European Heart Journal (2016) 37, 1410–1418 doi:10.1093/eurheartj/ehw131
Cardiovascular centre of excellence
Great Ormond Street Hospital London From pioneering the total cavopulmonary connection to rapid prototyping to guide treatment, Great Ormond Street Hospital has innovation at its core
New Morgan Stanley Building of the Mittal Children’s Medical Centre Great Ormond Street Hospital (GOSH) in London provides congenital and acquired cardiac services for children from 0 to 18 years. As the biggest centre in the UK, it performs 800 operations a year of which 590 are open heart operations, making it one of the top five worldwide for congenital procedures. The hospital provides highly specialized services for part or all of the UK. For cardiac care, these include heart transplants, bridge to transplant with ventricular assist devices (VADs) for children with severe heart failure, treatment for pulmonary hypertension, and complex tracheal surgery. Great Ormond Street Hospital provided the first inpatient care for children in the UK in the 1800s. When GOSH opened its doors in 1852, it was the first hospital in the UK to provide dedicated inpatient care for children and had just 10 beds. Today, it employs 27 consultant cardiologists across a whole array of specialties, including advanced imaging, inherited cardiac disease, pulmonary hypertension, heart failure and transplantation, echocardiography, and interventional cardiology. There are 5.5 full time cardiothoracic surgeons, 40–50 junior doctors, and 8 cardiac intensive care consultants. Of the 230 nurses, 34 are advanced nurse practitioners or clinical nurse specialists. The service has 19 beds in cardiac intensive care, 24 ward beds of which 8 are high dependency, and 6 day care beds. As divisional director, Professor Andrew Taylor manages the entirety of Cardiorespiratory Services. ‘It is relatively innovative having the whole range of services in one division,’ he says. ‘We manage the patient pathway which is crucial for interaction between teams.’
Innovation has been a core part of cardiac services at GOSH. Twenty years ago Professor Marc De Leval pioneered the total cavopulmonary connection (TCPC) which changed the way the Fontan operation was done. De Leval was also interested in human factors, particularly for surgeons. That has led to a novel weekly review of all patients. Taylor believes that the ‘no blame meeting’ has led to improvements in clinical practice. ‘I don’t think people truly know from a research perspective but it could be that the rigorous observation of what we do makes people more aware and therefore has the potential to reduce complications,’ he says. Around 15 years ago the then professor of cardiology at GOSH, John Deanfield, focused his research on how inflammatory disease in childhood has great consequences on the cardiovascular system. The aim was to predict which children would develop coronary artery disease or vascular disease. Over the last decade, trailblazing work has been done in percutaneous pulmonary valve implantation for children using what has become the Melodyw device. Professor Philip Bonhoeffer did the initial case in Paris then came to Great Ormond Street to conduct the first clinical study in 200 patients. A couple of years ago, the first paediatric tracheal transplant was conducted by Professor Martin Elliott. More recently, researchers at GOSH have performed a paediatric heart failure stem cell study. Patients with dilated cardiomyopathy were injected with autologous stem cells down their coronary arteries. There were marginal improvements in left ventricular function. Other methods of administration are being investigated that might stimulate a better response, such as putting a balloon in the coronary sinus to obstruct flow for a brief period so that the cells stay in the coronary arteries for slightly longer. While Taylor says that ‘all stem cell work is in its infancy’, it does have the potential to help resolve one of the biggest clinical issues facing his division. Great Ormond Street Hospital has more children waiting for heart transplant than ever before. It is becoming clear that cardiac transplantation is unlikely to become the long-term method to treat these patients. Smaller devices appear to provide an answer and GOSH has been using the Berlin Heart device, a type of VAD that sits outside the patient. But the pump and battery are sizeable and patients must stay in
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2016. For permissions please email: [email protected].
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hospital. The next-generation HeartWarew device is implanted internally and the battery is small enough that children have gone home. However, the lifetime of the device is unknown. ‘I think if you work towards even smaller devices, even smaller batteries, and potentially stem cells that might help the heart recover a little, you might be looking at alternatives to transplantation,’ says Taylor. Taylor is professor of cardiovascular imaging at the University College London Institute of Cardiovascular Science. His research group was the first to show that for cardiac disease, post mortem imaging can replace autopsy in children and foetuses. Often parents want to know what has happened and why. ‘Imaging is less distressing than autopsy for parents,’ says Taylor. ‘It has been very clear that people don’t want their child ‘cut open’. The information from post mortem imaging can help with planning for future pregnancies and also provide reassurance around what has caused sudden death in infancy.’ Taylor was impressed by the generosity of families when conducting the post-mortem studies. ‘I was amazed that parents would want to take part,’ he says. ‘I thought, I’m going to ask them at the worst time in their life and of course they’re going to say no. But exactly the opposite happened.’ Today a big area of research at GOSH is predictive medicine using genetic information, biomarkers, imaging, and outcome data. One study in obese children the Model-Driven European Paediatric Digital Repository (MD Paedigree), aims to identify those at risk of developing vascular problems. Other studies will attempt to risk stratify patients with heart failure and patients with complex congenital heart diseases. Percutaneous valve implantation is being taken to the next level with new and patient-specific devices for children. The procedure has progressed from one which required open heart surgery, a stay in the intensive care unit followed by the ward and time off school—to what is essentially a day care in 15 –20% of children. Also in the device arena, cardiovascular imagers at GOSH can now build a patient-specific model of the heart. They then use it to virtually implant devices—for pulmonary regurgitation, for example—and then advise the cardiologist which device is best suited to that particular patient. On the back of that they have developed an interest in using rapid prototyping of the heart and the great vessels to plan and guide treatments like the arterial switch operations. ‘These models are really good for explaining to patients exactly what it looks like,’ says Taylor. ‘It’s something they can hold in their hand and look at. What surprises me is that patients and families like the models.’ Clinicians say the models make it easy to explain what they are talking about. But research at GOSH which tested families’ knowledge before and after looking at a model found that there was no change. Further studies will investigate whether taking the model home improves understanding in the long term. GOSH accepts
1411 referrals from 23 hospitals in London, the South East and East Anglia, and patients who can explain their condition to local clinicians in an emergency may be more likely to get the care they need quickly. Advanced imaging is another area of current interest. Great Ormond Street Hospital performs 1000 cardiac MRIs a year. In younger patients, the scan has historically taken about an hour and in most cases it required breath holding. It meant that patients younger than 8 years needed a general anaesthetic. Great Ormond Street Hospital’s work on rapid imaging, led by Dr Vivek Muthurangu, has taken one of those scans from 60 to 11 min. It obviates the general anaesthetic requirement and enables clinicians to perform three scans instead of one in the same amount of time. ‘A lot of basic science has gone into making those things happen and it has a very direct effect on patients,’ says Taylor. Successes in ‘fixing the heart’ have turned researchers’ attentions, particularly in the USA, towards the impact of operations on children’s neurodevelopment. Great Ormond Street Hospital has a large National Institute for Health Research (NIHR) grant aimed at trying to understand children’s needs as they grow older. ‘What is interesting is that certain children do really well after a procedure but then they hit about 13 or 14 and they’re doing GCSE exams and they then find some things very difficult,’ says Taylor. ‘I think it’s because suddenly they have to do a lot of things more independently in their heads, called executive function.’ It appears from cognitive development research that there are interventions that may help children at school before they start having problems. Studies are beginning to document the sorts of issues children face. Taylor says: ‘It brings you back to how you do the shortest bypass time possible, what sort of neuroprotective measures you put in place when you’re doing those initial operations, and so on.’ Creating a complete pathway of care for congenital heart disease which encompasses foetal, paediatric, and adult care is also a priority at GOSH. It has a close relationship with the adult congenital heart disease service at the new Barts Heart Centre in London, with surgeons operating at both locations and advanced imaging done between the two centres. A transition clinic is held for children leaving the GOSH service in which they see a consultant and a nurse in the adult service they will attend at a different hospital. Taylor says: ‘From a paediatric perspective, knowing what happens to your patients 20 to 30 years down the line is a very important influence on what you do to correct those new children that are coming through.’
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What are the unmet needs in Grown-up Congenital Heart Disease? The introduction of open heart surgery—6 decades ago—has dramatically changed the fate of children born with congenital heart disease (CHD). Whereas historically only 15% of children with CHD survived to adulthood uncorrected, it is estimated that over 90% reach adult age in the current medical era.1 These developments have led to a dramatic increase in the number of patients entering adult cardiology care. These so-called grown-up congenital heart disease (GUCH) patients are by and large, not cured and continue to require life-long cardiac follow-up and specialized care. While good long-term survival prospects and near normal quality of life can be achieved in many patients, even today, some patients remain only amenable to palliative procedures, and long-term morbidity and mortality of many congenital defects are significantly increased compared with the general population. This, in turn, has prompted the development of a new discipline within cardiology. Over the last 2 decades, a growing number of specialized GUCH centers have been established in Europe to provide optimal care for this expanding and challenging patient population. Today, it is estimated that .50 such centers exist in Europe.2 These large supra-regional centers not only provide high-quality patient care but also, significantly contribute to research and are the mainstay for educating young physicians entering the field. Despite these encouraging aspects, challenges remain even in resource rich western countries. Three areas deserve particular attention and are briefly discussed. Firstly, service provision requires further improvements. Due to its highly specialized nature, centralizing GUCH care at appropriately equipped and staffed supra-regional centers is to be advocated. By necessity, this requires patients to travel further and may affect access to adequate care. The number and location of tertiary centers should be tailored to the specific geography of the respective country. While in densely populated areas many centers can co-exist in close proximity, sparsely populated regions (such as those in Canada and some areas of the USA) will naturally impose a greater travel burden on patients. It has been suggested that one GUCH center should ideally serve a population of 3–5 million people, although this figure is only based on experience and expert consensus. Whether this indeed represents the optimum remains to be demonstrated scientifically. Concentrating services creates economies of scale and scope and should improve outcomes, especially related to complex and rare procedures.3 Recent evidence suggests that GUCH patients treated at tertiary Canadian centers have superior outcomes compared with a historic cohort not necessarily linked to such supra-regional centres.4 In addition, lapses in care at tertiary centers have been identified as a risk factor for mortality in contemporary GUCH patients.5 On the other hand, monopolistic situations may have to be avoided, as some degree of competition between (large) tertiary centers has been shown to be associated with better survival after pulmonary valve replacement in adult life.6 The challenge, therefore, is to establish accessible services as close as possible to patients’ homes, while securing a sufficiently large volume for each center to achieve excellence. In addition, transparency of
results and quality assurance measures are to be recommended to drive quality improvements, patient choice, and accountability. Improving services will not only require ongoing efforts by healthcare professionals but also patient involvement and a clear commitment by payers and health politicians to invest heavily in this growing area of care. The financial investment today is likely to be well spent, given that complications and emergency admissions are main cost drivers in this still young but chronically ill population.7,8 Secondly, ongoing research efforts are required in this expanding patient population. Due to the specific anatomy and physiology of GUCH patients, applying study results from acquired heart disease directly to this population is questionable. As a consequence, we are in need of more data specific for CHD. The heterogeneity and relatively low mortality in GUCH compared with the much older heart failure and coronary artery disease population represent barriers to adequately powered studies. In addition, the GUCH population with its limited prevalence in the community is generally not perceived to be an attractive investment both by medical industry and national funding organizations. This has created a vacuum of prospective data on the efficacy and safety of drugs and devices in GUCH. Most of our current knowledge in CHD is therefore derived from observational, mostly retrospective studies, and registry data. While such studies reflect ‘reality-based medicine’ and have many merits they cannot fully replace adequately powered and conducted prospective randomized trials. The increasing availability of administrative electronic health care data may provide new opportunities but also challenges for research. Although these ‘big data’ are inherently difficult to analyses, such studies could represent a welcome adjunct to registry data. Nevertheless, detecting patterns and associations in retrospective data is—by nature—hypothesis-generating research and requires prospective studies to confirm the results statistically before widely applying them to patient care. Translational and basic science research have so far, only a limited scope in CHD and require increased attention. Especially, the progress in genetic research and the ability to genotype patients at low cost should provide further insights into the etiology of CHD. Concentrating selected research efforts at central (national) institutions and encouraging collaboration between centers is likely to increase scientific output while lowering transaction costs.9,10 Compiling and balancing the results of many retrospective studies is particularly challenging as the (mostly unstructured) results are not amenable to quantitative meta-analytic strategies. As a consequence, systematic reviews of the literature, highlighting evidence of particular clinical relevance, are increasingly required. The GUCH guidelines provided by the European Society of Cardiology (ESC)11 as well as scientific organizations from overseas, are of particular relevance in this regard. They provide an overview of the many conditions, focusing on the benefits and risks of common diagnostic and therapeutic procedures. The ESC and others should be commended for investing in these types of scientific documents and associated position papers, clarifying specific aspects of care.
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Thirdly, training an adequate workforce of physicians, nurses, and technicians to care for the growing GUCH population represents a challenge for many healthcare systems.12 Many of the currently practicing GUCH specialists have been educated at a small number of large international centers. This model for training GUCH specialists is unsustainable in the long run and both European and national efforts are required to develop training curricula and establish training posts at major national centers. In addition, accreditation in GUCH should be promoted as it encourages physicians to undergo formal training and signals competence to potential patients. Nevertheless, international training programs should also be offered to support collaboration between centers of excellence and provide clinical and academic training opportunities for the future leaders in the field of GUCH. Beyond educating and training the core GUCH providers, we also need to reach out to affiliated specialists involved in the daily care of GUCH patients. This includes for example general physicians, general cardiologists, radiologists, and obstetricians.13 Last but not least, educating patients about their condition and involving GUCH patients in their care should improve outcomes and help to avoid catastrophic events due to loss to follow-up or treatment at inadequate institutions. Beyond the issues discussed above for rich countries, developing countries face particular challenges related to GUCH care. It is estimated that due to the sheer numbers of the population and the
prevailing demographics the majority of GUCH patients currently live in developing countries. In these settings, adequate services are nearly absent due to a general lack of resources.14 Therefore, improving worldwide GUCH services should be a priority for health professionals and health politicians in affected countries, but also requires increased support by scientific and professional organizations as well as development assistance from resource rich countries.
References References are available as supplementary material at European Heart Journal online.
Pregnancy in women with congenital heart disease Difficulties that pregnant women with congenital heart defects encounter are discussed through two case vignettes Case vignette #1 A 33-year-old woman, born with transposition of the great arteries, is referred for counselling about the risks of pregnancy. She underwent intra-cardiac repair with the atrial switch operation (Senning operation) at the age of 14 months. At the age of 16 years, she was discharged from follow-up at the paediatric hospital and has had no regular follow-up since then. At the age of 23 years, she was seen by a general cardiologist who told her she had a high risk of complications during pregnancy and must not become pregnant. After marriage 2 years ago, she now desires to have children and she struggles with the earlier negative pregnancy advice, particularly as she has learned about women with the same cardiac condition who had successful pregnancies. She is asymptomatic but has mildly impaired exercise capacity on cardio-pulmonary exercise testing, reaching 78% of predicted workload. Oxygen saturation in ambient air is 97% and decreases to 92% during exercise. Echocardiography demonstrates mildly impaired systemic right ventricular systolic function, mild tricuspid regurgitation (systemic atrioventricular valve regurgitation) and mild sub pulmonic left ventricular outflow tract obstruction with a peak gradient of 40 mmHg. On bubble-contrast injection a shunt from the systemic venous baffle to the pulmonary venous baffle is demonstrated, consistent with a baffle leak. What should we advise this woman regarding the risks of pregnancy?
Congenital heart defects are common. With the advent of openheart surgery, the majority of affected patients now survive to adulthood and thus, cohorts of women with repaired congenital heart defects in childbearing age are rapidly evolving. The recognition that these patients are not cured and remain at risk of adverse events has emerged only over the past few decades and many patients have been lost to specialist follow-up. Pregnancy leads to profound haemodynamic changes with an increase in plasma volume and cardiac output of 50% by the end of
the second trimester and a decrease in systemic vascular resistance. Depending on the specific type of the underlying heart defect, residual haemodynamic lesions, impaired myocardial reserve and many other factors, the ability to adapt to the haemodynamic changes and needs of pregnancy may be substantially impaired in women with congenital heart defects. There is generally an increased risk of arrhythmias and heart failure during pregnancy and women with residual intra-cardiac shunts have an increased risk of paradoxical embolization in the event of thrombo-embolic
1414 complications. The effect of pregnancy on long-term outcomes depends on the type of the congenital heart defect, the type of repair and may be hard to predict, since there are insufficient data available. The risk of premature delivery may be substantially increased and depending on the type of defect, the risk of recurrence of congenital heart defects in the offspring ranges between 3 and 10% in non-syndromic patients. A few lesions are associated with particular high maternal mortality risk and pregnancy is generally discouraged in affected women. These include women with severe symptomatic aortic valve stenosis, severe left atrio-ventricular valve stenosis, pulmonary arterial hypertension, systemic ventricular ejection fraction ,30% or poor functional class (NYHA III and IV), markedly dilated ascending aorta in women with Marfan syndrome (.45 mm) or in women with bicuspid aortic valves (.50 mm). For most other women, careful individual assessment is required to allow individual risk stratification and counselling that will enable the woman to make an informed decision about whether or not she is willing to take the risks of a pregnancy. To make such a decision, it is important to distinguish between manageable cardiovascular complications (e.g. atrial arrhythmias, mild heart failure) and catastrophic events such as stroke, irreversible myocardial failure, and death. Comprehensive pre-conception counselling also includes an open discussion about the expected long-term risk of deterioration of the underlying cardiac condition and the risk of premature death.
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An important part in pre-conception assessment is the identification of modifiable conditions that can be improved prior to embarking on pregnancy to reduce the pregnancy risk (e.g. radiofrequency ablation of atrial arrhythmias). Careful review of a woman’s medication is important and medications with risk of foetal toxicity (e.g. angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or spironolactone) should either be stopped or changed to preparations compatible with pregnancy. The management of women with mechanical heart valve prosthesis is particularly difficult and these women should always be referred to a dedicated centre with a multi-disciplinary team experienced in the management of high-risk pregnancies. For women, who wish to embark on pregnancy, obstetrical review including an update of recommended vaccinations and the start of folic acid prophylaxis are important. For women not wishing to become pregnant or with a contraindication for pregnancy, counselling about safe and effective contraception is mandatory. The woman outlined in the case vignette above decided to become pregnant after a careful discussion of potential risks. She had an uneventful pregnancy and delivered a healthy baby boy by caesarean section for obstetric reasons. Five days after delivery she experienced increased shortness of breath and Pro-BNP-levels increased to 318 ng/l (upper limit of normal: 130 ng/l). Echocardiographic findings at that point remained unchanged and symptoms rapidly resolved without specific treatment. The patient had a stable clinical course since.
Case vignette #2 A 28-year-old woman with congenitally corrected transposition of the great arteries is referred to the specialist centre at 13 weeks of gestation in her first pregnancy. She had been asymptomatic before pregnancy and had an uneventful course until the 26th week of gestation, when she started experiencing shortness of breath on exertion with progressive worsening over the subsequent weeks. At 30 weeks of gestation, echocardiography shows systemic right ventricular dilatation with at least moderate tricuspid regurgitation and marked worsening of right ventricular systolic function. Pro-BNP-levels have increased from 140 ng/l pre-pregnancy to 1040 ng/l (upper limit of normal: 130 ng/l). Despite administration of loop diuretics, symptoms worsen, and the patient has to be admitted to the cardiology ward. When symptoms further deteriorate a decision for planned caesarean section at 34 weeks of gestation is made after multi-disciplinary case discussion. The patient is monitored for 48 h in a medical intensive care unit after delivery and intensive heart failure therapy is initiated immediately after delivery along with careful fluid balance. The patient’s condition improves and she is discharged from hospital 10 days after delivery with a plan for outpatient follow-up within 1 week after discharge. The new-born female had a birth weight of 1800 g and experienced mild respiratory distress syndrome but did not require mechanical ventilation. She was discharged home 3 weeks later.
Depending on the expected pregnancy risk, a clear follow-up plan has to be scheduled, as advised in the 2011 ESC guidelines for the management of cardiovascular diseases during pregnancy.1 During pregnancy, follow-up plans have to be adapted to the clinical course during pregnancy. Careful patient education about symptoms of potential complications (e.g. arrhythmias or heart failure) is important and all women should be provided emergency contact information. All women should be offered foetal echocardiography between the 18th and 20th week of gestation. A multi-disciplinary delivery plan should be established well before term, especially in women who experience complications or have a high risk of pre-term delivery. The written delivery plan should include detailed information about the underlying heart defect (including a schematic drawing in case of complex anatomy),
expected cardiac complications, and their immediate management in case of occurrence. The delivery plan should also include the planned type of delivery, the type of planned anaesthesia, type of monitoring during labour and delivery, and the type and duration of monitoring in the postpartum period. If specific precautions, such as air bubble filters for intravenous lines are required it should be ensured that these are available on the labour ward when needed. Before discharge from hospital, a follow-up plan should be established. For most women, the preferred mode of delivery is vaginal delivery, while early administration of epidural analgesia is often advised. Exceptions, in which caesarean section may be preferred, include women with a markedly dilated ascending aortic diameter (.45 mm), preterm labour while on oral anticoagulation with vitamin K-antagonists, women with severe aortic stenosis experiencing symptoms during
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pregnancy, and women with severe heart failure. For many women epidural anaesthesia is appropriate to decrease the haemodynamic effects of the delivery. However, single-shot spinal anaesthesia is contraindicated in most patients. A plan for the appropriate use of obstetric medication should also be in place, giving attention to possible adverse haemodynamic effects of these medications.
Reference 1. European Society of Gynecology (ESG), Association for European Paediatric Cardiology (AEPC), German Society for Gender Medicine (DGesGM), Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C, Cifkova R, Ferreira R, Foidart JM, Gibbs JS, Gohlke-Baerwolf C, Gorenek B, Iung B, Kirby M, Maas AH, Morais J, Nihoyannopoulos P, Pieper PG, Presbitero P, Roos-Hesselink JW, Schaufelberger M, Seeland U, Torracca L, ESC Committee for Practice Guidelines. ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J 2011;32:3147–3197.
Health insurance problems for adults with congenital heart disease The difficulty of obtaining health insurance coverage for adults with congenital heart defects is discussed through two real-life examples
Life insurance Case vignette 1: A 23-year-old male with complete transposition of the great arteries will get married next month and is planning to have children within the next 2 – 3 years. He underwent the arterial switch operation on his 6th day of life and subsequently had dilatation and stent placement of right branch pulmonary artery stenosis at the age of 9 years. He is left with moderate dilatation of the neo-aortic root, mild-to-moderate neo-aortic valve regurgitation and mild branch pulmonary artery stenosis. Although he considers himself as healthy and does not feel any limitations in his day-to-day life, he manages only 82% of predicted on cardiopulmonary exercise testing. In view of planning to have a family in his near future, he wishes to protect them and hence the patient is applying for life insurance. He is very surprised to learn that the insurance company declines coverage for the unknown and probably increased long-term risks of the underlying heart condition.
Congenital heart defects are the most common birth defects, affecting 0.8 of 1000 live-born. Without treatment many patients die in early childhood, but with the advent of modern heart surgery the vast majority survive into adult life. In adolescence and young adulthood most patients feel well, the majority have no significant limitations and most lead productive and active lives. Nonetheless, these patients are not cured and many are at substantially increased risk of cardiovascular complications and even premature death as young adults. Many of these young adults are confronted with their disease and its potential life-shortening nature when questions about insurability occur at the time of family planning, as illustrated above. Non-governmental insurance companies are allowed to categorize people according to mortality risks. Based on the individual
characteristics of a person increased mortality risks are expressed as mortality ratios with a mortality ratio of 100% equalling the mortality risk of an age- and gender-matched reference group. Based on such survival estimates, life-insurance protection for adults with congenital heart disease is often declined by insurers. However, unfortunately, survival data for adults with congenital heart defects are imperfect. Given that surgical repair techniques for most congenital heart defects were invented only a few decades ago, survival data beyond the fourth or fifth decade of life are sparse. For novel cohorts, such as adults after the arterial switch operation, as outlined in the case vignette above, robust outcome data may even be lacking for the third decade of life. In addition, timing and technique of surgical repair are constantly modified. This can be impressively demonstrated for patients with repaired Tetralogy of Fallot, the most common cyanotic heart defect. In a landmark multicentre study published by Gatzoulis and colleagues in the Lancet in 2000 the long-term risk of arrhythmias and sudden death were analysed in 793 patients with repaired Tetralogy of Fallot, operated before and alive in 1985. In this patient population median age at intracardiac repair was 5.7 years, 37% had previous palliation with a systemic to pulmonary artery shunt and almost all (91%) had undergone trans ventricular repair. Numerous studies have since confirmed that late repair, previous palliative shunts, and trans ventricular repair techniques are important risk factors for the long-term risk of ventricular arrhythmia and sudden death. This evidence has changed surgical practice and techniques profoundly. Affected patients are now typically repaired within the first year of life, shunt palliation prior to intracardiac repair has become the rare exception and whenever technically feasible, a trans atrial repair-approach is used. As a consequence, the average long-term arrhythmia-risk of a 20-year-old operated in
1416 the 1990s when compared with a patient operated in the 1970s with the same amount of residual haemodynamic lesions, is likely to be very different and more favourable in patients operated in the current era. As caregivers we can provide more detailed medical reports with more detailed reasoning on an individual patient’s situation and hence the individual risk for adverse events that may help the insurer to reach a fair assessment of the individual patient’s risk and may enhance the probability to receive coverage, even in patients with complex defects. In some countries, patient organizations (i.e. the Canadian congenital heart alliance) have negotiated group plans for non-medical life-insurance coverage for their members.
Disability pension Case vignette 2: A 33-year-old woman, born with tricuspid atresia was palliated with a modified Fontan operation at the age of 4 years. For many years, she was suffering from recurrent atrial arrhythmias for which she underwent several ablation procedures and numerous electrical cardioversions. She was turned down for Fontan conversion due to anatomic constraints. She underwent urgent thyroidectomy a year ago for amiodarone-induced thyrotoxicosis, which was complicated by transient renal failure. Despite device closure of large veno-venous collaterals, she remains mildly cyanotic with oxygen saturations 89– 91% in ambient air. Ejection fraction of the single left ventricle is normal. Currently, she is in NYHA functional class II– III and manages only 47% of the predicted workload on cardiopulmonary exercise testing, which is markedly ,5 years ago. She no longer copes with long working hours as a saleswoman and feels exhausted after 5 h at work. With the support of her cardiologist the patient applied for a part-time disability pension. The application was declined by the federal insurance company with the statement that the claim of heart failure was not supported by the finding of a normal left ventricular ejection fraction and that the patient’s exercise intolerance and low oxygen saturations were likely the consequence of poor motivation and lack of regular aerobic exercise training.
This real life case illustrates that our patients do also face important difficulties in getting a fair assessment for income replacement insurance (disability pension). Given that adult cohorts with congenital heart disease are just evolving, there is a general lack of understanding about the nature of these conditions and their impact on patients’ limitations. From the perspective of the medical caregiver, it is important to provide detailed information to insurance bodies to allow them to understand the structural defect, the nature
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and type of previous repairs and importantly the current residual lesions (e.g. valve dysfunction, myocardial dysfunction, cyanosis, or arrhythmias) that explain the patient’s symptomatology and limitations. Prevention of disability, however, starts long before the application for a disability pension. As caregivers it is an important task to inform young patients and their families about the nature of the heart defect and potential long-term complications and impact on long-term exercise capacity. Providing this information will enable the adolescent to choose an appropriate profession, which for example will not include physical work in later years.
Travel insurance Patients should be encouraged to investigate the coverage of their health care insurance when travelling abroad. If not sufficient, many companies offer packages with coverage for patients with congenital heart disease at reasonable premiums.
Summary and outlook Although congenital heart disease is a common condition, its awareness in the general population and governmental bodies is low and funding for large-scale multicentre research is sparse. This general lack of awareness impacts on improved outcome data and difficulties for affected patients in obtaining insurance coverage or a disability pension. Joint efforts between patient organizations and health care providers to increase the awareness of congenital heart disease and better information (and education) of insurers about the specific characteristics and needs of adults with congenital heart disease may improve the situation.
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New congenital coronary artery disease classification A new classification of congenital coronary artery diseases is set to help surgeons identify secondary defects in the operating room ‘It can be difficult to spot further defects in the stressful environment of the operating theatre.’ The scheme is outlined in a novel European Society of Cardiology (ESC) position paper published in Cardiovascular Research during January.1 Clinical cardiologists will also know what to look for on cardiovascular images. ‘Congenital coronary artery diseases affect less than 1% of new-borns but are an important cause of myocardial infarction and sudden death particularly in children and competitive athletes,’ said Professor Cristina Basso MD PhD, chairperson of the ESC Development, Anatomy and Pathology Working Group. ‘These conditions are often forgotten in the clinical setting because atherosclerotic coronary artery disease is far more common.’ The paper launches a new classification of coronary artery anomalies that explains common points of origin between different coronary defects. By identifying the origin of the primary defect, doctors can evaluate the probability of finding specific secondary defects with an origin related to the main anomaly. First author Dr Jose´ Marı´a Pe´rez-Pomares said: ‘We have established links between coronary congenital diseases sharing a common mechanism. When operating a diagnosed coronary anomaly, it can be difficult for surgeons to spot further defects in the stressful environment of the operating theatre and having an idea of the anomalies you might find can be extremely helpful. The new classification will also help clinicians using imaging to diagnose coronary artery anomalies and prevent future complications.’ He added: ‘We have been able to produce this classification because we understand more about how coronary arteries develop in the embryo and how they relate to major diseases. The paper provides basic cardiovascular research scientists with new, updated information on the complex embryonic development of coronary arteries to throw light on the aetiology of coronary congenital anomalies.’ The authors give their expert opinion on the embryonic origin of the coronary endothelium, which is a controversial topic in cardiovascular developmental biology. Dr Pe´rez-Pomares said: ‘For a long time scientists have wanted to identify a single and unique source for coronary endothelial cells but we now know that they come from different sources that merge together. This appears to have an impact on what happens to coronary vessels during embryonic development but perhaps also in the adult.’
Although not explicitly stated in the paper, the authors think that this heterogeneity of cell sources contributing to the endothelium may be important in the development of adult coronary disease, as endothelial cells with different origins might respond differentially to pathological stimuli. The diverse origin of coronary smooth muscle cells and fibroblasts are also described. Remarkably, adventitial fibroblasts that cover the arteries share a common embryonic origin with adult interstitial fibroblasts located between the myocardial fibres which are responsible for fibrotic scar formation after myocardial infarction. This finding also suggests that embryonic clues related to coronary development could be relevant for understanding cardiac fibrosis in the adult ischaemic heart. The authors say that this ‘mosaic-like embryonic development of the coronary vascular system’ is key to understanding the complex spectrum of coronary artery anomalies. Dr Pe´ rez-Pomares said: ‘The more we dig in, the more we have the impression that important events happening in the embryo, including the activation of regulatory gene networks, signalling molecular pathways, and specific cellular mechanisms also have a clear function in adult responses to pathological stimuli.’ Professor Basso concluded: ‘This is a translational paper written by basic scientists, including developmental biologists, anatomists and pathologists. It contains practical information to help clinicians diagnose coronary artery anomalies and prevent devastating complications including sudden death.’ A. Tofield ESC Press Office
Funding J.M.P.-P. was funded by grants BFU2012-35799 (MINECO); RD12/0019/ 0022, TERCEL (MINECO-ISCIII); PITN-GA-2011-289600 (‘CardioNet’, EU I+D+i FP7, Marie Curie ITNs). R.G.K., J.L.d.l.P., S.S., and M.v.d.H. were also funded by PITN-GA-2011-289600; C.B. and G.T. were funded by the Registry for Cardio-Cerebro-Vascular Pathology, Venice, Italy. Conflict of interest: none declared.
Reference 1. Pe´rez-Pomares JM, de la Pompa JL, Franco D, Henderson D, Ho SY, Houyel L, Kelly RG, Sedmera D, Sheppard M, Sperling S, Thiene G, van den Hoff M, Basso C. Congenital coronary artery anomalies: a bridge from embryology to anatomy and pathophysiology—a position statement of the development, anatomy, and pathology ESC Working Group. Cardiovasc Res 2016;109:204 –216.
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Book Review
Congenital heart disease molecular genetics, principles of diagnosis and treatment Editors: Maximilian Muenke (Bethesda, MD), Paul S. Kruszka (Bethesda, MD), Craig A. Sable (Washington, DC), John W. Belmont (Houston, TX). Publisher: Karger Pub date: June 2015 Hardback: 326 pages, 93 figures 49 in colour ISBN: 978-3-318-03003-7 E-ISBN: 978-3-318-03004-4 Heart malformations constitute a major fraction of clinically significant birth defects and represent an important component of paediatric and adult cardiovascular disease. In the last decades, there have been remarkable improvements in the clinical care of patients with congenital heart disease. Furthermore, basic research has provided considerable insight into normal cardiac and vascular development, which permits us to draw inferences concerning the genesis of congenital heart disease. Yet, significant challenges remain both in acute and longitudinal patient care and in deciphering the genetic and environmental factors that underlie the development of these diseases. This book, written by renowned leaders in genetics, basic science, and paediatric and adult cardiology, covers a comprehensive list of topics in congenital heart disease that spans from aetiology to treatment. The book is organized into seven sections, starting with a historical overview and a comprehensive review of current knowledge on the normal development of the heart. The next section deals with the epidemiology of congenital heart disease and focuses on prevention, congenital heart disease in a developing country, maternal non-genetic risk factors, and adult congenital heart disease. Congenital heart defects caused by chromosomal abnormalities and those caused by single gene disorders are organized into two separate subsequent sections. Surprisingly, the book also contains a section dedicated to the primary rhythm disorders (the ion channelopathies), the genetic cardiomyopathies and inherited forms of thoracic aortic aneurysms.
The penultimate section deals with patient evaluation and covers the genetic evaluation of patients including a discussion of state-of-the-art genetic technologies that are revolutionizing genetic diagnostics and gene discovery. This section also contains parts on imaging of congenital defects for the non-cardiologist and prenatal evaluation of congenital heart disease. The last section deals with treatment and covers surgical management, interventional cardiology, ethical considerations in the management of patients with congenital heart disease and finally, looks into the future by dwelling on new technologies such as stem cell biology, bioengineering, and gene therapy that may deliver new therapies in the future. As a geneticist performing research in inherited cardiac disease I liked this book, because it tackles a broad range of disorders and gathers the most relevant and up-to-date information in a concise fashion, spanning clinical aspects, basic science, and genetics. It will undoubtedly benefit geneticists and basic scientists studying these disorders as well as students, trainees, and clinicians from a variety of disciplines.
CardioPulse contact: Andros Tofield, Managing Editor. Email: [email protected]
Cardiovascular centre of excellence
Great Ormond Street Hospital London From pioneering the total cavopulmonary connection to rapid prototyping to guide treatment, Great Ormond Street Hospital has innovation at its core
New Morgan Stanley Building of the Mittal Children’s Medical Centre Great Ormond Street Hospital (GOSH) in London provides congenital and acquired cardiac services for children from 0 to 18 years. As the biggest centre in the UK, it performs 800 operations a year of which 590 are open heart operations, making it one of the top five worldwide for congenital procedures. The hospital provides highly specialized services for part or all of the UK. For cardiac care, these include heart transplants, bridge to transplant with ventricular assist devices (VADs) for children with severe heart failure, treatment for pulmonary hypertension, and complex tracheal surgery. Great Ormond Street Hospital provided the first inpatient care for children in the UK in the 1800s. When GOSH opened its doors in 1852, it was the first hospital in the UK to provide dedicated inpatient care for children and had just 10 beds. Today, it employs 27 consultant cardiologists across a whole array of specialties, including advanced imaging, inherited cardiac disease, pulmonary hypertension, heart failure and transplantation, echocardiography, and interventional cardiology. There are 5.5 full time cardiothoracic surgeons, 40–50 junior doctors, and 8 cardiac intensive care consultants. Of the 230 nurses, 34 are advanced nurse practitioners or clinical nurse specialists. The service has 19 beds in cardiac intensive care, 24 ward beds of which 8 are high dependency, and 6 day care beds. As divisional director, Professor Andrew Taylor manages the entirety of Cardiorespiratory Services. ‘It is relatively innovative having the whole range of services in one division,’ he says. ‘We manage the patient pathway which is crucial for interaction between teams.’
Innovation has been a core part of cardiac services at GOSH. Twenty years ago Professor Marc De Leval pioneered the total cavopulmonary connection (TCPC) which changed the way the Fontan operation was done. De Leval was also interested in human factors, particularly for surgeons. That has led to a novel weekly review of all patients. Taylor believes that the ‘no blame meeting’ has led to improvements in clinical practice. ‘I don’t think people truly know from a research perspective but it could be that the rigorous observation of what we do makes people more aware and therefore has the potential to reduce complications,’ he says. Around 15 years ago the then professor of cardiology at GOSH, John Deanfield, focused his research on how inflammatory disease in childhood has great consequences on the cardiovascular system. The aim was to predict which children would develop coronary artery disease or vascular disease. Over the last decade, trailblazing work has been done in percutaneous pulmonary valve implantation for children using what has become the Melodyw device. Professor Philip Bonhoeffer did the initial case in Paris then came to Great Ormond Street to conduct the first clinical study in 200 patients. A couple of years ago, the first paediatric tracheal transplant was conducted by Professor Martin Elliott. More recently, researchers at GOSH have performed a paediatric heart failure stem cell study. Patients with dilated cardiomyopathy were injected with autologous stem cells down their coronary arteries. There were marginal improvements in left ventricular function. Other methods of administration are being investigated that might stimulate a better response, such as putting a balloon in the coronary sinus to obstruct flow for a brief period so that the cells stay in the coronary arteries for slightly longer. While Taylor says that ‘all stem cell work is in its infancy’, it does have the potential to help resolve one of the biggest clinical issues facing his division. Great Ormond Street Hospital has more children waiting for heart transplant than ever before. It is becoming clear that cardiac transplantation is unlikely to become the long-term method to treat these patients. Smaller devices appear to provide an answer and GOSH has been using the Berlin Heart device, a type of VAD that sits outside the patient. But the pump and battery are sizeable and patients must stay in
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2016. For permissions please email: [email protected].
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hospital. The next-generation HeartWarew device is implanted internally and the battery is small enough that children have gone home. However, the lifetime of the device is unknown. ‘I think if you work towards even smaller devices, even smaller batteries, and potentially stem cells that might help the heart recover a little, you might be looking at alternatives to transplantation,’ says Taylor. Taylor is professor of cardiovascular imaging at the University College London Institute of Cardiovascular Science. His research group was the first to show that for cardiac disease, post mortem imaging can replace autopsy in children and foetuses. Often parents want to know what has happened and why. ‘Imaging is less distressing than autopsy for parents,’ says Taylor. ‘It has been very clear that people don’t want their child ‘cut open’. The information from post mortem imaging can help with planning for future pregnancies and also provide reassurance around what has caused sudden death in infancy.’ Taylor was impressed by the generosity of families when conducting the post-mortem studies. ‘I was amazed that parents would want to take part,’ he says. ‘I thought, I’m going to ask them at the worst time in their life and of course they’re going to say no. But exactly the opposite happened.’ Today a big area of research at GOSH is predictive medicine using genetic information, biomarkers, imaging, and outcome data. One study in obese children the Model-Driven European Paediatric Digital Repository (MD Paedigree), aims to identify those at risk of developing vascular problems. Other studies will attempt to risk stratify patients with heart failure and patients with complex congenital heart diseases. Percutaneous valve implantation is being taken to the next level with new and patient-specific devices for children. The procedure has progressed from one which required open heart surgery, a stay in the intensive care unit followed by the ward and time off school—to what is essentially a day care in 15 –20% of children. Also in the device arena, cardiovascular imagers at GOSH can now build a patient-specific model of the heart. They then use it to virtually implant devices—for pulmonary regurgitation, for example—and then advise the cardiologist which device is best suited to that particular patient. On the back of that they have developed an interest in using rapid prototyping of the heart and the great vessels to plan and guide treatments like the arterial switch operations. ‘These models are really good for explaining to patients exactly what it looks like,’ says Taylor. ‘It’s something they can hold in their hand and look at. What surprises me is that patients and families like the models.’ Clinicians say the models make it easy to explain what they are talking about. But research at GOSH which tested families’ knowledge before and after looking at a model found that there was no change. Further studies will investigate whether taking the model home improves understanding in the long term. GOSH accepts
1411 referrals from 23 hospitals in London, the South East and East Anglia, and patients who can explain their condition to local clinicians in an emergency may be more likely to get the care they need quickly. Advanced imaging is another area of current interest. Great Ormond Street Hospital performs 1000 cardiac MRIs a year. In younger patients, the scan has historically taken about an hour and in most cases it required breath holding. It meant that patients younger than 8 years needed a general anaesthetic. Great Ormond Street Hospital’s work on rapid imaging, led by Dr Vivek Muthurangu, has taken one of those scans from 60 to 11 min. It obviates the general anaesthetic requirement and enables clinicians to perform three scans instead of one in the same amount of time. ‘A lot of basic science has gone into making those things happen and it has a very direct effect on patients,’ says Taylor. Successes in ‘fixing the heart’ have turned researchers’ attentions, particularly in the USA, towards the impact of operations on children’s neurodevelopment. Great Ormond Street Hospital has a large National Institute for Health Research (NIHR) grant aimed at trying to understand children’s needs as they grow older. ‘What is interesting is that certain children do really well after a procedure but then they hit about 13 or 14 and they’re doing GCSE exams and they then find some things very difficult,’ says Taylor. ‘I think it’s because suddenly they have to do a lot of things more independently in their heads, called executive function.’ It appears from cognitive development research that there are interventions that may help children at school before they start having problems. Studies are beginning to document the sorts of issues children face. Taylor says: ‘It brings you back to how you do the shortest bypass time possible, what sort of neuroprotective measures you put in place when you’re doing those initial operations, and so on.’ Creating a complete pathway of care for congenital heart disease which encompasses foetal, paediatric, and adult care is also a priority at GOSH. It has a close relationship with the adult congenital heart disease service at the new Barts Heart Centre in London, with surgeons operating at both locations and advanced imaging done between the two centres. A transition clinic is held for children leaving the GOSH service in which they see a consultant and a nurse in the adult service they will attend at a different hospital. Taylor says: ‘From a paediatric perspective, knowing what happens to your patients 20 to 30 years down the line is a very important influence on what you do to correct those new children that are coming through.’
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What are the unmet needs in Grown-up Congenital Heart Disease? The introduction of open heart surgery—6 decades ago—has dramatically changed the fate of children born with congenital heart disease (CHD). Whereas historically only 15% of children with CHD survived to adulthood uncorrected, it is estimated that over 90% reach adult age in the current medical era.1 These developments have led to a dramatic increase in the number of patients entering adult cardiology care. These so-called grown-up congenital heart disease (GUCH) patients are by and large, not cured and continue to require life-long cardiac follow-up and specialized care. While good long-term survival prospects and near normal quality of life can be achieved in many patients, even today, some patients remain only amenable to palliative procedures, and long-term morbidity and mortality of many congenital defects are significantly increased compared with the general population. This, in turn, has prompted the development of a new discipline within cardiology. Over the last 2 decades, a growing number of specialized GUCH centers have been established in Europe to provide optimal care for this expanding and challenging patient population. Today, it is estimated that .50 such centers exist in Europe.2 These large supra-regional centers not only provide high-quality patient care but also, significantly contribute to research and are the mainstay for educating young physicians entering the field. Despite these encouraging aspects, challenges remain even in resource rich western countries. Three areas deserve particular attention and are briefly discussed. Firstly, service provision requires further improvements. Due to its highly specialized nature, centralizing GUCH care at appropriately equipped and staffed supra-regional centers is to be advocated. By necessity, this requires patients to travel further and may affect access to adequate care. The number and location of tertiary centers should be tailored to the specific geography of the respective country. While in densely populated areas many centers can co-exist in close proximity, sparsely populated regions (such as those in Canada and some areas of the USA) will naturally impose a greater travel burden on patients. It has been suggested that one GUCH center should ideally serve a population of 3–5 million people, although this figure is only based on experience and expert consensus. Whether this indeed represents the optimum remains to be demonstrated scientifically. Concentrating services creates economies of scale and scope and should improve outcomes, especially related to complex and rare procedures.3 Recent evidence suggests that GUCH patients treated at tertiary Canadian centers have superior outcomes compared with a historic cohort not necessarily linked to such supra-regional centres.4 In addition, lapses in care at tertiary centers have been identified as a risk factor for mortality in contemporary GUCH patients.5 On the other hand, monopolistic situations may have to be avoided, as some degree of competition between (large) tertiary centers has been shown to be associated with better survival after pulmonary valve replacement in adult life.6 The challenge, therefore, is to establish accessible services as close as possible to patients’ homes, while securing a sufficiently large volume for each center to achieve excellence. In addition, transparency of
results and quality assurance measures are to be recommended to drive quality improvements, patient choice, and accountability. Improving services will not only require ongoing efforts by healthcare professionals but also patient involvement and a clear commitment by payers and health politicians to invest heavily in this growing area of care. The financial investment today is likely to be well spent, given that complications and emergency admissions are main cost drivers in this still young but chronically ill population.7,8 Secondly, ongoing research efforts are required in this expanding patient population. Due to the specific anatomy and physiology of GUCH patients, applying study results from acquired heart disease directly to this population is questionable. As a consequence, we are in need of more data specific for CHD. The heterogeneity and relatively low mortality in GUCH compared with the much older heart failure and coronary artery disease population represent barriers to adequately powered studies. In addition, the GUCH population with its limited prevalence in the community is generally not perceived to be an attractive investment both by medical industry and national funding organizations. This has created a vacuum of prospective data on the efficacy and safety of drugs and devices in GUCH. Most of our current knowledge in CHD is therefore derived from observational, mostly retrospective studies, and registry data. While such studies reflect ‘reality-based medicine’ and have many merits they cannot fully replace adequately powered and conducted prospective randomized trials. The increasing availability of administrative electronic health care data may provide new opportunities but also challenges for research. Although these ‘big data’ are inherently difficult to analyses, such studies could represent a welcome adjunct to registry data. Nevertheless, detecting patterns and associations in retrospective data is—by nature—hypothesis-generating research and requires prospective studies to confirm the results statistically before widely applying them to patient care. Translational and basic science research have so far, only a limited scope in CHD and require increased attention. Especially, the progress in genetic research and the ability to genotype patients at low cost should provide further insights into the etiology of CHD. Concentrating selected research efforts at central (national) institutions and encouraging collaboration between centers is likely to increase scientific output while lowering transaction costs.9,10 Compiling and balancing the results of many retrospective studies is particularly challenging as the (mostly unstructured) results are not amenable to quantitative meta-analytic strategies. As a consequence, systematic reviews of the literature, highlighting evidence of particular clinical relevance, are increasingly required. The GUCH guidelines provided by the European Society of Cardiology (ESC)11 as well as scientific organizations from overseas, are of particular relevance in this regard. They provide an overview of the many conditions, focusing on the benefits and risks of common diagnostic and therapeutic procedures. The ESC and others should be commended for investing in these types of scientific documents and associated position papers, clarifying specific aspects of care.
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Thirdly, training an adequate workforce of physicians, nurses, and technicians to care for the growing GUCH population represents a challenge for many healthcare systems.12 Many of the currently practicing GUCH specialists have been educated at a small number of large international centers. This model for training GUCH specialists is unsustainable in the long run and both European and national efforts are required to develop training curricula and establish training posts at major national centers. In addition, accreditation in GUCH should be promoted as it encourages physicians to undergo formal training and signals competence to potential patients. Nevertheless, international training programs should also be offered to support collaboration between centers of excellence and provide clinical and academic training opportunities for the future leaders in the field of GUCH. Beyond educating and training the core GUCH providers, we also need to reach out to affiliated specialists involved in the daily care of GUCH patients. This includes for example general physicians, general cardiologists, radiologists, and obstetricians.13 Last but not least, educating patients about their condition and involving GUCH patients in their care should improve outcomes and help to avoid catastrophic events due to loss to follow-up or treatment at inadequate institutions. Beyond the issues discussed above for rich countries, developing countries face particular challenges related to GUCH care. It is estimated that due to the sheer numbers of the population and the
prevailing demographics the majority of GUCH patients currently live in developing countries. In these settings, adequate services are nearly absent due to a general lack of resources.14 Therefore, improving worldwide GUCH services should be a priority for health professionals and health politicians in affected countries, but also requires increased support by scientific and professional organizations as well as development assistance from resource rich countries.
References References are available as supplementary material at European Heart Journal online.
Pregnancy in women with congenital heart disease Difficulties that pregnant women with congenital heart defects encounter are discussed through two case vignettes Case vignette #1 A 33-year-old woman, born with transposition of the great arteries, is referred for counselling about the risks of pregnancy. She underwent intra-cardiac repair with the atrial switch operation (Senning operation) at the age of 14 months. At the age of 16 years, she was discharged from follow-up at the paediatric hospital and has had no regular follow-up since then. At the age of 23 years, she was seen by a general cardiologist who told her she had a high risk of complications during pregnancy and must not become pregnant. After marriage 2 years ago, she now desires to have children and she struggles with the earlier negative pregnancy advice, particularly as she has learned about women with the same cardiac condition who had successful pregnancies. She is asymptomatic but has mildly impaired exercise capacity on cardio-pulmonary exercise testing, reaching 78% of predicted workload. Oxygen saturation in ambient air is 97% and decreases to 92% during exercise. Echocardiography demonstrates mildly impaired systemic right ventricular systolic function, mild tricuspid regurgitation (systemic atrioventricular valve regurgitation) and mild sub pulmonic left ventricular outflow tract obstruction with a peak gradient of 40 mmHg. On bubble-contrast injection a shunt from the systemic venous baffle to the pulmonary venous baffle is demonstrated, consistent with a baffle leak. What should we advise this woman regarding the risks of pregnancy?
Congenital heart defects are common. With the advent of openheart surgery, the majority of affected patients now survive to adulthood and thus, cohorts of women with repaired congenital heart defects in childbearing age are rapidly evolving. The recognition that these patients are not cured and remain at risk of adverse events has emerged only over the past few decades and many patients have been lost to specialist follow-up. Pregnancy leads to profound haemodynamic changes with an increase in plasma volume and cardiac output of 50% by the end of
the second trimester and a decrease in systemic vascular resistance. Depending on the specific type of the underlying heart defect, residual haemodynamic lesions, impaired myocardial reserve and many other factors, the ability to adapt to the haemodynamic changes and needs of pregnancy may be substantially impaired in women with congenital heart defects. There is generally an increased risk of arrhythmias and heart failure during pregnancy and women with residual intra-cardiac shunts have an increased risk of paradoxical embolization in the event of thrombo-embolic
1414 complications. The effect of pregnancy on long-term outcomes depends on the type of the congenital heart defect, the type of repair and may be hard to predict, since there are insufficient data available. The risk of premature delivery may be substantially increased and depending on the type of defect, the risk of recurrence of congenital heart defects in the offspring ranges between 3 and 10% in non-syndromic patients. A few lesions are associated with particular high maternal mortality risk and pregnancy is generally discouraged in affected women. These include women with severe symptomatic aortic valve stenosis, severe left atrio-ventricular valve stenosis, pulmonary arterial hypertension, systemic ventricular ejection fraction ,30% or poor functional class (NYHA III and IV), markedly dilated ascending aorta in women with Marfan syndrome (.45 mm) or in women with bicuspid aortic valves (.50 mm). For most other women, careful individual assessment is required to allow individual risk stratification and counselling that will enable the woman to make an informed decision about whether or not she is willing to take the risks of a pregnancy. To make such a decision, it is important to distinguish between manageable cardiovascular complications (e.g. atrial arrhythmias, mild heart failure) and catastrophic events such as stroke, irreversible myocardial failure, and death. Comprehensive pre-conception counselling also includes an open discussion about the expected long-term risk of deterioration of the underlying cardiac condition and the risk of premature death.
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An important part in pre-conception assessment is the identification of modifiable conditions that can be improved prior to embarking on pregnancy to reduce the pregnancy risk (e.g. radiofrequency ablation of atrial arrhythmias). Careful review of a woman’s medication is important and medications with risk of foetal toxicity (e.g. angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or spironolactone) should either be stopped or changed to preparations compatible with pregnancy. The management of women with mechanical heart valve prosthesis is particularly difficult and these women should always be referred to a dedicated centre with a multi-disciplinary team experienced in the management of high-risk pregnancies. For women, who wish to embark on pregnancy, obstetrical review including an update of recommended vaccinations and the start of folic acid prophylaxis are important. For women not wishing to become pregnant or with a contraindication for pregnancy, counselling about safe and effective contraception is mandatory. The woman outlined in the case vignette above decided to become pregnant after a careful discussion of potential risks. She had an uneventful pregnancy and delivered a healthy baby boy by caesarean section for obstetric reasons. Five days after delivery she experienced increased shortness of breath and Pro-BNP-levels increased to 318 ng/l (upper limit of normal: 130 ng/l). Echocardiographic findings at that point remained unchanged and symptoms rapidly resolved without specific treatment. The patient had a stable clinical course since.
Case vignette #2 A 28-year-old woman with congenitally corrected transposition of the great arteries is referred to the specialist centre at 13 weeks of gestation in her first pregnancy. She had been asymptomatic before pregnancy and had an uneventful course until the 26th week of gestation, when she started experiencing shortness of breath on exertion with progressive worsening over the subsequent weeks. At 30 weeks of gestation, echocardiography shows systemic right ventricular dilatation with at least moderate tricuspid regurgitation and marked worsening of right ventricular systolic function. Pro-BNP-levels have increased from 140 ng/l pre-pregnancy to 1040 ng/l (upper limit of normal: 130 ng/l). Despite administration of loop diuretics, symptoms worsen, and the patient has to be admitted to the cardiology ward. When symptoms further deteriorate a decision for planned caesarean section at 34 weeks of gestation is made after multi-disciplinary case discussion. The patient is monitored for 48 h in a medical intensive care unit after delivery and intensive heart failure therapy is initiated immediately after delivery along with careful fluid balance. The patient’s condition improves and she is discharged from hospital 10 days after delivery with a plan for outpatient follow-up within 1 week after discharge. The new-born female had a birth weight of 1800 g and experienced mild respiratory distress syndrome but did not require mechanical ventilation. She was discharged home 3 weeks later.
Depending on the expected pregnancy risk, a clear follow-up plan has to be scheduled, as advised in the 2011 ESC guidelines for the management of cardiovascular diseases during pregnancy.1 During pregnancy, follow-up plans have to be adapted to the clinical course during pregnancy. Careful patient education about symptoms of potential complications (e.g. arrhythmias or heart failure) is important and all women should be provided emergency contact information. All women should be offered foetal echocardiography between the 18th and 20th week of gestation. A multi-disciplinary delivery plan should be established well before term, especially in women who experience complications or have a high risk of pre-term delivery. The written delivery plan should include detailed information about the underlying heart defect (including a schematic drawing in case of complex anatomy),
expected cardiac complications, and their immediate management in case of occurrence. The delivery plan should also include the planned type of delivery, the type of planned anaesthesia, type of monitoring during labour and delivery, and the type and duration of monitoring in the postpartum period. If specific precautions, such as air bubble filters for intravenous lines are required it should be ensured that these are available on the labour ward when needed. Before discharge from hospital, a follow-up plan should be established. For most women, the preferred mode of delivery is vaginal delivery, while early administration of epidural analgesia is often advised. Exceptions, in which caesarean section may be preferred, include women with a markedly dilated ascending aortic diameter (.45 mm), preterm labour while on oral anticoagulation with vitamin K-antagonists, women with severe aortic stenosis experiencing symptoms during
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pregnancy, and women with severe heart failure. For many women epidural anaesthesia is appropriate to decrease the haemodynamic effects of the delivery. However, single-shot spinal anaesthesia is contraindicated in most patients. A plan for the appropriate use of obstetric medication should also be in place, giving attention to possible adverse haemodynamic effects of these medications.
Reference 1. European Society of Gynecology (ESG), Association for European Paediatric Cardiology (AEPC), German Society for Gender Medicine (DGesGM), Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C, Cifkova R, Ferreira R, Foidart JM, Gibbs JS, Gohlke-Baerwolf C, Gorenek B, Iung B, Kirby M, Maas AH, Morais J, Nihoyannopoulos P, Pieper PG, Presbitero P, Roos-Hesselink JW, Schaufelberger M, Seeland U, Torracca L, ESC Committee for Practice Guidelines. ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J 2011;32:3147–3197.
Health insurance problems for adults with congenital heart disease The difficulty of obtaining health insurance coverage for adults with congenital heart defects is discussed through two real-life examples
Life insurance Case vignette 1: A 23-year-old male with complete transposition of the great arteries will get married next month and is planning to have children within the next 2 – 3 years. He underwent the arterial switch operation on his 6th day of life and subsequently had dilatation and stent placement of right branch pulmonary artery stenosis at the age of 9 years. He is left with moderate dilatation of the neo-aortic root, mild-to-moderate neo-aortic valve regurgitation and mild branch pulmonary artery stenosis. Although he considers himself as healthy and does not feel any limitations in his day-to-day life, he manages only 82% of predicted on cardiopulmonary exercise testing. In view of planning to have a family in his near future, he wishes to protect them and hence the patient is applying for life insurance. He is very surprised to learn that the insurance company declines coverage for the unknown and probably increased long-term risks of the underlying heart condition.
Congenital heart defects are the most common birth defects, affecting 0.8 of 1000 live-born. Without treatment many patients die in early childhood, but with the advent of modern heart surgery the vast majority survive into adult life. In adolescence and young adulthood most patients feel well, the majority have no significant limitations and most lead productive and active lives. Nonetheless, these patients are not cured and many are at substantially increased risk of cardiovascular complications and even premature death as young adults. Many of these young adults are confronted with their disease and its potential life-shortening nature when questions about insurability occur at the time of family planning, as illustrated above. Non-governmental insurance companies are allowed to categorize people according to mortality risks. Based on the individual
characteristics of a person increased mortality risks are expressed as mortality ratios with a mortality ratio of 100% equalling the mortality risk of an age- and gender-matched reference group. Based on such survival estimates, life-insurance protection for adults with congenital heart disease is often declined by insurers. However, unfortunately, survival data for adults with congenital heart defects are imperfect. Given that surgical repair techniques for most congenital heart defects were invented only a few decades ago, survival data beyond the fourth or fifth decade of life are sparse. For novel cohorts, such as adults after the arterial switch operation, as outlined in the case vignette above, robust outcome data may even be lacking for the third decade of life. In addition, timing and technique of surgical repair are constantly modified. This can be impressively demonstrated for patients with repaired Tetralogy of Fallot, the most common cyanotic heart defect. In a landmark multicentre study published by Gatzoulis and colleagues in the Lancet in 2000 the long-term risk of arrhythmias and sudden death were analysed in 793 patients with repaired Tetralogy of Fallot, operated before and alive in 1985. In this patient population median age at intracardiac repair was 5.7 years, 37% had previous palliation with a systemic to pulmonary artery shunt and almost all (91%) had undergone trans ventricular repair. Numerous studies have since confirmed that late repair, previous palliative shunts, and trans ventricular repair techniques are important risk factors for the long-term risk of ventricular arrhythmia and sudden death. This evidence has changed surgical practice and techniques profoundly. Affected patients are now typically repaired within the first year of life, shunt palliation prior to intracardiac repair has become the rare exception and whenever technically feasible, a trans atrial repair-approach is used. As a consequence, the average long-term arrhythmia-risk of a 20-year-old operated in
1416 the 1990s when compared with a patient operated in the 1970s with the same amount of residual haemodynamic lesions, is likely to be very different and more favourable in patients operated in the current era. As caregivers we can provide more detailed medical reports with more detailed reasoning on an individual patient’s situation and hence the individual risk for adverse events that may help the insurer to reach a fair assessment of the individual patient’s risk and may enhance the probability to receive coverage, even in patients with complex defects. In some countries, patient organizations (i.e. the Canadian congenital heart alliance) have negotiated group plans for non-medical life-insurance coverage for their members.
Disability pension Case vignette 2: A 33-year-old woman, born with tricuspid atresia was palliated with a modified Fontan operation at the age of 4 years. For many years, she was suffering from recurrent atrial arrhythmias for which she underwent several ablation procedures and numerous electrical cardioversions. She was turned down for Fontan conversion due to anatomic constraints. She underwent urgent thyroidectomy a year ago for amiodarone-induced thyrotoxicosis, which was complicated by transient renal failure. Despite device closure of large veno-venous collaterals, she remains mildly cyanotic with oxygen saturations 89– 91% in ambient air. Ejection fraction of the single left ventricle is normal. Currently, she is in NYHA functional class II– III and manages only 47% of the predicted workload on cardiopulmonary exercise testing, which is markedly ,5 years ago. She no longer copes with long working hours as a saleswoman and feels exhausted after 5 h at work. With the support of her cardiologist the patient applied for a part-time disability pension. The application was declined by the federal insurance company with the statement that the claim of heart failure was not supported by the finding of a normal left ventricular ejection fraction and that the patient’s exercise intolerance and low oxygen saturations were likely the consequence of poor motivation and lack of regular aerobic exercise training.
This real life case illustrates that our patients do also face important difficulties in getting a fair assessment for income replacement insurance (disability pension). Given that adult cohorts with congenital heart disease are just evolving, there is a general lack of understanding about the nature of these conditions and their impact on patients’ limitations. From the perspective of the medical caregiver, it is important to provide detailed information to insurance bodies to allow them to understand the structural defect, the nature
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and type of previous repairs and importantly the current residual lesions (e.g. valve dysfunction, myocardial dysfunction, cyanosis, or arrhythmias) that explain the patient’s symptomatology and limitations. Prevention of disability, however, starts long before the application for a disability pension. As caregivers it is an important task to inform young patients and their families about the nature of the heart defect and potential long-term complications and impact on long-term exercise capacity. Providing this information will enable the adolescent to choose an appropriate profession, which for example will not include physical work in later years.
Travel insurance Patients should be encouraged to investigate the coverage of their health care insurance when travelling abroad. If not sufficient, many companies offer packages with coverage for patients with congenital heart disease at reasonable premiums.
Summary and outlook Although congenital heart disease is a common condition, its awareness in the general population and governmental bodies is low and funding for large-scale multicentre research is sparse. This general lack of awareness impacts on improved outcome data and difficulties for affected patients in obtaining insurance coverage or a disability pension. Joint efforts between patient organizations and health care providers to increase the awareness of congenital heart disease and better information (and education) of insurers about the specific characteristics and needs of adults with congenital heart disease may improve the situation.
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New congenital coronary artery disease classification A new classification of congenital coronary artery diseases is set to help surgeons identify secondary defects in the operating room ‘It can be difficult to spot further defects in the stressful environment of the operating theatre.’ The scheme is outlined in a novel European Society of Cardiology (ESC) position paper published in Cardiovascular Research during January.1 Clinical cardiologists will also know what to look for on cardiovascular images. ‘Congenital coronary artery diseases affect less than 1% of new-borns but are an important cause of myocardial infarction and sudden death particularly in children and competitive athletes,’ said Professor Cristina Basso MD PhD, chairperson of the ESC Development, Anatomy and Pathology Working Group. ‘These conditions are often forgotten in the clinical setting because atherosclerotic coronary artery disease is far more common.’ The paper launches a new classification of coronary artery anomalies that explains common points of origin between different coronary defects. By identifying the origin of the primary defect, doctors can evaluate the probability of finding specific secondary defects with an origin related to the main anomaly. First author Dr Jose´ Marı´a Pe´rez-Pomares said: ‘We have established links between coronary congenital diseases sharing a common mechanism. When operating a diagnosed coronary anomaly, it can be difficult for surgeons to spot further defects in the stressful environment of the operating theatre and having an idea of the anomalies you might find can be extremely helpful. The new classification will also help clinicians using imaging to diagnose coronary artery anomalies and prevent future complications.’ He added: ‘We have been able to produce this classification because we understand more about how coronary arteries develop in the embryo and how they relate to major diseases. The paper provides basic cardiovascular research scientists with new, updated information on the complex embryonic development of coronary arteries to throw light on the aetiology of coronary congenital anomalies.’ The authors give their expert opinion on the embryonic origin of the coronary endothelium, which is a controversial topic in cardiovascular developmental biology. Dr Pe´rez-Pomares said: ‘For a long time scientists have wanted to identify a single and unique source for coronary endothelial cells but we now know that they come from different sources that merge together. This appears to have an impact on what happens to coronary vessels during embryonic development but perhaps also in the adult.’
Although not explicitly stated in the paper, the authors think that this heterogeneity of cell sources contributing to the endothelium may be important in the development of adult coronary disease, as endothelial cells with different origins might respond differentially to pathological stimuli. The diverse origin of coronary smooth muscle cells and fibroblasts are also described. Remarkably, adventitial fibroblasts that cover the arteries share a common embryonic origin with adult interstitial fibroblasts located between the myocardial fibres which are responsible for fibrotic scar formation after myocardial infarction. This finding also suggests that embryonic clues related to coronary development could be relevant for understanding cardiac fibrosis in the adult ischaemic heart. The authors say that this ‘mosaic-like embryonic development of the coronary vascular system’ is key to understanding the complex spectrum of coronary artery anomalies. Dr Pe´ rez-Pomares said: ‘The more we dig in, the more we have the impression that important events happening in the embryo, including the activation of regulatory gene networks, signalling molecular pathways, and specific cellular mechanisms also have a clear function in adult responses to pathological stimuli.’ Professor Basso concluded: ‘This is a translational paper written by basic scientists, including developmental biologists, anatomists and pathologists. It contains practical information to help clinicians diagnose coronary artery anomalies and prevent devastating complications including sudden death.’ A. Tofield ESC Press Office
Funding J.M.P.-P. was funded by grants BFU2012-35799 (MINECO); RD12/0019/ 0022, TERCEL (MINECO-ISCIII); PITN-GA-2011-289600 (‘CardioNet’, EU I+D+i FP7, Marie Curie ITNs). R.G.K., J.L.d.l.P., S.S., and M.v.d.H. were also funded by PITN-GA-2011-289600; C.B. and G.T. were funded by the Registry for Cardio-Cerebro-Vascular Pathology, Venice, Italy. Conflict of interest: none declared.
Reference 1. Pe´rez-Pomares JM, de la Pompa JL, Franco D, Henderson D, Ho SY, Houyel L, Kelly RG, Sedmera D, Sheppard M, Sperling S, Thiene G, van den Hoff M, Basso C. Congenital coronary artery anomalies: a bridge from embryology to anatomy and pathophysiology—a position statement of the development, anatomy, and pathology ESC Working Group. Cardiovasc Res 2016;109:204 –216.
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Book Review
Congenital heart disease molecular genetics, principles of diagnosis and treatment Editors: Maximilian Muenke (Bethesda, MD), Paul S. Kruszka (Bethesda, MD), Craig A. Sable (Washington, DC), John W. Belmont (Houston, TX). Publisher: Karger Pub date: June 2015 Hardback: 326 pages, 93 figures 49 in colour ISBN: 978-3-318-03003-7 E-ISBN: 978-3-318-03004-4 Heart malformations constitute a major fraction of clinically significant birth defects and represent an important component of paediatric and adult cardiovascular disease. In the last decades, there have been remarkable improvements in the clinical care of patients with congenital heart disease. Furthermore, basic research has provided considerable insight into normal cardiac and vascular development, which permits us to draw inferences concerning the genesis of congenital heart disease. Yet, significant challenges remain both in acute and longitudinal patient care and in deciphering the genetic and environmental factors that underlie the development of these diseases. This book, written by renowned leaders in genetics, basic science, and paediatric and adult cardiology, covers a comprehensive list of topics in congenital heart disease that spans from aetiology to treatment. The book is organized into seven sections, starting with a historical overview and a comprehensive review of current knowledge on the normal development of the heart. The next section deals with the epidemiology of congenital heart disease and focuses on prevention, congenital heart disease in a developing country, maternal non-genetic risk factors, and adult congenital heart disease. Congenital heart defects caused by chromosomal abnormalities and those caused by single gene disorders are organized into two separate subsequent sections. Surprisingly, the book also contains a section dedicated to the primary rhythm disorders (the ion channelopathies), the genetic cardiomyopathies and inherited forms of thoracic aortic aneurysms.
The penultimate section deals with patient evaluation and covers the genetic evaluation of patients including a discussion of state-of-the-art genetic technologies that are revolutionizing genetic diagnostics and gene discovery. This section also contains parts on imaging of congenital defects for the non-cardiologist and prenatal evaluation of congenital heart disease. The last section deals with treatment and covers surgical management, interventional cardiology, ethical considerations in the management of patients with congenital heart disease and finally, looks into the future by dwelling on new technologies such as stem cell biology, bioengineering, and gene therapy that may deliver new therapies in the future. As a geneticist performing research in inherited cardiac disease I liked this book, because it tackles a broad range of disorders and gathers the most relevant and up-to-date information in a concise fashion, spanning clinical aspects, basic science, and genetics. It will undoubtedly benefit geneticists and basic scientists studying these disorders as well as students, trainees, and clinicians from a variety of disciplines.
CardioPulse contact: Andros Tofield, Managing Editor. Email: [email protected]
