Paediatrics (RCH) - Theses
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ItemEnd-organ consequences of the Fontan circulation( 2022)The Fontan procedure is the last in a series of staged surgical procedures offered to children born with complex congenital heart disease in whom a two-ventricle repair is not feasible. Since its first description, the Fontan procedure has undergone a number of technical modifications which have further improved survival and reduced associated morbidity. Due to improved survival, the number of people living with a Fontan circulation is growing, and the average age is increasing. However, with more patients surviving into adulthood we are unfortunately seeing that many will develop complications. Ventricular dysfunction, circulatory failure, atrioventricular valve (AVV) regurgitation, cardiac arrhythmias, protein-losing enteropathy, plastic bronchitis and thromboembolic phenomena have all been increasingly recognized as potential complications after the Fontan operation. Hepatic fibrosis, cirrhosis and hepatocellular carcinoma have also been described, as well as renal dysfunction in the form of reduced glomerular filtration rate (GFR) and microalbuminuria. The aim of this thesis was to (i) characterize the prevalence and severity of hepatic and renal complications in patients with a Fontan circulation, (ii) identify potential risk factors that may contribute to the development of hepatic and renal complications after the Fontan procedure, and (iii) inform screening practices for end-organ complications in these patients. In this thesis I have demonstrated that: (i) the majority of patients with a Fontan circulation have non-invasive evidence of liver fibrosis by early adulthood, (ii) a smaller but significant proportion of patients will be diagnosed with liver cirrhosis by early adulthood, (iii) a minority of patients will develop hepatocellular carcinoma, which may occur in adolescence or early adulthood, (iv) history of cardiac arrhythmia or AVV failure is associated with an increased risk of advanced liver disease, (v) mild renal dysfunction is common in patients with a Fontan circulation, however, does not appear to negatively impact mid-term outcomes, (vi) creatinine based estimated GFR should be interpreted with caution in children with a Fontan circulation, and tends to over-estimate true or measured GFR in children and adults with a Fontan circulation, (vii) many of the patients who were found to have hepatic or renal dysfunction were identified on routine screening. This thesis has drawn attention to the significant proportion of patients with a Fontan circulation who will develop hepatic or renal dysfunction during long-term follow-up. These findings encourage us to consider the implications of end-organ dysfunction on the medical management of a population that is growing in numbers and age. This work emphasizes the importance of routine surveillance in identifying those with significant liver and kidney dysfunction after the Fontan procedure, and identifies a number of potentially modifiable risk factors for more advanced disease. In the absence of any proven pharmacological treatment for these complications, it is likely that optimisation of the Fontan circulation itself in combination with the avoidance of secondary end-organ insults will be the key to minimising the burden of hepatic and renal disease in this population.
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ItemAtrioventricular valve function during single ventricle palliation( 2021)Single ventricle anomalies encompass a spectrum of the most severe congenital heart disease. Staged surgical palliation culminates in the Fontan circulation, wherein the functional single ventricle pumps blood to the systemic circulation and returning blood flows passively through the pulmonary circulation, without the support of a subpulmonic ventricle. Surgical modifications and advancements in non-operative management have led to a significant decline in early mortality following the Fontan operation. As such, the population of patients living with a Fontan circulation is expected to double over the next 20 years, including a growing proportion of patients surviving well into adulthood. Due to inherent anatomical and physiological limitations, the Fontan circulation is characterised by elevated systemic venous pressure and reduced cardiac output. Atrioventricular valve (AVV) regurgitation impairs pulmonary venous return leading to increased post-capillary venous pressures and further increasing systemic venous pressure. Furthermore, AVV regurgitation increases the volume load on the single ventricle which can lead to ventricular dilatation and impaired function. Studies have demonstrated that AVV regurgitation and AVV surgery are associated with worse clinical outcomes during the initial stages of single ventricle palliation, but little is known about the cumulative impact of AVV regurgitation and AVV surgery over the lifetime of patients undergoing single ventricle palliation. The aim of this thesis was to (i) determine the cumulative incidence of, and risk factors for, moderate or greater AVV regurgitation during the lifetime of patients undergoing Fontan palliation, (ii) determine the impact of moderate or greater AVV regurgitation on clinical outcomes in patients with a Fontan circulation, and (iii) determine the impact of AVV surgery on long-term AVV competency and clinical outcomes in patients undergoing single ventricle palliation. The studies contained within this thesis were conducted with data primarily from the Australia and New Zealand Fontan Registry, which is the largest database of Fontan survivors in the world. In this thesis I have demonstrated that: (i) there is a high rate of moderate or greater AVV regurgitation during the lifetime of patients with a Fontan circulation, (ii) risk factors for moderate or greater AVV regurgitation and AVV surgery include right ventricular (RV) dominance, atrioventricular septal defect (AVSD), mitral atresia, right atrial isomerism, aortic atresia, and prior AVV repair, (iii) moderate or greater AVV regurgitation in patients with a Fontan circulation is associated with an over two-fold increased risk of death or transplantation, but only in patients with RV dominance, (iv) in patients with AVSD and a Fontan circulation, the high rate of moderate or greater AVV regurgitation is primarily due to the anatomy of the common AVV, and is not impacted by ventricular dominance, (v) AVV surgery itself is not a risk factor for death or transplantation in patients with a Fontan circulation, but rather it is the patient’s characteristics necessitating AVV surgery that are associated with an increased risk of death or transplantation, (vi) patients with tricuspid valve repair failure are at high risk of death or transplantation, but successful tricuspid valve repair improves transplantation-free survival rates in patients with moderate or greater AVV regurgitation, (vii) patients with functional AVV regurgitation and impaired ventricular systolic function are at increased risk of death or transplantation after AVV repair, (viii) AVV closure is a safe and effective surgical technique for management of AVV regurgitation in patients with a Fontan circulation and two AVVs, where the diminutive valve is regurgitant. This thesis has revealed the enormous burden of AVV regurgitation and AVV surgery in patients with a Fontan circulation. In doing so, it has drawn attention to AVV regurgitation as one of the most important issues in the management of patients undergoing single ventricle palliation. Ultimately, by improving our understanding of the incidence and natural history of AVV regurgitation, this thesis will improve the long-term outcomes of many patients living with a single ventricle circulation.