William Harvey Heart Centre

There are 1 billion people worldwide with high blood pressure and it is estimated that this contributes to 50 per cent of coronary disease and 75 per cent of stroke. Although blood pressure lowering therapies exist there remains an unmet need for novel therapies, as up to 50 per cent of those treated fail to achieve target, in part due to treatment resistance.

We lead international and national studies elucidating the genetic basis of these disorders and have identified and confirmed novel genes affecting blood pressure and coronary disease. To characterise the functional effects of these genes and establish whether they represent genuine drug targets is a vital next step for understanding whether they could help patients with blood pressure lowering or coronary disease. The drug development pipeline in this therapeutic area suffers from a paucity of drug targets.

Our aim is to unplug this scientific bottleneck and take this research to a completely new level through the creation of a major new group dedicated to the study of gene function or vascular pharmacology. This group provides a completely new skill set, working alongside existent gene discovery scientists, vascular biologists and pharmacologists. They significantly benefit from interaction with a vascular biomarkers group that serves to identify novel interactions between target genes and other pathways that could yield alternative therapies for exploration. 

Through our genetics programmes we have been able to develop an international partnership to study predisposing electrical features for dangerous rhythms on the electrocardiograph. These disordered rhythms are a significant cause of sudden death and hospitalisation, and many of the conventional therapies are variably effective. 

Professor Andrew Tinker leads a major group investigating disorders of heart rhythm. His work complements that Professor Richard Schilling of who leads the Clinical study of electrical activity in the heart. A basic science chair and group in electrophysiology (electrical activity of the heart) functionally characterise and investigates novel therapeutic targets generated from these genetic studies working alongside our strong clinical electrophysiology group at Barts Health NHS Trust. This clinical group have developed and translated into clinical care novel approaches to computer mapping of triggers for disorders of rhythm. They are developing approaches using 3-dimensional advanced imaging provided by the NIHR Barts Biomedical Research Centre to improve precision of the mapping and ablation of triggers for rhythm disorders within the heart muscle. The placement of the basic electrophysiology group alongside our stem cell group will enable the electrical behaviour of stem cells to be characterised prior to administration to humans.

In the UK there are 1.2 million survivors of heart attack and 900,000 people with heart failure. Although established therapies may delay progression of heart failure this may not last and, eventually, the only option may be transplantation. This has stimulated interest in the potential of stem cells as a regenerative therapy for heart disease.

At the William Harvey Heart Centre Professor Ken Suzuki and his team are driving translational programmes to evaluate a novel bioengineering technology using cellular sheets for surgical grafting onto damaged heart tissue, which we hope to take into human studies. This will establish the effectiveness and safety before translation into patients with heart failure.

In other work, we are testing administration of bone-marrow-derived stem cells for heart attack and failure in one of the largest clinical trial programmes funded by £1.2m from the UK Stem Cell Foundation and led by Professor Anthony Mathur. This has led to successful funding from the EU to undertake multicentre trials and develop new stem cell-coated stents. The essential next step towards becoming a premier international translational centre is to add further basic science stem cell chair appointments to evaluate alternative stem cell strategies, such as embryonic stem cells.

Inflammation in the cardiovascular system is a major contributor to heart disease. At the William Harvey Heart Centre we have a strong interest in understanding vascular inflammation and how it may be targeted to reduce ill-health. 

Early detection and prevention of cardiovascular disease is vital to addressing this burgeoning global epidemic understanding the genetic basis of vascular disease and novel modalities of therapy raise the possibility of identifying new biomarkers of disease and possibly of treatment effectiveness. Research into the identification of new biomarkers is an under capacity area of research in the UK and strongly complements other research strands in the Heart Centre.

Studies in the area of genetics, protein chemistry, microparticles and characterisation of the signatures of metabolism in body fluids are now beginning to generate candidate pathways or novel biomarkers which could improve risk prediction, unmask novel therapies or predict treatment effectiveness. This research theme will allow definition of changes at the level of proteins and in metabolic signatures in body fluids. This important avenue of vascular biomarkers research is crucial to understanding cellular processes and strongly complements the Heart Centre’s other work.

The ground floor of the new William Harvey Heart Centre houses a state-of-the-art centralised Clinical Trials Unit. This unit runs clinical studies for a range of sponsors, across multiple therapeutic areas including but not limited to: cardiovascular, respiratory, endocrinology, addiction and rheumatology. The Unit is staffed by an experienced team of research professionals consisting of clinicians, nurses and trial management who, in conducting these studies, can call upon a broad range of clinical experts from Barts Health NHS Trust and Queen Mary University of London.

In conjunction with Barts Health NHS Trust, the William Harvey Heart Centre is an integral part of the IQVIA (formerly Quintiles) Global Prime Site program. The vision of this program is to deliver the optimal patient research experience through professional, high-capacity, transformational research partnerships. Queen Mary University of London was IQVIA's first partnership within the Prime Site model and remains its most successful. This success is based on an open relationship placing the patient at the centre of all research activity and thus ensuring the highest standards of quality and delivery.

A key element is the resident IQVIA operations manager, based at the site to facilitate all aspects of clinical trial work. A critical strength of the relationship is that Queen Mary University of London and Barts Health NHS Trust hospitals retain complete freedom to accept and participate in non-IQVIA trials, highlighting IQVIA's commitment to developing research within the UK as a whole.

Advanced cardiovascular imaging of the heart and circulation is increasingly important for the diagnosis and treatment of patients with heart disease. In 2008 the National Institute for Health and Care Research (NIHR) awarded a Cardiovascular Biomedical Research Unit to Barts and The London from which we have attracted an excellent imaging faculty and created state-of-the-art advanced imaging infrastructure to more deeply characterise patients in early phase trials. This strongly complements our substantial expansion of clinical trials activity. We have committed funds to sustain this step-change in imaging with the new Barts Heart Hospital by increasing provision from 1 to 5 imaging suites.