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The population of adults with congenital heart disease (CHD) continues to grow in size but also evolves in anatomic and complexity case composition. Most patients with significant CHD are nowadays diagnosed prenatally, what often enables safe delivery and even occasionally intrautero therapy. There has been ongoing innovation and improvement of surgical and percutaneous interventions matched with better long-term follow-up and, with it, better understanding and treatment of late sequelae. The resulting survival benefit is most striking in patients with complex lesions, such as those born with a ‘single ventricle’.
Single-ventricle physiology, also called ‘univentricular circulation,’ ‘common ventricle’ or ‘functionally single ventricle’ encompasses several groups of lesions, characterised by the lack of two well-developed ventricles, one of which is typically hypoplastic or rudimentary. Therefore, lesions with two well-formed ventricles, which cannot be septated for other reasons, are not included in this definition.1 The hypoplastic left heart syndrome is included in the single-ventricle group, despite the different surgical strategy required.
Survival prospects and historical perspective
Survival prospects in patients with single ventricle have changed dramatically over the last four decades due to the advent of better and earlier diagnosis and advances in cardiac surgery. Surgical intervention is performed on one or several stages, and the final target is usually that of establishing a ‘Fontan circulation’ with systemic venous blood returning to the pulmonary arteries either through the right atrium or directly, but without the interposition of a subpulmonary ventricle. This approach was pioneered by Francis Fontan in Bordeaux, in 1968 and was first published in 1971.2 In its original version, the Fontan operation consisted of the superior vena cava being connected to the right pulmonary artery, while the inferior vena cava was directed with a homograft to the right atrium, which was, in turn, connected with another homograft to the left pulmonary artery. Clinical research, aided by advanced haemodynamic computer simulations, enabled optimisation of this surgical approach. The modern version of the ‘Fontan circulation’ (total cavopulmonary connection, TCPC) is established by routing the inferior vena cava flow to the pulmonary artery with a rigid conduit, whereas the superior vena cava is anastomosed to the right pulmonary artery using a Glenn shunt.
Despite the success of this radical concept of the Fontan circulation, surgery for single-ventricle physiology remains palliative and not reparative, and it is inevitably associated with increasing long-term morbidity and mortality. Complications and late sequelae include progressive ventricular dysfunction, arrhythmia, thromboembolism, protein loosing enteropathy, liver cirrhosis, renal dysfunction and bleeding. Exercise performance and quality of life are significantly reduced in many.3 ,4
The importance of estimating the current and future prevalence of patients with single-ventricle physiology and other adult CHD
Information on the current prevalence and estimates on future number of patients with single ventricle is, in this context, crucial. It enables appropriate allocation of clinical and research resources to refine management strategies and assist planning for a CHD healthcare network. State-of-the-art care requires ongoing education and quality improvement, but also further investment.5 Patients with single ventricle clearly require life-long tertiary care. With increasing age, morbidity increases and frequent hospitalisations for congestive heart failure, arrhythmia management and percutaneous intervention in the ‘Fontan’ circuit are becoming the norm. Highly selected patients with the older generation of Fontan circulation may benefit from the so-called TCPC conversion, a major endeavour, which should be undertaken only in designated centres within the adult congenital heart disease (ACHD) framework. For the majority of adult patients with Fontan circulation, TCPC conversion does not seem to be the way forward. By contrast, elective drug therapy, physical conditioning and management of other risk factors (obesity, smoking etc) or ultimately, transplantation, may be a better way forward. Evidence of a large and growing population of these patients may trigger the interest of pharmaceutical companies, who seem to be interested in ‘orphan’ disease, in trials to test, for example, the value of new drugs for lowering pulmonary resistance or novel anticoagulants in this setting. There are, also, new developments for long-term mechanical support aimed at increasing pulmonary blood flow and relieving central venous pressures, which may have a role in single-ventricle patients as destination therapy or more likely as a bridge to transplantation. Data on this in single-ventricle population at present are lacking, however. Finally, as ever larger numbers of patients with a ‘failing Fontan circulation’ become candidates for heart transplantation, pressure mounts on the already long transplant waiting lists in many Western countries. Accurate estimates on current and future number of patients with palliated single-ventricle physiology should contribute, therefore, to the ongoing debate on methods for reversing the negative trend seen in organ availability. Furthermore, patient selection from this ACHD subgroup and timing of transplantation need to be refined, and patients need to be selected before multiorgan failure ensues.
The paper by Coats et al6 is, therefore, timely. The authors assess the number of patients with single-ventricle physiology in the North East England and North Cumbria area, served by a single congenital surgical referral centre. They include both paediatric and adult cases, and analyse the number of foetal diagnoses, live births and terminations of pregnancy in cases with diagnosed single ventricle over the period 1997–2012. Data are retrieved from a regional survey database, established in 1985, as well as their own database from the only tertiary CHD referral centre serving their area, making their assessment of the prevalence of single ventricles in their region methodologically sound. Finally, the authors make estimates on the future number of patients with single ventricle in their area and in the UK overall, based on previously published survival statistics. From their estimates, it appears that the overall adult population with single ventricle will increase within 2023 by almost 60%, and over 45% of these patients will be above 30 years of age, adding to the complexity of care. The authors need to be congratulated for their work.
Challenges in assessing the prevalence and survival prospects
Making predictions on the natural or unnatural history of patients with CHD, especially those with complex lesions, remains challenging. Survival estimates from historical cohorts, such as those used by Coats et al, do not account for the considerable advances in care, which have occurred in recent years. For example, the survival of patients with unrepaired lesions who have developed Eisenmenger physiology has improved significantly in the last decade thanks to the advent of pulmonary arterial hypertension (PAH) therapies and better tertiary care within the PAH-UK and Ireland framework.7 TCPC patients seem to have better survival prospects compared to patients palliated with earlier surgical techniques,4 yet Coats et al use mortality estimates from cohorts with a relatively low percentage of TCPC patients.8 Therefore, the prevalence estimates for year 2023 calculated by Coats et al are likely to be an underestimate of the total number of patients with single ventricle, which reinforces the need for future planning and investments.
A great challenge in making prevalence predictions for rare disorders, is sample size and the accuracy of point estimates. Assuming that the Newcastle referral area is a random UK sample, and taking into account the low prevalence of patients with single ventricle, one can calculate a very wide 95% CI for the point estimate. A larger sample size obtained through national and international registries, combined with more sophisticated modelling of past and future burden of disease and rigorous validation exercises may provide more precise prediction.
Conclusions
There is clear evidence that the ACHD population, including patients with single-ventricle physiology, will continue to grow in the years to come. Work such as the one presented by Coats and co-authors informs us and the policy makers of the pressures ahead and of the magnitude of investment required, so that every patient with ACHD in the UK and around the world can reach his/her full life potential.
Footnotes
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Contributors All authors prepared the draft of the manuscript, revised the manuscript critically for important intellectual content, and have provided final approval of the manuscript.
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Competing interests AK has received unrestricted educational grant support from Actelion Global. MAG the Adult Congenital Heart Centre and National Centre for Pulmonary Hypertension have received support from the British Heart Foundation. This project was supported by the NIHR Cardiovascular Biomedical Research Unit of Royal Brompton and Harefield NHS Foundation Trust and Imperial College London.
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Provenance and peer review Commissioned; internally peer reviewed.