The evolving genetic etiology of conotruncal anomalies.

OBJECTIVE: To assess the diagnostic yield of genetic testing for antenatally detected conotruncal defects. METHOD: This was a retrospective analysis of all antenatally detected cases of conotruncal anomalies over a 4-year period. Patients were offered antenatal and postnatal genetic testing including QF-PCR, microarray and exome sequencing (ES) antenatally or genome sequencing (GS) postnatally on a case-by-case basis. RESULTS: There were 301 cases included. Overall, there were pathogenic genetic findings in 27.6% of the cases tested (53/192). The commonest finding was 22q11.21 deletion (20/192 cases, 10.4%), followed by trisomy 21 (6/192, 3.1%). There were 249 cases of isolated conotruncal anomalies, of which 59.8% (149/249) had genetic testing and 22.8% (34/149) had pathogenic findings. ES/GS was performed in five cases with no pathogenic findings. There were 52 cases of non-isolated contruncal anomalies, of which 82.7% (43/52) had genetic testing. ES/GS was performed in 11 cases in this group and increased the yield of clinically significant diagnoses from 32.6% (14/43) to 44.2% (19/43). CONCLUSION: Genetic abnormalities are present in over one quarter of cases of antenatally detected conotruncal anomalies. The commonest abnormality is 22q11.21 deletion. Exome sequencing or genome sequencing leads to a significant increase in genetic diagnosis in non-isolated cases.

British Congenital Cardiac Association Fetal Cardiology Standards: impact of Patient and Public involvement exercise on the development of clinical standards.

OBJECTIVE: To examine the impact of a Patient and Public Involvement exercise on the development of British Congenital Cardiac Association Fetal Cardiology Standards 2021. DESIGN: Open-ended, semi-structured interviews were undertaken to inform the design of a study to improve the quality of parents' experiences during antenatal and perinatal care of their child with CHD. This Patient and Public Involvement exercise was used to inform the final version of the drafted 'Standards'. SETTING: One-on-one interviews with parents who responded to a request on the closed Facebook page of the user group "Little Hearts Matter": "Would you be interested in helping us to design a study about parents' experience on learning that their child had CHD"? PATIENTS: Parents of children with single ventricle CHD. RESULTS: Twenty-one parents (18 mothers, 3 fathers) participated. Parents responses were reported to have variably reinforced, augmented, and added specificity in the later stages of drafting to six of the seven subsections of Section C Information and Support for Parents including: "At the time of the Scan"; "Counselling following the identification of an abnormality"; "Written information/resources"; "Parent support"; "Communication with other teams and ongoing care"; and "Bereavement support". CONCLUSIONS: This Patient and Public Involvement exercise successfully informed the development of Standards after the initial drafting. It contributed to the establishment of face validity of the 'Standards', especially when consistent with what is reported in the literature. Further research is needed to explore approaches to involving and standardising Patient and Public Involvement in the development of clinical standards.

Prenatal diagnosis of hypoplastic left heart syndrome on ultrasound using artificial intelligence: How does performance compare to a current screening programme?

BACKGROUND: Artificial intelligence (AI) has the potential to improve prenatal detection of congenital heart disease. We analysed the performance of the current national screening programme in detecting hypoplastic left heart syndrome (HLHS) to compare with our own AI model. METHODS: Current screening programme performance was calculated from local and national sources. AI models were trained using four-chamber ultrasound views of the fetal heart, using a ResNet classifier. RESULTS: Estimated current fetal screening programme sensitivity and specificity for HLHS were 94.3% and 99.985%, respectively. Depending on calibration, AI models to detect HLHS were either highly sensitive (sensitivity 100%, specificity 94.0%) or highly specific (sensitivity 93.3%, specificity 100%). Our analysis suggests that our highly sensitive model would generate 45,134 screen positive results for a gain of 14 additional HLHS cases. Our highly specific model would be associated with two fewer detected HLHS cases, and 118 fewer false positives. CONCLUSION: If used independently, our AI model performance is slightly worse than the performance level of the current screening programme in detecting HLHS, and this performance is likely to deteriorate further when used prospectively. This demonstrates that collaboration between humans and AI will be key for effective future clinical use.

COVID-19 in congenital heart disease (COaCHeD) study.

BACKGROUND: COVID-19 has caused significant worldwide morbidity and mortality. Congenital heart disease (CHD) is likely to increase vulnerability and understanding the predictors of adverse outcomes is key to optimising care. OBJECTIVE: Ascertain the impact of COVID-19 on people with CHD and define risk factors for adverse outcomes. METHODS: Multicentre UK study undertaken 1 March 2020-30 June 2021 during the COVID-19 pandemic. Data were collected on CHD diagnoses, clinical presentation and outcomes. Multivariable logistic regression with multiple imputation was performed to explore predictors of death and hospitalisation. RESULTS: There were 405 reported cases (127 paediatric/278 adult). In children (age <16 years), there were 5 (3.9%) deaths. Adjusted ORs (AORs) for hospitalisation in children were significantly lower with each ascending year of age (OR 0.85, 95% CI 0.75 to 0.96 (p<0.01)). In adults, there were 24 (8.6%) deaths (19 with comorbidities) and 74 (26.6%) hospital admissions. AORs for death in adults were significantly increased with each year of age (OR 1.05, 95% CI 1.01 to 1.10 (p<0.01)) and with pulmonary arterial hypertension (PAH; OR 5.99, 95% CI 1.34 to 26.91 (p=0.02)). AORs for hospitalisation in adults were significantly higher with each additional year of age (OR 1.03, 95% CI 1.00 to 1.05 (p=0.04)), additional comorbidities (OR 3.23, 95% CI 1.31 to 7.97 (p=0.01)) and genetic disease (OR 2.87, 95% CI 1.04 to 7.94 (p=0.04)). CONCLUSIONS: Children were at low risk of death and hospitalisation secondary to COVID-19 even with severe CHD, but hospital admission rates were higher in younger children, independent of comorbidity. In adults, higher likelihood of death was associated with increasing age and PAH, and of hospitalisation with age, comorbidities and genetic disease. An individualised approach, based on age and comorbidities, should be taken to COVID-19 management in patients with CHD.

Discordant Post-natal Patterns in Fetuses With Heterotaxy Syndrome: A Retrospective Single-Centre Series on Outcome After Fetal Diagnosis.

Objective: Cardiac and extra-cardiac anomalies in 46 pre-natally diagnosed cases of heterotaxy were compared to post-natal anatomical patterns in order to reveal discordant findings. Second, the outcome of these fetuses was evaluated. Methods: Fetuses with heterotaxy, diagnosed in a tertiary referral centre, were analysed retrospectively. Based on the foetal abdominal situs view, right atrial isomerism (RAI) and left atrial isomerism (LAI) were defined as foetal sub-types. Post-natally, discordant anatomical patterns for broncho-pulmonary branching, atrial appendage morphology, and splenic status were further clarified with CT scans. In summary, the spectrum of pre-natally and post-natally detected cardiac and extra-cardiac anomalies is systematically reviewed. Necessary surgical interventions and mid-long-term outcomes were compared between the two sub-types in surviving infants. Results: A total of 46 fetuses with heterotaxy were included; LAI was diagnosed in 29 (63%) fetuses and RAI was diagnosed in 17 (37%) fetuses. Extra-cardiac anomalies were noted in 35% of fetuses. Seven out of the 29 fetuses (24%) with LAI had atrio-ventricular block (AVB) and four of these cases presented with hydrops. Twenty nine out of the 46 participating fetuses (63%) were live births, with 62% in the LAI group and 65% in the RAI group. Five fetuses were lost to follow-up. At the age of 1 year, the overall survival of live births [estimate (95% CI)] was 67% (48; 92%) in patients with LAI and 55% (32; 94%) in patients with RAI. At the age of 5 years, the estimates were 67% (48; 92%) in the LAI group and 46% (24-87%) in the RAI group. The median survival (first quartile; third quartile) was 11.1 (0.1; 14) years for patients with LAI and 1.3 (0.09; NA) years for patients with RAI. Of 17 children who had undergone cardiac surgery, five (29%) children achieved a bi-ventricular repair and 12 (70%) children achieved a uni-ventricular palliation. Three were primarily palliated, but converted to bi-ventricular thereafter. Foetal subtype definition of heterotaxy based on the abdominal situs and post-natal thoracic imaging studies showed a discordant pattern of broncho-pulmonary branching and atrial appendage anatomy in 40% of our live-born children. Conclusion: Heterotaxy is a rare and complex condition with significant morbidity and mortality related to severe cardiac and extra-cardiac associations. Accurate pre-natal diagnosis can help identify the fetuses at risk and allow for timely intervention in a multi-disciplinary setting. Further studies are warranted to shed light on the exact sub-type definition in fetuses with heterotaxy and the presence of discordant post-natal patterns.

Foetal congenital heart disease: obstetric management and time to first cardiac intervention in babies delivered at a tertiary centre.

OBJECTIVES: The aim of this study was to determine the timing of neonatal cardiac intervention in babies with antenatally diagnosed congenital heart disease and the impact on obstetric management. METHODS: A retrospective review of all deliveries between January, 2008 and December, 2009 was conducted in a tertiary centre with foetal and paediatric cardiology, maternal-foetal medicine, and obstetric units. All live births with antenatally detected congenital heart disease were included. Data were collected from foetal, paediatric cardiology, and maternity databases and records. Induction, delivery mode, and timing of the first cardiac intervention in the neonate were studied. RESULTS: 205 deliveries were included. Induction and elective Caesarean section rates were 51.2% (105/205) and 14.1% (29/205), respectively. The vaginal delivery rate was 56% (115/205). There was a non-significant trend towards a higher rate of vaginal delivery after spontaneous labour than after induction (75% versus 66%; p = 0.234). The rate of neonatal cardiac intervention during the initial stay was 59.5% (122/205); it was 18.5% (38/205) within 48 hours and 25.8% (53/205) within 72 hours. The median time to first intervention was 4 days (interquartile range 2-8). Babies with hypoplastic left heart syndrome (median 3, interquartile range 2-6), transposition of the great arteries (median 1, interquartile range 0-4.5), and arrhythmia (median 0.5, interquartile range 0-1) had a significantly earlier time to first intervention compared with those with other conditions (p = 0.001). CONCLUSION: Vaginal delivery can be achieved in women delivering babies with major congenital heart disease at a tertiary centre. Delivery in or near a tertiary centre is recommended for patients requiring early intervention, of which many can be identified in advance.

Neurodevelopmental outcome in children with congenital heart disease.

Children with congenital heart disease (CHD) have multiple factors contributing toward their risk of later neurodevelopmental difficulties. With earlier diagnosis and improved survival rates, the management of CHD now includes the recognition of neurodevelopmental risks and optimisation of neurodevelopmental outcomes is emphasised. Neuroimaging studies have shown early differences in brain development for children with CHD, who then are vulnerable to additional brain injury in the perinatal period. For some children, complications and co-morbidities may further increase the risk of brain injury. Synthesis of multiple factors is necessary to estimate neurodevelopmental prognosis for an individual child. Long-term neurodevelopmental follow-up of children with CHD is warranted for early identification of and intervention for difficulties.

Prenatal diagnosis of left ventricular aneurysm in association with interruption of the aortic arch.

Left ventricular aneurysms in the foetus are a rare abnormality that can occur in isolation or associated with pentalogy of Cantrell. Here, we report a case of a foetus with a left ventricular aneurysm in association with interruption of the aortic arch, and no features of pentalogy of Cantrell. To our knowledge, this is the first report of such an association.

Timing of removal of pacing wires following paediatric cardiac surgery.

BACKGROUND: Temporary percutaneous epicardial pacing wires are routinely placed in children following cardiac surgery. There is uncertainty in clinical practice about the optimum timing for their removal, and practice varies widely both within and between different institutions. AIM: The aim of our study was to describe the use of temporary pacing in children undergoing cardiac surgery. METHODS: We performed a prospective audit of 140 children following cardiac surgery in two institutions. Information on diagnosis, surgical procedure, occurrence of arrhythmias, use of pacing wires, timing of removal of the wire, and complications related to removal was recorded on a daily basis from clinical records. RESULTS: We studied 140 patients undergoing a total of 141 operations. Of these, 39 (28%) required pacing postoperatively. In 38, pacing was required within the first 24 hours. One patient, who was in nodal rhythm for the first 24 hours, required pacing on the second postoperative day, while 29 patients required pacing beyond the first 24 hours. No patient in sinus rhythm on the first postoperative day required new pacing after this time. The median time to removal of the pacing wires was 4.5 days, with an inter-quartile range from 2 to 9 days. Complications included malfunction of atrial wires in 2 patients. CONCLUSIONS: Our study shows that no patient who was in sinus rhythm for the first 24 hours post-operatively required pacing before their discharge from hospital. This suggests that, in those patients in a stable state of sinus rhythm, and who have not required pacing within the first 24 hours, it may be safe to remove pacing wires after 24 hours. This could be timed to coincide with the removal of chest drains, thus avoiding the need for multiple distressing procedures.

Low-bandwidth teleconsultations for patients with complex congenital heart diseases.

We have reviewed our experience with a low-bandwidth paediatric telecardiology link (using ISDN at 128 kbit/s) between a tertiary centre in Belgrade and a tertiary centre in London. Over a two-year period, 12 videoconferences were held, during which 40 case histories of 38 patients were presented from Belgrade. The patients were aged 7 days to 20 years, and most of them had complex congenital heart defects. Changes in diagnosis and/or therapy occurred in 21 cases. Clinically relevant changes in diagnosis occurred in 2/40 cases (5%). In 12 cases, there were slight differences in opinion which resulted in minor changes in therapy for 9 of the patients. In another 9 patients, major changes in therapy occurred. There were no major problems with the quality of image and sound in any of the videoconferences. Our experience suggests that when there are experienced paediatric cardiologists at both ends of the connection, transmission via a single ISDN line is safe and accurate.