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Technology and guidelines
PHG Foundation, Cambridge, UK
Correspondence to
Dr Hilary Burton, PHG
Foundation, 2 Worts Causeway,
Cambridge CB1 8RN, UK; hilary.burton@phgfoundation.org
Accepted 15 December 2009
Cardiovascular services must develop to meet the opportunities and challenges of genomic science.
That is the main conclusion of the report Heart to
Heart , recently published by the Foundation for
Genomics and Population Health and representing the fi ndings of a 1-year expert working group of cardiologists, geneticists, public health specialists, voluntary organisations and others.
1
The 2003 Genetics White Paper
2 predicted that genetics would begin to move from the specialist arena into mainstream medical services, as advances in understanding the molecular mechanisms underlying inherited disorders began to offer opportunities for improved prevention and care.
This prediction is already being ful fi lled for inherited cardiovascular conditions (ICCs), a group of monogenic disorders primarily affecting the heart, its conducting system or vasculature. The report
Heart to Heart suggests that the main requirement now is for services to evolve to meet the needs of patients and families affected by ICCs. It recommends the development of specialised, multidisciplinary services with the necessary organisational structures and professional skills to embed genetic innovations. Such services must be built on the premise that the diagnosis of patients requires a genuine equal partnership between cardiologist and geneticist.
Our understanding of the molecular structure and operation of the ion channels responsible for the regular and coordinated contraction of cardiac myocytes is only just over 10 years old. Knowledge of these structures and the ways in which they are altered by genetic variation has paved the way for a greater understanding of arrhythmias such as long
QT syndrome. In a similar way, our understanding of the molecular pathology of inherited cardiomyopathies, inherited arteriopathies such as Marfan syndrome, some muscular dystrophies that can affect the heart and disorders of cholesterol metabolism such as familial hypercholesterolaemia means that management can be tailored to the precise condition. In some cases, the fi rst indication that an individual has an ICC is their sudden death, often in adolescence or early adulthood. The identi fi cation of a pathological mutation in someone who has died suddenly or who is diagnosed with one of these conditions means that family members can also be assessed for their risk, and even if they do not have overt symptoms can receive appropriate clinical surveillance, presymptomatic treatment or advice.
What are the implications for services ?
The impetus for service development in the UK began in
2004 with a high-pro fi le Private Members Bill in the
UK Parliament seeking ‘ effective and automatic
NHS screening for all families at risk of sudden cardiac death [SCD] ’ . It responded principally to the concerns of families who had experienced the sudden death of an apparently healthy young person. In response, a new chapter in the National
Service Framework for Coronary Heart Disease
(chapter 8 on arrhythmias and sudden cardiac death)
3 included quality requirements related to
SCD and commented on the importance of good awareness in primary care, the role of coroners and the need for effective evaluation of relatives.
Since that time, some progress has been made across the UK on SCD. In 2006, a national network of pathologists aimed at improving standards for cardiac post-mortems was established. The British
Heart Foundation has provided funds for cardiac genetic nurses in 11 trusts and, in 2009, launched a Genetic Information Service through which relatives of SCD victims can receive advice about risk and referral to appropriate specialist services for assessment.
Sudden cardiac death is, however, only the tip of an iceberg, representing the most severe consequences of inherited cardiovascular disease and affecting approximately 500 young people each year in England. These deaths (often also known as sudden arrhythmic death syndrome) are those where the heart appears normal on post-mortem examination; many are attributed to arrhythmia syndromes. The literature review of epidemiology for ICCs undertaken by the working group showed that the total burden of disease is much larger.
More than 50 ICCs are now recognised and, overall in the UK, such conditions might affect > 200 000 people with a further 120 000 people affected by familial hypercholesterolaemia, which also might result in cardiac symptoms. Most prominent among these conditions, each with a prevalence of several thousand individuals, are hypertrophic cardiomyopathies, arrhythmogenic right ventricular dysplasia/cardiomyopathy, long QT syndrome,
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Technology and guidelines dilated cardiomyopathy, Marfan syndrome, Brugada syndrome, myotonic dystrophy and catecholaminergic polymorphic ventricular tachycardia.
Many people with these conditions may not have overt symptoms. The report includes a characteristic case history provided by the Marfan Syndrome Association describing aortic rupture and death in an undiagnosed patient, which did nonetheless lead to genetic testing and diagnosis of a daughter in time to make sure that appropriate surveillance and management could be put in place for her. This illustrates the major challenge for health services: to identify patients and family members at high risk of serious cardiac morbidity and mortality while avoiding intervention when the risk is low.
Diagnosing and managing patients and their families require specialised services. The working group established unequivocally that the core of such a service should be a partnership of cardiology and genetics. Cardiologists have an essential role in assessing the phenotype: the features d often subtle d revealed by clinical history, physical examination, echocardiography, ECG and other specialist forms of testing that might signify inherited disease. Geneticists bring their extensive knowledge of family history, their ability to diagnose dysmorphologies and syndromes where the heart pathology may be part of a wider disorder and, critically, their understanding of the complexity and potential clinical utility of genetic testing and their expertise in interpreting genetic test results. Furthermore, where risk is identi fi ed to family members, regional genetic services have the experience and organisational systems for keeping family records, contacting and informing relatives and dealing with problematic ethical issues such as misattributed paternity, the testing of children and follow-up of estranged relatives, all with due regard to the regulation around the sharing of samples and personal data including genetic test results.
The working group recommended that patients with ICCs should be looked after by specialist multidisciplinary teams, which, critically, would be integrated with other specialist and general cardiology services, primary care and other clinical specialties. The report sets out expert agreement on the features of such a specialist service, describing professional roles in a way that will convey to commissioners and others the scope and complexity of care provision. It goes on to consider the necessary access to specialist investigations and the importance of nonclinical elements such as bereavement counselling and good links with voluntary services, which can provide valuable support to families. Finally, it considers the necessity for outreach to secondary services and primary care to ensure equity of access; the importance of close working with coroners; and the need for referral guidelines, patient information and organisational mechanisms for cascade testing in families.
Sadly, such multidisciplinary specialist services are largely aspirational at present in the UK. The working group surveyed all providers of ICC services in the UK and concluded that the current service capacity is inadequate, that there are major inequalities in access across the country and that none of the current services are able at present to provide all the elements of a specialist service to their population. The survey identi fi ed 19 providers of specialist ICC services spread across the UK in most of the regions. However, some of them were very small, with four seeing < 100 new patients per year. The overall capacity was highly London-centred, with 59% of outpatient clinics and 60% of medical consultant time being provided in the capital.
Extrapolating from the most active services in terms of patient throughput, we estimated that there was a shortfall of approximately 7000 new patients per annum in the UK, representing
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patients who do not receive specialist attention. In addition, our analysis of service provision based on Strategic Health Authority
(SHA) populations on all measures (eg, number of outpatient clinics, consultant sessions, total patients seen, genetic tests carried out) revealed signi fi cant inequity in service provision, with typically 10-fold to 20-fold variation between the best and the worst provided areas.
What of the future ?
Our challenge is to translate scienti fi c and clinical advances in our understanding of ICC into highquality services with better health outcomes. So far, these advances have been championed by patient-support groups and taken forward by committed clinicians, most of whom have an important research interest, and all of whom have argued energetically for the development of their own regional services.
Best practice now needs to be systematised and diffused to all regions. In discussing the necessary elements for strategic development, the report highlights the need for ICC services to be integrated within cardiac networks and for cardiology and specialist commissioners to specify and formalise their expectations for these services. In this regard, the inclusion of ICC services as part of the new de fi nitions set, placing it clearly within the remit of specialist commissioning, is an important step forward.
4
Three contentious areas arise. First, the positioning of the service within cardiology rather than genetics, although disputed as a model by some geneticists, re fl ects the reality that genetics is becoming part of diagnostic and management processes in many areas of mainstream medicine and that the role of specialist genetics should be to provide ʽ expert support ʼ centred on accurate diagnosis of the patient and management of familial issues. Second, the budgets for genetic tests are currently held by the genetics service, which operates as a gatekeeper. Some mechanism must be found to allow appropriately accredited specialist services access to tests under monitored referral criteria.
Third, the working group made a clear recommendation that each cardiac network should not seek to develop its own ICC service. Because of the need to ensure critical mass, there should be a relatively small number of services with some need for consolidation and integration of the current services.
Importantly for cardiologists, there is a need for education. This must include growing a skilled workforce with the necessary subspecialisation to lead on ICC services. For this the Royal Colleges and regulatory bodies such as the Postgraduate Medical Education and Training Board and providers of education to other relevant health professionals should be encouraged to develop curricula, specialist modules and training programmes. However, education must extend beyond those committed to this sub-specialism. All cardiologists and primary care services must also be able to recognise individuals at risk, refer appropriately, support patients and families in interpreting and acting on specialist advice, and provide a partnership for shared care and follow-up.
The working group undertook a detailed consideration of the legal and regulatory frameworks that apply, and the ethical issues that may arise from the sharing of human tissue samples,
DNA or personal information for the bene fi t of family members.
Some of its recommendations, such as support for legislative changes extending the statutory role of coroners to include
“ preventing future deaths, by retaining appropriate samples ” , will need to be progressed at a national level. However, the report also includes a number of recommendations for individual services, which should be pursued by the professions. These include the development of systems for improving care for at risk relatives after sudden cardiac death; developing clinical guidance on consent for data and tissue sharing; and the development of
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Technology and guidelines best practice guidance for storage, processing and retention of individual and family records and pedigrees.
There is much still to be learned about the diagnosis and management of ICCs, particularly the natural history of the conditions in asymptomatic patients diagnosed by family cascade testing and the effectiveness of interventions based on genotypic sub-classi fi cation of disease. The comparative rarity of these disorders means that such research must be funded and undertaken on a national and international collaborative basis.
The report Heart to Heart has provided the impetus for further work on ICCs in the UK. Work to support commissioning and the formulation of standards is being led by the Department of
Health, and a new professional group, the Association for
Inherited Cardiac Conditions (http://www.improvement.nhs.
uk/aicc/), has been launched. These developments are to be welcomed as fi rst steps in a process that will eventually equip UK cardiology services to embed developments in genetics into the mainstream. For it is clear that this is just a beginning. On the horizon are next-generation sequencing technologies that will allow faster and more comprehensive genetic testing for a wider range of cardiovascular conditions, detailed molecular diagnosis to direct treatments, pharmacogenetics applications relating to cardiovascular disease, array-based technology for the diagnosis of chromosomal abnormalities underlying congenital heart disease and, fi nally, the inclusion of genetic factors in determining susceptibility to complex cardiovascular conditions.
Over the last 10 years, there has been much talk of ‘ mainstreaming ’ genetics d of moving it out from specialist genetics departments into other areas of clinical medicine. This is nowhere more true than for cardiology; the time is now right for this speciality to develop and expand to bring genomic technologies into its own specialist remit.
Acknowledgements The authors wish to acknowledge the contribution of expert input from members of the Inherited Cardiovascular Conditions Working Group to the content of the report Heart to Heart: Inherited Cardiovascular Conditions Services d
A
Needs Assessment and Service Review . Working group members were Corinna
Alberg (PHG Foundation), Dr Elijah Behr (St George’s Hospital, University of London),
Dr Ed Blair (The Churchill Hospital, Oxford), Dr Paul Brennan (James Cook Hospital,
Middlesborough), Dr Hilary Burton (PHG Foundation), Dr Steve Cox (Cardiac Risk in the Young (CRY)), Genevieve Dalton (Anglia Stroke and Heart Network), Dr Perry
Elliott (The Heart Hospital, London), Dr Iain Findlay (Royal Alexandra Hospital,
Paisley), Dr Helen Firth (Addenbrooke’s Hospital, Cambridge), Professor Clifford
Garratt (Manchester Royal Infirmary, Manchester), Dr Martin Goddard (Papworth
Hospital, Cambridge), Alison Hall (PHG Foundation), Robert Hall (Cardiomyopathy
Association), Professor Steve Humphries (BHF Laboratories, London), Anne Jolly
(SADS UK), Dr Mike Knapton (BHF, London), Dr Dhavendra Kumar (University
Hospital of Wales, Cardiff), Dr Peter Lunt (St Michael’s Hospital, Bristol), Dr Pascal
McKeown (Belfast Health & Social Care Trust, Belfast), Dr Vicky Murday (Yorkhill
Hospital Glasgow), Diane Rust (Marfan Association UK), Robin Rust (Marfan
Association UK), Dr Gurdeep Sagoo (PHG Foundation), Dr Simon Sanderson (PHG
Foundation), Dr Anneke Seller (The Churchill Hospital, Oxford), Dr Alison Stewart
(PHG Foundation), Dr Fiona Stewart (Belfast City Hospital, Belfast), Dr Graham Stuart
(Bristol Royal Infirmary & Hospital for Sick Children, Bristol), Dr Jenny Taylor (Oxford
NIHR Biomedical Research Centre, Oxford), Professor Hugh Watkins (John Radcliffe
Hospital, Oxford), Jacquie Westwood (Bexley Care Trust, Bexleyheath) and Mike
Yates (Department of Health). HB, CA, AH, GS and AS are supported by the PHG
Foundation.
The PHG Foundation is the working name of the Foundation for Genomics and
Population Health, a charitable company registered in England and Wales: Charity No.
118664, Company No. 5823194.
Competing interests None.
Provenance and peer review Not commissioned; not externally peer reviewed.
1.
Burton H, Alberg C, Stewart A.
Heart to heart: inherited cardiovascular conditions services - a needs assessment and service review . Cambridge, UK: PHG Foundation,
2009.
2.
Department of Health.
Our inheritance, our future: realising the potential of genetics in the NHS. 2003. http://www.dh.govuk/en/Publicationsandstatistics/Publications/
PublicationsPolicyAndGuidance/DH_4006538.
3.
Department of Health.
National service framework for coronary heart disease.
Chapter 8: arrhythmias and sudden cardiac death. 2005. http://www.dh.gov.uk/en/
Healthcare/NationalServiceFrameworks/Coronaryheartdisease/DH_4117048.
4.
SSNDS Definition No 13. Specialised Cardiology & Cardiac Surgery Services (adult) 3rd edn. 2009. http://www.nscg.nhs.uk/index.php/key-documents/specialised-servicesnational-definitions-set/ (accessed 29 October 2009).
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