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.

Exploring a new paradigm for the fetal anomaly ultrasound scan: Artificial intelligence in real time.

OBJECTIVE: Advances in artificial intelligence (AI) have demonstrated potential to improve medical diagnosis. We piloted the end-to-end automation of the mid-trimester screening ultrasound scan using AI-enabled tools. METHODS: A prospective method comparison study was conducted. Participants had both standard and AI-assisted US scans performed. The AI tools automated image acquisition, biometric measurement, and report production. A feedback survey captured the sonographers' perceptions of scanning. RESULTS: Twenty-three subjects were studied. The average time saving per scan was 7.62 min (34.7%) with the AI-assisted method (p < 0.0001). There was no difference in reporting time. There were no clinically significant differences in biometric measurements between the two methods. The AI tools saved a satisfactory view in 93% of the cases (four core views only), and 73% for the full 13 views, compared to 98% for both using the manual scan. Survey responses suggest that the AI tools helped sonographers to concentrate on image interpretation by removing disruptive tasks. CONCLUSION: Separating freehand scanning from image capture and measurement resulted in a faster scan and altered workflow. Removing repetitive tasks may allow more attention to be directed identifying fetal malformation. Further work is required to improve the image plane detection algorithm for use in real time.

Outcome and Impact of Associated Left-Sided Cardiac Lesions in Coarctation of the Aorta Diagnosed During Fetal Life.

Significant effort has been put into the optimization of the antenatal diagnosis of coarctation of the aorta (CoA). However, although left-sided cardiac lesions are known to cluster, the necessity to intervene postnatally for other left-sided cardiac lesions has not been reported in a cohort of fetuses with suspected CoA. We report a study of all 89 fetuses with antenatally suspected and postnatally confirmed diagnosis of CoA who underwent CoA repair as the primary procedure at a single tertiary congenital heart disease center over 10 years (January 1, 2010, to December 31, 2019). Almost 1 in 5 patients (18%) had to undergo surgery and/or transcatheter intervention on additional left-sided cardiac lesions (14%) and/or reintervention on the aortic arch (12%) during follow-up to median age of 2.85 years. Freedom from intervention at 5 years was 78% (95% confidence interval [CI] 67 to 88%) if reintervention on CoA was excluded, and 72% (95% CI 60 to 82%) if this was included. Five-year survival was 95% (95% CI 90 to 100%). Furthermore, 20% of affected infants had genetic (10%) and/or extracardiac (16%) abnormalities. Our study highlights the need for comprehensive antenatal counseling, including the prognosis of primary repair of CoA and the potential development of additional left-sided cardiac lesions, which may be difficult to diagnose prenatally even in expert hands or impossible to diagnose because of the physiology of the fetal circulation.

Fetal Speckle-Tracking: Impact of Angle of Insonation and Frame Rate on Global Longitudinal Strain.

BACKGROUND: There is a growing body of research on fetal speckle-tracking echocardiography because it is considered to be an angle-independent modality. The primary aim of this study was to investigate whether angle of insonation and acquisition frame rate (FR) influence left ventricular endocardial global longitudinal peak strain (GLS) in the fetus. METHODS: Four-chamber views of 122 healthy fetuses were studied at three different angles of insonation (apex up/down, apex oblique, and apex perpendicular) at high and low acoustic FRs. GLS was calculated, and a linear mixed-model analysis was used for analysis. Six hundred fifty-six fetal echocardiographic clips were analyzed (288 in the second trimester, at a median gestation of 21 weeks [interquartile range (IQR), 1 week], and 368 in the third trimester, at a median gestation of 36 weeks [IQR, 2 weeks]). RESULTS: Angle of insonation and FRs were significant determinants of GLS. Ventricular septum perpendicular to the ultrasound beam was associated with higher (more negative) GLS compared with apex up/down (at high FR: -21.8% vs -19.7%, P < .001; at low FR: -24.1% vs -21.4%, P < .001). Higher frames per second (FPS; median 149 FPS [IQR, 33 FPS] = 61 frames per cycle [FPC] [IQR, 17 FPC]) compared with lower FPS (median 51 FPS [IQR, 15 FPS] = 22 FPC [IQR, 7 FPC]) at the same insonation angle resulted in lower GLS (apex up/down: -19.7% vs -21.4%, P < .001; apex oblique: -21.2% vs -22.7%, P < .001; apex perpendicular: -21.8% vs -24.1%, P < .001). CONCLUSIONS: The present findings show that insonation angle and FR influence GLS significantly. These factors need to be considered when comparing studies with different acquisition protocols, when establishing normative values, and when interpreting pathology. Speckle-tracking echocardiography cannot be considered an angle-independent modality during fetal life.

Postnatal Outcome Following Prenatal Diagnosis of Discordant Atrioventricular and Ventriculoarterial Connections.

Discordant atrioventricular and ventriculoarterial connection(s) (DAVVAC) are a rare group of congenital heart lesions. DAVVAC can be isolated or associated with a variety of other cardiac abnormalities. Previous studies examining the outcome of prenatally diagnosed DAVVAC have described only fetal and early postnatal outcome in small cohorts. We aimed to describe the medium-term outcome of these fetuses. Cases were identified by searching the fetal cardiac databases of two centers. Follow-up data were collected from the electronic patient records. We identified 98 fetuses with DAVVAC. 39 pregnancies were terminated and 51 resulted in a liveborn infant. Postnatal data were available for 43 patients. The median length of follow-up was 9.5 years (range 36 days to 22.7 years). The overall 5-year survival of the cohort was 80% (95% confidence interval 74-86%), no deaths were seen after this period. Associated cardiac lesions had a significant effect on both survival and surgery-free survival. Isolated DAVVAC and DAVVAC with pulmonary stenosis ± ventricular septal defect had a low mortality (89% and 100% 5-year survival, respectively). Poorer survival was seen in the group with Ebstein's anomaly of the tricuspid valve, and other complex cardiac abnormalities. Antenatal tricuspid regurgitation had a significant negative impact on postnatal survival. In conclusion, the short- and medium-term outlook for fetuses with isolated DAVVAC, and those with DAVVAC and pulmonary stenosis are good. Antenatal risk factors for postnatal mortality include Ebstein's anomaly of the tricuspid valve, especially if associated with tricuspid regurgitation, and the presence of complex associated lesions.

Idiopathic pulmonary arterial hypertension with coexisting CHD.

Sinus venosus atrial septal defect can result in an increase in pulmonary blood flow and vascular resistance, leading to pulmonary hypertension. Rarely, the degree of pulmonary hypertension is out of proportion to the degree of intra-cardiac shunting. This case outlines the differences between pulmonary hypertension secondary to CHD and idiopathic pulmonary hypertension, and illustrates the investigation and management strategy used in a patient with features of both.

Chylothorax following paediatric cardiac surgery: a case-control study.

OBJECTIVES: The aims of this study were to investigate risk factors for the development of postoperative chylothorax following paediatric congenital heart surgery and to investigate the impact of a management guideline on management strategies and patient outcome. METHODS: All patients with chylothorax following cardiac surgery at the Royal Children's Hospital, Melbourne, over a 48-month period beginning in January 2008 were identified. A control group, matched for age, date of surgery, and sex, was identified. To investigate potential risk factors, univariable and multivariable logistic regression models were constructed with paired analysis. To examine the effect of a standardised management protocol, data before and after the implementation of the guideline were compared. RESULTS: In total, 121 cases of chylothorax were identified, with 121 controls, matched for age at surgery, date of surgery, and sex. The incidence of chylothorax was 5.23%. Increasing surgical complexity (univariable OR 0.17 for the least complex versus the most complex group, p=0.02), closed-heart surgeries (OR 0.07 for open versus closed, p<0.001), and redo chest incisions (OR 10.0 for redo versus virgin, p<0.001) were significantly associated with chylothorax. The standardised management protocol had no significant impact on either drainage duration or management strategy. CONCLUSIONS: We have replicated the previously reported association between surgical complexity and chylothorax risk, and have shown, for the first time, that redo chest openings are also associated with a significantly increased risk. The implementation of a standardised management protocol in our institution did not result in a significant change in either chylothorax drainage duration or management strategy.

The association between blood pressure and carotid intima-media thickness in children: a systematic review.

High blood pressure is a risk factor for atherosclerosis in adults, but whether the same is true in children and young people is not known. This is important to guide management of high blood pressure in children and young people. We aimed to investigate the association in children and young people between blood pressure and carotid intima-media thickness, a non-invasive marker of atherosclerosis, through a systematic review. Studies were retrieved from MEDLINE and EMBASE. Articles were eligible for inclusion if they included at least one measurement of blood pressure and at least one measurement of ultrasound-derived carotid intima-media thickness, both measured during childhood (0-19 years), and a measure of effect size or correlation between the two measurements. A total of 3748 studies were identified in the initial search, of which 28 studies were included in this review. The results were mixed, but the largest and highest-quality studies suggested an independent positive association between blood pressure and carotid intima-media thickness in children and young people, even after adjustment for other cardiovascular risk factors. There was no indication of a clear threshold level for the effect of blood pressure on carotid intima-media thickness, hence there are insufficient data to support a pharmacological treatment threshold for the treatment of high blood pressure in children and young people to prevent future cardiovascular disease. The studies included varied widely in terms of quality and design, and it was not possible to combine the data in a meta-analysis. There is likely to be an independent association between blood pressure and carotid intima-media thickness in childhood, but it is not clear at what point this should be treated.

Autoinflammatory gene polymorphisms and susceptibility to UK juvenile idiopathic arthritis.

BACKGROUND: To investigate the autoinflammatory hereditary periodic fever syndrome genes MVK and TNFRSF1A, and the NLRP1 and IL1 genes, for association with juvenile idiopathic arthritis (JIA). METHODS: For MVK, TNFRSF1A and NLRP1 pair-wise tagging SNPs across each gene were selected and for IL1A SNPs from a prior meta-analysis were included. 1054 UK Caucasian JIA patients were genotyped by Sequenom iPlex MassARRAY and allele and genotype frequencies compared with 5380 unrelated healthy UK Caucasian controls. RESULTS: Four SNPs were significantly associated with UK JIA: rs2071374 within intron 4 of IL1A (ptrend=0.006), rs2228576 3' of TNFRSF1A (ptrend=0.009) and 2 SNPs, rs11836136 and rs7957619, within MVK (ptrend=0.006, ptrend=0.005 respectively). In all cases the association appeared to be driven by the systemic-onset JIA (SoJIA) subtype. Genotype data for the two MVK SNPs was available in a validation cohort of 814 JIA (oligoarticular and RF negative polyarticular) cases and 3058 controls from the US. Replication was not confirmed, however, further suggesting that this association is specific to SoJIA. CONCLUSIONS: These findings extend the observations of the relevance of studying monogenic loci as candidates for complex diseases. We provide novel evidence of association of MVK and TNFRSF1A with UK JIA, specifically driven by association with SoJIA and further confirm that the IL1A SNP association with SoJIA is subtype specific. Replication is required in independent cohorts.

An unusual case of incomplete Kawasaki disease in an adolescent returning from holiday in Montana.

Here we present an unusual case of incomplete Kawasaki disease in a 15-year-old boy returning from a holiday with his family in Montana. His symptoms were initial diarrhoea and lethargy, with fever, rash, conjunctivitis, and arthralgia developing during the course of his illness. His condition worsened while he was at his local hospital, and he was transferred to the regional tertiary paediatric hospital. An initial echocardiogram was normal; however, repeat echocardiogram showed dilated coronary arteries with subsequent development of peeling of the skin on the hands and feet. The patient was started on intravenous immunoglobulin and high-dose aspirin and improved clinically. He was discharged home and remains under follow-up by the infectious diseases and cardiology teams.

Association between hemolysis and albuminuria in adults with sickle cell anemia.

Studies have questioned whether renal dysfunction in sickle cell disease is linked to hemolysis-associated vasculopathy. We have investigated renal function and markers of hemolysis in a cohort of 424 adult African-British patients with sickle cell disease. While significant associations were found in HbSS and HbSß(0) (sickle cell anemia) patients with and without controlling for covariates between hemolytic markers and albuminuria, the associations were not significant in patients with HbSC. Estimated glomerular filtration rate, a marker of renal function, correlated significantly with reticulocyte count and bilirubin. Alpha thalassemia, present in 34% of the sickle cell anaemia patients, had a protective effect against albuminuria in this group. Altogether, the incidence of hyperfiltration was 71% and microalbuminuria 37%, making nephropathy a common complication of sickle cell anemia.

Changing pattern of hospital admissions of children with sickle cell disease over the last 50 years.

A study published in 1981 examined the causes of hospital admission for a cohort of children with sickle cell disease (SCD). Since that time, the incidence and prevalence of SCD has increased markedly in the UK, and there have been many changes in the management of this disease. We undertook a study examining the causes of hospital admission of children with SCD to the same hospital as the previous study, over the 2-year period from 2008 to 2009. We found that the numbers of children being cared for by our hospital had dramatically increased over the last 50 years, but rates of hospital admission had significantly fallen (41 hospital admissions per 100 patient-years, compared with 111.3 admissions per 100 patient-years in the original study). This fall in admission rates is accounted for by 2 major components: acute painful episodes (15.7 admissions per 100 patient-years compared with 39.3 in the previous study) and admission for elective blood transfusion (0.2 admissions per 100 patient-years compared with 26.7 in the previous study). It is interesting to note that, 541 elective transfusions were carried out during the study period, but in a day-care setting rather than requiring overnight admission. This study illustrates the changes in management of SCD over the past 30 years, and reflects the overall trend common to most hospital specialties of increasing community and ambulatory care.

Is manipulation of mediastinal chest drains useful or harmful after cardiac surgery?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: in patients who have undergone cardiothoracic surgery does manipulation of drainage tubes affect drainage volumes or post-surgical outcome? Altogether 681 papers were found using the reported search, of which four represented the best evidence to answer the clinical question. Duncan and Erickson in 1982 found that chest tube stripping can lead to very low negative intrathoracic pressures. The authors report that this has the potential to cause tissue injury. Issacson et al. in 1986 compared two different methods of drain manipulation. They found no significant differences in the milking and stripping methods, suggesting that they are of similar efficacy in enhancing drainage. Lim-Levy et al. in 1986 also compared milking vs. stripping, with a control group that received no manipulation. They found no significant differences between the three groups in drainage volume. Furthermore, they recorded no incidences of tube occlusion in any of the three groups, implying that leaving the drains free of manipulation is acceptable in terms of clot clearance in the majority of patients. The milking and stripping methods were also compared by Pierce et al. in 1991. They also found no significant differences between the two manipulation methods. The studies by Issacson et al., Lim-Levy et al., and Pierce et al. were included in a Cochrane systematic review by Wallen et al. in 2002. No other relevant studies other than the three mentioned above were found after an extensive search of the literature. Overall, the authors concluded that there was insufficient evidence to recommend one type of drain manipulation technique over another, or to support or refute the need for drain manipulation at all. In our paper the authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that due to possible tissue damage and lack of demonstrable benefit, in most patients drainage tube manipulation should not be performed. No differences in either safety or efficacy have been demonstrated between the milking and stripping methods of manipulation.

Motor neuron disease mortality in Great Britain continues to rise: examination of mortality rates 1975 - 2004.

Motor neuron disease (MND) mortality rates are rising in Europe and the USA. The most comprehensive UK study was conducted more than 15 years ago. This study examines trends in mortality from MND in England & Wales, and Scotland, between 1975 and 2004. Age, gender, and cause-specific mortality rates were calculated for the period 1975-2004 using national data from England & Wales, and Scotland. Rates were directly age-standardized to the European standard population. Trends in mortality rates over time were examined for men and women separately, as well as by the age groups 0-59 years, and 60 or more years. MND mortality rates rose steadily over the 30-year period 1975-2004 in both sexes in England & Wales, and Scotland. There is a clear upward trend in all four groups (p for trend <0.001). All increases were largely restricted to the age group 60 years and above, with rates showing increases of 70-80%, and no evidence of a flattening of this trajectory. Rates for the 0-59 years age group remained stable over the period. There is evidence of a narrowing of the male-female gap in mortality rates for the age group over 60 years in England and Wales.