Optimal Timing of Transplant Listing for Patients with Congenital Heart Disease

In much of the latest research on cardiac transplantation of patients with congenital heart disease, it has been pointed out that transplanting these patients at the optimal time is key to improving outcomes. Of course, cardiologists cannot choose when the transplant will take place, but they can decide about when to list. The issue of determining when to list patients with congenital heart disease is unclear and controversial and, as such, there have been calls in the literature for more tools to help guide clinicians in making this complex decision. 

Laura Delaney, an expert in Financial Mathematics at Kings College London, has devised a mathematical model, based on techniques used in corporate decision making, to determine the optimal time to list a patient with CHD for transplant. 

The model accounts for factors such as rate of clinical decline, long term life expectancy without getting the transplant, expected waiting time, as well as the risk factors cardiologists look for in a patient when deciding about listing. The theoretical prescriptions of the model are intuitive and in line with reality; for example, it prescribes that patients who are declining rapidly ought to be listed sooner than a more stable patient, ceteris paribus.

In collaboration with Louise Coats, Katrijn Jansen, Guy MacGowan and Zdenka Reinhardt, Laura is trialling this model using real world data in order to determine its effectiveness in prescribing the correct course of action. If validated, the model could provide an important assistive tool to cardiologists deciding the optimal timing for listing of a particular patient. 

For more information, contact laura.delaney@kcl.ac.uk

Exercise keeps hearts healthy, but does not reverse ageing.

We know quite a lot about how cardiomyocytes develop and mature and now recognise that they  continue to divide throughout life. Less is known about what happens to individual myocytes as they age, but we recognise global ventricular fibrosis and diminishing function. Whilst attempts to enhance regeneration or reverse senescence have been disappointing, a simple increase in daily activity seems to have a beneficial effect on the ageing heart.

Over the last decade the Chaudhry/Henderson research group have been using zebrafish to study how the heart ages, why fibrosis occurs and if long term increased activity in adulthood prevents the changes of ageing. We found that, as in people, cardiomyocyte proliferation in the zebrafish continues throughout life, but discovered programmed cell death suddenly accelerates in middle age and is then followed by fibrosis. This is “good fibrosis” as it fills in the holes made by lost cardiomyocytes. We found that whilst long term exercise gave the fish stronger hearts, it also led to increased levels of myocardial fibrosis, which might lead to other problems such as atrial fibrillation. In addition, we also found that the ability of cardiomyocytes to proliferate in response to stressful situations diminishes with age and exercise has no effect on this. Exercise gives us healthier hearts, but cannot turn back the clock on cardiomyocyte ageing. Read the full study in the journal Disease Models and Mechanisms.

For more information contact Bill Chaudhry or Deborah Henderson

Lindsay B. Murphy, Adrian Santos-Ledo, Tamilvendhan Dhanaseelan, Lorraine Eley, David Burns, Deborah J. Henderson, Bill Chaudhry. Exercise, programmed cell death and exhaustion of cardiomyocyte proliferation in aging zebrafish. Dis Model Mech (2021) 14 (7): dmm049013

 This work was funded by the British Heart Foundation


Supporting hearts, supporting lives.

Children requiring mechanical support for heart failure are usually committed to staying within an intensive care unit or hospital ward. Emma Simpson, Paediatric Intensivist at the Freeman Hospital has recently led a multi-disciplinary collaboration with Aachen University and industry partner ‘Berlin Heart GmBH’, funded by European Institute of Innovation and Technology. The aim is to bring to market a mobile driving device for the Berlin Heart Ventricular Assist (VAD) and thus transform patient experience. Qualitative work, with Judith Rankin and Lisa Crowe, exploring parents and children’s views contributed to the development of a new educational platform for professionals and families to learn about VAD therapy and the team was awarded the prestigious Horizon Impact Award along with a prize of €5k to support future work. 

For more information please contact: emma.simpson29@nhs.net

PhD Studentship success!

Simon Bamforth, in collaboration with Helen Phillips, is now recruiting a suitable candidate to undertake a 3-year PhD Studentship, funded by the British Heart Foundation, to study the role of the extracellular matrix in aortic arch artery development. This research project hopes to understand the complex processes that are required for correct formation of these large and important blood vessels, and what may go wrong during development, resulting in congenital heart defects. The successful candidate will use a range of laboratory techniques including microscopy and cell sorting to identify the genetics underlying development of the aortic arch.

For more information, contact: simon.bamforth@newcastle.ac.uk

Reviving the Ross Operation

The adult congenital heart unit at the Freeman hospital has joined a multi-centre study, the REVIVAL study, designed to compare the Ross procedure with other surgical options for aortic valve replacement. 

Heart valves help control blood flow through the heart and, if diseased, may need to be replaced. There are different methods for doing this, each with their own advantages and disadvantages. In young adults, replacing the aortic heart valve with a mechanical valve can reduce life expectancy. Mechanical valves tend to form blood clots so they need long-term blood thinners which themselves can cause bleeding and lower quality of life. Animal tissue valves reduce clotting and bleeding risks but wear out sooner and shorten patient life-span. An operation, called the Ross procedure, replaces a patient’s diseased aortic valve with his/her own pulmonary valve and uses a donor valve in the pulmonary position which receives less stress than the aortic valve. The Ross procedure aims to improve valve durability with less clotting whilst avoiding use of blood thinners. REVIVAL is a research study investigating the efficacy and safety of the Ross procedure compared to conventional valve replacement. Specifically we are interested in learning the number of patients who survive without a life-threatening valve related complication, long term postoperatively.

For more information contact: mohamed.nassar2@nhs.net

Aortic arch grant success

Abnormalities of the heart are the most common birth defect and can affect the aortic arch arteries (the large blood vessels that carry blood away from the heart and deliver it to the whole body). Simon Bamforth and Helen Phillips in collaboration with Prof Nicoletta Bobola at the University of Manchester, have been awarded a 3-year project grant from the British Heart Foundation to study the genetic control of arch artery development. Combining the study of anatomy with state-of-the-art single cell transcriptomics they hope to unravel the complex networks of genes that are required to be expressed at the right time and in the correct place to ensure that our heart and blood vessels will develop properly and effectively deliver oxygenated blood around the body.

For more information, contact: simon.bamforth@newcastle.ac.uk

Mitral valve development

From Bill Chaudhry and Deb Henderrson

Mr Francis Wells, the internationally recognised cardiac surgeon from Papworth Hospital Cambridge, and our longstanding colleague Professor Bob Anderson, are in the late stages of producing a book for Springer Nature Publishers about the degenerating mitral valve. The work is aimed at clinicians and provides a broad discussion of the mitral valve from a scientific perspective. It is especially timely as the  developmental basis of many degenerative conditions, for example mitral valve prolapse, are increasingly recognised. We are honoured to be involved and have written a chapter explaining the developmental molecular genetics that control mitral valve development. Our chapter is specifically written for the clinician, outlining important aspects, but not burdening with scientific jargon. It is of relevance to topics of our research including hypoplastic left heart syndrome, atrioventricular septal defects and bicuspid aortic valve. Developmental anatomy and surgical aspects are provided by Bob and Francis in other chapters, and a host of international experts are adding their expertise in clinical genetics and physiology. We will post publication details in due course.

What do patients with ACHD really think?

The physical and emotional long-term effects of having CHD are usually seen from the medical viewpoint. But increasingly we are aware that the clinic is not always aligned to what patients might actually want or feel. The ACHD team in Newcastle have joined the Approach IS II study lead by Philip Moons in Belgium. This international study will explore how patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs), differ between patients in different countries and also try to identify the healthcare needs of older adults with congenital heart disease, who may be quite frail. 

To find out more contact louise.coats@newcastle.ac.uk

Hello, Hello – Its Good to be Back!

from Newcastle University Congenital Heart Disease Group

The Faculty of Medical Sciences at Newcastle University was completely reorganised in 2019. We reduced our number of institutes from six to three: the BiosciencesTranslational and Clinical Research and Population Health Sciences Institutes.

As part of this restructuring the old research centres, including the Cardiovascular Research Centre, were dissolved. In their place are Themes that cut across all three Institutes and are focussed on the future direction of academic research in our University. 

We, congenital heart researchers, have taken the opportunity to make new connections with others in the Reproduction, Development and Child Health (RDCH) Theme. We remain closely linked, but distinct from our colleagues in the Vascular Biology and Medicine (VBM) Theme and some colleagues have joint affiliation. Congenital heart clinicians in Newcastle hospitals, who are active in research, are affiliated to the Congenital Heart Disease research group and the RDCH Theme. We are also part of a wider community through the North East and North Cumbria Congenital Heart Disease Network.

On these web pages, we will post information about our research, our meetings and list contact details about our members. Enquiries about congenital heart disease research should be directed to louise.coats@ncl.ac.uk or bill.chaudhry@ncl.ac.uk and we will try to connect you with the right people.