Molecular Pathways and Animal Models of Tricuspid Atresia and Univentricular Heart.

The process of valve formation is a complex process that involves intricate interplay between various pathways at precise times. Although we have not completely elucidated the molecular pathways that lead to normal valve formation, we have identified a few major players in this process. We are now able to implicate TGF-ß, BMP, and NOTCH as suspects in tricuspid atresia (TA), as well as their downstream targets: NKX2-5, TBX5, NFATC1, GATA4, and SOX9. We know that the TGF-ß and the BMP pathways converge on the SMAD4 molecule, and we believe that this molecule plays a very important role to tie both pathways to TA. Similarly, we look at the NOTCH pathway and identify the HEY2 as a potential link between this pathway and TA. Another transcription factor that has been implicated in TA is NFATC1. While several mouse models exist that include part of the TA abnormality as their phenotype, no true mouse model can be said to represent TA. Bridging this gap will surely shed light on this complex molecular pathway and allow for better understanding of the disease process.

Human Genetics of Tricuspid Atresia and Univentricular Heart.

Tricuspid atresia (TA) is a rare congenital heart condition that presents with a complete absence of the right atrioventricular valve. Because of the rarity of familial and/or isolated cases of TA, little is known about the potential genetic abnormalities contributing to this condition. Potential responsible chromosomal abnormalities were identified in exploratory studies and include deletions in 22q11, 4q31, 8p23, and 3p as well as trisomies 13 and 18. In parallel, potential culprit genes include the ZFPM2, HEY2, NFATC1, NKX2-5, MYH6, and KLF13 genes. The aim of this chapter is to expose the genetic components that are potentially involved in the pathogenesis of TA in humans. The large variability in phenotypes and genotypes among cases of TA suggests a genetic network that involves many components yet to be unraveled.

A rare case of severe Ebstein's anomaly and hepatoblastoma in a neonate.

Primary liver tumours in neonates with single-ventricle palliation are exceedingly rare. We present the first reported case of neonatal hepatoblastoma with severe Ebstein's anomaly following Starnes procedure. The patient's postoperative course highlights the challenges and complications in simultaneous management of these diagnoses. Transition from shunted single-ventricle physiology to bidirectional cavopulmonary connection improved end-organ function, permitting more aggressive hepatic malignancy treatment.

Fontan surgery failure: risk factors and experience in a Colombian reference centre.

BACKGROUND: The Fontan procedure is considered one of the most remarkable achievements in paediatric cardiology and cardiac surgery. Its final anatomical objective is a venous return through the superior and inferior vena cava. The complications inherent to this procedure and subsequent failure are its limitations. OBJECTIVE: To describe the clinical and haemodynamic characteristics of patients with Fontan failure and define the risk factors associated with it, with its short- and long-term outcomes during a 21-year observation period. METHODS: This is a retrospective follow-up study in which 15 patients diagnosed with Fontan failure in the single-ventricle programme of a high-complexity hospital in Medellín, Colombia, between 2001 and 2022 were included. RESULTS: One hundred and eight patients were identified in whom the Fontan procedure was performed, and 17 met the failure criteria. 82.4% were men, with a median age of 4.3 years. Ebstein's anomaly was the most common diagnosis, 29.4%. All patients underwent Fontan with an extracardiac tube following the procedure. According to the type of failure, 58.8% of patients presented protein-losing enteropathy and 17.6% plastic bronchitis. During follow-up, 5.9% of patients died. CONCLUSION: Fontan surgery in our centre is an option for patients with univentricular physiology. The correct selection of the patient is essential to mitigate failure risks.

Atrioventricular valve surgery in patients with univentricular heart and two separate atrioventricular valves.

OBJECTIVES: Atrioventricular valve regurgitation in patients with univentricular heart is a well-known risk factor for adverse outcomes and atrioventricular valve repair remains a particular surgical challenge. METHODS: We reviewed all surgical atrioventricular valve procedures in patients with univentricular heart and two separate atrioventricular valves who underwent surgical palliation. Endpoints of the study were reoperation-free survival and cumulative incidence of reoperation. RESULTS: Between 1994 and 2021, 202 patients with univentricular heart and two separate atrioventricular valve morphology underwent surgical palliation, with 15.8% (32/202) requiring atrioventricular valve surgery. Primary diagnoses were double inlet left ventricle (n = 14, 43.8%), double outlet right ventricle (n = 7, 21.9%), and congenitally corrected transposition of the great arteries (n = 7, 21.9%). Median weight at valve surgery was 10.6 kg (interquartile range, 7.9-18.9). Isolated left or right atrioventricular valve surgery was required in nine (28.1%) and 22 patients (68.8%), respectively. Concomitant left and right atrioventricular valve surgery was performed in one patient (3.1%). Closure of the left valve was conducted in four patients (12.5%) and closure of the right valve in three (9.4%). Operative and late mortality were 3.1% and 9.7%, respectively. Reoperation-free survival and cumulative incidence of reoperation at 10 years after surgery were 62.3% (standard error of the mean: 6.9) and 30.9% (standard error of the mean: 9.6), respectively. CONCLUSIONS: In patients with univentricular heart and two separate atrioventricular valves, surgical intervention on these valves is required in a minority of patients and is associated with low mortality but high incidence of reoperation.

Pulmonary artery coarctation repair in univentricular heart: indications and optimal timing.

BACKGROUND: To analyse surgical outcomes of pulmonary artery coarctation in univentricular hearts, focusing on surgical indications and optimal timing. METHODS: We retrospectively reviewed 49 patients with pulmonary artery coarctation in univentricular hearts treated at our institution between 1993 and 2022. Twenty-eight patients were diagnosed before first-stage palliation. Of these, 14 underwent systemic-pulmonary shunt only as first-stage palliation (Group 1), and 14 underwent systemic-pulmonary shunt plus surgical pulmonary artery plasty as first-stage palliation (Group 2). Twenty-one patients diagnosed after first-stage palliation underwent surgical pulmonary artery plasty at the time of bidirectional Glenn procedure (Group 3). RESULTS: Follow-up period after initial palliation was 6±8 years. The Fontan procedure was successful in 35 patients (71%) aged 28±26 months (range 18-139). Freedom from interstage death (Group 1, 53%; Group 2, 85%; Group 3, 93%) and interstage reintervention (Group 1, 50%; Group 2, 75%; Group 3, 73%) rates were significantly lower in Group 1 (p = 0.01). Five and four patients in Group 1 and Group 3, respectively, needed additional shunts before the bidirectional Glenn procedure. In Group 1, one patient with a non-confluent pulmonary artery achieved hemi-lung Fontan circulation. In Group 2, one patient suffering with a non-confluent pulmonary artery could not achieve Fontan circulation, whereas another patient with pulmonary venous obstruction achieved hemi-lung Fontan circulation. CONCLUSIONS: Surgical pulmonary artery plasty performed at first-stage palliation improved outcomes of pulmonary artery coarctation in univentricular hearts, particularly when pulmonary artery coarctation had already progressed during the neonatal period or early infancy.

Gabapentin as a novel adjunct for postoperative irritability after superior cavopulmonary connection operation in children.

OBJECTIVES: Describing our institution's off-label use of gabapentin to treat irritability after superior cavopulmonary connection surgery and its impact on subsequent opiate and benzodiazepine requirements. METHODS: This is a single-center retrospective cohort study including infants who underwent superior cavopulmonary connection operation between 2011 and 2019. RESULTS: Gabapentin was administered in 74 subjects (74/323, 22.9%) during the observation period, with a median (IQR) starting dose of 5.7 (3.3, 15.0) mg/kg/day and a maximum dose of 10.7 (5.5, 23.4) mg/kg/day. Infants who underwent surgery in 2015-19 were more likely to receive gabapentin compared with those who underwent surgery in 2011-14 (p < 0.0001). Infants prescribed gabapentin were younger at surgery (137 versus 146 days, p = 0.007) and had longer chest tube durations (1.8 versus 0.9 days, p < 0.001), as well as longer postoperative intensive care (5.8 versus 3.1 days, p < 0.0001) and hospital (11.5 versus 7.0 days, p < 0.0001) lengths of stays. The year of surgery was the only predisposing factor associated with gabapentin administration in multivariate analysis. In adjusted linear regression, infants prescribed gabapentin on postoperative day 0-4 (n = 64) had reduced benzodiazepine exposure in the following 3 days (-0.29 mg/kg, 95% CI -0.52 - -0.06, p = 0.01) compared with those not prescribed gabapentin, while no difference was seen in opioid exposure (p = 0.59). CONCLUSIONS: Gabapentin was used with increasing frequency during the study period. There was a modest reduction in benzodiazepine requirements associated with gabapentin administration and no reduction in opioid requirements. A randomised controlled trial could better assess gabapentin's benefits postoperatively in children with congenital heart disease.

Assessment of liver fibrosis using a 3-dimensional high-resolution late gadolinium enhancement sequence in children and adolescents with Fontan circulation.

OBJECTIVES: To assess abnormal liver enhancement on 15-20 min delayed 3D high-resolution late gadolinium enhancement (3D HR LGE) sequence in patients with Fontan circulation. METHODS: Retrospective study of pediatric Fontan patients (< 18 years old) with combined cardiac-liver MRI from January 2018 to August 2021. Abnormal hepatic enhancement was graded (0-3) for each lobe, summed for a total liver enhancement score (0-6), and compared to repaired tetralogy of Fallot (rTOF) patients. Correlations with other hepatic imaging biomarkers were performed. Temporal relationships of enhancement compared to traditional early portal venous and 5-7-min delayed phase liver imaging were analyzed. RESULTS: The Fontan group (n = 35, 13 ± 3.4 years old, median time from Fontan 10 (9-12) years) had 23/35 (66%) with delayed 3D HR LGE total liver enhancement score > 0 (range 0-5), with greater involvement of the right lobe (1 (0-1) vs 0 (0-1), p < 0.01). The rTOF group (n = 35, 14 ± 2.6 years old) had no abnormal enhancement. In the Fontan group, total liver enhancement was 3 (2-4) in the early portal venous phase, lower at 1 (1-2) in the 5-7-min delayed phase (p < 0.01), and lowest at 1 (0-2) in the 15-20-min delayed phase (p = 0.03). 3D HR LGE enhancement correlated inversely with portal vein flow (rs = - 0.42, p = 0.01) and positively with left lobe stiffness (rs = 0.51, p < 0.01). The enhancement score decreased in 13/35 (37%) between the 5-7- and 15-20-min delayed phases. CONCLUSIONS: Liver fibrosis can be assessed on 3D HR LGE sequences in patients with Fontan circulation, correlates with other imaging biomarkers of Fontan liver disease, and may add information for hepatic surveillance in this population. KEY POINTS: • Abnormal liver enhancement on 3D HR LGE sequences in Fontan patients likely represents liver fibrosis and is seen in up to 66% of children and adolescents with variable distribution and severity. • The degree of 3D HR LGE liver enhancement correlates with decreased portal vein flow and increased left hepatic lobe stiffness.

Single-inlet univentricular heart with persistent truncus arteriosus in a Sumatran orangutan (Pongo abelii).

Univentricular heart malformations are rarely described in the veterinary literature. This case report describes a single-inlet univentricular heart with persistent truncus arteriosus as a cause of death of a captive-bred, 2-day-old, female Sumatran orangutan (Pongo abelii), a critically endangered species.

Support with Single Ventricle-Ventricular Assist Device (sVAD) in Patients with Functionally Univentricular Circulation Prior to Fontan Operation.

Some patients with functionally univentricular circulation develop cardiac failure refractory to maximal management and are supported with a ventricular assist device (VAD). The purpose of this manuscript is to summarize our previous publications related to single ventricle-ventricular assist device (sVAD) support in patients with functionally univentricular circulation and to describe our current institutional approach at University of Florida to sVAD support in neonates, infants, and children prior to Fontan. Our programmatic philosophy at University of Florida is to strive to identify the minority of neonates with functionally univentricular circulation who are extremely high-risk prior to initiating staged palliation and to stabilize these neonates with primary preemptive sVAD in preparation for cardiac transplantation; our rationale for this approach is related to the challenges associated with failed staged palliation and subsequent bail-out sVAD support and transplantation. A subset of extremely high-risk neonates and infants with functionally univentricular ductal-dependent circulation undergo primary preemptive sVAD insertion and subsequent cardiac transplantation. Support with VAD clearly facilitates survival on the waiting list during prolonged wait times and optimizes outcomes after Norwood (Stage 1) by providing an alternative pathway for extremely high-risk patients. Therefore, the selective utilization of sVAD in extremely high-risk neonates facilitates improved outcomes for all patients with functionally univentricular ductal-dependent circulation. At University of Florida, our programmatic approach to utilizing sVAD support as a bridge to transplantation in the minority of neonates with functionally univentricular circulation who are extremely high-risk for staged palliation is associated with Operative Mortality after Norwood (Stage 1) Operation of 2.9% (2/68) and a one-year survival of 91.1% (82/90) for all neonates presenting with hypoplastic left heart syndrome (HLHS) or HLHS-related malformation with functionally univentricular ductal-dependent systemic circulation. Meanwhile, at University of Florida, for all 82 consecutive neonates, infants, and children supported with pulsatile paracorporeal VAD: Kaplan-Meier survival estimated one year after VAD insertion = 73.3% (95% confidence interval [CI] = 64.1-83.8%), and Kaplan-Meier survival estimated five years after VAD insertion = 68.3% (95% CI = 58.4-79.8%). For all 48 consecutive neonates, infants, and children at University of Florida with biventricular circulation supported with pulsatile paracorporeal VAD: Kaplan-Meier survival estimated one year after VAD insertion = 82.7% (95% CI = 72.4-94.4%), and Kaplan-Meier survival estimated five years after VAD insertion = 79.7% (95% CI = 68.6-92.6%). For all 34 consecutive neonates, infants, and children at University of Florida with functionally univentricular circulation supported with pulsatile paracorporeal sVAD: Kaplan-Meier survival estimated one year after VAD insertion = 59.7% (95% CI = 44.9-79.5%), and Kaplan-Meier survival estimated five years after VAD insertion = 50.5% (95% CI = 35.0-73.0%). These Kaplan-Meier survival estimates for patients supported with pulsatile paracorporeal VAD are better in patients with biventricular circulation in comparison to patients with functionally univentricular circulation both one year after VAD insertion (P=0.026) and five years after VAD insertion (P=0.010). Although outcomes after VAD support in functionally univentricular patients are worse than in patients with biventricular circulation, sVAD provides a reasonable chance for survival. Ongoing research is necessary to improve the outcomes of these challenging patients, with the goal of developing strategies where outcomes after sVAD support in functionally univentricular patients are equivalent to the outcomes achieved after VAD support in patients with biventricular circulation.

Congenital Non-Confluent Pulmonary Artery Sourced from Bilateral Arterial Ducts: A Rare Anomaly.

This study aimed to identify the influence of the non-confluent pulmonary artery originating from the bilateral arterial ducts (AD) on the outcomes of the Fontan circulation. We retrospectively reviewed the records of nine patients with bilateral AD and a non-confluent pulmonary artery in a single ventricle at our institution between 1993 and 2023. Three patients showed maintained AD or underwent a systemic-pulmonary shunt for stenotic AD, followed by the Glenn procedure. Four patients underwent systemic-pulmonary shunt with angioplasty as the first palliation, followed by the Glenn procedure. Two patients underwent systemic-pulmonary shunt or AD stenting as the first palliation and systemic-pulmonary shunt with angioplasty as the second palliation. There were no cases of interstage mortality. Pulmonary arteries grew and achieved a good balance (pre-Fontan pulmonary artery index [PAI], 164 ± 27 mm2/m2; right/left PAI ratio, 1.06 ± 0.23). All patients underwent the Fontan procedure (median, 3.5 years; range, 2.3-6.4 years) and were followed up for 7.8 years (range, 0.1-16.4 years) after the procedure. One patient required hospitalization for heart failure at 1.8 years, and three patients required catheter intervention for pulmonary stenosis within 2 months after the Fontan procedure. Non-confluent pulmonary arteries originating from the bilateral AD do not preclude Fontan completion and good Fontan outcomes by restoring balance to pulmonary blood flow. Due to the limited sample size in this study, additional research is imperative to delve deeper into our findings and enhance understanding of the most effective surgical approach for this disease.

Common arterial trunk in functionally univentricular hearts: a case series.

INTRODUCTION: The association of a univentricular heart defect with common arterial trunk is extremely rare. There is a lack of population-based outcome studies reported in the literature. METHODS: The hospital records, echocardiographic and other imaging modality data, outpatients' records, operation notes, and other electronic data were reviewed. Patients were reviewed, and the final outcomes of surgery were observed. RESULTS: Six cases (two males) with common arterial trunk presented over a 30-year period. Five had a complete unbalanced atrioventricular septal defect (83%) and one (17%) had tricuspid atresia associated with common arterial trunk. All had antenatal diagnosis. Two cases (33%) were excluded from initial surgical palliation due to Trisomy 21 in one and severe truncal valve regurgitation in one. Initial surgical palliation was performed in four cases (67%) at median age of 31 days (2-60) and consisted of disconnection and reconstruction of the pulmonary arteries and establishing controlled pulmonary blood flow. There were no early deaths. Conversion to cavopulmonary shunt was not possible in two due to severe airway problems in one and pulmonary arteries anatomy in one. They died at 11 and 16 months, respectively. Two patients (33%) underwent cavopulmonary shunt with 1 (17%) being alive at 18 months - 12 months after cavopulmonary shunt. The second patient proceeded to Fontan completion at 19 months but required catheter takedown 3 months later and died 3.5 years later. CONCLUSIONS: Univentricular hearts with common arterial trunk carry extremely poor short- to medium-term outcomes. This should inform antenatal and postnatal counselling and decision-making.

Plication for diaphragm paralysis after paediatric cardiac surgery: a single-centre experience.

OBJECTIVE: Diaphragm paralysis is a well-known complication following surgery for CHDs, which increases morbidity, mortality, and length of hospital stay as well as costs. Herein, we present our experience with diaphragm plication following paralysis of the phrenic nerve encountered after paediatric cardiac surgery. METHODS: This study retrospectively reviewed the medical records of 23 diaphragm plications in 20 patients who underwent paediatric cardiac surgery between January 2012 and January 2022. The patients were carefully selected based on aetiology and a combination of clinical manifestation and chest imaging characteristics including chest X-ray, ultrasonography, and fluoroscopy. RESULTS: Twenty-three successful plications were performed in 20 patients (15 males and 5 females) out of a total of 1938 operations performed in our centre. Mean age and body weight were 18.2 ± 17.1 months and 8.3 ± 3.7 kg, respectively. The period between the cardiac surgery and diaphragmatic plication was 18.7 ± 15.1 days. The highest incidence of diaphragm paralysis was encountered in systemic to pulmonary artery shunt patients with 7 out of 152 patients (4.6%). Any mortality was not encountered during a mean follow-up period of 4.3 ± 2.6 years. CONCLUSIONS: Early results of plication of the diaphragm following phrenic nerve palsy in symptomatic patients who underwent paediatric cardiac surgery are encouraging. Evaluation of the diaphragmatic function should be a routine part of post-operative echocardiography. Diaphragm paralysis may be a consequence of dissection, contusion, stretching, and thermal injury both in terms of hypothermia and hyperthermia.

Inferior vena cava thrombosis-rope ladder sign.

Congenital heart disease comprises one of the largest groups of congenital defects, affecting approximately 1% of births. Advances in pre- and postoperative critical care treatment as well as surgery and interventional procedures have improved survival rates, but treatment and long-term care of children with complex congenital heart disease remains challenging, and is associated with a number of complications.Here, we report on a 17-month-old infant with congenital univentricular heart disease who devloped post-operatively inferior vena cava (IVC) thrombosis. IVC thrombosis was confirmed by a bedside contrast media study (X-ray) demonstrating collateral paravertebral circulation along the paravertebral sinuses bilaterally into the azygos and hemiazygos vein ("rope ladder sign"), with no contrast media detected in the IVC. The infant was subsequently started on aspirin and clopidogrel.

Conception by assisted reproductive technology in infants with critical congenital heart disease in Japan.

RESEARCH QUESTION: What is the proportion of infants born as a result of assisted reproductive technology ART across different types of neonatal critical congenital heart disease (CCHD) in a Japanese population? DESIGN: A retrospective analysis of 418 consecutive infants with CCHD that required catheter treatment or surgery within the first 28 days of life or ductal-dependent lesions, in two paediatric centres in Japan, between January 2014 and December 2019. The proportion of ART in infants with each type of CCHD was evaluated. The proportion of ART in infants with univentricular heart defect (UVH) compared with those with biventricular heart defect (BVH) was evaluated. RESULTS: The study group included 229 boys and 189 girls, with a gestational age of 38 ± 2 weeks. Overall, 61 infants (14.6%) were conceived by fertility treatment with 46 (11.0%) conceived by ART. Univentricular heart defect and BVH were identified in 111 infants (26.6%) and 307 infants (73.4%), respectively. The proportion of infants conceived by ART was significantly higher in UVH (16.2%) than in BVH (9.1%) (OR 2.28, 95% CI 1.11 to 4.68, P = 0.025), regardless of maternal age and maternal history of miscarriage. CONCLUSIONS: The proportion of ART in infants with CCHD, especially UVH, was high. These findings could form the basis of a rationale for carrying out fetal echocardiography in fetuses conceived by ART.

Fontan circulation has improved life expectancy for infants born with complex heart disease over the last 50 years but has also resulted in significant morbidity.

The prognosis for infants born with complex heart disease improved dramatically with the introduction of the Fontan circulation 50 years ago. With today's carefully designed and staged operations to a Fontan circulation, life expectancy has increased and most children will survive into adult life. The Fontan circulation entails an unphysiological circulation with high risk for multiple organ system dysfunction. Neurodevelopmental disabilities with adverse psychosocial effects are prevalent. The Fontan circulation may eventually fail and necessitate heart transplantation. CONCLUSION: Fifty years development of the Fontan circulation to today's staged surgical procedures has improved survival but also revealed the burden of a high morbidity for a growing number of patients.

Exercise Prescription Enhances Maximal Oxygen Uptake and Anaerobic Threshold in Young Single Ventricle Patients with Fontan Circulation.

A modified Fontan procedure is performed to palliate single ventricle malformations. This hemodynamic arrangement sets systemic venous pressure unphysiologically high which predisposes the patient to severe long-term complications. As a means of self-care, exercise may ease transpulmonary flow. We investigated the effects of 6-month exercise prescription on pediatric Fontan patients. Eighteen stable Fontan patients (14 ± 2.6 years, 160.4 ± 11.3 cm, and 51.4 ± 14.4 kg) were recruited. Baseline fitness was assessed by physical activity questionnaire, body composition, cardiorespiratory performance, and muscle fitness tests. Exercise prescription was individually tailored for a 6-month training period at home. At entrance to the study, Fontan patients had lower than normal maximal oxygen uptake (VO2max) of 28. ± 5.9 ml/kg/min (61 ± 11% of normal). VO2max significantly correlated with weekly amount of habitual exercise and muscle mass of the lower limbs (p < 0.001 for both). After 6 months of training, the patients had improved their anaerobic threshold of 18 ± 3.5 vs 20 ± 4.8 ml/kg/min, p = 0.007, and workload tolerance of 119 ± 39 vs 132.4 ± 44 W, p = 0.001. At EUROFIT tests, the patient muscle fitness was below age-matched reference, but correlations existed between VO2max and lower limb muscle tests. Our patients with Fontan hemodynamics were able to positively respond to an exercise program by enhancing submaximal performance which should be beneficial for getting through daily activities. Future studies should correlate whether hemodynamic findings at Fontan completion influence physical activity and exercise reserves, and whether these predict predisposition to chronic complications.

Surgical management of hearts with isomeric atrial appendages.

BACKGROUND AND AIM: On the basis of previously published accounts, coupled with our own experience, we have assessed the surgical approaches to patients with isomeric atrial appendages. METHODS: We reviewed pertinent published studies on surgical treatment of individuals with isomeric atrial appendages, with the pertinent surgical details provided by most of the manuscripts. RESULTS: Half of patients with right isomerism, and two-thirds of those with left isomerism have bilateral superior caval veins. Azygos extension of the inferior caval vein is reported in three-quarters of those with left isomerism. The coronary sinus is universally absent in right isomerism, along with totally anomalous pulmonary venous connection, and is absent in two-fifths of those with left isomerism. Univentricular atrioventricular connections are expected in up to three-quarters of those with right isomerism. Atrioventricular septal defect is reported in up to four-fifths, more frequently in right isomerism, with such patients typically having discordant ventriculoatrial connections or double outlet right ventricle. Reported mortalities extend to 85% for those with right, and 50% for those with left isomerism. In right isomerism, mortality is up to 54% for systemic-to-pulmonary arterial shunting, up to 75% for univentricular repair, and up to 95% for repair of totally anomalous pulmonary venous connection itself. No more than one-quarter had undergone Fontan completion, with reported mortalities of 21%. CONCLUSION: Early surgical results are satisfactory in patients with left isomerism, but disappointing for those with right. Recent advances in cardiac and liver transplantation may offer improved survival.

Adolescents and adults with Fontan circulation: insights from the PREpArE-Fontan registry.

The Patient Registry for Adolescents and Adults with Stable Fontan Circulation aims to describe a contemporary cohort of Fontan patients who could be eligible for a clinical trial investigating macitentan, an endothelin receptor antagonist. This international, non-interventional, multicentre, cross-sectional, observational registry enrolled patients with "stable" Fontan circulation ≥10 years following extra-cardiac conduit or lateral tunnel procedure. Main exclusion criteria were NYHA functional class IV, reoperation of Fontan circulation, or signs of disease worsening. Patient characteristics at enrolment are described; available data were collected during a single registration visit. Of the 266 screened patients, 254 were included in this analysis. At enrolment, median (interquartile range) age was 24 (20;30) years, 37%/63% of patients were from the USA/Europe, 54% were male, 54%/47% had undergone extra-cardiac conduit/lateral tunnel procedures, and 95% were in NYHA functional class I or II. History of arrhythmia was more common in older patients and patients with lateral tunnel; overall prevalence was 19%. Most laboratory values were within the normal range but mean creatinine clearance was abnormally low (87.7 ml/min). Angiotensin-converting enzyme inhibitors were used by 48% of patients and their use was associated with creatinine clearance <90 ml/min (p = 0.007), as was Fontan completion at an older age (p = 0.007). 53.4% of patients had clinical characteristics that could potentially meet an endothelin receptor antagonist trial's eligibility criteria. The PREpArE-Fontan registry describes a cohort of patients who could potentially participate in an endothelin receptor antagonist trial and identified early subtle signs of Fontan failure, even in "stable" patients.

Fontan failure: phenotypes, evaluation, management, and future directions.

OBJECTIVES: Management of "failing" and "failed" Fontan circulation, particularly the indications, timing, and type of re-intervention, currently remains nebulous. Factors contributing to pathogenesis and mortality following Fontan procedure differ between children and adults. METHODS: Since organ systems in individual patients are affected differently, we searched the extant literature for a "failing" and "failed" Fontan reviewing the clinical phenotypes, diagnostic modalities, pharmacological, non-pharmacological, and surgical techniques employed, and their outcomes. RESULTS: A total of 410 investigations were synthesised. Although proper candidate selection, thoughtful technical modifications, timely deployment of mechanical support devices, tissue-engineered conduits, and Fontan takedown have decreased the peri-operative mortality from 9 to 15% and 1 to 3% per cent in recent series, pernicious changes in organ function are causing long-term patient attrition. In the setting of a failed Fontan circulation, literature documents three surgical options: Fontan revision, Fontan conversion, or cardiac transplantation. The reported morbidity of 25% and mortality of 8-10% among Fontan conversion continue to improve in select institutions. While operative mortality following cardiac transplantation for Fontan failure is 30% higher than for other CHDs, there is no difference in long-term survival with actuarial 10-year survival of around 54%. Mechanical circulatory assistance, stem cells, and tissue-engineered Fontan conduit for destination therapy or as a bridge to transplantation are in infancy for failing Fontan circulation. CONCLUSIONS: An individualised management strategy according to clinical phenotypes may delay the organ damage in patients with a failing Fontan circulation. At present, cardiac transplantation remains the last stage of palliation with gradually improving outcomes.