Research

The overall research interests of the Hatter Cardiovascular Institute (HCI) include myocardial (heart) protection and the pathophysiology of ischaemia/reperfusion injury. More specifically we also focus on developing ways to protect those patients with co-morbidities, such as diabetes and chronic kidney disease, all of which have an adverse effect of the heart. This has involved an understanding of the pathophysiology of ischaemic heart disease at both the cellular, molecular and clinical levels. The HCI is noted for its translational (i.e. bench to bedside) approach to research, incorporating cellular-based models through to the clinical setting. 

An important component of our research interests include the concept of “myocardial and remote preconditioning and post-conditioning”, potent endogenous adaptive mechanisms for protecting the heart against ischaemia-reperfusion injury. Concurrently, we are developing new pharmacological and therapeutic strategies to protect the myocardium from reperfusion-induced injury based upon our understanding of pro-survival signal transduction pathways and the contribution of mitochondria to cell survival that can be exploited to the benefit of the patient with ischaemic heart disease.

Complementing our cardioprotection programme are now three additional research arms: (1) neuroprotection specific to ischaemic stroke, (2) the cardio-renal syndrome, protecting the heart from the damage caused by chronic kidney disease and (3) cardio-oncology, investigating how best to reduce the damage to the heart following chemotherapy. 

It should be emphasised that all of the above research is made possible by the  generous support of The Hatter Foundation who continue to underpin our ongoing research aims. This has allowed us to seek additional support for specific research programmes from major grant awarding bodies including the British Heart Foundation, the Medical Research Council, the Welcome Trust, and the Rosetrees Trust.

Below is a synopsis of each research programme.

The Hatter Cardiovascular Institute undertakes translational research focusing on the pathophysiology of Ischaemic Heart Disease in the young and aging myocardium in both the normal heart as well as in settings of co-morbidities such as diabetes and the metabolic syndrome. The research undertaken within the HCI explores the treatment strategies for protecting the heart at both a cellular & molecular level as well as in patients at risk of myocardial infarction.

This is undertaken in our purpose built and well-equipped laboratories through a wholly integrated approach employing a variety of experimental models. The research is directly translational, using the primary animal and human cardiomyocyte, the in vitro and in vivo perfused transgenic animal models and human muscle/artery through to clinical studies of patients with coronary heart disease undergoing CABG surgery and primary PCI. In all these settings, basic and clinical scientists focus on identifying the mechanism and signalling pathways associated with cellular injury and protection, with the ultimate aim of identifying new therapeutic targets and agents to protect the heart from acute myocardial infarction.

Over the past decades, through research funded by the British Heart Foundation (BHF), we have now developed a novel, drug called UCL-TRO-1938 that stimulates pro-survival pathways in the heart and brain. We propose to use this drug as a tool to improve its potential effectiveness in humans. Through a further 5-year BHF Programme Grant, we will progress this research via a variety of laboratory-based studies to confirm our hypothesis that our new drug will be effective in the setting of relevant co-morbidities such as age, diabetes, and chronic kidney disease, all of which are common in heart attack patients.

KEY PUBLICATIONS

The Hatter Cardiovascular Institute has initiated a Neuroprotection Group with the aim of using the knowledge we have gained in the cardiovascular ischaemia-reperfusion field to protect the brain from ischaemic stroke, whose pathology is similar to that of a heart attack. This has also been underpinned by a significant grant from the British Heart Foundation.

The management of stroke and acute myocardial infarction are similar and consist primarily of achieving rapid and complete reperfusion of the ischaemic tissue by endovascular procedures.

Working together, basic and clinical researchers seek to translate basic science findings into the design of novel appropriate adjunctive therapies which can protect from the reperfusion injury that occurs in the heart and brain.

Key Publications

Patients with chronic kidney disease (CKD) have damaged kidneys which prevent them from eliminating toxic waste and bodily fluids. CKD not only affects the kidneys but also affects the function of other organs, especially the heart. Hence, patients with CKD have a higher risk of developing heart and circulatory problems such as heart attacks.

Through generous support of the British Heart Foundation and the Thompson Family Trust, we have developed a cardio-renal research programme to identify novel cardioprotective targets and also investigate innovative therapeutic options for the treatment of heart attack in the setting of CKD.

Key Publications

Cardio-oncology is a rapidly emerging research area.  The Hatter Cardiovascular Institute has established a Cardio-Oncology Program which brings together Cardiologists, Oncologists and basic & clinical scientists from the HCI and the Macmillan Cancer Hospital at UCL/UCLH who all work together in promoting the cardiovascular health of UCLH cancer patients.

Our comprehensive cardio-oncology program provides care for patients who may have cardiac side-effects from traditional cancer therapies, such as anthracyclines and radiation, or novel targeted therapies.

This is underpinned by a comprehensive basic & clinical research group whose aim is to use the skills and knowledge obtained in the cardiovascular protection field, to protect the heart of patients on chemotherapy.

Key Publications

The RIC-Africa Study

Acute ST-segment elevation myocardial infarction (STEMI, also commonly referred to as a heart attack) and the heart failure that often follows, are among the leading causes of death and disability in Africa. For these patients, the treatment priority for reducing the risk of death by preventing heart failure, is to restore coronary artery blood flow using a surgical technique called primary percutaneous coronary intervention, (PPCI). However, in the majority of countries in Africa, PPCI is not widely available, and most patients are treated using a more basic approach called thrombolysis to dissolve the blood clot. This procedure is time limited and only effective at restoring coronary artery blood flow in up to 60% of patients, thereby increasing the risk of death and heart failure in heart attack. Due to several socio-economic factors, patients from Africa are at significantly higher risk compared to those from more developed countries. As such, there remains an urgent need to discover new treatments for these high-risk patients to improve clinical outcomes following heart attack.

To achieve this goal, we have partnered with Professor Mpiko Ntsekhe, Professor & Head of Cardiology at the University of Cape Town, to create the RIC-Africa study, in which we evaluate a simple, non-invasive, low-cost treatment that has the potential to improve clinical outcomes following STEMI, called Remote Ischaemic Conditioning (RIC).

RIC is a non-invasive procedure in which a blood-pressure cuff is applied to an arm and inflated above systolic blood pressure for brief periods, alternating with periods of deflation. Inflation (20 mmHg above normal) temporarily reduces blood flow in the limb (ischaemia). This procedure has been shown to active pro-survival biological pathways and can protect organs, including the heart, from severe ischaemia-reperfusion injury (heart attack).

The RIC-Africa trial began a small pilot for recruitment in January 2022 across 4 African countries (South Africa, Kenya, Uganda and Sudan) to assess feasibility of undertaking this study in Africa. A clinical study announcement paper was published in November 2021 (read here). Since that time, the study has successfully expanded to over 20 hospital sites across 8 African countries: South Africa, Uganda, Kenya, Mozambique, Namibia, Senegal, Ethiopia and Mauritius. RIC Africa has been fortunate to receive significant funding from the Novo Nordisk Foundation to undertake this important work.

Importantly and independent of the outcome of the study, RIC-Africa aims to establish clinical research infrastructure and education at all local participating sites across all 8 countries. It is envisaged that the RIC-Africa study will facilitate new and improved research foundations and capacity within Africa, eliminating barriers, creating new research networks and partnerships with an underlying aim of improved patient outcomes from heart attack across Africa.