Contact SADS UK for details of our SADS memorial candle lighting, Annual Retreat and Stride to STOP SADS
“Timothy syndrome is a rare and very lethal disorder without treatment, thus finding living individuals affected with this syndrome to genetically study was extremely difficult. Being invited to the SADS UK sponsored conference wherein medical professionals and families suffering with arrhythmias and issues surrounding unexplained sudden death were included in attendance was a perfect setting for me to explain the specifics of this LQT/syndactyly associated anomaly. With the addition of families participating, it helped to clarify the spontaneous nature in which this abnormality genetically arises.
My gratitude to Anne Jolly at SADS UK cannot be measured, for her wisdom in bringing the 1st International SADS Conference together, for her tireless work in helping others to try and find answers for the issues which surround the devastating effects of unexplained sudden death and her personal friendship. Her efforts personally and specifically helped to further our search and the ultimate identification of this new gene." Katherine Timothy, University of Utah, Dept of Human Genetics
The central hypothesis is that the determinants of arrhythmic risk including atrial and ventricular fibrillation lie within the heart itself and that much of this risk is genetic. Our team's core activities are therefore concerned with linking genetic alterations determining fibrillation syndromes to arrhythmogenic phenotypes through the use of mouse and human induced pluripotent stem cell (iPSC) models.
My clinical research involves electrophysiological phenotyping and is firmly based on the laboratory models. A large, wide-ranging referral base allows the efficient delivery of this translational limb of the program. I have also developed links with industry based on translational principles that provide novel approaches (drugs and devices) for patient management – largely based on the insights obtained through the pre-clinical programmes.
The heart is an efficient, generally reliable mechanical pump driven by electricity. On occasion the usually smooth electrical activation breaks down and when this occurs electrical chaos ensues and can manifest as ventricular fibrillation that leads to a failure of contraction and the sudden death of an individual. There is a substantial body of data indicating there is a predisposition amongst certain individuals to ventricular fibrillation and furthermore that this susceptibility can be detected through an examination of the passage of electrical signals through the chambers when the person is in normal rhythm.
The project will involve the analysis of electrograms (electrical signals from the heart) obtained directly from heart disease patients being managed at Royal Papworth Hospital and then annotated with colleagues in the Department of Engineering in the University of Cambridge.
Doctors managing these patients routinely place catheters in the heart and record electrical signals. The recordings are the result of complex activation processes and reflect the characteristics of the underlying tissue. The signals are recorded either during normal rhythms or during artificial pacing over a range of frequencies from multiple sites. Data will be analysed and characteristics highlighted. A training set will be established and the responses of signals to differing interventions (pacing rates, premature stimulation etc.) will be explored.
The objective is to generate an algorithm based on statistical inference and probabilistic data modelling to allow a model of cardiac activation under different conditions to be predicted.
We have great hopes that we will be able to develop a test that will predict patients at risk and on that basis provide them with protection through the use of an implanted defibrillator. The work should be ground-breaking and have substantial impact in improving risk prediction and thereby helping both involved individuals and their families.
Dr Andrew Grace, Papworth Heart Hospital.
Support from SADS UK is helping scientists and clinicians understand and combat a rare condition called short QT syndrome that is associated with an increased risk of sudden cardiac death. For the heart to pump blood round the body, electrical activity must spread through the heart’s chambers in an orderly sequence. This depends on the coordinated opening and closing of proteins called 'ion channels' in heart muscle cells. Mutations to genes encoding ion channels have been found in individuals and families diagnosed with the short QT syndrome. A number of these mutations affect ion channels that carry potassium ions, causing them to pass too much potassium out of heart cells and consequently altering electrical excitability in ways that increase vulnerability to cardiac arrhythmias.
For the heart to pump blood round the body, electrical activity must spread through the heart’s chambers in an orderly sequence. This depends on the coordinated opening and closing of proteins called 'ion channels' in heart muscle cells. Mutations to genes encoding ion channels have been found in individuals and families diagnosed with the short QT syndrome. A number of these mutations affect ion channels that carry potassium ions, causing them to pass too much potassium out of heart cells and consequently altering electrical excitability in ways that increase vulnerability to cardiac arrhythmias.
Short QT syndrome has been proposed as an eligible disorder for the 100,000 genomes initiative. The aim in doing this is to enable the identification of novel genetic causes of the syndrome and thereby better understand causation and help treatments. If new gene associations with the syndrome can be found, this is likely both to increase understanding of mechanisms that regulate cardiac electrical activity and to feed into rational treatment strategies for this rare, but important heart condition.
Graham Stuart, lead cardiologist for the inherited cardiac conditions service in Bristol and Jules Hancox, Professor of Cardiac Electrophysiology at the University of Bristol have worked together to understand how particular gene mutations (called “I560T” and “S631A”) lead to altered potassium channel activity in the heart in the short QT syndrome. Through laboratory studies of cells engineered to express these mutant ion channels, their research team has characterized the changes in function that lead to excessive potassium ion movement in these forms of short QT syndrome.
Patients who are identified to have short QT syndrome are often fitted with implantable defibrillators, which protect against potentially lethal cardiac events. Some patients may not be suitable for such electrical devices and the administration of appropriate antiarrhythmic drugs can help reduce the likelihood of patients who have devices needing defibrillation shocks. The Bristol team has demonstrated that for both of these mutations, an antiarrhythmic drug called quinidine reduces the excessive potassium ion movement that they produce. This indicates that quinidine may be an effective antiarrhythmic treatment in these forms of the short QT syndrome.
“We are immensely grateful for the support SADS UK has given us in conducting this work”, they said. “The hard work of SADS UK fund-raisers has helped us work towards identifying a potential therapeutic strategy for these particular forms of the short QT syndrome.”
The outcomes of these studies have now been published and are available with open access:
Butler A, Zhang Y, Stuart AG, Dempsey CE, Hancox JC (2018) Action potential clamp characterization of the S631A hERG mutation associated with short QT syndrome. Physiological Reports, 6(17) e13845. doi: 10.14814/phy2.13845.
Butler A, Zhang Y, Stuart AG, Dempsey CE, Hancox JC (2018) Functional and pharmacological characterization of an S5 domain hERG mutation associated with short QT syndrome.
Heliyon, 5(4):e01429. doi: 10.1016/j.heliyon.2019.e01429.
(Neuro)psychological care after out of hospital cardiac arrest – the CARE clinic model
It is not uncommon for survivors of sudden cardiac arrest and their families to experience significant challenges in returning to their day-to-day life after discharge from hospital. Memory difficulties, anxiety, depression and post traumatic stress disorders are some of the fairly common complications experienced after this life-changing event, but until recently no appropriate (neuro)psychological follow-up has been offered, despite recommendation from clinical guidelines. Thanks to support from SADS UK, we are now able to offer in our Cardio Thoracic Centre at Basildon Hospital (Essex) the first care after resuscitation (CARE) clinic, focussed on providing cardiac arrest survivors and their carers with psychological, cognitive and medical support up to one year after discharge from hospital.
In this clinic, a senior intensive care nurse identifies patients on de-escalation from ITU to a cardiology ward and introduces them to the service, providing information in multiple forms (leaflet, bespoke video and via social media) to answer questions around common reasons for a cardiac arrest, possible post cardiac arrest changes (physical and psychological) and peer support available in the community. Every survivor is then offered by a clinical psychologist a cognitive and psychological assessment before discharge from hospital, with early interventions where appropriate (including early cognitive neurorehabilitation). Caregivers, if present, are offered an early psychosocial adjustment screen and provided time-limited support or signposted to appropriate services. Reports are generated and shared with GPs and other professionals involved to ensure continuity of care. A follow-up call is initiated 48h after discharge by the senior ICU nurse to identify any early problems, and a dedicated phone helpline is available via the critical care outreach team.
Two follow-ups are offered by the clinical psychologist, at 3 and 9 months, when cognitive changes and psychosocial adjustment (respectively) often reach a plateau, for further investigation into unmet needs, and recommendations/brief interventions/signposting are made if appropriate. A senior ICU nurse offers a review at 6 and 12 months to address any potential medical issue. If any psychological/medical issue is identified during nursing/psychology review (respectively), this is promptly discussed with the other MDT member for further management.
In our specialist centre we see in excess of 70 survivors of out of hospital cardiac arrest every year. By providing this service, and documenting the impact it has on our patients and their families’ ability to return to their day to day life, we are leading the way in post-cardiac arrest psychological care.
Just enter your details below