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Research

The Academic Cardiovascular Unit and the Portex Unit of Paediatric Anaesthesia, Pain Research, Critical Care, Respiratory Medicine, Physiology and Physiotherapy comprise the Cardiorespiratory Theme led by Professor John Deanfield.  We are the largest paediatric cardiology and research department in the UK with over £30 million received in grants over the last six years and over 400 peer-reviewed papers published since 2003. 

Activities cover both basic research in cardiovascular developmental biology and cardiovascular genetics at ICH along with translational clinical research (funded either by the Institute of Child Health, UCL or by Great Ormond Street Hospital for research-active clinicians).

Our research portfolio has contributed substantially to the success of the Research Assessment Exercise (RAE) return, which placed UCL top in the Biomedical Sciences and Life Sciences category.

Within the Cardiac Unit itself, research is divided into themes.  For information on each of these themes and their respective research including current projects please click on the links below.

Anatomy/Biology

Andrew Cook and his team comprising Gemma Price and Vi Tran focus on education and research into the structure of the congenitally malformed heart and how this relates to surgical correction or intervention, to specific animal models and to normal development.

Current education projects include the building of a large digital library of cardiac morphology and the development of the world's first interactive virtual heart simulator www.heartworks.me.uk.  The digital library is being built as an educational resource from a number of existing collections, examples of which can be seen at www.cardiacmorphology.com (part funded by the British Heart Foundation).  The team interacts closely with and provides material for other groups such as www.ctsnet.org and the archiving group of the International Society for the Nomenclature of Paediatric and Congenital Heart Disease.  In addition, the group is now investigating, with colleagues at the Institute of Child Health and UCL, to extend these activities to aid the production of patient specific virtual models of congenital heart disease.

Heart/Muscle Disease and Heart Transplantation

Led by Mike Burch, current research involves collaboration with Great Ormond Street Hospital on understanding the role of stem cells in cardiac repair in the young.  A clinical trial of stem cell therapy has begun.  Paul Riley is collaborating on a project involving an investigation of Prox-1 in human myocardial tissue.  Further ongoing research involves looking at the development of vascular disease in the largest cohort of paediatric transplant patients in Europe.

A collaboration with Nigel Klein is investigating the role of CMV in post transplant vasculopathy.  Ex-vivo staining for CMV specific CD-4 and CD-8 cells will be used and NK cells also investigated.  Cytokine production by CMV specific T cells will be assessed.  New imaging techniques are being investigated for coronary vasculopathy using Magnetic Resonance in comparison to intra-vascular ultrasound.  Other current studies involve an investigation of diet and exercise post-transplant.

Imaging

Led by Andrew Taylor, the aim of this theme is to incorporate MR techniques into the assessment of congenital and acquired heart disease in the young.  With cardiovascular MR, anatomy can be assessed three-dimensionally, and can be presented in a format that can provide virtually unrestricted cross-sectional and volume-rendered views. Anatomical views can be combined with functional physiological information that can be rapidly acquired in a single breath-hold with vastly improved spatial and temporal resolution.

This physiological data includes accurate measurement of ventricular volumes, mass and function as well as quantification of blood flow. MR imaging is now uniquely helpful for defining pathophysiology in both cross sectional and longitudinal studies, including assessment of therapeutic treatments and intervention.  Excitingly, it has recently become possible to perform invasive techniques with MR in combination with x-ray cardiac catheterization.

This raises the possibility of more accurate quantification of cardiac/vascular physiology with simultaneous measurement of pressure, flow and ventricular function. Furthermore, improved interventional treatments with MR-guidance should soon become possible in children, (such as accurate placement of devices for closure of atrial septal defects with reduced exposure to radiation).   

Research by the imaging theme itself is divided into three parts

  1. Magnetic Resonance assessment of pulmonary and systemic vascular changes.
  2. Modelling of new devises for the treatment of structural heart disease.
  3. Tissue characterisation of myocardium in a range of heart muscle diseases in conjunction with James Moon at University College Hospitals London (UCHL)

Please see website for further information: www.ccmr.org.uk

Outcomes

Led by Kate Brown and Kate Bull, current research themes include patient related reported outcomes in children with congenital heart disease and other complex cardio-respiratory disorders.  This research group, led by Jo Wray and Kate Brown has recently completed recruitment to a multi centre study to validate a disease specific measure: The Paediatric Cardiac Quality of Life Index (PCQLI), for assessing health related quality of life in children with heart conditions by addressing questions on this topic directly to children and their parents.  Funding for this study came from the NIH in the USA and an 'Angel Donor' in the UK.  The group is now initiating qualitative studies to identify optimal measures for the evaluation of health related quality of life in children with other complex disorders treated as part of the hospital's commitment to the National Specialist Commissioning Group (NCG).  Pilot work is also underway to test the use of the PCQLI as a quality improvement measure for children undergoing certain operations at the hospital.

A further theme is risk adjustment for congenital heart surgery: a collaboration between Victor Tsang, Kate Brown and the Clinical Operational Research Unit at UCL, which is led by Martin Utley. This group has a publication track record for risk adjustment and monitoring methods for early survival outcomes of congenital heart surgery in children. The group is currently undertaking a collaboration with the Central Cardiac Audit Database (CCAD), which is the national audit database for cardiac surgery in the UK and holds 35,000 procedure records. The current direction of the research group, which is fully supported by the CCAD steering committee, is to investigate the feasibility of introducing routine risk adjustment for use in UK centres performing paediatric cardiac surgery. This will involve the use of graphical monitoring methods and tools developed at the Clinical Operational Research Unit by Martin Utley and his team.

Kate Bull leads a large cross sectional study of Tetralogy of Fallot funded by the Great Ormond Street Children's Charity.  More than 1,000 patients have had Fallot repairs at the hospital since 1964 and a formal study looking at cardiac function and quality of life of volunteer survivors from each decade since the 1960's is in progress with the aim of contributing to decision making about elective pulmonary valve replacement in this patient group.

Paediatric Intensive Care

Led by Allan Goldman, the team of Intensivist's major research themes include studying the systemic inflammatory response (SIRS) after congenital heart surgery on cardiopulmonary bypass with previous research focused on the role of monocyte HLA DR on SIRS as well as patient outcome related to of genetic polymorphism of IL6 and IL10 in this group.  The team have also received an award to develop a paediatric post-operative morbidity survey after congenital heart surgery.

Great Ormond Street Hospital is one of two designated paediatric Cardiac Centres in the UK to use mechanical blood pumps ('artificial hearts') to support the severely failing heart until the patient's own heart has recovered or a donor organ for transplantation has become available.  The group works in close collaboration with the ECMO, transplant, and heart failure groups.  They have a growing theme of research, led by Ann Karimova, on the use of the Berlin Heart Assist Device for infants and children with intractable cardio-respiratory failure as a bridge to transplant.

The Clinical Outcomes Team has gathered a wealth of information on various groups of infants and children supported on ECMO for intractable respiratory failure, including babies with congenital diaphragmatic hernia and pertussis.  They have also reviewed the outcome of a National ECMO service for babies with the spectrum of diseases leading to acute hypoxaemic respiratory failure in the newborn.  Kate Brown received a grant from the International Extracorporeal Life Support Organization to look at the influence of ventilation prior to ECMO (days ventilated pre ECMO) on outcomes after ECMO.

Cho Ng is leading our work into the use of blood products for congenital heart surgery.  This includes the evaluation of the role of TEG and Factor VII in managing postoperative bleeding and bleeding on ECMO. 

Aparna Hoskote is leading on a theme of neuromonitoring, neuroprotection and long-term outcome to improve service delivery and ultimate quality of life.  She has established collaboration with well established research groups:

  • UCL Medical Physics (Clare Elwell) to study brain and tissue oxygenation by Near Infra-Red Spectroscopy (NIRS) on ECMO as well as multi-site NIRS and optical topography.
  • the Department of Developmental Cognitive Neurosciences, ICH (Faraneh Vargha-Khadem) looking at hippocampal volumes and memory impairment in TGA survivors.
  • University of Leicester and National Perinatology Unit recruiting neonate with hypoxaemic respiratory failure to the multicentre RCT - Neonatal ECMO Study of Temperature (NEST) funded by the British Heart Foundation.
  • NHS Blood and Transplant looking at mathematical modelling to predict heart transplant waiting times in infants
  • The Hospital for Sick Children, Toronto in a multicentre RCT of hypothermia after cardiac arrest and follow-up neurodevelopmental outcome.

The next focus is to establish measures to identify neurological impairment and neurodisability pre and post major cardiac surgery, to study the effect of neuroprotective interventions and outcome and to study cerebral NIRS as an early marker of brain ischaemia.

Another emerging theme of research is focussing on human factors and risk management in improving patient outcomes.  We have conducted a research study on team training for critical interfaces in handover of patients from the operating theatre to intensive care using the analogy of a Formula 1 motor racing pit stop and current research work includes a newly funded grant by BUPA on improving the safety and quality of hospital handovers. Planning for the 'Cardiology in the Young' (CiTY) Conference from 12 to 15 April 2010 and 'Risky Business - Learning from other Industries Conference, from 17 to 19 November 2010 is well underway.

Pulmonary Hypertension

Led by Ingram Schulze-Neick, this team was first established in 2002 and funded since 2007 by the National Commissioning Group of the NHS (NCG) and  focuses on clinical care of approximately 320 children with pulmonary hypertension children in the UK. 

Current work priorities include the highly necessary enhancement and technical update of the clinical and administrative database that covers the clinical and scientific data of these children with the aim of integrating it with all the different hospital systems.

In conjunction with the MRI Vascular team, protocols for MRI guided pulmonary vascular resistance studies for clinical and research use are being developed and tested.  Other current research includes collaboration with the Vascular Physiology team to study pulmonary endothelial cell biopsies in the Catherisation Laboratory.  Future studies will focus on long-term pulmonary vascular consequences of complex post operative circulation such as after Fontan repair.

Structural Heart Disease

Led by Alessandro Giardini, current work includes the assessment of long-term functional outcomes of surgical repair of congenital heart defects.  Recent topics include transposition of the great arteries and Fontan operation. 

Theme members participate in a European Research Network which was established in 2006 to facilitate multi-centric research in the field of paediatric cardiology.  The first International conference organised by the Network is planned for March 2010.  The team is also involved in a National Heart Lung and Blood Institute-funded multicentre observational cohort study that aims to discover the genetic architecture of congenital heart defects.  The team is also currently participating in writing guidelines for exercise testing and training in children and adults with structural heart defects, which will be endorsed by the ESC.

Tracheal /Surgery

Led by Martin Elliott, the tracheal/surgery team has been instrumental in the development of tracheal reconstructive surgery in children.  Established in 2001 to provide specialist care for children with long segment tracheal stenosis (either congenital or acquired), severe tracheo-bronchomalacia and other rare conditions.  The service became the National Service for Severe Tracheal Disease in Children in 2006, funded by NCG.  It is now the largest service in the world for tracheal reconstructive surgery in children and currently has the best results.  The team have been very successful in developing management strategies for these conditions and the research has been directed towards further clinical improvement in outcome, better risk stratification, reducing the costs of care, cross-skilling within teams, improved morphological classification of long segment stenosis and formal quality of life assessment.

Current research includes the use and development of absorbable airway stents in children; the development and use of stem-cell tissue engineered tracheal transplants, using the child's own stem cells (in collaboration with Professor Martin Birchall at UCL and Professor Paolo Macchiarini from Florence.  Other studies include objective follow up of respiratory function, thymic function and the genetics of tracheal stenosis are also being undertaken.  Collaboration is planned with Imaging to look at the airways of children with severe tracheal stenosis with a view to performing airflow function studies in the MRI scanner.  Furthermore, a UCL Airways Group is being established to bridge paediatric and adult practice.

Vascular Disease

Led by Professor Deanfield, the Vascular Physiology Unit researches the pathophysiology of the pre-clinical phase of atherosclerosis from childhood.  The aim of this work has been to understand the genetic and novel environmental influences on initiation and progression of disease and the potential for prevention.

Traditional clinical endpoints can not be used to evaluate early disease.  We have therefore continued to develop robust measurements of intermediate atherosclerosis phenotypes as outcome variables.  In parallel, we are evaluating the relationship of these measures to the progression of arterial disease and to clinical cardiovascular events.   Non-invasive techniques have been developed and are now established as the gold standard method of evaluating endothelial function in children and young adults who have not yet developed any clinical manifestations of disease.

Current research involves the study of inflammation, lipid functionality (including HDL cholesterol) and endothelial cell biopsy in humans; the investigation of the role of obesity and body composition; early post natal growth and inflammation and oxidative stress on early atherogenesis and investigating the influence of vascular progenitor cells on arterial repair.

The team has established several strong collaborations, which includes:

  • A productive programme of research with the UCL Division of Medicine exploring the potential of remote ischaemic preconditioning in organ protection. 
  • A close relationship with the UCLH Obesity Clinic to explore the early and late cardiovascular complication related to obesity.
  • A productive collaboration with the Eastman Dental Hospital to study the impact of acute and chronic exposure to inflammation and oxidative stress on the cardiovascular phenotype.

 Current research also includes two ongoing cohort studies:

  1. The AdDIT Study.  Looking at children with Type 1 Diabetes who have an increased risk of cardiovascular disease.  The research is a collaboration between different centres in the UK, Australia and Canada which aims to prevent long term diabetic complications.  Patients undergo treatment with Statins, ACE-Inhibitors, a combination of Statins plus ACE-Inhibitors or placebo, over a period of four years to examine whether this will reduce their risk of cardiovascular disease in later life.
  2. The ALSPAC study.  Designed specifically to determine ways in which an individual's genotype combines with environmental pressures to influence health and development.  This research provides a unique opportunity for our team to assess the importance of early life influences, notably different growth trajectories and patterns of obesity in determining blood pressure, a major cardiovascular risk factor, and associated functional and structural damage to the vasculature.

Page last modified on 04 aug 10 10:01