Shear-wave elastography for monitoring Fontan-associated liver disease: A prospective cohort study.

The spectrum of Fontan-associated liver disease (FALD) varies from abnormal liver function tests to fibrosis and even cirrhosis. In this prospective study, we evaluated the role of shear-wave elastography (SWE) in predicting the presence of advanced FALD. Forty-eight patients (30 males, 13.9 [6-21] years) with a Fontan circulation were evaluated at 8.3 (2.1-18.7) years since the Fontan surgery. The median liver stiffness measurement (LSM) value was higher than values in normal children at 15.4 (9.5-38.7) kPa. The LSMs had a weak but significant correlation with age at the time of LSM (r = 0.25, p = 0.01) and duration post-Fontan surgery (r = 0.31, p = 0.02). It had a poor correlation with the concomitant aspartate transaminase-to-platelet ratio index (r = 0.1, p = 0.39). No difference in the elastography values between children with and without ultrasound evidence of advanced liver disease (17.7 [interquartile range, IQR: 4] vs. 16.1 [IQR: 6], p = 0.62] was observed. Further studies are required to determine the precise role of SWE as a noninvasive marker of liver fibrosis in FALD.

Early Experience With the Bentley BeGraft Aortic Stent for the Management of Aortic Arch Pathology in the Paediatric Population.

BACKGROUND: Aortic arch pathology in older children is often treated preferentially with stenting. Both bare metal and covered stents have been utilised, with potential advantages of covered stents. The search for the ideal covered stent continues. METHODS: Retrospective review of all paediatric patients undergoing treatment of aortic arch pathology utilising the Bentley BeGraft Aortic stent (BeGraft Aortic, Bentley InnoMed, Hechingen, Germany) from June 2017 to May 2021. Outcome measures were procedural success, complications, medium-term patency and need for re-intervention. RESULTS: Fourteen (14) stents were placed in 12 children (seven males). Indications were coarctation of the aorta in 10 and aneurysm in two. Median age was 11.8 years (8.7-16.6 years) and median weight 42.5 kg (24.8-84 kg). Median coarctation narrowing of 4 mm (range 1-9 mm), improved to 11 mm (range 9-15 mm). The median coarctation gradient improved from 32 mmHg (range 11-42 mmHg) to 7 mmHg (range 0-14 mmHg). Both aneurysms were successfully occluded. There was no mortality or major morbidity. In one patient balloon rupture occurred requiring a second balloon for full inflation and one patient had a minor access site bleed. Follow-up median was 28 months (range 13-65 months). One patient underwent repeat balloon dilation for increased blood pressure gradient at 47 months post implant and a second patient additional stent insertion for a mid-stent aneurysm at 65 months. CONCLUSION: The Bentley BeGraft Aortic stent can be safely deployed in children for the treatment of aortic arch pathology. Medium-term patency is acceptable. Longer term follow-up in larger series will be required to assess stent performance.

Balloon dilatation versus surgical valvotomy for congenital aortic stenosis: a propensity score matched study.

BACKGROUND: Balloon valvuloplasty and surgical aortic valvotomy have been the treatment mainstays for congenital aortic stenosis in children. Choice of intervention often differs depending upon centre bias with limited relevant, comparative literature. OBJECTIVES: This study aims to provide an unbiased, contemporary matched comparison of these balloon and surgical approaches. METHODS: Retrospective analysis of patients with congenital aortic valve stenosis who underwent balloon valvuloplasty (Queensland Children's Hospital, Brisbane) or surgical valvotomy (Royal Children's Hospital, Melbourne) between 2005 and 2016. Patients were excluded if pre-intervention assessment indicated ineligibility to either group. Propensity score matching was performed based on age, weight, and valve morphology. RESULTS: Sixty-five balloon patients and seventy-seven surgical patients were included. Overall, the groups were well matched with 18 neonates/25 infants in the balloon group and 17 neonates/28 infants in the surgical group. Median age at balloon was 92 days (range 2 days - 18.8 years) compared to 167 days (range 0 days - 18.1 years) for surgery (rank-sum p = 0.08). Mean follow-up was 5.3 years. There was one late balloon death and two early surgical deaths due to left ventricular failure. There was no significant difference in freedom from reintervention at latest follow-up (69% in the balloon group and 70% in the surgical group, p = 1.0). CONCLUSIONS: Contemporary analysis of balloon aortic valvuloplasty and surgical aortic valvotomy shows no difference in overall reintervention rates in the medium term. Balloon valvuloplasty performs well across all age groups, achieving delay or avoidance of surgical intervention.

Management of Fetal Supraventricular Tachycardia: Case Series from a Tertiary Perinatal Cardiac Center.

BACKGROUND: Fetal supraventricular tachycardia is a relatively uncommon cardiac rhythm abnormality which is often associated with adverse perinatal outcomes if untreated. Although there are several treatment modalities and protocols in use globally, there is no consensus as to the most effective antiarrhythmic to manage this condition. AIM: This study aimed to evaluate perinatal outcomes following prenatal maternal therapy for fetal supraventricular tachycardia. MATERIALS AND METHODS: This was a 20-year retrospective cohort study. Institutional records were reviewed for antenatal therapy choice and maternal and fetal outcomes. RESULTS: Sixty-nine cases met diagnostic criteria for fetal SVT, of which 56 (81%) received maternal antiarrhythmic therapy. Digoxin was the most common, but least effective, first-line therapy in 28 patients, achieving successful rate reversion in 35.7%. Thirty-one patients (55%) required second-line therapy, and this was most successful with digoxin and flecainide polytherapy achieving rate reversion in 17 of 18 cases (94.5%) at a median of 3 days (1.5-7). Hydrops was present in 23 (33%) cases at initial presentation, 16 of which achieved rate reversion. There was minimal difference in treatment efficacy comparing single- or multiple-agent treatment in the setting of hydrops (50% vs. 42.8%). Side effects occurred in 14/56 treated patients (25%) but were severe in only 8 (14.3%) women, most commonly with digoxin and flecainide polytherapy (6 of 8 cases). There were 3 (4%) fetal deaths amongst the study cohort. CONCLUSIONS: Digoxin and flecainide polytherapy were well tolerated and successfully achieved rhythm and rate control in fetuses with prenatally diagnosed supraventricular tachycardia. The presence of hydrops was a poor prognostic feature.

The Gore Septal Occluder (GSO) for Multiple Indications in Children - An Intention to Treat Analysis.

OBJECTIVE: To assess the safety and efficacy of all uses of the Gore septal occluder (GSO) (WL Gore and Associates, Flagstaff, AZ, USA) in a tertiary children's hospital. BACKGROUND: The GSO is widely used in atrial septal communication closure in the adult population. Usage in the paediatric population is expanding. Device design potentially confers some benefits in this population. METHODS: Single centre retrospective data review over 6 years to July 2019 in a tertiary paediatric cardiac centre. All instances of intended GSO use were identified. Outcome measures were closure rates and procedural complications. RESULTS: Fifty-four (54) patients with median age 7.9 years (3-17 years) and weight 26.5 kg (12.6-76 kg) underwent attempted GSO implantation. Indications were atrial septal defect (ASD) with volume loading (39); abolition of right to left shunt (8); stroke prevention (3) and Fontan fenestration (4). Successful GSO deployment in 46/50 (92%) of the ASD/PFO group and 100% of the Fontan group. Occlusion rate was assessed at 24 hours and at medians of 1.4 months (IQR 1.1 mo), 9 months (IQR 8.3 mo) and 25.4 months (IQR 28.1 mo). Complete occlusion documented at these points was 91%, 87%, 93% and 98% respectively. Major complications prevented GSO implantation in four patients. Two (2) patients had transient rhythm disorder. There was no incidence of erosion, further arrhythmia, venous access complications or death during follow-up. CONCLUSIONS: The GSO can be safely deployed in both the atrial septum and Fontan fenestration with a low rate of complications. Trivial residual shunt is present in a number of cases early after deployment, although improves with time. Delivery sheath size was not a cause of significant complications in this patient cohort.

Queensland Paediatric Cardiac Service: Lessons from evolution to a unified service in a tertiary children's hospital.

We describe a complex change process for the paediatric cardiac service in Queensland that involved transitioning the service out of an essentially adult hospital into one of two children's hospitals in Brisbane. This initial step was complex as the governance was changed from Queensland Health to Mater Health, an independent faith-based organisation who became the new employer. Six years later, the service was again transitioned; this time to the newly constructed Queensland Children's Hospital, with a Hospital and Health Services Board as the employer under the aegis of Queensland Health. This was a complex journey. As with all change processes there was resistance to change on the part of some individuals. Five years on from the second major change, the service is settled, has an excellent workplace culture, has excellent clinical outcomes and has become research intensive.

Balloon Aortic Valvuloplasty for Congenital Aortic Stenosis: A 14-Year Single Centre Review.

BACKGROUND: The approach to intervention for congenital aortic valve stenosis (AS) differs depending upon centre bias toward a primary catheter or surgical approach. We therefore investigated associations with freedom from re-intervention (FFI) in the cohort of children who underwent primary balloon aortic valvuloplasty (BAV) for congenital AS in our centre. METHODS: All patients who underwent BAV as a primary procedure in the period between 2001 and 2015 in a single service were included. Echocardiographic parameters before and after catheterisation and procedural data was collected on all patients. RESULTS: Sixty-four (64) patients underwent BAV as the primary intervention during the study period. Follow-up data was available for 60 of these. Balloon aortic valvuloplasty was performed at a median age of 143 days (range 2 days-18.8 years). Freedom from re-intervention was observed in 75% of patients with a median follow-up of 6.8 years and a mean follow-up of 3 years. Catheter-based peak-to-peak aortic valve gradients decreased from 58±15.9mmHg to 22.9±13.1mmHg. There was no short- or long-term mortality. FFI was predicted by aortic valve morphology (p<0.01), post-BAV mean echo gradient (p=0.03) and post-BAV regurgitation (p<0.01). No patient had re-intervention for restenosis with post-BAV mean echo gradient <30mmHg. Catheter gradients before and after BAV approached significance for predicting FFI (p=0.06 and p=0.09 respectively). Fifteen (15) patients were neonates with significantly lower aortic valve (AoV) Z-scores (mean 0.63 vs 1.76, p=0.002) and no difference in FFI (p=0.19). Annulus size, balloon/annulus ratio (within the range utilised) and pre-BAV echo findings were not predictive for re-intervention. CONCLUSIONS: Balloon aortic valvuloplasty is an effective primary approach to congenital valvular AS with the potential of avoiding surgical intervention in the majority of patients at all ages. Freedom from re-intervention in our cohort was associated with valve morphology and the degree of stenosis and regurgitation immediately post BAV.

A replicating adenovirus capsid display recombinant elicits antibodies against Plasmodium falciparum sporozoites in Aotus nancymaae monkeys.

Decades of success with live adenovirus vaccines suggest that replication-competent recombinant adenoviruses (rAds) could serve as effective vectors for immunization against other pathogens. To explore the potential of a live rAd vaccine against malaria, we prepared a viable adenovirus 5 (Ad5) recombinant that displays a B-cell epitope from the circumsporozoite protein (CSP) of Plasmodium falciparum on the virion surface. The recombinant induced P. falciparum sporozoite-neutralizing antibodies in mice. Human adenoviruses do not replicate in mice. Therefore, to examine immunogenicity in a system in which, as in humans, the recombinant replicates, we constructed a similar recombinant in an adenovirus mutant that replicates in monkey cells and immunized four Aotus nancymaae monkeys. The recombinant replicated in the monkeys after intratracheal instillation, the first demonstration of replication of human adenoviruses in New World monkeys. Immunization elicited antibodies both to the Plasmodium epitope and the Ad5 vector. Antibodies from all four monkeys recognized CSP on intact parasites, and plasma from one monkey neutralized sporozoites in vitro and conferred partial protection against P. falciparum sporozoite infection after passive transfer to mice. Prior enteric inoculation of two animals with antigenically wild-type adenovirus primed a response to the subsequent intratracheal inoculation, suggesting a route to optimizing performance. A vaccine is not yet available against P. falciparum, which induces the deadliest form of malaria and kills approximately one million children each year. The live capsid display recombinant described here may constitute an early step in a critically needed novel approach to malaria immunization.

Transcatheter closure of the patent ductus arteriosus: an intention to treat analysis.

BACKGROUND: In patients with patent ductus arteriosus (PDA), transcatheter closure is the current procedure of choice. There are multiple devices available with limited current comparative data and varied recommendations for device selection. OBJECTIVE: To assess the efficacy and safety of the Flipper coil (FC) and the Amplatzer Duct Occluder (ADO). METHODS: An intention to treat analysis of all children admitted to the catheter laboratory at a single institution for occlusion of PDA from 2003 to 2011 was performed. Patient and device selection were determined by the treating physician. Standard techniques for FC and ADO implantation were used. RESULTS: Two hundred and twenty eight children with median weight of 14.2 kg (range; 5.5-68 kg) underwent cardiac catheterisation, with successful occlusion in 96.2% of patients when attempted. In 16 patients, median angiographic PDA diameter of 0.8 mm (range; 0.4-1.2 mm), was considered too small to warrant closure. Eight patients with large PDA's underwent surgical ligation. FC was successfully used in 70 (34.3%) and ADO in 134 (66.7%) patients. ADO patients were smaller (P=0.004) with larger PDA's (P<0.0001) than the FC group. Median fluoroscopy time was longer for ADO patients (10.1 min vs 8.0 min; P<0.0001). ADO had a lower embolisation rate (0% vs 6.6%; P=0.005) and a higher complete occlusion rate at follow-up (100% vs 73.4%; P<0.0001). Length of hospital admission decreased with time in both groups. CONCLUSION: Transcatheter closure of the PDA has a high degree of safety and efficacy. This study suggests that the ADO may be the device of first choice in the current era.

Comparison of homografts and bovine jugular vein conduits in the pulmonary position in patients <20 years of age.

OBJECTIVE: To compare the performance of homografts and bovine jugular vein (BJV) conduits in the pulmonary position. METHODS: All patients with congenital heart disease up to age 20 years who underwent pulmonary valve replacement with homografts or BJV at 3 centers in Australia were evaluated. There were 674 conduits, with 305 (45%) pulmonary homografts (PHs), 303 (45%) BJV conduits, and 66 (10%) aortic homografts (AHs). Endpoints were freedom from reintervention, structural valve degeneration (SVD), and infective endocarditis (IE). Propensity score matching was used to balance the comparison of PH and BJV conduits. RESULTS: The median follow-up was 6.4 years (interquartile range, IQR, 3.1-10.7 years). Freedom from reintervention at 5 and 10 years was 92% and 80%, respectively, for PH, 74% and 37% for BJV, and 75% and 47% for AH. BJV conduits had a higher risk of reintervention (P < .001) and SVD (P < .001) compared with PHs. These findings were confirmed with propensity score matching valid for conduit size >15 mm. AHs >15 mm had a higher risk of reintervention (P < .001) and SVD (P < .001) compared with PHs >15 mm. The performance of AHs and BJV conduits was similar across all sizes (reintervention, P = .94; SVD, P = .72). The incidence of IE was 1% for PH, 10% for BJV, and 1.5% for AH. CONCLUSIONS: In patients age <20 years with a conduit >15 mm, PHs outperformed BJV conduits and AHs in the pulmonary position. The performance of AH and BJV was comparable. Small conduits (≤15 mm) had similar performance across all conduit types.

Evaluation of the Repeatability of the LacryDiag Ocular Surface Analyzer for Assessment of the Meibomian Glands and Tear Film.

Purpose: This study aimed to determine the intra- and interobserver repeatability of the new LacryDiag Ocular Surface Analyzer and compare it to a similar all-in-one device, the OCULUS Keratograph 5M. Methods: Thirty healthy subjects aged 18 years and above were recruited for this study. All patients were free of any existing ocular pathology. The LacryDiag Ocular Surface Analyzer was used to evaluate tear meniscus height, interferometry, noninvasive tear break-up time (NIBUT), and meibography. The same or analogous exams were performed using the OCULUS Keratograph 5M. Test equivalation was used to compare data from corresponding examinations. Paired t-tests and coefficient of variation were used to determine inter- and intraobserver repeatability. Bland-Altman analysis was used to determine level of agreement between devices. Results: There were no differences in mean values for tear meniscus height, NIBUT, or tear film interferometry between observers for either device. Significant differences were found between observers for meibography when using the LacryDiag (P = 0.008 for percent loss calculation and P = 0.004 for grading scale). Intra-observer variability for NIBUT was significantly higher for the Keratograph (P = 0.0003 for observer A and P < 0.0001 for observer B). Conclusions: There was a good correlation but poor agreement between devices for a given observer. This was likely influenced by the use of repeated testing and the non-dry eye cohort. Translational Relevance: Both the repeatability of the testing device and the use of multiple outcome measures are essential for the diagnosis and monitoring of patients with dry eye disease (DED).

Infective Endocarditis in Children in Queensland, Australia: Epidemiology, Clinical Features and Outcome.

BACKGROUND: Infective endocarditis (IE) is a rare entity in children associated with significant morbidity and mortality. To optimize management, it is important to understand local epidemiology, risk factors, clinical features and outcome. These are investigated in this retrospective 10-year study of endocarditis in children in Queensland. METHODS: Children <18 years with IE were identified from the state-wide pediatric cardiology center (Mater Children's Hospital, 2009-2014; Queensland Children's Hospital, 2014-2018) through International Classification of Diseases codes and local cardiology database. Clinical records were assessed by a clinician and echocardiograms by a cardiologist. Incidence was calculated using Australian Bureau of Statistics Queensland Estimated Resident Population data, 2019. RESULTS: Fifty-one children were identified, with an overall estimated incidence of 0.84 per 100,000 per year; 0.69 per 100,000 in 2009-2013 and 0.99 per 100,000 in 2014-2018, respectively. Twenty-four (47.1%) children were male and 10 (19.6%) were identified as Aboriginal or Torres Strait Islander peoples. Underlying cardiac conditions were present in 29 (56.9%): 25 congenital heart disease, 3 rheumatic heart disease and 1 cardiomyopathy. A causative pathogen was identified in 46 (90.2%) children with Staphylococcus aureus most common. Thirty-six (70.6%) met criteria for "Definite IE" as per modified Duke criteria, with the remainder "Possible IE." Surgery was required in 26 (51%). Median duration of antibiotics was 42 (interquartile range = 32-51) days and hospitalization 49 (interquartile range = 34-75) days. One child died due to IE. CONCLUSIONS: IE in children in Queensland is increasing in incidence and is higher than the reported incidence in New Zealand and the United States. Congenital heart disease is the most common risk factor and S. aureus is the commonest responsible organism. Aboriginal or Torres Strait Islander children are over-represented. Mortality remains low.

Reconfiguration of the Amplatzer Vascular Plug II 5 months after occlusion of venovenous collateral in a bidirectional cavopulmonary circulation.

Venovenous anomalous vessels are a common complication seen in the bidirectional cavopulmonary circulation. In this report, we describe the use of the Amplatzer Vascular Plug II and subsequent demonstration of nitinol device memory with significant device reconfiguration at 5 months follow-up.

Isolated innominate artery as a cause of subclavian steal and cerebral hemisphere atrophy.

A rare case of isolated innominate artery arising from a left persistent arterial duct with a right aortic arch is presented. Of interest in this case is the retrograde flow in the left carotid system, the history of developmental delay, and the magnetic resonance image (MRI) brain findings suggestive of asymmetric volume loss affecting the left cerebral hemisphere. The authors postulate a possible mechanism of subclavian steal.

Bronchial varices in a child with tricuspid atresia six years post Fontan correction.

Tracheal and bronchial varices are rarely found in children. However, they have been described in adults with failing Fontan circuits or secondary to vascular pathology, such as portal and pulmonary hypertension. We report the presentation of haemoptysis and bronchial varices in a child, six years after a Fontan procedure for tricuspid atresia. She had tortuous mediastinal and transpleural arterial collaterals on computed tomography (CT) angiography and cardiac catheterization and subsequently underwent embolization of these collaterals. While the haemoptysis settled post embolization, the bronchial varices persisted on repeat bronchoscopy. She has since been clinically well with no further haemoptysis.

Cardiac outcomes of hydrops as a result of twin-twin transfusion syndrome treated with laser surgery.

AIM: To determine cardiac outcomes of foetal hydrops as a result of twin-twin transfusion syndrome treated with laser surgery. METHODS: Hydrops identified in 16 recipient foetuses with twin-twin transfusion syndrome was treated with laser ablation surgery to anastomotic vessels. Prior to laser surgery, the foetuses were assessed by echocardiography for cardiac abnormalities and ventricular and valvular dysfunction. After delivery, echocardiography was performed on 15 of the 16 newborn infants. RESULTS: Foetal echocardiography indicated impaired biventricular function in the 16 hydropic foetuses. Five foetuses had little or no forward flow through the pulmonary valve, while four had pulmonary regurgitation. Following laser surgery performed at a mean of 22.9 weeks gestation, hydrops resolved in all cases. Delivery occurred at a mean of 33.6 weeks gestation. Post-natal echocardiography revealed cardiac abnormalities in five neonates, of whom three had right ventricular outflow tract obstruction. One preterm infant with severe pulmonary stenosis died with intractable cardiac failure. CONCLUSION: The majority of hydropic infants with twin-win transfusion syndrome have normal cardiac outcomes following intrauterine laser surgery. As up to one-third may have cardiac abnormalities, cardiological monitoring is recommended during the first year of life.

The use of recombinant tissue plasminogen activator in the management of infective intracardiac thrombi in pre-term infants with thrombocytopaenia.

Bacterial endocarditis complicated by the development of intra-cardiac thrombus presents a difficult management dilemma in the pre-term infant. Here we present our experience with three infants who had this condition, all of whom were successfully managed using therapy with recombinant tissue plasminogen activator (r-TPA). Therapy in one of the infants was particularly instructive, as the condition was further complicated by severe thrombocytopaenia, making the decision to treat using r-TPA difficult.

Obstetric and perinatal outcomes in pregnancies with isolated foetal congenital heart abnormalities.

Objective: To determine obstetric, intrapartum, and perinatal outcomes for pregnancies with isolated foetal congenital heart defects (CHDs). Methods: This was a retrospective cohort study of women that delivered an infant with an isolated major CHD between January 2010 and April 2017 at a major Australian perinatal centre. The study cohort was compared with a cohort of women with infants without CHD. Cardiac abnormalities were broadly subdivided into the following five categories using the International Classification of Diseases Tenth Revision (ICD-10) as a guide - transposition of the great arteries (TGA), septal defects, right heart lesions (RHL), left heart lesions (LHL), and "other". Demographic characteristics and obstetric, intrapartum, and perinatal outcomes were compared between the two cohorts. Results: The final study cohort comprised of 342 infants with isolated CHD and 68,911 controls. Of the infants with CHD, 20.4% (70/342) had transposition of the great vessels, 23% (79/342) had septal lesions, 14.6% (50/342) had right sided lesions, 23.3% (80/342) left sided, and 18.4% (63/342) categorised as "other". Women with foetal CHD had a higher BMI and had higher rates of cardiac disease, diabetes mellitus, and hypertension, be smokers and consume alcohol compared to controls. The CHD cohort had lower odds of spontaneous vaginal delivery (SVD) (OR 0.73, 95%CI 0.58-0.90) and higher odds of caesarean for nonreassuring foetal status (aOR 1.65, 95%CI 1.07-2.55), birth weight <5th (aOR 3.44, 95%CI 2.38-4.98) and <10th (aOR 2.49, 95%CI 1.82-3.40) centiles, neonatal intensive care unit (NICU) admission (aOR 109.14, 95%CI 74.44-160.02), severe respiratory distress (aOR 2.90, 95%CI 2.33-3.76), 5 minutes Apgar score <7 (aOR 2.48, 95%CI 1.46-4.20), severe acidosis (aOR 1.80, 95%CI 1.14-2.85), stillbirth (aOR 4.09, 95%CI 1.62-10.33), neonatal death (aOR 24.30, 95%CI 13.24-44.61), and overall perinatal death (aOR 13.42, 95%CI 8.08-22.30). Infants with TGA had the lowest overall risk of complications whilst infants with RHL, LHL, and "others" had the highest risk of adverse outcomes, particularly death. Conclusion: Infants with CHD have overall worse obstetric and perinatal outcomes compared with controls. Infants with TGA have the best perinatal outcomes of all the CHD subcategories.