largest in the world. In 2006-7 the clinical throughput was 3900 patients and 34 peer reviewed research papers were published identifying the value of CMR in diagnosis, treatment and prevention of heart disease. Senior staff delivered many lectures on this research worldwide.
A new state-of-the-art Siemens Avanto CMR scanner was installed in 2006 to replace the HEFCE Siemens Sonata scanner. Siemens donated both scanners in direct recognition of the Unit’s leading role in CMR research. CORDA’s mobile scanner has been operational since December 2003.
The major research areas in 2006-2007 were early vascular disease perfusion and thalassaemia.
Early vascular disease
Following the publication of the paper on the findings of the CASPAR project (CORDA Asymptomatic Subject Plaque Assessment Research), the investigation and treatment of early vascular disease has continued to be pursued. Dr Niall Keenan, CORDA Research Fellow, has worked with colleagues at the Department of Computing at Imperial College (Professor Guang-Zhong Yang) to validate new software that semi-automatically analyses the 3D images and constructs a carotid model with quantification of the atheroma burden. These techniques have been used in a trial to define the atheroma burden of normal healthy volunteers aged 20 to 70. The results show that atheroma is progressive in its earliest stages throughout life, and that patients with coronary artery disease can be distinguished from normals by the aged appearance of their carotid arteries. Dr Keenan has also collaborated with Professor Dorian Haskard from Hammersmith Hospital in the scanning of patients with inflammatory conditions including arthritis in which atheroma is thought to be accelerated, and shown that carotid wall thickening is significantly advanced for age. These results suggest that assessing wall thickening is a valuable technique for the identification of early atheroma.
Perfusion
CORDA Research Fellow Dr Chiara Bucciarelli-Ducci, has recently started in the Unit and is pursuing the measurement of myocardial perfusion. She is examining the role of myocardial perfusion in groups of patients where CMR has particular advantage over conventional techniques using injectable radiation, such as young women. The aim of this research is to start bringing CMR perfusion imaging into clinical practice for selected patients groups within two years.
Thalassaemia
Thalassaemia is the most common single gene disorder in the world. More than 60,000 children annually are born with this very serious condition, with the highest prevalence in the Mediterranean and Asia. Death occurs in infancy from anaemia unless monthly blood transfusions are given.
These transfusions however, load the body with iron that causes heart failure and eventually death unless adequate iron removal treatment is given. The Unit has pioneered a new CMR test to measure cardiac iron, which allows for the first time, the proper planning of cardiac therapy for these patients.
In 2006-2007, the Unit published two world-leading randomised controlled trials of therapy in thalassaemia. The first was a multicenter CMR study conducted in Italy and Greece for which the Unit was the coordinating centre, which showed for the first time that a new drug (deferiprone) is significantly better at removing excess iron from the heart than the conventional drug (deferoxamine given by injection). This study was published in the prestigious journal Blood.
The second randomised controlled trial reported the outcome of the project using the CORDA mobile scanner, which had travelled three times to Cagliari, Sardinia, for a randomised controlled trial of a new drug called deferiprone. One hundred and sixty three patients were screened, and sixty one included into the trial. Patients were treated with either standard management using standard daily-injected deferoxamine or standard management combined with deferiprone. The trial showed that combined treatment is very effective. These landmark trials open the door to better treatment and lives saved.
John Deanfield
By John Deanfield, Professor of Cardiology
The research efforts of the Vascular Physiology Unit, where CORDA supports the salaries of Ann Donald (Clinical Vascular Scientist) and Elizabeth Redmond (Research Nurse), continues to focus on the emerging phenotype of early arterial disease and the impact of genetic and environmental risk factors, as well as the effect of injury and repair mechanisms. CORDA has also provided funding for Ann Donald’s part-time PhD.
Periodontitis and Endothelial Function
In conjunction with the Department of Oral Health at the University of Connecticut and the Eastman Dental Institute at University College London, 120 patients with severe periodontitis (gum disease) were studied. Half were given intensive treatment, and the remainder received ‘normal’ gum care. All were examined using FMD (flow mediated dilatation) and other measures of inflammation immediately after treatment commenced, then after a week, a month, two months and six months. The results were significant and showed that the endothelial function of those receiving intensive treatment immediately became worse, and they also showed signs of systemic inflammation. However, after two months their improved oral health was associated with a significant improvement in their endothelial function.
It has been known now for some time that inflammation plays a role in the development of atherosclerosis and subsequent cardiovascular disease. Similarly, gum disease is associated with inflammation (a reaction of the body to fight disease). This was the first time research had shown that reducing the gum disease, and hence the inflammation can cause such rapid improvement in the functioning of the arteries, and so helping to prevent the onset of cardiovascular disease.
The results of this study were published in a paper in The New England Journal of Medicine, in February 2007.
The ALSPAC (Avon Longitudinal Study of Parents and Children) Study
This remains one of the core activities of the Unit. Following the completion last year of the study of four vascular measurements of structure and function (flow mediated dilatation, pulse wave velocity, pulse wave analysis and distensibility) in children aged 10 years, the genetic and environmental factors which relate to impaired arterial function in this group continue to be studied.The effect of childhood infections on vascular function in the young, and their potential for recovery one year later has already been reported, and the data obtained is being analysed in terms of both the environmental and genetic influences on vascular function. Analysis of blood samples collected at aged 9 and 11 years will greatly enhance the understanding of the risk factors and vascular responses.
The ALSPAC cohort will be re-studied at 17 years to examine the impact of puberty and teenage lifestyle and the emerging of structural arterial disease.
1946 birth cohort
A pilot study of the people born in 1946 is underway in Manchester. These 60 year olds have been followed from birth and their lifetime exposure to risk factors has been documented. They are now being assessed for health in ageing, incorporating measures of cardiovascular health, bone and muscle health, cognitive function and genetics. The cardiovascular measures, which include electrocardiogram, echocardiogram, ultrasound of the carotid arteries, pulse wave velocity and heart rate variability, are being co-ordinated in the Vascular Physiology Unit. Extension of the study into four other centres around the United Kingdom is being planned.
The MEND Programme
The Vascular Physiology Unit are involved in the MEND Programme (mind, exercise, nutrition and diet), one of the United Kingdom’s most innovative and effective obesity prevention and treatment programmes for children, which, by the end of 2008 will be running at over 300 locations in the UK. MEND’s mission is to educate and motivate children and their parents to change unhealthy food habits to ones that support a healthier lifestyle and encourage them to take adequate exercise. Great Ormond Street and the Institute of Child Health have been participating in the first studies and the Vascular Physiology Unit has carried out vascular monitoring of the children involved.