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.

Health Related Quality of Life of Ugandan Children Following Valve Replacement Surgery for Rheumatic Heart Disease.

Background: Valve replacement surgery (VRS) improves clinical outcomes in patients with severe rheumatic heart disease (RHD). However, lifelong anticoagulation and frequent monitoring are required, which potentially impacts health-related quality of life (HRQoL). In this study, we assessed the HRQoL of people with RHD in Uganda following VRS. Methods: This was a hospital-based, cross-sectional study conducted between March and August 2021. Eligible participants were individuals who had VRS before the age of 18 years. The Pediatric Quality of Life Inventory-Cardiac Module (PedsQL-Cardiac module) was used to evaluate HRQoL. A total mean score of ≥ 80% was considered as optimal HRQoL. Results: Of the 83 eligible participants, 52 (60.5%) were female, with a median age of 18 (interquartile range: 14-22) years. Most participants had NYHA I functional status (n = 79, 92%). Most (n = 73, 92.4%) surgeries were performed outside of Uganda, and 61 (72.6%) were single mechanical valve replacement. Almost half (n = 45, 54%) expressed no concern about being on life-long warfarin therapy. However, 24 (29.3%) feared bleeding. The optimal mean score of cardiac-specific HRQoL was achieved in 50 (60.2%) of participants. Factors associated with optimal HRQoL were body mass index (BMI) (adjusted odds ratio (aOR), 1.2, 95% Confidence Interval: 1.1-1.3, p = 0.006), being afraid of bleeding or bruising (aOR: 1.5, 95% CI: 1.21-2.47, p = 0.004), acceptance of having an artificial valve (aOR: 2.7, 95% CI; 1.64-3.81, p < 0.001). Conclusion: HRQoL was optimal in about three in five participants following VRS. Increasing BMI and acceptance of artificial valve were significantly associated with optimal HRQoL.

Rationale, Design, and the Baseline Characteristics of the RHDGen (The Genetics of Rheumatic Heart Disease) Network Study†.

BACKGROUND: The genetics of rheumatic heart disease (RHDGen) Network was developed to assist the discovery and validation of genetic variations and biomarkers of risk for rheumatic heart disease (RHD) in continental Africans, as a part of the global fight to control and eradicate rheumatic fever/RHD. Thus, we describe the rationale and design of the RHDGen study, comprising participants from 8 African countries. METHODS: RHDGen screened potential participants using echocardiography, thereafter enrolling RHD cases and ethnically-matched controls for whom case characteristics were documented. Biological samples were collected for conducting genetic analyses, including a discovery case-control genome-wide association study (GWAS) and a replication trio family study. Additional biological samples were also collected, and processed, for the measurement of biomarker analytes and the biomarker analyses are underway. RESULTS: Participants were enrolled into RHDGen between December 2012 and March 2018. For GWAS, 2548 RHD cases and 2261 controls (3301 women [69%]; mean age [SD], 37 [16.3] years) were available. RHD cases were predominantly Black (66%), Admixed (24%), and other ethnicities (10%). Among RHD cases, 34% were asymptomatic, 26% had prior valve surgery, and 23% had atrial fibrillation. The trio family replication arm included 116 RHD trio probands and 232 parents. CONCLUSIONS: RHDGen presents a rare opportunity to identify relevant patterns of genetic factors and biomarkers in Africans that may be associated with differential RHD risk. Furthermore, the RHDGen Network provides a platform for further work on fully elucidating the causes and mechanisms associated with RHD susceptibility and development.

Positive impact of training rural health workers in identification and prevention of acute rheumatic fever in eastern Uganda.

BACKGROUND: Diagnosis of acute rheumatic fever (ARF) is mainly clinical. Delayed or missed diagnosis and failure to administer appropriate and timely treatment of ARF leads to rheumatic heart disease (RHD), which could necessitate expensive treatments such as open-heart surgery. Implementation of preventative guidelines depends on availability of trained healthcare workers. As part of the routine support supervision, the Uganda Heart Institute sent out a team to rural eastern Uganda to evaluate health workers' knowledge level regarding management of ARF. METHODS: Health workers from selected health facilities in Tororo district, eastern Uganda, were assessed for their knowledge on the clinical features and role of benzathine penicillin G (BPG) in the treatment and prevention of ARF recurrence. Using the RHD Action Needs assessment tool, we generated and administered a pre-test, then conducted training and re-administered a post-test. Eight months later, health workers were again assessed for knowledge retention and change in practices. Statistical analysis was done using Stata version 15. RESULTS: During the initial phase, 34 of the 109 (31%) health workers passed the pre-test, indicating familiarity with clinical features of ARF. The level of knowledge of BPG use in ARF was very poor in all the health units [25/109 (22.6%)] but improved after training to 80%, as shown by the chi-squared test ( χ2 = 0.000). However, retention of this knowledge waned after eight months and was not significantly different compared to pre-training (χ2 ≥ 0.2). CONCLUSIONS: A critical knowledge gap is evident among health workers, both in awareness and treatment of ARF, and calls for repetitive training as a priority strategy in prevention.

Makerere University-Uganda Heart Institute collaborative cardiovascular disease training and research since 1988.

Background: Makerere University College of Health Sciences has been collaborating with the Uganda Heart Institute to build capacity for research, training and clinical care in cardiovascular medicine for the last 34 years to appropriately respond to rising societal needs for advanced cardiovascular care which was lacking before this period. Aim: To describe the major milestones in the MakCHS-UHI cardiovascular training collaboration and chart way for future collaborations. Method: This short communication highlights some of the salient features and important milestones in the collaboration journey of the two institutions. Conclusion: Clinical centres of excellence in specialised fields of health care, such as the Uganda Heart Institute for Cardiology, provide a conducive academic environment for MakCHS clinical scientists to provide high quality evidence-based care to meet societal needs.

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.).

Trends in Annual Incidence Rates of Newly Diagnosed Endomyocardial Fibrosis Cases at the Uganda Heart Institute: A 14-Year Review.

Background: First described in Uganda over seven decades ago, Endomyocardial fibrosis (EMF) is a rare form of restrictive cardiomyopathy found in the tropics. EMF occurs mainly in two phenotypes; biventricular involvement and right ventricular (RV) form. Previously endemic in several countries, there are reports suggesting that the disease is on the decline. Objectives: To describe trends in annual incidence rates of newly diagnosed EMF cases at the Uganda Heart Institute (UHI). Methods: This was a retrospective chart review of all newly diagnosed EMF cases at UHI from January 2007 to December 2020. Cases were divided into two groups A (2007-2013) and B (2014-2020). Results: A total of 155 cases were diagnosed during the period (Group A, n = 124; Group B, n = 31). There were no significant differences between the two groups A and B regarding median age at diagnosis (14 vs. 12 years, p = 0.0940), gender (48.4% female vs. 35.5%, p = 0.1987), and EMF type (66.9% RV EMF vs. 71.0%, p = 0.6634), respectively. The presence of complications such as intracardiac thrombus (5.6 vs. 32.2%, p = 0.0002) and pericardial effusion (57.3% vs. 80.6, p = 0.0172) were more frequent in group B than A, respectively. Pulmonary hypertension (PHT) was predominantly seen in cases with biventricular EMF compared to those with RV EMF (26 vs. 3.8%, p = 0.0001). The number of new cases diagnosed per year remained largely stable in the period 2007-2011, ranging 14-21 per year, peaked in 2012 (26 new cases), and thereafter declined from 10 cases seen in 2013 to 1-5 cases seen per year in the period 2017-2020. Similarly, the annual incidence rates of new EMF diagnosis remained relatively stable in the period 2007-2012, ranging between 22.7 and 29.7 per 10,000 patients seen in the echo labs, and then dramatically declined after 2012 to range between 1.0 and 4.5 new cases per 10,000 patients in the period between 2017 and 2020. Conclusion: There has been a steady decline in the number of new cases of EMF seen at the UHI. However, there were no significant differences in the gender, age at diagnosis and EMF subtype of cases during the period under review. Complication rates were more frequent in the later cohort.

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.

Clinical outcomes of children with rheumatic heart disease.

OBJECTIVE: To evaluate the long-term clinical outcomes of children with rheumatic heart disease (RHD) in Uganda, and determine characteristics that predict adverse outcomes. METHODS: This retrospective cohort study evaluated the risk of death in Ugandan children with clinical RHD from 2010 to 2018; enrolling children aged 5-18 years old from an existing registry. Demographic data and clinical data (baseline complications, RHD severity, cardiac interventions) were collected. The primary outcome was survival. Univariable and multivariable hazard ratios (HR) were obtained from Cox proportional hazards regression. Survival probabilities were developed using Kaplan-Meier curves; log-rank tests compared survival based on cardiac interventions, disease severity and time of enrolment. RESULTS: 612 cases met inclusion criteria; median age 12.8 years (IQR 5.3), 37% were male. Thirty-one per cent (187 of 612) died during the study period; median time to death 7.8 months (IQR 18.3). In univariable analysis, older age (HR 1.26, 95% CI=1.0 to 1.58), presence of baseline complications (HR 2.06, 95% CI=1.53 to 2.78) and severe RHD (HR 5.21, 95% CI=2.15 to 12.65) were associated with mortality. Cardiac intervention was associated with a lower risk of mortality (HR 0.06, 95% CI=0.02 to 0.24). In multivariable models, baseline complications (HR 1.78, 95% CI=1.31 to 2.41), severe RHD (HR 4.58, 95% CI=1.87 to 11.23) and having an intervention (HR 0.05, 95% CI=0.01 to 0.21) remained statistically significant. Kaplan-Meier survival curves demonstrated >25% mortality in the first 30 months, with significant differences in mortality based on intervention status and severity of disease. CONCLUSIONS: The mortality rate of children with clinical RHD in Uganda exceeds 30%, over an 8-year time frame, despite in-country access to cardiac interventions. Children at highest risk were those with cardiac complications at baseline and severe RHD.

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.).

Establishment of a cardiac telehealth program to support cardiovascular diagnosis and care in a remote, resource-poor setting in Uganda.

INTRODUCTION: To address workforce shortages and expand access to care, we developed a telemedicine program incorporating existing infrastructure for delivery of cardiovascular care in Gulu, Northern Uganda. Our study had three objectives: 1) assess feasibility and clinical impact 2) evaluate patient/parent satisfaction and 3) estimate costs. METHODS: All cardiology clinic visits during a two-year study period were included. All patients received an electrocardiogram and echocardiogram performed by a local nurse in Gulu which were stored and transmitted to the Uganda Heart Institute in the capital of Kampala for remote consultation by a cardiologist. Results were relayed to patients/families following cardiologist interpretation. The following telemedicine process was utilized: 1) clinical intake by nurse in Gulu; 2) ECG and echocardiography acquisition in Gulu; 3) echocardiography transmission to the Uganda Heart Institute in Kampala, Uganda; 4) remote telemedicine consultation by cardiologists in Kampala; and 5) communication of results to patients/families in Gulu. Clinical care and technical aspects were tracked. Diagnoses and recommendations were analyzed by age groups (0-5 years, 6-21 years, 22-50 years and > 50 years). A mixed methods approach involving interviews and surveys was used to assess patient satisfaction. Healthcare sector costs of telemedicine-based cardiovascular care were estimated using time-driven activity-based costing. RESULTS: Normal studies made up 47%, 55%, 76% and 45% of 1,324 patients in the four age groups from youngest to oldest. Valvular heart disease (predominantly rheumatic heart disease) was the most common diagnosis in the older three age groups. Medications were prescribed to 31%, 31%, 24%, and 48% of patients in the four age groups. The median time for consultation was 7 days. A thematic analysis of focus group transcripts displayed an overall acceptance and appreciation for telemedicine, citing cost- and time-saving benefits. The cost of telemedicine was $29.48/visit. CONCLUSIONS: Our data show that transmission and interpretation of echocardiograms from a remote clinic in northern Uganda is feasible, serves a population with a high burden of heart disease, has a significant impact on patient care, is favorably received by patients, and can be delivered at low cost. Further study is needed to better assess the impact relative to existing standards of care and cost effectiveness.

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.

Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals: Findings From the RHDGen Study.

Importance: Rheumatic heart disease (RHD), a sequela of rheumatic fever characterized by permanent heart valve damage, is the leading cause of cardiac surgery in Africa. However, its pathophysiologic characteristics and genetics are poorly understood. Understanding genetic susceptibility may aid in prevention, control, and interventions to eliminate RHD. Objective: To identify common genetic loci associated with RHD susceptibility in Black African individuals. Design, Setting, and Participants: This multicenter case-control genome-wide association study (GWAS), the Genetics of Rheumatic Heart Disease, examined more than 7 million genotyped and imputed single-nucleotide variations. The 4809 GWAS participants and 116 independent trio families were enrolled from 8 African countries between December 31, 2012, and March 31, 2018. All GWAS participants and trio probands were screened by use of echocardiography. Data analyses took place from May 15, 2017, until March 14, 2021. Main Outcomes and Measures: Genetic associations with RHD. Results: This study included 4809 African participants (2548 RHD cases and 2261 controls; 3301 women [69%]; mean [SD] age, 36.5 [16.3] years). The GWAS identified a single RHD risk locus, 11q24.1 (rs1219406 [odds ratio, 1.65; 95% CI, 1.48-1.82; P = 4.36 × 10-8]), which reached genome-wide significance in Black African individuals. Our meta-analysis of Black (n = 3179) and admixed (n = 1055) African individuals revealed several suggestive loci. The study also replicated a previously reported association in Pacific Islander individuals (rs11846409) at the immunoglobulin heavy chain locus, in the meta-analysis of Black and admixed African individuals (odds ratio, 1.16; 95% CI, 1.06-1.27; P = 1.19 × 10-3). The HLA (rs9272622) associations reported in Aboriginal Australian individuals could not be replicated. In support of the known polygenic architecture for RHD, overtransmission of a polygenic risk score from unaffected parents to affected probands was observed (polygenic transmission disequilibrium testing mean [SE], 0.27 [0.16] SDs; P = .04996), and the chip-based heritability was estimated to be high at 0.49 (SE = 0.12; P = 3.28 × 10-5) in Black African individuals. Conclusions and Relevance: This study revealed a novel candidate susceptibility locus exclusive to Black African individuals and an important heritable component to RHD susceptibility in African individuals.

Starting and Operating a Public Cardiac Catheterization Laboratory in a Low Resource Setting: The Eight-Year Story of the Uganda Heart Institute Catheter Laboratory.

Background: Low- and-middle-income-countries (LMICs) currently bear 80% of the world's cardiovascular disease (CVD) mortality burden. The same countries are underequipped to handle the disease burden due to critical shortage of resources. Functional cardiac catheterization laboratories (cath labs) are central in the diagnosis and management of CVDs. Yet, most LMICs, including Uganda, fall remarkably below the minimum recommended standards of cath lab:population ratio due to a host of factors including the start-up and recurring costs. Objectives: To review the performance, challenges and solutions employed, lessons learned, and projections for the future for a single cath lab that has been serving the Ugandan population of 40 million people in the past eight years. Methods: A retrospective review of the Uganda Heart Institute cath lab clinical database from 15 February 2012 to 31 December 2019 was performed. Results: In the initial two years, this cath lab was dependent on skills transfer camps by visiting expert teams, but currently, Ugandan resident specialists independently operate this lab. 3,542 adult and pediatric procedures were conducted in 8 years, including coronary angiograms and percutaneous coronary interventions, device implantations, valvuloplasties, and cardiac defect closures, among others. There was a consistent expansion of the spectrum of procedures conducted in this cath lab each year. The initial lack of technical expertise and sourcing for equipment, as well as the continual need for sundries present(ed) major roadblocks. Government support and leveraging existing multi-level collaborations has provided a platform for several solutions. Sustainability of cath lab services remains a significant challenge especially in relation to the high cost of sundries and other consumables amidst a limited budget. Conclusion: A practical example of how centers in LMIC can set up and sustain a public cardiac catheterization laboratory is presented. Government support, research, and training collaborations, if present, become invaluable leverage opportunities.

Examining the Ugandan health system's readiness to deliver rheumatic heart disease-related services.

BACKGROUND: In 2018, the World Health Assembly mandated Member States to take action on rheumatic heart disease (RHD), which persists in countries with weak health systems. We conducted an assessment of the current state of RHD-related healthcare in Uganda. METHODOLOGY/PRINCIPAL FINDINGS: This was a mixed-methods, deductive simultaneous design study conducted in four districts of Uganda. Using census sampling, we surveyed health facilities in each district using an RHD survey instrument that was modeled after the WHO SARA tool. We interviewed health workers with experience managing RHD, purposively sampling to ensure a range of qualification and geographic variation. Our final sample included 402 facilities and 36 health workers. We found major gaps in knowledge of clinical guidelines and availability of diagnostic tests. Antibiotics used in RHD prevention were widely available, but cardiovascular medications were scarce. Higher levels of service readiness were found among facilities in the western region (Mbarara district) and private facilities. Level III health centers were the most prepared for delivering secondary prevention. Health worker interviews revealed that limited awareness of RHD at the district level, lack of diagnostic tests and case management registries, and absence of clearly articulated RHD policies and budget prioritization were the main barriers to providing RHD-related healthcare. CONCLUSIONS/SIGNIFICANCE: Uganda's readiness to implement the World Health Assembly RHD Resolution is low. The forthcoming national RHD strategy must focus on decentralizing RHD diagnosis and prevention to the district level, emphasizing specialized training of the primary healthcare workforce and strengthening supply chains of diagnostics and essential medicines.

Pattern of congenital heart disease among children presenting to the Uganda Heart Institute, Mulago Hospital: a 7-year review.

BACKGROUND: Congenital heart disease (CHD) is the most common congenital anomaly in children. Over half of the deaths due to CHD occur in the neonatal period. Most children with unrepaired complex heart lesions do not live to celebrate their first birthday. We describe the spectrum of congenital heart disease in Uganda. METHODS: We retrospectively reviewed the data of children with CHD who presented to the Uganda Heart Institute (UHI), Mulago Hospital Complex from 2007 to 2014. RESULTS: A total of 4621 children were seen at the UHI during the study period. Of these, 3526 (76.3%) had CHD; 1941(55%) were females. Isolated ventricular septal defect (VSD) was the most common CHD seen in 923 (27.2%) children followed by Patent ductus arteriosus (PDA) 760 (22%) and atrial septal defects (ASD) 332 (9.4%). Tetralogy of Fallot (TOF) and Truncus arteriosus were the most common cyanotic heart defects (7% and 5% respectively). Dysmorphic features were diagnosed in 185 children, of which 61 underwent genetic testing (Down syndrome=24, 22q11.2 deletion syndrome n=10). Children with confirmed 22q11.2 deletion had conotruncal abnormalities. CONCLUSION: Isolated VSD and Tetralogy of Fallot are the most common acyanotic and cyanotic congenital heart defects. We report an unusually high occurrence of Truncus arteriosus.

Active Case Finding for Rheumatic Fever in an Endemic Country.

Background Despite the high burden of rheumatic heart disease in sub-Saharan Africa, diagnosis with acute rheumatic fever (ARF) is exceedingly rare. Here, we report the results of the first prospective epidemiologic survey to diagnose and characterize ARF at the community level in Africa. Methods and Results A cross-sectional study was conducted in Lira, Uganda, to inform the design of a broader epidemiologic survey. Key messages were distributed in the community, and children aged 3 to 17 years were included if they had either (1) fever and joint pain, (2) suspicion of carditis, or (3) suspicion of chorea, with ARF diagnoses made by the 2015 Jones Criteria. Over 6 months, 201 children met criteria for participation, with a median age of 11 years (interquartile range, 6.5) and 103 (51%) female. At final diagnosis, 51 children (25%) had definite ARF, 11 (6%) had possible ARF, 2 (1%) had rheumatic heart disease without evidence of ARF, 78 (39%) had a known alternative diagnosis (10 influenza, 62 malaria, 2 sickle cell crises, 2 typhoid fever, 2 congenital heart disease), and 59 (30%) had an unknown alternative diagnosis. Conclusions ARF persists within rheumatic heart disease-endemic communities in Africa, despite the low rates reported in the literature. Early data collection has enabled refinement of our study design to best capture the incidence of ARF and to answer important questions on community sensitization, healthcare worker and teacher education, and simplified diagnostics for low-resource areas. This study also generated data to support further exploration of the relationship between malaria and ARF diagnosis in rheumatic heart disease/malaria-endemic countries.

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.