Quality of Life and Well-Being in Adults With Fontan Physiology: Findings From the Australian and New Zealand Fontan Registry Quality of Life Study.

BACKGROUND: To characterize global and health-related quality of life (QOL) among adults with Fontan physiology enrolled in the Australian and New Zealand Fontan Registry (ANZFR), and identify sociodemographic, clinical, psychological, and relational factors associated with outcomes. METHODS AND RESULTS: Using a cross-sectional survey design, 66 adults with Fontan physiology (58% women; mean age, 29.6±7.7 years; range, 18-50 years) completed validated self-report measures. Health-related QOL was assessed using the Pediatric Quality of Life Inventory, and global QOL was assessed using a visual analog scale (0-10). Participants reported lower total health-related QOL (P<0.001), as well as lower physical (P<0.001) and social (P=0.002) functioning compared with normative data. Median global QOL was 7.0 (interquartile range: 5.0-8.0) and most participants (71%) rated their QOL ≥6. For health-related QOL, age, sex, university education, and length of hospital stay in the past 12 months explained 27% of the variance in scores, while general psychological stress, medical traumatic stress, communication problems, and access to emotional support explained a further 44% of variance (final model: 71% of variance explained). For global QOL, sociodemographic and clinical factors explained 20% of the variance in scores, while psychological stress and sense of coherence explained a further 24% (final model: 44% of variance explained). CONCLUSIONS: Adults with Fontan physiology reported lower overall health-related QOL compared with community-based norms. Variance in QOL outcomes were predominantly attributable to psychological and relational factors. Tailored screening and assessment to identify Fontan patients at greatest risk of lower QOL, and a proactive approach to supportive care, are needed.

Wellbeing in Children and Adolescents with Fontan Physiology.

OBJECTIVE: To assess health-related quality of life (HRQOL) and global quality of life (QOL) in children and adolescents with Fontan physiology and identify key predictors influencing these outcomes. STUDY DESIGN: Cross-sectional analysis of 73 children and adolescents enrolled in the Australia and New Zealand Fontan Registry aged 6-17 years, at least 12 months post-Fontan operation. Assessments included the Pediatric Quality of Life Inventory (PedsQL) for HRQOL and a developmentally-tailored visual analogue scale (0-10) for global QOL, along with validated sociodemographic, clinical, psychological, relational, and parental measures. Clinical data were provided by the Australia and New Zealand Fontan Registry. RESULTS: Participants (mean age: 11.5 ± 2.6 years, 62% male) reported lower overall HRQOL (P < .001), and lower scores across all HRQOL domains (all P < .0001), compared with normative data. Median global QOL score was 7.0 (IQR 5.8-8.0), with most participants (79%) rating their global QOL ≥6. Anxiety and depressive symptoms requiring clinical assessment were reported by 21% and 26% of participants, respectively. Age, sex, and perceived seriousness of congenital heart disease explained 15% of the variation in HRQOL scores, while depressive symptoms and treatment-related anxiety explained an additional 37% (final model: 52% of variance explained). For global QOL, sociodemographic and clinical factors explained 13% of the variance in scores, while depressive symptoms explained a further 25% (final model: 38% of variance explained). Parental factors were not associated with child QOL outcomes. CONCLUSIONS: Children and adolescents with Fontan physiology experience lower HRQOL than community-based norms, despite reporting fair overall QOL. Psychological factors predominantly influenced QOL outcomes, indicating strategies to bolster psychological health could improve QOL in this population.

Early outcomes after post-cardiotomy extracorporeal membrane oxygenation in paediatric patients: a contemporary, binational cohort study.

OBJECTIVES: The aim of this study was to assess the early outcomes and risk factors of paediatric patients requiring extracorporeal membrane oxygenation after cardiac surgery (post-cardiotomy). METHODS: Retrospective binational cohort study from the Australia and New Zealand Congenital Outcomes Registry for Surgery database. All patients younger than 18 years of age who underwent a paediatric cardiac surgical procedure from 1 January 2013 to 31 December 2021 and required post-cardiotomy extracorporeal membrane oxygenation (PC-ECMO) in the same hospital admission were included in the study. RESULTS: Of the 12 290 patients included in the study, 376 patients required post-cardiotomy ECMO (3%). Amongst these patients, hospital mortality was 35.6% and two-thirds of patients experienced a major complication. Hypoplastic left heart syndrome was the most common diagnosis (17%). The Norwood procedure and modified Blalock-Taussig shunts had the highest incidence of requiring PC-ECMO (odds ratio of 10 and 6.8 respectively). Predictors of hospital mortality after PC-ECMO included single-ventricle physiology, intracranial haemorrhage and chylothorax. CONCLUSIONS: In the current era, one-third of patients who required PC-ECMO after paediatric cardiac surgery in Australia and New Zealand did not survive to hospital discharge. The Norwood procedure and isolated modified Blalock-Taussig shunt had the highest incidence of requiring PC-ECMO. Patients undergoing the Norwood procedure had the highest mortality (48%). Two-thirds of patients on PC-ECMO developed a major complication.

Longitudinal cohort study investigating neurodevelopmental and socioemotional outcomes in school-entry aged children after open heart surgery in Australia and New Zealand: the NITRIC follow-up study protocol.

INTRODUCTION: Despite growing awareness of neurodevelopmental impairments in children with congenital heart disease (CHD), there is a lack of large, longitudinal, population-based cohorts. Little is known about the contemporary neurodevelopmental profile and the emergence of specific impairments in children with CHD entering school. The performance of standardised screening tools to predict neurodevelopmental outcomes at school age in this high-risk population remains poorly understood. The NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial randomised 1371 children <2 years of age, investigating the effect of gaseous nitric oxide applied into the cardiopulmonary bypass oxygenator during heart surgery. The NITRIC follow-up study will follow this cohort annually until 5 years of age to assess outcomes related to cognition and socioemotional behaviour at school entry, identify risk factors for adverse outcomes and evaluate the performance of screening tools. METHODS AND ANALYSIS: Approximately 1150 children from the NITRIC trial across five sites in Australia and New Zealand will be eligible. Follow-up assessments will occur in two stages: (1) annual online screening of global neurodevelopment, socioemotional and executive functioning, health-related quality of life and parenting stress at ages 2-5 years; and (2) face-to-face assessment at age 5 years assessing intellectual ability, attention, memory and processing speed; fine motor skills; language and communication; and socioemotional outcomes. Cognitive and socioemotional outcomes and trajectories of neurodevelopment will be described and demographic, clinical, genetic and environmental predictors of these outcomes will be explored. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Children's Health Queensland (HREC/20/QCHQ/70626) and New Zealand Health and Disability (21/NTA/83) Research Ethics Committees. The findings will inform the development of clinical decision tools and improve preventative and intervention strategies in children with CHD. Dissemination of the outcomes of the study is expected via publications in peer-reviewed journals, presentation at conferences, via social media, podcast presentations and medical education resources, and through CHD family partners. TRIAL REGISTRATION NUMBER: The trial was prospectively registered with the Australian New Zealand Clinical Trials Registry as 'Gene Expression to Predict Long-Term Neurodevelopmental Outcome in Infants from the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) Study - A Multicentre Prospective Trial'. TRIAL REGISTRATION: ACTRN12621000904875.

A machine learning approach to predicting 30-day mortality following paediatric cardiac surgery: findings from the Australia New Zealand Congenital Outcomes Registry for Surgery (ANZCORS).

OBJECTIVES: We aim to develop the first risk prediction model for 30-day mortality for the Australian and New Zealand patient populations and examine whether machine learning (ML) algorithms outperform traditional statistical approaches. METHODS: Data from the Australia New Zealand Congenital Outcomes Registry for Surgery, which contains information on every paediatric cardiac surgical encounter in Australian and New Zealand for patients aged <18 years between January 2013 and December 2021, were analysed (n = 14 343). The outcome was mortality within the 30-day period following a surgical encounter, with ∼30% of the observations randomly selected to be used for validation of the final model. Three different ML methods were used, all of which employed five-fold cross-validation to prevent overfitting, with model performance judged primarily by the area under the receiver operating curve (AUC). RESULTS: Among the 14 343 30-day periods, there were 188 deaths (1.3%). In the validation data, the gradient-boosted tree obtained the best performance [AUC = 0.87, 95% confidence interval = (0.82, 0.92); calibration = 0.97, 95% confidence interval = (0.72, 1.27)], outperforming penalized logistic regression and artificial neural networks (AUC of 0.82 and 0.81, respectively). The strongest predictors of mortality in the gradient boosting trees were patient weight, STAT score, age and gender. CONCLUSIONS: Our risk prediction model outperformed logistic regression and achieved a level of discrimination comparable to the PRAiS2 and Society of Thoracic Surgery Congenital Heart Surgery Database mortality risk models (both which obtained AUC = 0.86). Non-linear ML methods can be used to construct accurate clinical risk prediction tools.

Liver Cirrhosis After the Fontan Procedure: Impact of Atrioventricular Valve Failure.

BACKGROUND: Liver cirrhosis is now well recognized as a potential complication after the Fontan procedure, although associated risk factors and optimal timing of liver screening remain unclear. METHODS: All patients who underwent an extracardiac conduit Fontan procedure at The Royal Children's Hospital, Melbourne, were identified using the Australia and New Zealand Fontan Registry. Cirrhosis was diagnosed based on liver biopsy, or a combination of imaging findings and clinical evaluation by a hepatologist. RESULTS: Between 1997 and 2020, 398 patients underwent an extracardiac conduit Fontan procedure at our center, and 276 had ongoing follow-up in Victoria. Ninety-five patients (34%) underwent liver assessment at a mean age of 18.2 ± 6.7 years (11.8 ± 5.5 years post-Fontan). Fifteen patients (16%) were diagnosed with cirrhosis at a mean age of 22.7 ± 5.9 years (14.0 ± 5.2 years post-Fontan). The need for prior or concomitant atrioventricular valve repair or replacement was associated with an increased risk of cirrhosis (univariable hazard ratio [HR] 7.09, 95% confidence interval [CI] 2.13-23.61, P = .001). By multivariable analysis, factors associated with development of cirrhosis were atrioventricular valve failure prior to Fontan (HR 3.27, 95% CI 1.15-9.31, P = .026) and older age at Fontan operation (HR 1.13 per year increase, 95% CI 1.01-1.26, P = .034). The proportion of patients alive, nontransplanted, and without cirrhosis at 10, 15, and 20 years was 93.4% (95% CI 88.4%-98.7%), 79.6% (95% CI 69.7%-90.8%), and 64.6% (95% CI 51.0%-81.9%), respectively. CONCLUSIONS: Early commencement of liver screening should be considered for patients with a history of atrioventricular failure during Fontan palliation.

Atrioventricular septal defect in Fontan circulation: Right ventricular dominance, not valve surgery, adversely affects survival.

OBJECTIVE: The effect of ventricular dominance and previous atrioventricular valve (AVV) surgery on patient outcomes after Fontan operation remains unclear. We sought to determine the effect of ventricular dominance and previous AVV surgery on transplantation-free survival and long-term AVV competency in patients with atrioventricular septal defect (AVSD) and Fontan circulation. METHODS: We conducted a retrospective study of 1703 patients in the Australia and New Zealand Fontan Registry, who survived Fontan operation between 1987 and 2021. RESULTS: Of 174 patients with AVSD, 60% (105/174) had right ventricular (RV) dominance and 40% (69/174) had left ventricular (LV) dominance. The cumulative incidence of moderate or greater AVV regurgitation at 25 years after Fontan operation in patients with LV dominance was 56% (95% CI, 35%-72%), compared with 54% (95% CI, 40%-67%) in patients with RV dominance (P = .6). Nonetheless, transplantation-free survival at 25 years in patients with LV dominance was 94% (95% CI, 86%-100%), compared with 67% (95% CI, 52%-87%) in patients with RV dominance (hazard ratio, 5.9; 95% CI, 1.4-25.4; P < .01). Of note, transplantation-free survival was not different in patients who underwent AVV surgery before or at Fontan completion compared with those who did not (15 years: 81% [95% CI, 62%-100%] vs 88% [95% CI, 81%-95%]; P = .3). CONCLUSIONS: In patients with AVSD and Fontan circulation the rate of moderate or greater common AVV regurgitation is similar in those with LV and RV dominance. RV dominance, rather than previous AVV surgery, is a risk factor for death or transplantation.

Impact of Aortic Atresia After Fontan Operation in Patients With Hypoplastic Left Heart Syndrome.

BACKGROUND: Patients with aortic atresia have the worst prognosis in the spectrum of hypoplastic left heart syndrome. It remains unknown whether patients with aortic atresia continue to do poorly after Fontan operation. This study aimed to determine the association between aortic atresia and atrioventricular valve (AVV) function and clinical outcomes after Fontan operation in patients with hypoplastic left heart syndrome. METHODS: We performed a retrospective study of 1731 patients who survived the Fontan operation from the Australia and New Zealand Fontan Registry between 1975 and 2020. RESULTS: We identified 188 patients with hypoplastic left heart syndrome, including 99 (53%) with aortic atresia. Overall transplant-free survival and freedom from failure of Fontan circulation at 15 years was 91% (95% CI, 86%-96%) and 79% (95% CI, 71%-88%), respectively. The cumulative incidence of AVV operation at 15 years of age for patients with aortic atresia and aortic stenosis was 28% (95% CI, 19%-38%) and 14% (95% CI, 7%-22%; P = .03), respectively. The cumulative incidence of AVV failure (moderate or greater regurgitation or AVV operation) at 15 years of age for patients with aortic atresia and aortic stenosis was 50% (95% CI, 37%-61%) and 30% (95% CI, 19%-42%; P = .01). Patients with AVV failure were at increased risk of having moderately, or worse, decreased systolic ventricular function (odds ratio 6.7; 95% CI, 1.7-33; P = .01) and failure of Fontan circulation (hazard ratio 3.7; 95% CI, 1.5-9.1; P < .01). CONCLUSIONS: In patients with hypoplastic left heart syndrome, there is no significant difference in transplant-free survival after Fontan operation between patients with aortic atresia and patients with aortic stenosis. However, patients with aortic atresia have a much higher burden of AVV failure than patients with aortic stenosis. Atrioventricular valve failure is associated with failure of Fontan circulation.

Does leaving native antegrade pulmonary blood flow at the time of the superior cavopulmonary connection impact long-term outcomes after the Fontan?

Objectives: Antegrade pulmonary blood flow (APBF) may be left or eliminated at the time of the superior cavopulmonary connection (SCPC). Our aim was to assess the impact of leaving native APBF at the SCPC on long-term Fontan outcomes. Methods: In the Australia and New Zealand Fontan Registry (1985-2021), 587 patients had pre-existing native APBF at the SCPC. At the SCPC, 302 patients had APBF eliminated (APBF-) and 285 patients had APBF maintained (APBF+). The incidence of Fontan failure (composite end point of Fontan takedown, transplant, plastic bronchitis, protein losing enteropathy and death) and atrioventricular (AV) valve repair/replacement post SCPC was compared between the 2 groups. Results: Sex, predominant-ventricle morphology, isomerism, primary diagnosis, and age/type of Fontan were similar between groups. APBF- versus APBF+ had a higher incidence of arch obstruction/coarctation (17% vs 7%) and previous pulmonary artery band (54% vs 45%) and a lower rate of Fontan fenestration (27% vs 41%). The risk of Fontan failure was similar between the 2 groups (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.58-1.78; P = .96). The risk of AV-valve repair/replacement was greater in APBF+ versus APBF- (HR, 2.32; CI, 1.13-4.75; P = .022). The risk of AV-valve repair/replacement remained after adjustment for arch obstruction/coarctation, previous pulmonary artery band and Fontan fenestration (HR, 2.27; CI, 1.07-4.81; P = .033). Conclusions: Maintaining APBF at the time of the SCPC does not impact the risk of Fontan failure but may increase the incidence of AV-valve repair and/or replacement post-SCPC.

A diffusion MRI study of brain white matter microstructure in adolescents and adults with a Fontan circulation: Investigating associations with resting and peak exercise oxygen saturations and cognition.

INTRODUCTION: Adolescents and adults with a Fontan circulation are at risk of cognitive dysfunction; Attention and processing speed are notable areas of concern. Underlying mechanisms and brain alterations associated with worse long-term cognitive outcomes are not well determined. This study investigated brain white matter microstructure in adolescents and adults with a Fontan circulation and associations with resting and peak exercise oxygen saturations (SaO2), predicted maximal oxygen uptake during exercise (% pred VO2), and attention and processing speed. METHODS: Ninety-two participants with a Fontan circulation (aged 13-49 years, ≥5 years post-Fontan completion) had diffusion MRI. Averaged tract-wise diffusion tensor imaging (DTI) metrics were generated for 34 white matter tracts of interest. Resting and peak exercise SaO2 and % pred VO2 were measured during cardiopulmonary exercise testing (CPET; N = 81). Attention and processing speed were assessed using Cogstate (N = 67 and 70, respectively). Linear regression analyses adjusted for age, sex, and intracranial volume were performed to investigate associations between i) tract-specific DTI metrics and CPET variables, and ii) tract-specific DTI metrics and attention and processing speed z-scores. RESULTS: Forty-nine participants were male (53%), mean age was 23.1 years (standard deviation (SD) = 7.8 years). Mean resting and peak exercise SaO2 were 93.1% (SD = 3.6) and 90.1% (SD = 4.7), respectively. Mean attention and processing speed z-scores were -0.63 (SD = 1.07) and -0.72 (SD = 1.44), respectively. Resting SaO2 were positively associated with mean fractional anisotropy (FA) of the left corticospinal tract (CST) and right superior longitudinal fasciculus I (SLF-I) and negatively associated with mean diffusivity (MD) and radial diffusivity (RD) of the right SLF-I (p ≤ 0.01). Peak exercise SaO2 were positively associated with mean FA of the left CST and were negatively associated with mean RD of the left CST, MD of the left frontopontine tract, MD, RD and axial diffusivity (AD) of the right SLF-I, RD of the left SLF-II, MD, RD and AD of the right SLF-II, and MD and RD of the right SLF-III (p ≤ 0.01). Percent predicted VO2 was positively associated with FA of the left uncinate fasciculus (p < 0.01). Negative associations were identified between mean FA of the right arcuate fasciculus, right SLF-II and right SLF-III and processing speed (p ≤ 0.01). No significant associations were identified between DTI-based metrics and attention. CONCLUSION: Chronic hypoxemia may have long-term detrimental impact on white matter microstructure in people living with a Fontan circulation. Paradoxical associations between processing speed and tract-specific DTI metrics could be suggestive of compensatory white matter remodeling. Longitudinal investigations focused on the mechanisms and trajectory of altered white matter microstructure and associated cognitive dysfunction in people with a Fontan circulation are required to better understand causal associations.

The Australia and New Zealand Congenital Outcomes Registry for Surgery (ANZCORS): methodology and preliminary results.

BACKGROUND: Analysis of multi-institutional data and benchmarking is an accepted accreditation standard in cardiac surgery. Such a database does not exist for congenital cardiac surgery in Australia and New Zealand (ANZ). To fill this gap, the ANZ Congenital Outcomes Registry for Surgery (ANZCORS) was established in 2017. METHODS: Inclusion criteria included all cardiothoracic and extracorporeal membrane oxygenation (ECMO) procedures performed at five participating centres. Data was collected by data managers, validated by the surgical team, and securely transmitted to a central repository. RESULTS: Between 2015 and 2019, 9723 procedures were performed in 7003 patients. Cardiopulmonary bypass was utilized for 59% and 9% were ECMO procedures. Fifty-seven percent (n = 5531) of the procedures were performed in children younger than 1 year of age. Twenty-four percent of procedures (n = 2365) were performed in neonates (≤28 days) and 33% (n = 3166) were performed in children aged 29 days to 1 year (infants). The 30-day mortality for cardiac cases (n = 6572) was 1.3% and there was no statistical difference between the participating centres (P = 0.491). Sixty-nine percent of cases had no major post-operative complications (5121/7456). For cardiopulmonary bypass procedures (n = 5774), median stay in intensive care and hospital was 2 days (IQR 1, 4) and 9 days (IQR 5, 18), respectively. CONCLUSION: ANZCORS has facilitated pooled data analysis for paediatric cardiac surgery across ANZ for the first time. Overall mortality was low. Non-risk-adjusted 30-day mortality for individual procedures was similar in all units. The continued evaluation of surgical outcomes through ANZCORS will drive quality assessment in paediatric cardiac surgery across ANZ.

Impact of Fontan Fenestration on Long-Term Outcomes: A Propensity Score-Matched Analysis.

Background The long-term impact of fenestration at the time of Fontan operation remains unclear. We aimed to review the early and long-term impact of Fontan fenestration in the Australia and New Zealand cohort. Methods and Results We reviewed 1443 patients (621 fenestrated, 822 nonfenestrated) from the Australia and New Zealand Fontan registry. Data were collected on preoperative demographics, operative details, and follow-up. Propensity-score matching was performed to account for the various preoperative and operative differences and risk factors. Primary outcomes were survival and freedom from failure. Median follow-up was 10.6 years. After propensity-score matching (407 matched pairs), there was no difference in survival (87% versus 90% at 20 years; P=0.16) or freedom from failure (73% versus 80% at 20 years; P=0.10) between patients with and without fenestration, respectively. Although patients with fenestration had longer bypass and cross-clamp times (P<0.001), there was no difference in hospital length of stay or prolonged pleural effusions (P=0.80 and P=0.46, respectively). Freedom from systemic and Fontan circuit thromboembolism was higher in the nonfenestrated group (89%; 95% CI, 88%-95%) than the fenestrated group (84%; 95% CI, 77%-89%; P=0.03). There was no difference in incidence of plastic bronchitis, protein-losing enteropathy, New York Heart Association Class III/IV symptoms, or Fontan takedown. Conclusions In the propensity score-matched analysis we have demonstrated no difference in long-term survival or freedom from Fontan failure in patients with and without fenestration. There was a higher incidence of long-term thromboembolic events in patients with fenestration. Overall, it appears that fenestration in Fontan circulation does not bring long-term benefits.

Natural and Modified History of Atrioventricular Valve Regurgitation in Patients With Fontan Circulation.

BACKGROUND: Atrioventricular valve (AVV) regurgitation is increasingly prevalent in patients with a Fontan circulation. OBJECTIVES: We sought to determine the impact of ventricular dominance and AVV operation on outcomes in patients with a Fontan circulation and ≥moderate AVV regurgitation. METHODS: We conducted a retrospective study, including propensity score matching analysis, of 1,703 patients who survived Fontan operation in Australia and New Zealand from 1987 to 2021. RESULTS: Patients undergoing AVV operation were more likely to have right ventricular (RV) dominance or an atrioventricular septal defect. In the entire cohort, death or transplantation after Fontan operation was significantly higher in patients who underwent AVV operation before or at Fontan completion compared with those who did not (20 years: 18%; 95% CI: 8%-26% vs 13%; 95% CI: 10%-15%; P = 0.03). After propensity score matching, including for RV dominance, there was no significant difference in death or transplantation between the groups (20 years: 18%; 95% CI: 8%-26% vs 16%; 95% CI: 10%-22%; P = 0.41). Only patients with RV dominance who developed ≥moderate AVV regurgitation after Fontan operation were at increased risk of death or transplantation (HR: 2.8; 95% CI: 1.4-5.3; P < 0.01). In patients with left ventricular dominance, there was no significant difference in death or transplantation between patients with ≥moderate AVV regurgitation compared with those with 

Surveillance of End-Organ Damage in Fontan Patients Prior to Transition to Adult Care: Are We There Yet?

BACKGROUND: Recently published guidelines and consensus statements have outlined recommended screening practices for monitoring of end-organ dysfunction in Fontan patients. We reviewed the current approach to end-organ screening in a local population of Fontan patients at the time of transition to adult care. METHODS: Patient data from the Australia and New Zealand Fontan Registry and patient medical records were used to review investigations performed in Fontan patients transitioned from The Royal Children's Hospital Melbourne to an adult centre between 1 July 2015 and 30 June 2020. RESULTS: A total of 32 patients were referred for transition to an adult centre between 1 July 2015 and 30 June 2020 at a mean age of 18.5±0.7 years (12.7±2.5 years post-Fontan). Liver function tests were performed in 22 patients (69%) within 5 years prior to transition and were abnormal in 15 patients (68%). Liver ultrasound was performed in 13 patients (41%) within 5 years prior to the date of transition, of whom 10 (77%) had abnormal findings (features suggestive of hepatic fibrosis in seven [54%], cirrhosis in two [15%], and portal hypertension in three [23%]). Fourteen (14) patients (44%) had no record of a liver ultrasound being performed between the date of the Fontan procedure and the time of transition to adult care. Hepatocellular carcinoma was diagnosed in one patient at 18 months following transition. A total of 24 patients (75%) had a serum creatinine measured within the 5 years prior to transition, and two (8%) had an estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73 m2. No patient had a urine protein-creatinine ratio measured between the date of the Fontan procedure and the time of transition to adult care. CONCLUSIONS: In this study we have identified that the majority of patients transitioned from a tertiary paediatric centre to an adult centre within the last 5 years did not undergo routine surveillance for end-organ dysfunction. Routine screening for end-organ complications of the Fontan circulation should be incorporated into clinical practice and is an important part of Fontan patient care both pre- and post-transition to adult services.

Pre- and Post-operative determinants of transplantation-free survival after Fontan. The Australia and New Zealand experience.

BACKGROUND: This review identifies the predictors of late mortality and heart transplantation that remain relevant in the contemporary population of patients with a Fontan circulation, focusing on the potential impact of post-Fontan morbidities on the late outlook of these patients. METHODS AND RESULTS: A total of 1561 patients who had survived the Fontan operation in Australia or New Zealand from 1975 to 2018 were included in this review. Over a median duration of 11.4 years, there was a total of 117 deaths (7%) and 32 heart transplantations (2%). Freedom from death and heart transplantation at 10, 20 and 35 years post Fontan surgery were 94% (95% CI 93-95%), 87% (95 %CI 85-90%) and 66% (95 %CI 57-78%) respectively. Being male, having an atriopulmonary Fontan, pre-Fontan atrioventricular valve intervention, or prolonged pleural effusions post Fontan were predictive of late death or heart transplantation. However, time-dependent variables such as the development of atrial arrhythmia, protein/losing enteropathy or late ventricular dysfunction were stronger predictors of the same outcome. Patients who developed a time-dependent risk factor had a freedom from death and heart transplantation rate of 54% (95 %CI 43-66) at 15 years and 44% (95 %CI 33-57) at 25 years post Fontan. However, 95% (95 %CI 91-99) of patients without any of the identified risk factors were free from death or heart transplantation rate at 25 years post Fontan. CONCLUSION: In conclusion, the occurrence of post-operative complications such as PLE, arrhythmia and ventricular dysfunction will likely precede the late demise of these patients.

Long-term outcomes following Fontan takedown in Australia and New Zealand.

OBJECTIVE: Fontan takedown remains an option for the management of Fontan failure. We sought to evaluate early and late outcomes after Fontan takedown. METHODS: The Australia and New Zealand Fontan Registry was interrogated to identify all patients who had a Fontan takedown. RESULTS: Over a 43-year study period (1975-2018), 36 of 1540 (2.3%) had a Fontan takedown. The median age at takedown was 5.1 years (interquartile range [IQR], 3.7, 7.0). Nine (25%) patients had a takedown within 48 hours, 6 (16%) between 2 days and 3 weeks, 14 (39%) between 3 weeks and 6 months, whereas 7 (19%) had a late takedown (>6 months). Median interval to takedown was 26 days (IQR, 1.5, 127.5). Sixteen (44%) patients died at a median of 57.5 days (IQR, 21.8, 76.8). The greatest mortality occurred between 3 weeks and 6 months (<2 days: 1/9, 11%; 2 days to 3 weeks: 2/6, 33%; 3 weeks to 6 months: 11/14, 79%; >6 months: 2/7, 28%; P = .007). At median follow-up of 9.4 years (IQR, 4.5, 15.3), 11 (31%) patients were alive with an intermediate circulation (10 in New York Heart Association class I/II). Five (14%) patients underwent a successful second Fontan. Freedom from death/transplant after Fontan takedown was 59%, 56%, and 52% at 1, 5, and 10 years, respectively. CONCLUSIONS: The incidence of Fontan takedown is low, but mortality is high. The majority of takedowns occurred within 6 months. Mortality was lowest when takedown occurred <2 days and highest between 3 weeks and 6 months. A second Fontan is possible in a small proportion of survivors.

Protein-losing enteropathy and plastic bronchitis after the Fontan procedure.

OBJECTIVES: Protein losing enteropathy and plastic bronchitis are severe complications in Fontan circulation, with 5-year survival ranging from 46% to 88%. We report risk factors and outcomes of protein losing enteropathy and plastic bronchitis in patients undergoing the Fontan. METHODS: We performed a retrospective analysis of 1561 patients from the Australia New Zealand Fontan Registry. Two end points were death and cardiac transplantation examined with Cox regression (if no competing risks) or cumulative incidence curves and cause-specific Cs regression. RESULTS: A total of 55 patients with protein losing enteropathy/plastic bronchitis were included. Their median age at the Fontan was 5.7 years, and time to onset after the Fontan for protein losing enteropathy was 5.0 years and plastic bronchitis was 1.7 years. Independent predictors for developing protein losing enteropathy/plastic bronchitis were right-ventricular morphology with hypoplastic left-heart syndrome (hazard ratio, 2.30; confidence interval, 1.12-4.74), older age at Fontan (hazard ratio, 1.13; confidence interval, 1.03-1.23), and pleural effusions after Fontan (hazard ratio, 2.43; confidence interval, 1.09-5.41); left-ventricular morphology was protective (hazard ratio, 0.36; confidence interval, 0.18-0.70). In the protein losing enteropathy/plastic bronchitis population, freedom from death or transplantation after protein losing enteropathy/plastic bronchitis diagnosis at 5, 10, and 15 years was 70% (confidence interval, 58-85), 65% (confidence interval, 51-83), and 43% (confidence interval, 26-73), respectively; only older age (hazard ratio, 1.23; confidence interval, 1.01-1.52) was an independent predictor. Twenty-six surgical interventions were performed in 20 patients, comprising Fontan revisions (n = 5), fenestrations (n = 11), Fontan conversions (n = 5), atrioventricular valve repairs (n = 3), and hepatic vein diversion (n = 2). CONCLUSIONS: Protein losing enteropathy and plastic bronchitis remain severe complications, preferably affecting patients with dominant right single ventricle, with older age at Fontan being a predictor of developing protein losing enteropathy/plastic bronchitis and poorer prognosis. Heart transplantation remains the ultimate treatment, with 30% dying or requiring transplantation within 5 years, and the remaining being stable for long periods.

Acute and Chronic Kidney Disease Following Congenital Heart Surgery: A Review.

BACKGROUND: There is an increasing prevalence of chronic kidney disease in the population of adults currently living with congenital heart disease. A considerable proportion of children who undergo congenital heart surgery experience postoperative acute kidney injury. Whether there is an association between acute kidney injury after cardiac surgery in childhood and development of chronic kidney disease is unclear. METHODS: Three electronic databases were searched to capture relevant studies exploring the relationship between acute kidney injury after congenital heart surgery in children and progression to chronic kidney disease. RESULTS: A literature search identified a total of 212 research articles, 7 of which were selected for in-depth review. CONCLUSIONS: There is a likely association between acute kidney injury in children undergoing congenital heart surgery and progression to chronic kidney disease. Research should be developed to mitigate factors contributing to postoperative acute kidney injury in neonates, infants, and children undergoing cardiac surgery. Better targeted follow-up protocols to monitor renal function in children undergoing cardiac surgery should be implemented. A universal definition for acute kidney injury and chronic kidney disease is needed to improve detection and research in this field.