Assessment of cardiac dimensions in children diagnosed with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is an inherited autosomal dominant heart disease, characterized by increased left ventricular wall thickness and abnormal loading conditions. Imaging modalities are the first choice for diagnosis and risk stratification. Although heart dimensions have been characterized widely in HCM adults from cardiac imaging, there is limited information about children affected by HCM. The aim of this study is to evaluate left ventricular function and left heart dimensions in a small population of children diagnosed with HCM. METHODS: A total of 16 (seven male, nine female) pediatric patients with an average age of 14.0 ± 2.5 years diagnosed with HCM at Great Ormond Street Hospital for Children were included in this study. Cardiac magnetic resonance (CMR) images were used to measure left and right ventricular dimensions, and septal and left ventricular free wall thicknesses in Simpleware ScanIP. The gender groups were compared using student t-test or non-parametric Mann-Whitney U-test depending on the sample distribution. RESULTS: Differences in heart rate, left ventricular end-diastolic volume and end-diastolic volume index, left ventricular stroke volume and stroke volume index, left ventricular end-systolic long axis length, left ventricular end-systolic long axis length index, left ventricular end-diastolic mid-cavity diameter, left ventricular end-diastolic free wall thickness, left ventricular end-diastolic free wall thickness index, right ventricular end-diastolic long axis length were statistically significant in males and females. CONCLUSION: Left ventricular wall and intraventricular septal thickness increase affecting left ventricle cavity dimensions and there may be differences in anatomical and physiological parameters in males and females affected by HCM.

Quality in Clinical Consultations: A Cross-Sectional Study.

The coronavirus disease 2019 pandemic may have affected the quality of clinical consultations. The objective was to use 10 proposed quality indicator questions to assess outpatient consultation quality; to assess whether the recent shift to telemedicine during the pandemic has affected consultation quality; and to determine whether consultation quality is associated with satisfaction and consultation outcome. A cross-sectional study was used to survey clinicians and patients after outpatient consultations (1 February to 31 March 2021). The consultation quality score (CQS) was the sum of 'yes' responses to the survey questions. In total, 78% (538/690) of consultations conducted were assessed by a patient, clinician, or both. Patient survey response rate was 60% (415/690) and clinician 42% (291/690). Face-to-face consultations had a greater CQS than telephone (patients and clinicians < 0.001). A greater CQS was associated with higher overall satisfaction (clinicians log-odds: 0.77 ± 0.52, p = 0.004; patients log-odds: 1.35 ± 0.57, p < 0.001) and with definitive consultation outcomes (clinician log-odds: 0.44 ± 0.36, p = 0.03). In conclusion, consultation quality is assessable; the shift to telemedicine has negatively impacted consultation quality; and high-quality consultations are associated with greater satisfaction and definitive consultation outcome decisions.

Patient-Specific Modelling and Parameter Optimisation to Simulate Dilated Cardiomyopathy in Children.

PURPOSE: Lumped parameter modelling has been widely used to simulate cardiac function and physiological scenarios in cardiovascular research. Whereas several patient-specific lumped parameter models have been reported for adults, there is a limited number of studies aiming to simulate cardiac function in children. The aim of this study is to simulate patient-specific cardiovascular dynamics in children diagnosed with dilated cardiomyopathy, using a lumped parameter model. METHODS: Patient data including age, gender, heart rate, left and right ventricular end-systolic and end-diastolic volumes, cardiac output, systolic and diastolic aortic pressures were collected from 3 patients at Great Ormond Street Hospital for Children, London, UK. Ventricular geometrical data were additionally retrieved from cardiovascular magnetic resonance images. 23 parameters in the lumped parameter model were optimised to simulate systolic and diastolic pressures, end-systolic and end-diastolic volumes, cardiac output and left and right ventricular diameters in the patients using a direct search optimisation method. RESULTS: Difference between the haemodynamic parameters in the optimised cardiovascular system models and clinical data was less than 10%. CONCLUSION: The simulation results show the potential of patient-specific lumped parameter modelling to simulate clinical cases. Modelling patient specific cardiac function and blood flow in the paediatric patients would allow us to evaluate a variety of physiological scenarios and treatment options.

Weighted burden analysis of exome-sequenced late-onset Alzheimer's cases and controls provides further evidence for a role for PSEN1 and suggests involvement of the PI3K/Akt/GSK-3ß and WNT signalling pathways.

Previous studies have implicated common and rare genetic variants as risk factors for late-onset Alzheimer's disease (LOAD). Here, weighted burden analysis was applied to over 10,000 exome-sequenced subjects from the Alzheimer's Disease Sequencing Project. Analyses were carried out to investigate whether rare variants predicted to have a functional effect within a gene were more commonly seen in cases or in controls. Confirmatory results were obtained for TREM2, ABCA7, and SORL1. Additional support was provided for PSEN1 (p = 0.0002), which previously had been only weakly implicated in LOAD. There was suggestive evidence that functional variants in PIK3R1, WNT7A, C1R, and EXOC5 might increase risk and that variants in TIAF1 and/or NDRG2 might have a protective effect. Overall, there was strong evidence (p = 5 × 10-6 ) that variants in tyrosine phosphatase genes reduce the risk of developing LOAD. Because PIK3R1 variants are expected to impair PI3K/Akt/GSK-3ß signalling while variants in tyrosine phosphatase genes would enhance it, these findings are in line with those from animal models, suggesting that this pathway is protective against Alzheimer's disease.