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.).

Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation.

BACKGROUND: Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited. METHODS: We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis. RESULTS: Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted. CONCLUSIONS: Among patients with rheumatic heart disease-associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.).

Primary surgical repair of tetralogy of fallot at the Uganda Heart Institute: a ten-year review of 30day mortality and morbidity.

BACKGROUND: Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease (CHD) worldwide. It accounts for 7% of CHD cases in Uganda and leads to fatal outcomes in the long term without surgery. Surgery is often delayed in developing countries like Uganda due to limited resources. OBJECTIVE: This study aimed to determine the early surgical outcomes of patients with TOF who underwent primary intracardiac repair at the Uganda Heart Institute (UHI) and to identify factors associated. METHODOLOGY: This retrospective chart review evaluated outcomes of primary TOF repair patients at UHI from February 2012 to October 2022. Patient outcomes were assessed from surgery until 30 days post-operation. RESULTS: Out of the 104 patients who underwent primary TOF repair at UHI, records of 88 patients (84.6%) were available for review. Males accounted for 48.9% (n = 43). The median age at the time of operation was 4 years (with an interquartile range of 2.5-8.0 years), ranging from 9 months to 16 years. Genetic syndromes were present in 5/88 (5.7%). These included 2 patients with trisomy 21, 2 with Noonan's, and 1 with 22q11.2 deletion syndrome. Early postoperative outcomes for patients included: residual ventricular septal defects in 35/88 (39.8%), right ventricular dysfunction in 33/88 (37.5%), residual pulmonary regurgitation in 27/88 (30.7%), residual right ventricular outflow tract obstruction in 27/88 (30.0%), pleural effusion in 24/88 (27.3%), arrhythmias in 24/88(27.3%), post-operative infections in 23/88(26.1%) and left ventricular systolic dysfunction in 9/88 (10.2%). Out of the children who underwent surgery after one year of age, 8% (7 children) died within the first 30 days. There was a correlation between mortality and post-operative ventilation time, cardiopulmonary bypass (CPB) time, aortic cross-clamp time, preoperative oxygen saturations, RV and LV dysfunction and the operating team. CONCLUSION: The most frequent outcomes after surgery were residual ventricular septal defects and right ventricular failure. In our study, the 30-day mortality rate following TOF repair was 8%. Deceased patients had lower pre-operative oxygen levels, longer CPB and cross-clamp times, longer post-operative ventilation, RV/LV dysfunction, and were more likely operated by the local team.

Mortality and Morbidity in Adults With Rheumatic Heart Disease.

Importance: Rheumatic heart disease (RHD) remains a public health issue in low- and middle-income countries (LMICs). However, there are few large studies enrolling individuals from multiple endemic countries. Objective: To assess the risk and predictors of major patient-important clinical outcomes in patients with clinical RHD. Design, Setting, and Participants: Multicenter, hospital-based, prospective observational study including 138 sites in 24 RHD-endemic LMICs. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality, heart failure (HF) hospitalization, stroke, recurrent rheumatic fever, and infective endocarditis. This study analyzed event rates by World Bank country income groups and determined the predictors of mortality using multivariable Cox models. Results: Between August 2016 and May 2022, a total of 13 696 patients were enrolled. The mean age was 43.2 years and 72% were women. Data on vital status were available for 12 967 participants (94.7%) at the end of follow-up. Over a median duration of 3.2 years (41 478 patient-years), 1943 patients died (15% overall; 4.7% per patient-year). Most deaths were due to vascular causes (1312 [67.5%]), mainly HF or sudden cardiac death. The number of patients undergoing valve surgery (604 [4.4%]) and HF hospitalization (2% per year) was low. Strokes were infrequent (0.6% per year) and recurrent rheumatic fever was rare. Markers of severe valve disease, such as congestive HF (HR, 1.58 [95% CI, 1.50-1.87]; P < .001), pulmonary hypertension (HR, 1.52 [95% CI, 1.37-1.69]; P < .001), and atrial fibrillation (HR, 1.30 [95% CI, 1.15-1.46]; P < .001) were associated with increased mortality. Treatment with surgery (HR, 0.23 [95% CI, 0.12-0.44]; P < .001) or valvuloplasty (HR, 0.24 [95% CI, 0.06-0.95]; P = .042) were associated with lower mortality. Higher country income level was associated with lower mortality after adjustment for patient-level factors. Conclusions and Relevance: Mortality in RHD is high and is correlated with the severity of valve disease. Valve surgery and valvuloplasty were associated with substantially lower mortality. Study findings suggest a greater need to improve access to surgical and interventional care, in addition to the current approaches focused on antibiotic prophylaxis and anticoagulation.

Data-independent acquisition mass spectrometry in severe rheumatic heart disease (RHD) identifies a proteomic signature showing ongoing inflammation and effectively classifying RHD cases.

BACKGROUND: Rheumatic heart disease (RHD) remains a major source of morbidity and mortality in developing countries. A deeper insight into the pathogenetic mechanisms underlying RHD could provide opportunities for drug repurposing, guide recommendations for secondary penicillin prophylaxis, and/or inform development of near-patient diagnostics. METHODS: We performed quantitative proteomics using Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectrometry (SWATH-MS) to screen protein expression in 215 African patients with severe RHD, and 230 controls. We applied a machine learning (ML) approach to feature selection among the 366 proteins quantifiable in at least 40% of samples, using the Boruta wrapper algorithm. The case-control differences and contribution to Area Under the Receiver Operating Curve (AUC) for each of the 56 proteins identified by the Boruta algorithm were calculated by Logistic Regression adjusted for age, sex and BMI. Biological pathways and functions enriched for proteins were identified using ClueGo pathway analyses. RESULTS: Adiponectin, complement component C7 and fibulin-1, a component of heart valve matrix, were significantly higher in cases when compared with controls. Ficolin-3, a protein with calcium-independent lectin activity that activates the complement pathway, was lower in cases than controls. The top six biomarkers from the Boruta analyses conferred an AUC of 0.90 indicating excellent discriminatory capacity between RHD cases and controls. CONCLUSIONS: These results support the presence of an ongoing inflammatory response in RHD, at a time when severe valve disease has developed, and distant from previous episodes of acute rheumatic fever. This biomarker signature could have potential utility in recognizing different degrees of ongoing inflammation in RHD patients, which may, in turn, be related to prognostic severity.

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

BACKGROUND: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. METHODS: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. CONCLUSION: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.

Latent Rheumatic Heart Disease: Identifying the Children at Highest Risk of Unfavorable Outcome.

BACKGROUND: Screening echocardiography has emerged as a potentially powerful tool for early diagnosis of rheumatic heart disease (RHD). The utility of screening echocardiography hinges on the rate of RHD progression and the ability of penicillin prophylaxis to improve outcome. We report the longitudinal outcomes of a cohort of children with latent RHD and identify risk factors for unfavorable outcomes. METHODS: This was a prospective natural history study conducted under the Ugandan RHD registry. Children with latent RHD and ≥1 year of follow-up were included. All echocardiograms were re-reviewed by experts (2012 World Heart Federation criteria) for inclusion and evidence of change. Bi- and multivariable logistic regression, Kaplan-Meier analysis, and Cox proportional hazards models, as well, were developed to search for risk factors for unfavorable outcome and compare progression-free survival between those treated and not treated with penicillin. Propensity and other matching methods with sensitivity analysis were implemented for the evaluation of the penicillin effect. RESULTS: Blinded review confirmed 227 cases of latent RHD: 164 borderline and 63 definite (42 mild, 21 moderate/severe). Median age at diagnosis was 12 years and median follow-up was 2.3 years (interquartile range, 2.0-2.9). Penicillin prophylaxis was prescribed in 49.3% with overall adherence of 84.7%. Of children with moderate-to-severe definite RHD, 47.6% had echocardiographic progression (including 2 deaths), and 9.5% had echocardiographic regression. Children with mild definite and borderline RHD showed 26% and 9.8% echocardiographic progression and 45.2% and 46.3% echocardiographic improvement, respectively. Of those with mild definite RHD or borderline RHD, more advanced disease category, younger age, and morphological mitral valve features were risk factors for an unfavorable outcome. CONCLUSIONS: Latent RHD is a heterogeneous diagnosis with variable disease outcomes. Children with moderate to severe latent RHD have poor outcomes. Children with both borderline and mild definite RHD are at substantial risk of progression. Although long-term outcome remains unclear, the initial change in latent RHD may be evident during the first 1 to 2 years following diagnosis. Natural history data are inherently limited, and a randomized clinical trial is needed to definitively determine the impact of penicillin prophylaxis on the trajectory of latent RHD.

Prevalence and characteristics of primary left-sided valve disease in a cohort of 15,000 patients undergoing echocardiography studies in a tertiary hospital in Uganda.

BACKGROUND: Although rheumatic heart disease remains the leading cause of valve heart disease (VHD) in developing countries, other forms of valve disease have been over shadowed and not regarded as a public health problem. However, several facts suggest that the role of non-rheumatic VHD as a significant cardiovascular disease should be reconsidered. We aimed to assess the prevalence and characteristics of different forms of primary left sided valve diseases from a series of 15,009 echocardiographic studies. METHODS: This was a retrospective review of echocardiographic reports for studies performed between January 2012 and December 2013 (24 months) at Uganda Heart Institute. All patients with primary left-sided valve disease were classified into one of five major diagnostic categories and in each diagnostic category; patients were sub-classified into stages A-D of primary valve disease as defined by the American College of Cardiology. RESULTS: Three thousand five hundred eighty-two echocardiography reports qualified for final data analysis. The "sclerotic valve changes with normal valve function", a Stage A sub-class of "degenerative valve disease" overwhelmingly overshadowed all the other diagnostic categories in this stage. "Rheumatic Heart Disease", "Degenerative Valve Disease", "Bicuspid Aortic Valve", "Mitral Valve Prolapse" and "Endomyocardial Fibrosis" diagnostic categories accounted for 53.0%, 41.8%, 2.2%, 1.4% and 1.7% respectively in stages B-D of primary VHD. Rheumatic heart disease disproportionately affected the young, productive age groups. It was the major risk factor for infective endocarditis; and was the indication for valve surgery in 44 of 50 patients who had undergone valve replacement procedures. CONCLUSIONS: We acknowledge that rheumatic heart disease remains a leading cause of progressive and severe primary left-sided valve disease among young adults in Uganda. But we bring to light the contemporary footprints of other forms of primary valve disease that require coordinated multidisciplinary approach to research, education and clinical management to ensure improved patient outcomes.

Clinical Outcomes in 3343 Children and Adults With Rheumatic Heart Disease From 14 Low- and Middle-Income Countries: Two-Year Follow-Up of the Global Rheumatic Heart Disease Registry (the REMEDY Study).

BACKGROUND: There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease or information on their predictors. We report the 2-year follow-up of individuals with rheumatic heart disease from 14 low- and middle-income countries in Africa and Asia. METHODS: Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for 2 years to assess mortality, congestive heart failure, stroke or transient ischemic attack, recurrent acute rheumatic fever, and infective endocarditis. RESULTS: Vital status at 24 months was known for 2960 (88.5%) patients. Two-thirds were female. Although patients were young (median age, 28 years; interquartile range, 18-40), the 2-year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.80-3.11), congestive heart failure (HR, 2.16; 95% CI, 1.70-2.72), New York Heart Association functional class III/IV (HR, 1.67; 95% CI, 1.32-2.10), atrial fibrillation (HR, 1.40; 95% CI, 1.10-1.78), and older age (HR, 1.02; 95% CI, 1.01-1.02 per year increase) at enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54-0.85) and female sex (HR, 0.65; 95% CI, 0.52-0.80) were associated with lower risk of death. Two hundred and four (6.9%) patients had new congestive heart failure (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/transient ischemic attack or systemic embolism. Patients from low- and lower-middle-income countries had significantly higher age- and sex-adjusted mortality than patients from upper-middle-income countries. Valve surgery was significantly more common in upper-middle-income than in lower-middle- or low-income countries. CONCLUSIONS: Patients with clinical rheumatic heart disease have high mortality and morbidity despite being young; those from low- and lower-middle-income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and the treatment of clinical rheumatic heart disease are required to improve outcomes.

Noonan syndrome in diverse populations.

Noonan syndrome (NS) is a common genetic syndrome associated with gain of function variants in genes in the Ras/MAPK pathway. The phenotype of NS has been well characterized in populations of European descent with less attention given to other groups. In this study, individuals from diverse populations with NS were evaluated clinically and by facial analysis technology. Clinical data and images from 125 individuals with NS were obtained from 20 countries with an average age of 8 years and female composition of 46%. Individuals were grouped into categories of African descent (African), Asian, Latin American, and additional/other. Across these different population groups, NS was phenotypically similar with only 2 of 21 clinical elements showing a statistically significant difference. The most common clinical characteristics found in all population groups included widely spaced eyes and low-set ears in 80% or greater of participants, short stature in more than 70%, and pulmonary stenosis in roughly half of study individuals. Using facial analysis technology, we compared 161 Caucasian, African, Asian, and Latin American individuals with NS with 161 gender and age matched controls and found that sensitivity was equal to or greater than 94% for all groups, and specificity was equal to or greater than 90%. In summary, we present consistent clinical findings from global populations with NS and additionally demonstrate how facial analysis technology can support clinicians in making accurate NS diagnoses. This work will assist in earlier detection and in increasing recognition of NS throughout the world.

Prevalence of group a streptococcus pharyngeal carriage and clinical manifestations in school children aged 5-15 yrs in Wakiso District, Uganda.

BACKGROUND: Beta-hemolytic streptococci carrier rates in children living in low-income countries are high ranging from 10 to 50%. Although most of these children are asymptomatic, they are a reservoir and pose a risk of transmission. The aim of this study was to determine the prevalence of group a streptococcus pharyngeal carriage and clinical manifestations in school going children in Wakiso district, Uganda. METHODS: A cross sectional study targeting children age 5-15 years in primary schools in one sub-county of Wakiso district was carried out. Three hundred and sixty-six children from five primary schools were enrolled and evaluated for group a streptococcus (GAS) carriage. A semi-structured questionnaire was used to collect data that included social demographics, school environment and clinical findings. For every enrolled child a throat swab was taken and cultured for GAS and blood was drawn for anti-streptolysin-O titres. Analysis of data was done using STATA. RESULTS: The prevalence of GAS carriage was 16%. The children with GAS positive cultures were mainly females. The factor associated with GAS carriage was the school location, with peri-urban schools more likely to have children with GAS compared to rural schools; AOR 2.48 (95% CI: 1.01 - 6.11), P = 0.049. There was no significant difference between the characteristic of children with GAS positive verses GAS negative throat swab cultures. CONCLUSION: There is a high prevalence of GAS pharyngeal carriage among children aged 5-15 years attending primary schools in Wakiso District, Uganda.

Rheumatic heart disease in Uganda: predictors of morbidity and mortality one year after presentation.

BACKGROUND: Rheumatic heart disease (RHD), the long-term consequence of rheumatic fever, accounts for most cardiovascular morbidity and mortality among young adults in developing countries. However, data on contemporary outcomes from resource constrained areas are limited. METHODS: A prospective cohort study of participants aged 5-60 years with established RHD was conducted in Kampala, Uganda, in which clinical exam, echocardiography, electrocardiography (ECG), and laboratory evaluation were done every 3 months and every 4-week benzathine penicillin prophylaxis was prescribed. Participants were followed up for 12 months and outcomes and predictors of morbidity and mortality were assessed using Kaplan Meier curves and Cox proportional hazards models. RESULTS: Of 449 subjects, 66.8% (300/449) were females, median age was 30 (interquartile range 20). 73.7% (331/449) had atleast one follow up visit. Among these, 35% (116/331) developed decompensated heart failure and, 63.7% (211/331) developed atrial fibrillation. Heart failure was associated with poor penicillin adherence (OR = 3.3, CI 2-5.4, p = 0.001), and left ventricular end diastolic diameter greater than 55 mm (OR = 3.16, CI 1.73-5.76, p = 0.001). Atrial fibrillation was associated with left atrial diameter >40 mm (OR = 7.5, CI 2.4-9.8, p = 0.001). There were 59 deaths with a 1-year mortality rate of 17.8%. Most deaths occurred within the first three months of presentation. Subjects whose average adherence to benzathine penicillin was <80% had significantly greater mortality (31% vs. 9%, log rank p < 0.001). In multivariate analysis, the risk of death among those with poor penicillin adherence was 3.81 times higher than those with better adherence (HR = 3.81, CI 1.92-7.63, p = 0.001). Other predictors of 1 year mortality included heart failure (HR 8.36, CI 3.28-21.31, p = 0.001) and left ventricular end diastolic diameter greater than 55 mm (HR = 1.93, CI 1.07-3.49, p = 0.02). CONCLUSION: In this study of RHD in Uganda, morbidity and mortality within 1 year of presentation were higher than in recently published from other low and middle income countries. Suboptimal adherence to benzathine penicillin injections was associated with incident heart failure and mortality over 1 year. Future studies should test interventions to improve adherence among patients with advanced disease who are at the highest risk of mortality.

Wasting, underweight and stunting among children with congenital heart disease presenting at Mulago hospital, Uganda.

BACKGROUND: Children with congenital heart disease are at increased risk of malnutrition. The aim of this study was to describe the prevalence of wasting, underweight and stunting among children with congenital heart disease attending Mulago National Referral Hospital, Uganda. METHODS: A cross-sectional study among 194 children aged 0-15 years was conducted between August 2013 and March 2014. Anthropometric measurements and clinical assessments were carried out on all children. Anthropometric z-scores based on WHO 2007 reference ranges were generated for each child. Weight-for-height z-scores were generated for children 0-5 years, weight-for-age z-scores for children 0-10 years, and height-for-age and BMI-for-age z-scores for all children. Risk factors associated with malnutrition were determined by Poisson regression. RESULTS: One hundred and forty five (74.7%) children were aged 0-5 years; and 111 of 194 (57.2%) were female. Forty five of 145 (31.5%) children aged 0-5 years were wasted; 77 of 181 (42.5%) children aged 0-10 years were underweight; 88 of 194 (45.4%) children were stunted; and 53 of 194 (27.3%) children were thin (BMI for age z score < -2). Moderate to severe anaemia (RR 1.11, 95% CI: 1.01-1.22) and moderate to severe heart failure (RR 1.24, 95% CI: 1.13-1.36) were associated with wasting and underweight respectively. Stunting was associated with moderate to severe heart failure (RR 1.11, 95% CI: 1.01-1.21) while thinness was associated with moderate to severe heart failure (RR 1.12, 95% CI: 1.04-1.21) and moderate to severe anaemia (RR 1.15, 95% CI: 1.06-1.25). CONCLUSION: Malnutrition is common in children with congenital heart disease, and is associated with anaemia and heart failure. There is need to integrate strategies to identify and manage malnutrition during the care of children with congenital heart disease.

Cardiac strain findings in children with latent rheumatic heart disease detected by echocardiographic screening.

BACKGROUND: Identification of patients with latent rheumatic heart disease by echocardiography presents a unique opportunity to prevent disease progression. Myocardial strain is a more sensitive indicator of cardiac performance than traditional measures of systolic function. OBJECTIVE: The objective of this study was to test the hypothesis that abnormalities in myocardial strain may be present in children with latent rheumatic heart disease. METHODS: Standard echocardiography images with electrocardiogram gating were obtained from Ugandan children found to have latent rheumatic heart disease as well as control subjects. Traditional echocardiography measures of systolic function were obtained, and offline global longitudinal strain analysis was performed. Comparison between groups was performed using strain as a continuous (Mann-Whitney U-test) and categorical (cut-off 5th percentile for age) variable. RESULTS: Our study included 14 subjects with definite rheumatic heart disease, 13 with borderline rheumatic heart disease, and 112 control subjects. None of the subjects had abnormal left ventricular size or ejection fraction. Global longitudinal strain was lower than the 5th percentile in 44% of the subjects with any rheumatic heart disease (p=0.002 versus controls) and 57% of the subjects with definite rheumatic heart disease (p=0.03). The mean absolute strain values were significantly lower when comparing subjects with any rheumatic heart disease with controls (20.4±3.95 versus 22.4±4.35, p=0.025) and subjects with definite rheumatic heart disease with controls (19.9±4.25 versus 22.4±4.35, p=0.033). CONCLUSION: Global longitudinal strain is decreased in subjects with rheumatic heart disease in the absence of abnormal systolic function. Larger studies with longer-term follow-up are required to determine whether there is a role for strain to help better understand the pathophysiology of latent rheumatic heart disease.

Child and teacher acceptability of school-based echocardiographic screening for rheumatic heart disease in Uganda.

Introduction Rheumatic heart disease causes substantial morbidity in children in low-income countries. School-based echocardiographic screening has been suggested as a means to identify children with latent disease; however, little is known about the experience of children and teachers participating in screenings. The aim of our study was to assess students' and teachers' experience of school-based echocardiographic screening and identify areas for improvement. Materials and methods A school-based echocardiographic screening programme was conducted in five schools in Northern Uganda in 2013. After 8 months, an age- and gender-stratified population that included 5% of the participating students and teachers completed a questionnaire via an in-person interview. Responses were reviewed by question and coded to identify key themes. RESULTS: A total of 255 students (mean 10.7 years; 48% male) and 35 teachers participated in our study. In total, 95% of the students and 100% of the teachers were happy to have participated in the screening; however, students reported feeling scared (35%) and nervous (48%) during the screening process. Programmatic strengths included the following: knowing one's health status, opportunity to receive treatment, and staff interactions. Although 43% of the patients did not suggest a change with open-ended questioning, concerns regarding privacy, fear of the screening process, and a desire to include others in the community were noted. Discussion School-based echocardiographic rheumatic heart disease screening was well received by students and teachers. Future programmes would likely benefit from improved pre-screening education regarding the screening process and diagnosis of rheumatic heart disease. Furthermore, education of teachers and students could improve screening perception and establish realistic expectations regarding the scope of screening.

The Impact of Echocardiographic Screening for Rheumatic Heart Disease on Patient Quality of Life.

OBJECTIVE: To assess the impact of rheumatic heart disease (RHD) on child-reported health-related quality of life (HRQOL) in the context of a Ugandan school-based echocardiographic screening program. Echocardiography-based screening has emerged as a tool for the early detection of RHD, but little is known about its impact on those screened. STUDY DESIGN: Participants included 358 children from Gulu and 28 children from Kampala Uganda. The Pediatric Quality of Life Inventory Version 4.0 was used to assess HRQOL in 4 groups of children: Gulu prescreen, Gulu postscreen, Gulu previously linked to care, and Kampala previously linked to care. Children in the pre- and postscreen groups were selected from a single school before and after screening occurred and matched by age and sex. Children previously linked to care were recruited from previous screening studies. RESULTS: When the echocardiogram was normal, there was no difference in HRQOL in the prescreen and postscreen groups. In the postscreen group, identification of latent RHD resulted in lower physical (75.3 vs 68.3, P = .03) and emotional (71.7 vs 63.4, P < .01) HRQOL, despite a lack of symptoms. The Kampala group had longer linkage to care (42 months vs 6 months, P < .01) and demonstrated greater HRQOL scores compared with the Gulu-linked group (70.7 vs 77.8, P < .01) and the combined Gulu cohort (77.8 vs 69.4, P = .02). CONCLUSIONS: Echocardiography-based screening for RHD does not diminish HRQOL in Ugandan children; rather, a diminished HRQOL score may be associated with being identified as RHD positive. Further investigation is needed to understand if longer linkage to care may ultimately normalize or improve HRQOL.

Prevalence of arrhythmias among children below 15 years of age with congenital heart diseases attending Mulago National Referral Hospital, Uganda.

BACKGROUND: In Uganda, few children with congenital heart diseases (CHD) benefit from early corrective cardiac surgery. These children are at high risk of developing heart failure and electrolyte imbalances; factors which increase their risk of developing arrhythmias. This study aimed to determine the prevalence and factors associated with arrhythmias among children with congenital heart diseases receiving care at Mulago Hospital. METHODS: This was a cross-sectional study carried out from August 2013 to March 2014 at Mulago Hospital. Children were consecutively enrolled into the study. Standard 12-lead electrocardiograms (ECGs) were performed on 194 children with CHD (age range 10 days-15 years). Data was analysed using SPSS 16.0. RESULTS: Out of 194 children studied, 53/194 (27.3 %, 95 % CI 21.0 - 33.6) children had arrhythmias. Of the CHD children, 44/194 (22.7 %, 95 % CI 16.8 - 28.6) had first degree AV block while 9/194 (4.6 %, 95 % CI 1.7 - 7.6) children had either ectopic atrial rhythm, premature atrial contractions, junctional rhythm, complete atrioventricular (AV) dissociation or premature ventricular contractions. Children using digoxin were more likely to have first degree AV block (OR 3.75, 95 % CI 1.60-8.86) while those aged 5 years and below were less likely to have first degree AV block (OR 0.16, 95 % CI 0.07-0.37). CONCLUSION: Arrhythmias are common among children with CHD receiving care from Mulago Hospital. These are associated with digoxin use, child's age and electrolyte imbalances; factors which can easily be assessed, managed and where possible modified in these children during their care.

Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study).

AIMS: Rheumatic heart disease (RHD) accounts for over a million premature deaths annually; however, there is little contemporary information on presentation, complications, and treatment. METHODS AND RESULTS: This prospective registry enrolled 3343 patients (median age 28 years, 66.2% female) presenting with RHD at 25 hospitals in 12 African countries, India, and Yemen between January 2010 and November 2012. The majority (63.9%) had moderate-to-severe multivalvular disease complicated by congestive heart failure (33.4%), pulmonary hypertension (28.8%), atrial fibrillation (AF) (21.8%), stroke (7.1%), infective endocarditis (4%), and major bleeding (2.7%). One-quarter of adults and 5.3% of children had decreased left ventricular (LV) systolic function; 23% of adults and 14.1% of children had dilated LVs. Fifty-five percent (n = 1761) of patients were on secondary antibiotic prophylaxis. Oral anti-coagulants were prescribed in 69.5% (n = 946) of patients with mechanical valves (n = 501), AF (n = 397), and high-risk mitral stenosis in sinus rhythm (n = 48). However, only 28.3% (n = 269) had a therapeutic international normalized ratio. Among 1825 women of childbearing age (12-51 years), only 3.6% (n = 65) were on contraception. The utilization of valvuloplasty and valve surgery was higher in upper-middle compared with lower-income countries. CONCLUSION: Rheumatic heart disease patients were young, predominantly female, and had high prevalence of major cardiovascular complications. There is suboptimal utilization of secondary antibiotic prophylaxis, oral anti-coagulation, and contraception, and variations in the use of percutaneous and surgical interventions by country income level.