Quality of Life in Ugandan Children and Young Adults After Surgery for Congenital Heart Disease: Mixed Methods Approach.

Background: Health-related quality of life (HRQOL) is a critical issue for patients undergoing surgery for congenital heart disease (CHD) but has never been assessed in a low-income country. We conducted a cross-sectional mixed methods study with age-matched healthy siblings serving as controls at the Uganda Heart Institute. Methods: One-hundred fifteen CHD pediatric and young adult patients and sibling control participants were recruited. Health-related quality of life was assessed using the Pediatric Quality of Life Inventory Version 4.0 in participants ages 5-17 and 36-Item Short Form Survey for young adults aged 18-25. A subset of 27 participants completed face-to-face interviews to supplement quantitative findings. Results: Eighty-six pediatric (age 5-17) sibling and parent pairs completed Peds QOL surveys, and 29 young adult (age 18-25) sibling pairs completed SF-36 surveys. One third of patients had surgery in Uganda. Ventricular septal defects and tetralogy of Fallot were the most common diagnoses. Health-related quality of life scores in patients were lower across all domains compared to control participants in children. Reductions in physical and emotional domains of HRQOL were also statistically significant for young adults. Variables associated with lower HRQOL score on multivariate analysis in pediatric patients were younger age in the physical and emotional domains, greater number of surgeries in the physical domain and surgery outside Uganda in the school domain. The only predictor of lower HRQOL score in young adults was surgery outside Uganda in the social domain. Qualitative interviews identified a number of themes that correlated with survey results including abandonment by family, isolation from peers and community, financial hardship and social stigmatization. Conclusion: Health-related quality of life was lower in Ugandan patients after CHD surgery than siblings. Younger patients and those who had surgery outside of Uganda had lower HRQOL. These data have important implications for patients undergoing CHD surgery in LMIC and have potential to inform interventions.

Using Artificial Intelligence for Rheumatic Heart Disease Detection by Echocardiography: Focus on Mitral Regurgitation.

BACKGROUND: Identification of children with latent rheumatic heart disease (RHD) by echocardiography, before onset of symptoms, provides an opportunity to initiate secondary prophylaxis and prevent disease progression. There have been limited artificial intelligence studies published assessing the potential of machine learning to detect and analyze mitral regurgitation or to detect the presence of RHD on standard portable echocardiograms. METHODS AND RESULTS: We used 511 echocardiograms in children, focusing on color Doppler images of the mitral valve. Echocardiograms were independently reviewed by an expert adjudication panel. Among 511 cases, 229 were normal, and 282 had RHD. Our automated method included harmonization of echocardiograms to localize the left atrium during systole using convolutional neural networks and RHD detection using mitral regurgitation jet analysis and deep learning models with an attention mechanism. We identified the correct view with an average accuracy of 0.99 and the correct systolic frame with an average accuracy of 0.94 (apical) and 0.93 (parasternal long axis). It localized the left atrium with an average Dice coefficient of 0.88 (apical) and 0.9 (parasternal long axis). Maximum mitral regurgitation jet measurements were similar to expert manual measurements (P value=0.83) and a 9-feature mitral regurgitation analysis showed an area under the receiver operating characteristics curve of 0.93, precision of 0.83, recall of 0.92, and F1 score of 0.87. Our deep learning model showed an area under the receiver operating characteristics curve of 0.84, precision of 0.78, recall of 0.98, and F1 score of 0.87. CONCLUSIONS: Artificial intelligence has the potential to detect RHD as accurately as expert cardiologists and to improve with more data. These innovative approaches hold promise to scale echocardiography screening for RHD.

Outcomes of latent rheumatic heart disease: External validation of a simplified score in patients with and without secondary prophylaxis.

BACKGROUND: Secondary antibiotic prophylaxis reduces progression of latent rheumatic heart disease (RHD) but not all children benefit. Improved risk stratification could refine recommendations following positive screening. We aimed to evaluate the performance of a previously developed echocardiographic risk score to predict mid-term outcomes among children with latent RHD. METHODS: We included children who completed the GOAL, a randomized trial of secondary antibiotic prophylaxis among children with latent RHD in Uganda. Outcomes were determined by a 4-member adjudication panel. We applied the point-based score, consisting of 5 variables (mitral valve (MV) anterior leaflet thickening (3 points), MV excessive leaflet tip motion (3 points), MV regurgitation jet length ≥ 2 cm (6 points), aortic valve focal thickening (4 points) and any aortic regurgitation (5 points)), to panel results. Unfavorable outcome was defined as progression of diagnostic category (borderline to definite, mild definite to moderate/severe definite), worsening valve involvement or remaining with mild definite RHD. RESULTS: 799 patients (625 borderline and 174 definite RHD) were included, with median follow-up of 24 months. At total 116 patients (14.5%) had unfavorable outcome per study criteria, 57.8% not under prophylaxis. The score was strongly associated with unfavorable outcome (HR = 1.26, 95% CI 1.16-1.37, p < 0.001). Unfavorable outcome rates in low (≤6 points), intermediate (7-9 points) and high-risk (≥10 points) children at follow-up were 11.8%, 30.4%, and 42.2%, (p < 0.001) respectively (C-statistic = 0.64 (95% CI 0.59-0.69)). CONCLUSIONS: The simple risk score provided an accurate prediction of RHD status at 2-years, showing a good performance in a population with milder RHD phenotypes.

Serum Immune Responses to Group A Streptococcal Antigens following Pharyngeal Acquisitions among Children in Cape Town, South Africa.

There is limited information on the human immune response following infection with group A Streptococcus (Strep A). Animal studies have shown, in addition to the M protein, that shared Strep A antigens elicit protective immunity. This study aimed to investigate the kinetics of antibody responses against a panel of Strep A antigens in a cohort of school-aged children in Cape Town, South Africa. Participants provided serial throat cultures and serum samples at two-monthly follow-up visits. Strep A recovered were emm-typed, and serum samples were analyzed by enzyme-linked immunosorbent assay (ELISA) to assess immune responses to thirty-five Strep A antigens (10-shared and 25-M peptides). Serologic evaluations were performed on serial serum samples from 42 selected participants (from 256 enrolled) based on the number of follow-up visits, the frequency of visits, and throat culture results. Among these, there were 44 Strep A acquisitions, 36 of which were successfully emm-typed. Participants were grouped into three clinical event groups based on culture results and immune responses. A preceding infection was most convincingly represented by a Strep A-positive culture with an immune response to at least one shared antigen and M peptide (11 events) or a Strep A-negative culture with antibody responses to shared antigens and M peptides (9 events). More than a third of participants demonstrated no immune response despite a positive culture. This study provided important information regarding the complexity and variability of human immune responses following pharyngeal acquisition of Strep A, as well as demonstrating the immunogenicity of Strep A antigens currently under consideration as potential vaccine candidates. IMPORTANCE There is currently limited information regarding the human immune response to group A streptococcal throat infection. An understanding of the kinetics and specificity of antibody responses against a panel of Group A Streptococcus (GAS) antigens will serve to refine diagnostic approaches and contribute to vaccine efforts, which together will serve to reduce the burden of rheumatic heart disease, a major source of morbidity and mortality especially in the developing world. This study, utilizing an antibody-specific assay, uncovered three patterns of response profiles following GAS infection, among 256 children presenting with sore throat to local clinics. Overall, the response profiles were complex and variable. Of note, a preceding infection was most convincingly represented by a GAS-positive culture with an immune response to at least one shared antigen and M peptide. Also, more than a third of participants demonstrated no immune response despite a positive culture. All antigens tested were immunogenic, providing guidance for future vaccine development.

Reasons for disagreement between screening and standard echocardiography in primary care: data from the PROVAR + study : Disagreement between screening and standard echo.

We aimed to evaluate the reasons for disagreement between screening echocardiography (echo), acquired by nonexperts, and standard echo in the Brazilian primary care (PC). Over 20 months, 22 PC workers were trained on simplified handheld (GE VSCAN) echo protocols. Screening groups, consisting of patients aged 17-20, 35-40 and 60-65 years, and patients referred for clinical indications underwent focused echo. Studies were remotelyinterpreted in US and Brazil, and those diagnosed with major or severe HD were referred for standard echoperformed by an expert. Major HD was defined as moderate to severe valve disease, ventriculardysfunction/hypertrophy, pericardial effusion or wall-motion abnormalities. A random sample of exams wasselected for evaluation of variables accounting for disagreement. A sample of 768 patients was analyzed, 651(85%) in the referred group. Quality issues were reported in 5.8%, and the random Kappa for major HD between screening and standard echo was 0.51. The most frequent reasons for disagreement were: overestimation of mitral regurgitation (MR) (17.9%, N=138), left ventricular (LV) dysfunction (15.7%, N=121), aortic regurgitation (AR) (15.2%, N=117), LV hypertrophy (13.5%, N=104) and tricuspid regurgitation (12.7%, N=98). Misdiagnosis of mitral and aortic morphological abnormalities was observed in 12.4% and 3.0%, and underestimation of AR and MR occurred in 4.6% and 11.1%. Among 257 patients with suspected mild/moderate MR, 129 were reclassified to normal. In conclusion, although screening echo with task-shifting in PC is a promising tool in low-income areas, estimation of valve regurgitation and LV function and size account for considerable disagreement with standard exams.

Investigation of the Familial Risk of Rheumatic Heart Disease with Systematic Echocardiographic Screening: Data from the PROVAR+ Family Study.

We aimed to use echocardiographic (echo) screening to evaluate the risk of Rheumatic Heart Disease (RHD) among the relatives of patients with advanced RHD, who were enrolled in the University Hospital's outpatient clinics from February 2020 to September 2021. Consenting first-degree relatives were invited for echo screening using handheld devices (GE VSCAN) by non-physicians, with remote interpretation. Matched controls (spouses, neighbors) living in the same household were enrolled in a 1:5 fashion. A standard echo (GE Vivid-IQ) was scheduled if abnormalities were observed. In 16 months, 226 relatives and 47 controls of 121 patients were screened, including 129 children, 77 siblings and 20 parents. The mean age was 40 ± 17 years, 67% of the patients were women, and 239 (88%) lived with the index case for >10 years. Echo findings suggestive of RHD were confirmed in zero controls and 14 (7.5%) relatives (p = 0.05): 11 patients had mild/moderate mitral regurgitation, and four were associated with mitral stenosis and abnormal morphology. Two patients had mild aortic regurgitation and abnormal morphology, which were associated with mild aortic and mitral stenosis, and two patients with advanced RHD had bioprostheses in the mitral (2) and aortic (1) positions. In conclusion, first-degree relatives of individuals with clinical RHD are at greater risk of having RHD, on top of socioeconomic conditions.

Penicillin Reactions in Patients With Severe Rheumatic Heart Disease: A Presidential Advisory From the American Heart Association.

Secondary antibiotic prophylaxis with regular intramuscular benzathine penicillin G (BPG) is the cornerstone of rheumatic heart disease management. However, there is a growing body of evidence that patients with rheumatic heart disease who have severe valvular heart disease with or without reduced ventricular function may be dying from cardiovascular compromise following BPG injections. This advisory responds to these concerns and is intended to: (1) raise awareness, (2) provide risk stratification, and (3) provide strategies for risk reduction. Based on available evidence and expert opinion, we have divided patients into low- and elevated-risk groups, based on symptoms and the severity of underlying heart disease. Patients with elevated risk include those with severe mitral stenosis, aortic stenosis, and aortic insuffiency; those with decreased left ventricular systolic dysfunction; and those with no symptoms. For these patients, we believe the risk of adverse reaction to BPG, specifically cardiovascular compromise, may outweigh its theoretical benefit. For patients with elevated risk, we newly advise that oral prophylaxis should be strongly considered. In addition, we advocate for a multifaceted strategy for vasovagal risk reduction in all patients with rheumatic heart disease receiving BPG. As current guidelines recommend, all low-risk patients without a history of penicillin allergy or anaphylaxis should continue to be prescribed BPG for secondary antibiotic prophylaxis. We publish this advisory in the hopes of saving lives and avoiding events that can have devastating effects on patient and clinician confidence in BPG.

Global, regional, and national time trends in mortality for congenital heart disease, 1990-2019: An age-period-cohort analysis for the Global Burden of Disease 2019 study.

BACKGROUND: Congenital heart disease (CHD) is the leading cause of morbidity and mortality from birth defects worldwide. We report an overview of trends in CHD mortality in 204 countries and territories over the past 30 years and associations with age, period, and birth cohort. METHODS: Cause-specific CHD mortality estimates were derived from the Global Burden of Disease 2019 study. We utilised an age-period-cohort model to estimate overall annual percentage changes in mortality (net drifts), annual percentage changes from 0 to 4 to 65-69 years (local drifts), period and cohort relative risks (period/cohort effects) between 1990 and 2019. This approach allows for the examination and differentiation of age, period, and cohort effects in the mortality trends, with the potential to identify disparities and treatment gaps in cardiac care. FINDINGS: CHD is the leading cause of deaths from non-communicable diseases (NCDs) in those under 20 years. Global CHD deaths in 2019 were 217,000 (95% uncertainty interval 177,000-262,000). There were 129 countries with at least 50 deaths. India, China, Pakistan, and Nigeria had the highest mortality, accounting for 39.7% of deaths globally. Between 1990 and 2019, the net drift of CHD mortality ranged from -2.41% per year (95% confidence interval [CI] -2.55, -2.67) in high Socio-demographic Index (SDI) countries to -0.62% per year (95% CI: -0.82, -0.42) in low-SDI countries. Globally, there was an emerging transition in the age distribution of deaths from paediatric to adult populations, except for an increasing trend of mortality in those aged 10-34 years in Mexico and Pakistan. During the past 30 years, favourable mortality reductions were generally found in most high-SDI countries like South Korea (net drift = -4.0% [95% CI -4.8 to -3.1] per year) and the United States (-2.3% [-2.5 to -2.0]), and also in many middle-SDI countries like Brazil (-2.7% [-3.1 to 2.4]) and South Africa (-2.5% [-3.2 to -1.8]). However, 52 of 129 countries had either increasing trends (net drifts ≥0.0%) or stagnated reductions (≥-0.5%) in mortality. The relative risk of mortality generally showed improving trends over time and in successively younger birth cohorts amongst high- and high-middle-SDI countries, with the exceptions of Saudi Arabia and Kazakhstan. 14 middle-SDI countries such as Ecuador and Mexico, and 16 low-middle-SDI countries including India and 20 low-SDI countries including Pakistan, had unfavourable or worsening risks for recent periods and birth cohorts. INTERPRETATION: CHD mortality is a useful and accessible indicator of trends in the provision of congenital cardiac care both in early childhood and across later life. Improvements in the treatment of CHD should reduce the risk for successively younger cohorts and shift the risk for all age groups over time. Although there were gains in CHD mortality globally over the past three decades, unfavourable period and cohort effects were found in many countries, raising questions about adequacy of their health care for CHD patients across all age groups. These failings carry significant implications for the likelihood of achieving the Sustainable Development Goal targets for under-5 years and NCD mortality. FUNDING: Supported by the National Natural Science Foundation of China (81525002, 31971048, 82073573 to ZZ and HZ), Shanghai Outstanding Medical Academic Leader program (2019LJ22 to HZ), and Collaborative Innovation Program of Shanghai Municipal Health Commission (2020CXJQ01 to HZ), the Bill & Melinda Gates Foundation for the Global Burden of Disease Project (to NJK) and NHMRC fellowship administered through the University of Melbourne (to GCP).

Cardiac echocardiogram findings of severe acute respiratory syndrome coronavirus-2-associated multi-system inflammatory syndrome in children.

BACKGROUND: A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic. OBJECTIVES: To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children. METHODS: Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher's exact, and Wilcoxon rank sum. RESULTS: Thirty-nine children with median (interquartile range) age 7.8 (3.6-12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26-61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04). CONCLUSION: Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.

Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease.

BACKGROUND: Rheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown. METHODS: We conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years. RESULTS: Among 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, -7.5 percentage points; 95% confidence interval, -10.2 to -4.7; P<0.001). Two participants in the prophylaxis group had serious adverse events that were attributable to receipt of prophylaxis, including one episode of a mild anaphylactic reaction (representing <0.1% of all administered doses of prophylaxis). CONCLUSIONS: Among children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended. (Funded by the Thrasher Research Fund and others; GOAL ClinicalTrials.gov number, NCT03346525.).

Incidence of acute rheumatic fever in northern and western Uganda: a prospective, population-based study.

BACKGROUND: Acute rheumatic fever is infrequently diagnosed in sub-Saharan African countries despite the high prevalence of rheumatic heart disease. We aimed to determine the incidence of acute rheumatic fever in northern and western Uganda. METHODS: For our prospective epidemiological study, we established acute rheumatic fever clinics at two regional hospitals in the north (Lira district) and west (Mbarara district) of Uganda and instituted a comprehensive acute rheumatic fever health messaging campaign. Communities and health-care workers were encouraged to refer children aged 3-17 years, with suspected acute rheumatic fever, for a definitive diagnosis using the Jones Criteria. Children were referred if they presented with any of the following: (1) history of fever within the past 48 h in combination with any joint complaint, (2) suspicion of acute rheumatic carditis, or (3) suspicion of chorea. We excluded children with a confirmed alternative diagnosis. We estimated incidence rates among children aged 5-14 years and characterised clinical features of definite and possible acute rheumatic fever cases. FINDINGS: Data were collected between Jan 17, 2018, and Dec 30, 2018, in Lira district and between June 5, 2019, and Feb 28, 2020, in Mbarara district. Of 1075 children referred for evaluation, 410 (38%) met the inclusion criteria; of these, 90 (22%) had definite acute rheumatic fever, 82 (20·0%) had possible acute rheumatic fever, and 24 (6%) had rheumatic heart disease without evidence of acute rheumatic fever. Additionally, 108 (26%) children had confirmed alternative diagnoses and 106 (26%) had an unknown alternative diagnosis. We estimated the incidence of definite acute rheumatic fever among children aged 5-14 years as 25 cases (95% CI 13·7-30·3) per 100 000 person-years in Lira district (north) and 13 cases (7·1-21·0) per 100 000 person-years in Mbarara district (west). INTERPRETATION: To the best of our knowledge, this is the first population-based study to estimate the incidence of acute rheumatic fever in sub-Saharan Africa. Given the known rheumatic heart disease burden, it is likely that only a proportion of children with acute rheumatic fever were diagnosed. These data dispel the long-held hypothesis that the condition does not exist in sub-Saharan Africa and compel investment in improving prevention, recognition, and diagnosis of acute rheumatic fever. FUNDING: American Heart Association Children's Strategically Focused Research Network Grant, THRiVE-2, General Electric, and Cincinnati Children's Heart Institute Research Core.

Towards automatic diagnosis of rheumatic heart disease on echocardiographic exams through video-based deep learning.

OBJECTIVE: Rheumatic heart disease (RHD) affects an estimated 39 million people worldwide and is the most common acquired heart disease in children and young adults. Echocardiograms are the gold standard for diagnosis of RHD, but there is a shortage of skilled experts to allow widespread screenings for early detection and prevention of the disease progress. We propose an automated RHD diagnosis system that can help bridge this gap. MATERIALS AND METHODS: Experiments were conducted on a dataset with 11 646 echocardiography videos from 912 exams, obtained during screenings in underdeveloped areas of Brazil and Uganda. We address the challenges of RHD identification with a 3D convolutional neural network (C3D), comparing its performance with a 2D convolutional neural network (VGG16) that is commonly used in the echocardiogram literature. We also propose a supervised aggregation technique to combine video predictions into a single exam diagnosis. RESULTS: The proposed approach obtained an accuracy of 72.77% for exam diagnosis. The results for the C3D were significantly better than the ones obtained by the VGG16 network for videos, showing the importance of considering the temporal information during the diagnostic. The proposed aggregation model showed significantly better accuracy than the majority voting strategy and also appears to be capable of capturing underlying biases in the neural network output distribution, balancing them for a more correct diagnosis. CONCLUSION: Automatic diagnosis of echo-detected RHD is feasible and, with further research, has the potential to reduce the workload of experts, enabling the implementation of more widespread screening programs worldwide.

Ambulatory cardiology telemedicine: a large academic pediatric center experience.

We performed a retrospective study of cardiology telemedicine visits at a large academic pediatric center between 2016 and 2019 (pre COVID-19). Telemedicine patient visits were matched to data from their previous in-person visits, to evaluate any significant differences in total charge, insurance compensation, patient payment, percent reimbursement and zero reimbursement. Miles were measured between patient's home and the address of previous visit. We found statistically significant differences in mean charges of telemedicine versus in-person visits (2019US$) (172.95 vs 218.27, p=0.0046), patient payment for telemedicine visits versus in-person visits (2019US$) (11.13 vs 62.83, p≤0.001), insurance reimbursement (2019US$) (65.18 vs 110.85, p≤0.001) and insurance reimbursement rate (43% vs 61%, p=0.0029). Rate of zero reimbursement was not different. Mean distance from cardiology clinic was 35 miles. No adverse outcomes were detected. This small retrospective study showed cost reduction and a decrease in travel time for families participating in telemedicine visits. Future work is needed to enhance compensation for telemedicine visits.

Expanding Access to Fetal Telecardiology During the COVID-19 Pandemic.

Background: This study aims to describe one center's experience in expanding a fetal telecardiology program through collaborative work with maternal fetal medicine (MFM) clinics with the goal of safely reaching mothers during the COVID-19 pandemic. We sought to define the extent of fetal telehealth conversion at a large fetal cardiac care center and evaluate the diagnostic accuracy for studies performed. Methods: At our center, fetal telemedicine expanded from one MFM site before the pandemic to four additional sites by May 2020. A retrospective review of fetal telecardiology visits between March 15 and July 15, 2020, was performed. The chart was reviewed for confirmation of diagnosis postnatally. Results: With pandemic onset, there was a large increase in the number of telemedicine visits with a total of 122 mothers seen between five MFM clinics. Fourteen mothers (11.5%) had abnormal fetal echocardiograms requiring additional follow-up, and seven mothers (5.8%) had a fetal echocardiogram suspicious for a critical congenital heart disease (CCHD). All the fetal echocardiograms suspicious for CCHD were confirmed on postnatal echocardiogram. To our knowledge, none of the normal fetal echocardiograms were found to have congenital heart disease postnatally. Conclusions: In response to the COVID-19 pandemic, we rapidly transitioned to fetal telecardiology using a variety of formats. This has reduced potential infectious exposure for pregnant mothers and minimized contact between physicians without compromising diagnostic accuracy. In our experience, the expansion of a telemedicine program requires strong initial infrastructure, prior relationships with MFM providers, and appropriate training among obstetric sonographers.

Cytokine gene functional polymorphisms and phenotypic expression as predictors of evolution from latent to clinical rheumatic heart disease.

INTRODUCTION: Inflammation associated with rheumatic heart disease (RHD) is influenced by gene polymorphisms and inflammatory cytokines. There are currently no immunologic and genetic markers to discriminate latent versus clinical patients, critical to predict disease evolution. Employing machine-learning, we searched for predictors that could discriminate latent versus clinical RHD, and eventually identify latent patients that may progress to clinical disease. METHODS: A total of 212 individuals were included, 77 with latent, 100 with clinical RHD, and 35 healthy controls. Circulating levels of 27 soluble factors were evaluated using Bio-Plex ProTM® Human Cytokine Standard 27-plex assay. Gene polymorphism analyses were performed using RT-PCR for the following genes: IL2, IL4, IL6, IL10, IL17A, TNF and IL23. RESULTS: Serum levels of all cytokines were higher in clinical as compared to latent RHD patients, and in those groups than in controls. IL-4, IL-8, IL-1RA, IL-9, CCL5 and PDGF emerged in the final multivariate model as predictive factors for clinical, compared with latent RHD. IL-4, IL-8 and IL1RA had the greater power to predict clinical RHD. In univariate analysis, polymorphisms in IL2 and IL4 were associated with clinical RHD and in the logistic analysis, IL6 (GG + CG), IL10 (CT + TT), IL2 (CA + AA) and IL4 (CC) genotypes were associated with RHD. CONCLUSION: Despite higher levels of all cytokines in clinical RHD patients, IL-4, IL-8 and IL-1RA were the best predictors of clinical disease. An association of polymorphisms in IL2, IL4, IL6 and IL10 genes and clinical RHD was observed. Gene polymorphism and phenotypic expression of IL-4 accurately discriminate latent versus clinical RHD, potentially instructing clinical management.

Impact of incorporating echocardiographic screening into a clinical prediction model to optimise utilisation of echocardiography in primary care.

INTRODUCTION: Access to public subspecialty healthcare is limited in underserved areas of Brazil, including echocardiography (echo). Long waiting lines and lack of a prioritisation system lead to diagnostic lag and may contribute to poor outcomes. We developed a prioritisation tool for use in primary care, aimed at improving resource utilisation, by predicting those at highest risk of having an abnormal echo, and thus in highest need of referral. METHODS: All patients in the existing primary care waiting list for echo were invited for participation and underwent a clinical questionnaire, simplified 7-view echo screening by non-physicians with handheld devices, and standard echo by experts. Two derivation models were developed, one including only clinical variables and a second including clinical variables and findings of major heart disease (HD) on echo screening (cut point for high/low-risk). For validation, patients were risk-classified according to the clinical score. High-risk patients and a sample of low-risk underwent standard echo. Intermediate-risk patients first had screening echo, with a standard echo if HD was suspected. Discrimination and calibration of the two models were assessed to predict HD in standard echo. RESULTS: In derivation (N = 603), clinical variables associated with HD were female gender, body mass index, Chagas disease, prior cardiac surgery, coronary disease, valve disease, hypertension and heart failure, and this model was well calibrated with C-statistic = 0.781. Performance was improved with the addition of echo screening, with C-statistic = 0.871 after cross-validation. For validation (N = 1526), 227 (14.9%) patients were classified as low risk, 1082 (70.9%) as intermediate risk and 217 (14.2%) as high risk by the clinical model. The final model with two categories had high sensitivity (99%) and negative predictive value (97%) for HD in standard echo. Model performance was good with C-statistic = 0.720. CONCLUSION: The addition of screening echo to clinical variables significantly improves the performance of a score to predict major HD.

Pulse Oximetry and Congenital Heart Disease Screening: Results of the First Pilot Study in Morocco.

Congenital heart disease (CHD) is the most common congenital malformation. Diagnosis of critical congenital heart disease (CCHD), the most severe type of congenital heart disease, in a newborn may be difficult. The addition of CCHD screening, using pulse oximetry, to clinical assessment significantly improves the rate of detection. We conducted a pilot study in Morocco on screening neonates for critical congenital heart disease. This study was conducted in the maternity ward of Mohammed VI University Hospital of Marrakesh, Morocco, and included asymptomatic newborns delivered between March 2019 and January 2020. The screening of CCHD was performed by pulse oximetry measuring the pre- and post-ductal saturation. Screening was performed on 8013/10,451 (76.7%) asymptomatic newborns. According to the algorithm, 7998 cases passed the screening test (99.82%), including one inconclusive test that was repeated an hour later and was normal. Fifteen newborns failed the screening test (0.18%): five CCHD, five false positives, and five CHD but non-critical. One false negative case was diagnosed at 2 months of age. Our results encourage us to strengthen screening for CCHD by adding pulse oximetry to the routine newborn screening panel.

Cardiac changes in pediatric cancer survivors.

Cardiac damage from chemotherapy is a known phenomenon leading to significant morbidity and mortality in the cancer surviving population, and identifying high-risk pediatric patients early is challenging. The purpose of this pilot study was to evaluate whether echo strain, cardiac MRI (CMR), and serum biomarkers are more sensitive methods for detecting cardiac toxicity than standard echo and to examine the relationship between biomarkers in patients without decreased systolic function as determined by standard echo. In this pilot study, we prospectively enrolled pediatric subjects after completion of anthracycline inclusive chemotherapy. Each subject underwent a post-treatment echocardiogram (standard with strain), serum biomarkers (N-terminal brain natriuretic peptide (NT-pro-BNP) and interleukin 1 receptor-like 1 protein (ST2)), and CMR (standard and extracellular volumes (ECVs)). We correlated the markers using Pearson correlation. We enrolled 30 subjects, 11F/19M, aged 8-21 years. Cumulative anthracycline dose (CAD) correlated with BNP (p=0.06), CMR ECV 4-chamber (p=0.05) and sagittal (p=0.01), and mitral valve E/A (p=0.02). BNP correlated with CMR ECV 4-chamber (p=0.001) and sagittal (p=0.001) and with echo average longitudinal strain (ALS) (p=0.05). This study demonstrated a significant correlation of CAD with BNP and CMR ECV. There was also a significant correlation of NT-pro-BNP with CMR ECV and ALS. Combining these parameters with standard echo has the potential to identify high-risk patients early. Further studies are needed for long-term follow-up and management in this vulnerable population.