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Hypoplastic left heart: the next chapter in our unsolved problem

By Professor David Winlaw 

Paediatric cardiac surgeon and former Victor Chang Cardiac Research Institute Faculty member, Professor David Winlaw provides commentary on a recent study published in Heart, BMJ on long term outcomes in children born with a type of severe congenital heart disease known as hypoplastic left heart syndrome (HLHS).

The story of paediatric cardiac care over the last 35 years can be told through the many successes and failures in the surgical management of hypoplastic left heart (HLH). In their Heart paper, 1 Rogers and colleagues bring the second chapter to a close and foreshadow the next chapter for a specialty which, in the UK, is never far from newspaper headlines.

In chapter 1 (pre-2000), neonates with HLH faced daunting odds of survival despite consistent success in other forms of complex neonatal cardiac repair. Many services and some countries did not offer surgery for this condition and the balance between the benefits of procedural volume versus local access to care was constantly debated. The ethical foundation of treating newborns with HLH was constantly questioned, and success or failure of entire surgical programmes was predicated on acceptable early survival of this cohort.

The second chapter spans 2000–2015, when patients described in this report were born and began their surgical pathway. Consistent and excellent results were being achieved by units in the UK2 and USA. There was rapid dissemination of techniques and philosophies of care to the point where most large programmes routinely managed HLH and achieved good early outcomes.

Truly team-based care, a focus on the intensive care needs of the postsurgical neonate and tight integration of surgery with cardiology became understood as fundamental to achieve optimal outcomes. This hospital and human infrastructure lifted early outcomes for all other forms of paediatric cardiac surgery; part-time paediatric cardiac surgical practice became uncommon and expectations continued to grow.

This report of outcomes is particularly important and will be welcomed by the international community working in congenital heart disease (CHD). Unlike most other reports of outcome in HLH, this report is population based (England and Wales). Further, the raw data are derived from a mandatory national audit scheme, the outcomes of almost a thousand patients is reported and survival has been validated using a national death register. We can be confident that this report is a true picture of overall outcomes, free of selection bias and representing the outcomes from all units who undertake such work. The results have been achieved in the context of resources provided by the National Health Service, a public-sector provider. It is real, and the benchmarks are believable.

Rogers and colleagues1 describe the multiple pathways children follow to achieve a total cavopulmonary connection (the Fontan operation). This is the last of the planned operations for children with HLH and other morphologies where a single ventricle supports the entire circulation. The objective of the surgical pathway is to achieve Fontan completion—if that is not possible, children face a difficult and limited future. Fontan completion is usually followed by several decades of good quality life, although the incidence of new medical problems increases over time.3

In the current era, outcomes after individual components of the pathway, for example, survival after initial ‘Norwood’ surgery, are important for surgical audit purposes but do not describe quality of the whole programme. This study is how outcomes in CHD should be reported, that is, taking into account the whole journey travelled, in this case en route to Fontan completion. It would be very useful to have similar knowledge of outcomes for patients with other forms of congenital heart disease. The utility of such information is in the subsequent tailoring and optimisation of care, a better understanding of where resources are best deployed and to inform prenatal counselling. Analyses of financial burden to patients, parents and the community might also prompt consideration of how to lessen the impact on income and productivity, an inevitable consequence of caring for children with a chronic illness.

The report includes analysis of more recent surgical strategies to improve early outcomes. Application of the ‘hybrid approach’, where the major operation involving aortic arch reconstruction is deferred beyond the neonatal period, has been used mostly to manage patients with high-risk characteristics for routine first-stage surgery. This approach was utilised in just over 6% of patients, mostly high-risk candidates (extracardiac anomalies, prematurity, low birth weight) and as expected the hospital mortality for this group is high. Outcomes for the traditional pathway have improved in the recent era, although it is uncertain whether this is as a result of iterative improvements in surgery and perioperative care or that some of the high-risk patients have been transferred from the traditional to the hybrid pathway. This study does not address the potential utility of the hybrid approach in high-risk or normal-risk patients as entry criteria were not defined, and the role of this approach remains to be established.

Two studies from North America are the most direct comparators for this study. Despite differences in inclusion criteria, outcomes are remarkably similar for early and late outcomes. The first was a comparison between different surgical strategies to create a source of pulmonary blood flow during the first operation (the Single Ventricle Reconstruction (SVR) trial).4 It was conducted in largely academic centres in mostly normal-risk patients and provided a contemporary (2005–2014) understanding of survival after surgery for HLH. The SVR trial reported that 32% of patients were deceased at 3 years versus 36% in this study. There are differences in the way transplantation was considered as an endpoint in the two studies, but the number of transplants in the Rogers study was very small and this difference is not central in a comparison of outcomes. It is regrettable that adequacy of raw data in the UK study did not allow comparison of outcomes according to shunt type.

The second study5 is not directly comparable in its approach but also provides a useful benchmark for survival—that around 60% of patients will be alive at 6 years after birth. Again, an outcome which is broadly comparable with outcomes demonstrated in this study. Taken together, we have an evidence base to counsel parents considering a future for their fetus or neonate with HLH. The take-home message is that at 3 years after birth, survival is likely to be around 65%–70% and 60% at 6 years.

The inadequacy of survival as the only endpoint in assessing outcomes is well recognised. Neurodevelopmental disability affects around 30% of survivors, with a range of outcomes from delay in reaching developmental milestones, through learning and behavioural disorders such as autism, and in rare cases cerebral palsy. This is not just about HLH, however, with similar rates seen in others undergoing neonatal cardiac surgery, including those where a ‘normal’ circulation is restored in a single operation. Numerous variants in shared pathways determining brain and heart development are likely to play a major role.6 Psychological concerns for child and family are highly prevalent and also highly modifiable through interventions starting at time of antenatal diagnosis. Provision of such multidisciplinary care speaks to the nature of the institutions required to provide optimal care and the costs involved.

With such concordance in outcomes between major studies in HLH, it is reasonable to ask whether a ceiling has been reached and if this is as good as it gets? Can further improvements be expected with current approaches, other than through incremental and iterative group learning? We have improved outcomes of the standard pathway by having more stringent selection criteria, minimising the impacts of high-risk characteristics including low birth weight and prematurity through adaptions of the hybrid approach and delayed Norwood surgery. Should we expect more?

Some of the answers may lie in the developmental origins of HLH itself. Present understandings point towards HLH not being a simple consequence of ventricular growth arrest as a result of mitral or aortic valve atresia. Instead, HLH is the end result of a pan-cardiac developmental disorder including the cardiomyocyte.7 Our operations address inflows and outflows but the development of ventricular dysfunction is an important and common pathway towards deterioration in clinical performance and sometimes death. Developmental defects evident within myocytes may well reduce the ability of the right ventricle to perform in the long term and explain some of the morbidity and mortality in patients with ‘perfect’ technical outcomes. Cell therapy approaches are being trialled to address this problem and medium-term outcomes are awaited.

In this, the year that saw the passing of Francis Fontan, we are more aware than ever that achievement of the Fontan is just the beginning of another journey for child and family. HLH may2 or may not8 represent a worse substrate for long-term outcomes, but further improvements can be expected as mechanisms of Fontan failure are better understood. For most, we can expect that today’s patients with HLH surviving to Fontan will have an adult life and that education, employment and family are achievable in most.

In the next chapter, subspecialisation of care for those with a single ventricle and seamless transition of multidisciplinary management into adult life will improve the quality of life for child and family. But there is more to learn in pre-Fontan care and through patient cohorts such as this, we need to identify and address modifiable factors that might produce a better substrate for the Fontan. Optimisation of pulmonary arteries prior to Fontan completion through stenting or additional surgery might also be important. Timing of Fontan completion—varying starkly in this study—highlights the lack of an evidence base to support firm clinical guidelines for something as simple as timing of the last procedure.

The imperfections of the Fontan are well recognised but for now it is what we have. Let us hope the next chapter brings a new treatment paradigm for HLH.

Professor David Winlaw is a paediatric cardiac surgeon and researcher. He is based at The Children’s Hospital at Westmead and is Professor in Paediatric Cardiac Surgery at the University of Sydney. He is the Head of Paediatric Cardiothoracic Surgery in the Sydney Children’s Hospitals Network. A former Faculty leader, Professor Winlaw continues to work very closely with Professor Sally Dunwoodie from the Victor Chang Cardiac Research Institute.  

References

 1. Rogers LPagel CSullivan IDet alInterventional treatments and risk factors in patients born with hypoplastic left heart syndrome in England and Wales from 2000 to 2015. Heart 2018doi: 10.1136/heartjnl-2017-312448. [Epub ahead of print 25 Jan 2018].doi:10.1136/heartjnl-2017-312448

2. McGuirk SPGriselli MStumper OFet alStaged surgical management of hypoplastic left heart syndrome: a single institution 12 year experience. Heart 2006;92:36470.doi:10.1136/hrt.2005.068684

3. d’Udekem YIyengar AJGalati JCet alRedefining expectations of long-term survival after the Fontan procedure: twenty-five years of follow-up from the entire population of Australia and New Zealand. Circulation 2014;130:S32S38.doi:10.1161/CIRCULATIONAHA.113.007764 

4. Ohye RGSleeper LAMahony Let alComparison of shunt types in the Norwood procedure for single-ventricle lesions. N Engl J Med 2010;362:198092.doi:10.1056/NEJMoa0912461

5. Wilder TJMcCrindle BWPhillips ABet alSurvival and right ventricular performance for matched children after stage-1 Norwood: modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery conduit. J Thorac Cardiovasc Surg2015;150:144052Discussion 50-2.doi:10.1016/j.jtcvs.2015.06.069

6. Jin SCHomsy JZaidi Set alContribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nat Genet 2017;49:1593601.doi:10.1038/ng.3970

7. Liu XYagi HSaeed Set al49:11529.doi:10.1038/ng.3870

8. Downing TEAllen KYGlatz ACet al. Long-term survival after the fontan operation: twenty years of experience at a single center. J Thorac Cardiovasc Surg 2017;154:24353.doi:10.1016/j.jtcvs.2017.01.056

Originally published in Heart, BMJ.