Agreement between Handheld and Standard Echocardiography for Diagnosis of Latent Rheumatic Heart Disease in Brazilian Schoolchildren from High-Prevalence Settings (Agreement between Screening and Standard Echo for RHD).

Introduction: Handheld echocardiography (echo) is the tool of choice for rheumatic heart disease (RHD) screening. We aimed to assess the agreement between screening and standard echo for latent RHD diagnosis in schoolchildren from an endemic setting. Methods: Over 14 months, 3 nonphysicians used handheld machines and the 2012 WHF Criteria to determine RHD prevalence in consented schoolchildren from Brazilian low-income public schools. Studies were interpreted by telemedicine by 3 experts (Brazil, US). RHD-positive children (borderline/definite) and those with congenital heart disease (CHD) were referred for standard echo, acquired and interpreted by a cardiologist. Agreement between screening and standard echo, by WHF subgroups, was assessed. Results: 1390 students were screened in 6 schools, with 110 (7.9%, 95% CI 6.5-9.5) being screen positive (14 ± 2 years, 72% women). Among 16 cases initially diagnosed as definite RHD, 11 (69%) were confirmed, 4 (25%) reclassified to borderline, and 1 to normal. Among 79 cases flagged as borderline RHD, 19 (24%) were confirmed, 50 (63%) reclassified to normal, 8 (10%) reclassified as definite RHD, and 2 had mild CHD. Considering the 4 diagnostic categories, kappa was 0.18. In patients with borderline RHD reclassified to non-RHD, the most frequent WHF criterion was B (isolated mitral regurgitation, 64%), followed by A (2 mitral valve morphological features, 31%). In 1 patient with definite RHD reclassified to normal, the WHF criterion was D (borderline RHD in aortic and mitral valves). After standard echo, RHD prevalence was 3.2% (95% CI 2.3-4.2). Conclusions: Although practical, RHD screening with handheld devices tends to overestimate prevalence.

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.

Bedside echocardiography to predict mortality of COVID-19 patients beyond clinical data: Data from the PROVAR-COVID study.

INTRODUCTION: Cardiac involvement seems to impact prognosis of COVID-19, being more frequent in critically ill patients. We aimed to assess the prognostic value of right ventricular (RV) and left ventricular (LV) dysfunction, evaluated by bedside echocardiography (echo), in patients hospitalized with COVID-19. METHODS: Patients admitted in 2 reference hospitals in Brazil from Jul to Sept/2020 with confirmed COVID-19 and moderate/severe presentations underwent clinical and laboratory evaluation, and focused bedside echo (GE Vivid-IQ), at the earliest convenience, with remote interpretation. The association between demographics, clinical comorbidities and echo variables with all-cause hospital mortality was assessed, and factors significant at p<0.10 were put into multivariable models. RESULTS: Total 163 patients were enrolled, 59% were men, mean age 64±16 years, and 107 (66%) were admitted to intensive care. Comorbidities were present in 144 (88%) patients: hypertension 115 (71%), diabetes 61 (37%) and heart failure 22 (14%). In-hospital mortality was 34% (N=56). In univariate analysis, echo variables significantly associated with death were: LV ejection fraction (LVEF, OR=0.94), RV fractional area change (OR=0.96), tricuspid annular plane systolic excursion (TAPSE, OR=0.83) and RV dysfunction (OR=5.3). In multivariate analysis, after adjustment for clinical and demographic variables, independent predictors of mortality were age≥63 years (OR=5.53, 95%CI 1.52-20.17), LVEF<64% (OR=7.37, 95%CI 2.10-25.94) and TAPSE<18.5 mm (OR=9.43, 95% CI 2.57-35.03), and the final model had good discrimination, with C-statistic=0.83 (95%CI 0.75-0.91). CONCLUSION: Markers of RV and LV dysfunction assessed by bedside echo are independent predictors of mortality in hospitalized COVID-19 patients, after adjustment for clinical variables.

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.

Echocardiographic screening of pregnant women by non-physicians with remote interpretation in primary care.

BACKGROUND: Impact of heart disease (HD) on pregnancy is significant. OBJECTIVE: We aimed to evaluate the feasibility of integrating screening echocardiography (echo) into the Brazilian prenatal primary care to assess HD prevalence. METHODS: Over 13 months, 20 healthcare workers acquired simplified echo protocols, utilizing hand-held machines (GE-VSCAN), in 22 primary care centres. Consecutive pregnant women unaware of HD underwent focused echo, remotely interpreted in USA and Brazil. Major HD was defined as structural valve abnormalities, more than mild valve dysfunction, ventricular systolic dysfunction/hypertrophy, or other major abnormalities. Screen-positive women were referred for standard echo. RESULTS: At total, 1 112 women underwent screening. Mean age was 27 ± 8 years, mean gestational age 22 ± 9 weeks. Major HD was found in 100 (9.0%) patients. More than mild mitral regurgitation was observed in 47 (4.2%), tricuspid regurgitation in 11 (1.0%), mild left ventricular dysfunction in 4 (0.4%), left ventricular hypertrophy in 2 (0.2%) and suspected rheumatic heart disease in 36 (3.2%): all, with mitral valve and two with aortic valve (AV) involvement. Other AV disease was observed in 11 (10%). In 56 screen-positive women undergoing standard echo, major HD was confirmed in 45 (80.4%): RHD findings in 12 patients (all with mitral valve and two with AV disease), mitral regurgitation in 40 (14 with morphological changes, 10 suggestive of rheumatic heart disease), other AV disease in two (mild/moderate regurgitation). CONCLUSIONS: Integration of echo screening into primary prenatal care is feasible in Brazil. However, the low prevalence of severe disease urges further investigations about the effectiveness of the strategy.

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.

Bedside echocardiography to predict mortality of COVID-19 patients beyond clinical data: Data from the PROVAR-COVID study

Abstract INTRODUCTION: Cardiac involvement seems to impact prognosis of COVID-19, being more frequent in critically ill patients. We aimed to assess the prognostic value of right ventricular (RV) and left ventricular (LV) dysfunction, evaluated by bedside echocardiography (echo), in patients hospitalized with COVID-19. METHODS: Patients admitted in 2 reference hospitals in Brazil from Jul to Sept/2020 with confirmed COVID-19 and moderate/severe presentations underwent clinical and laboratory evaluation, and focused bedside echo (GE Vivid-IQ), at the earliest convenience, with remote interpretation. The association between demographics, clinical comorbidities and echo variables with all-cause hospital mortality was assessed, and factors significant at p<0.10 were put into multivariable models. RESULTS: Total 163 patients were enrolled, 59% were men, mean age 64±16 years, and 107 (66%) were admitted to intensive care. Comorbidities were present in 144 (88%) patients: hypertension 115 (71%), diabetes 61 (37%) and heart failure 22 (14%). In-hospital mortality was 34% (N=56). In univariate analysis, echo variables significantly associated with death were: LV ejection fraction (LVEF, OR=0.94), RV fractional area change (OR=0.96), tricuspid annular plane systolic excursion (TAPSE, OR=0.83) and RV dysfunction (OR=5.3). In multivariate analysis, after adjustment for clinical and demographic variables, independent predictors of mortality were age≥63 years (OR=5.53, 95%CI 1.52-20.17), LVEF<64% (OR=7.37, 95%CI 2.10-25.94) and TAPSE<18.5 mm (OR=9.43, 95% CI 2.57-35.03), and the final model had good discrimination, with C-statistic=0.83 (95%CI 0.75-0.91). CONCLUSION: Markers of RV and LV dysfunction assessed by bedside echo are independent predictors of mortality in hospitalized COVID-19 patients, after adjustment for clinical variables.

Health Education about Rheumatic Heart Disease: A Community-Based Cluster Randomized Trial: Rheumatic Heart Disease Educational Strategies.

Introduction: The burden of rheumatic heart disease (RHD) is still high in Brazil. Lack of population awareness about the disease limits the efficacy of prevention programs. We aimed to evaluate the effectiveness of education on RHD in schools, comparing the conventional expository teaching method with tablet-based worked examples. Method: A prospective, cluster randomized trial was conducted over eight months in six randomly selected low-income Brazilian public schools. Each class was considered a cluster (total: 90), being randomized 1:1 to receive one of the educational methods. Pre-test evaluated students' prior knowledge on RHD. Post-tests, 10 days, and three months later, evaluated retention of knowledge. Results: At total 1,301 students (52% female) completed the study, being 63% from high school. Baseline knowledge about RHD was universally low (average score expository classes [G1] 33.9% vs. worked examples [G2] 32.5%, p = 0.23). A significant but similar improvement was observed in both groups in the immediate post-test (pre- vs. post: p < 0.001): G1 57.5% vs. G2 56.7%, p = 0.69. In the late post-test, a significant 20% worsening was observed in both groups and the final scores were again similar: G1 45.0% vs. G2 45.9%, p = 0.87. Highschool students had higher scores (p < 0.001), and girls had better overall performances than boys (p < 0.001). Conclusion: The novel technology of tablet-based worked examples had similar results compared with expository classes for RHD education in schools. Both educational processes resulted in modest gains in knowledge, with low retention. More studies are needed to determine if increased knowledge leads to behavioral changes that could reduce RHD burden. Highlights: In a cluster-randomized trial, two different educational strategies about Rheumatic Heart Disease (RHD) for children - standard expository classes and worked examples based on interactive modules in tablet computers - were compared in public schools of underserved Brazilian neighborhoods.Baseline knowledge was low, and the novel tablet-based technology had similar results compared with traditional teaching for RHD education in schools, with no differences in acquisition and mid-term retention of knowledge.Both educational interventions resulted in similar 71% improvement in the immediate post-test, although with suboptimal retention, with over 20% worsening in three months in both groups.Our data suggests that the optimal strategy for RHD education is yet to be determined, and future studies should be warranted to determine if increased knowledge leads to behavioral changes that could reduce disease burden in endemic areas.

Cost-Effectiveness of Rheumatic Heart Disease Echocardiographic Screening in Brazil: Data from the PROVAR+ Study: Cost-effectiveness of RHD screening in Brazil.

Introduction: In recent years, new technologies - noticeably ultra-portable echocardiographic machines - have emerged, allowing for Rheumatic Heart Disease (RHD) early diagnosis. We aimed to perform a cost-utility analysis to assess the cost-effectiveness of RHD screening with handheld devices in the Brazilian context. Methods: A Markov model was created to assess the cost-effectiveness of one-time screening for RHD in a hypothetical cohort of 11-year-old socioeconomically disadvantaged children, comparing the intervention to standard care using a public perspective and a 30-year time horizon. The model consisted of 13 states: No RHD, Undiagnosed Asymptomatic Borderline RHD, Diagnosed Asymptomatic Borderline RHD, Untreated Asymptomatic Definite RHD, Treated Asymptomatic Definite RHD, Untreated Mild Clinical RHD, Treated Mild Clinical RHD, Untreated Severe Clinical RHD, Treated Severe Clinical RHD, Surgery, Post-Surgery and Death. The initial distribution of the population over the different states was derived from primary echo screening data. Costs of the different states were derived from the Brazilian public health system database. Transition probabilities and utilities were derived from published studies. A discount rate of 3%/year was used. A cost-effectiveness threshold of $25,949.85 per Disability Adjusted Life Year (DALY) averted is used in concordance with the 3x GDP per capita threshold in 2015. Results: RHD echo screening is cost-effective with an Incremental Cost-Effectiveness Ratio of $10,148.38 per DALY averted. Probabilistic modelling shows that the intervention could be considered cost-effective in 70% of the iterations. Conclusion: Screening for RHD with hand held echocardiographic machines in 11-year-old children in the target population is cost-effective in the Brazilian context. Highlights: A cost-effectiveness analysis showed that Rheumatic Heart Disease (RHD) echocardiographic screening utilizing handheld devices, performed by non-physicians with remote interpretation by telemedicine is cost-effective in a 30-year time horizon in Brazil.The model included primary data from the first large-scale RHD screening program in Brazilian underserved populations and costs from the Unified Health System (SUS), and suggests that the Incremental Cost-Effectiveness Ratio of the intervention is considerably below the acceptable threshold for Brazil, even after a detailed sensitivity analysis.Considering the high prevalence of subclinical RHD in Brazil, and the significant economic burden posed by advanced disease, these data are important for the formulation of public policies and surveillance approaches.Cost-saving strategies first implemented in Brazil by the PROVAR study, such as task-shifting to non-physicians, computer-based training, routine use of affordable devices and telemedicine for remote diagnosis may help planning RHD control programs in endemic areas worldwide.

Validation of a simplified score for predicting latent rheumatic heart disease progression using a prospective cohort of Brazilian schoolchildren.

OBJECTIVES: Echocardiographic (echo) screening is an important tool to estimate rheumatic heart disease (RHD) prevalence, but the natural history of screen-detected RHD remains unclear. The PROVAR+ (Programa de RastreamentO da VAlvopatia Reumática) study, which uses non-experts, telemedicine and portable echo, pioneered RHD screening in Brazil. We aimed to assess the mid-term evolution of Brazilian schoolchildren (5-18 years) with echocardiography-detected subclinical RHD and to assess the performance of a simplified score consisting of five components of the World Heart Federation criteria, as a predictor of unfavourable echo outcomes. SETTING: Public schools of underserved areas and private schools in Minas Gerais, southeast Brazil. PARTICIPANTS: A total of 197 patients (170 borderline and 27 definite RHD) with follow-up of 29±9 months were included. Median age was 14 (12-16) years, and 130 (66%) were woman. Only four patients in the definite group were regularly receiving penicillin. PRIMARY AND SECONDARY OUTCOME MEASURES: Unfavourable outcome was based on the 2-year follow-up echo, defined as worsening diagnostic category, remaining with mild definite RHD or development/worsening of valve regurgitation/stenosis. RESULTS: Among patients with borderline RHD, 29 (17.1%) progressed to definite, 49 (28.8%) remained stable, 86 (50.6%) regressed to normal and 6 (3.5%) were reclassified as other heart diseases. Among those with definite RHD, 13 (48.1%) remained in the category, while 5 (18.5%) regressed to borderline, 5 (18.5%) regressed to normal and 4 (14.8%) were reclassified as other heart diseases. The simplified echo score was a significant predictor of RHD unfavourable outcome (HR 1.197, 95% CI 1.098 to 1.305, p<0.001). CONCLUSION: The simple risk score provided an accurate prediction of RHD status at 2-year follow-up, showing a good performance in Brazilian schoolchildren, with a potential value for risk stratification and monitoring of echocardiography-detected RHD.

Atrial fibrillation detection with a portable device during cardiovascular screening in primary care.

INTRODUCTION: A novel handheld dual-electrode stick is a portable atrial fibrillation (AF) screening device (AFSD). We evaluated AFSD performance in primary care patients referred for echocardiogram (echo). METHODS: The AFSD has a light indication of irregular rhythm and single-lead ECG recording. Patients were instructed to hold the device for 1 min, and AF indication was recorded. A 12-lead ECG was performed for all AFSD-positive patients and 250 patients with negative AFSD screen. Echos were performed based on a clinical risk score: all high-risk patients and a sampling of low-risk patients underwent complete echo. Intermediate risk patients first had a screening echocardiogram, with a follow-up complete study if abnormality was suspected. RESULTS: In 5 days, 1518 patients underwent clinical evaluation and cardiovascular risk stratification: mean age 58±16 years, 66% women. The AFSD was positive in 6.4%: 12.6% high risk, 6.1% intermediate risk and 2.2% low risk. Older age was a risk factor (9.3% vs 4.8% in those more than and less than 65 years, p=0.001). AFSD positive was independently associated with heart disease in echo (OR=3.9, 95% CI 2.1 to 7.2, p<0.001). Compared with 12-lead ECG, the AFSD had sensitivity of 90.2% (95% CI 77.0% to 97.3%) and specificity of 84.0% (95% CI 79.3% to 88.0%) for AF detection. CONCLUSION: AFSD demonstrated high sensitivity for AF detection in primary care patients referred for echo. AF prevalence was substantial and independently associated with structural or functional heart disease, suggesting that AFSD screening could be a useful primary care tool to stratify risk and prioritise echo.

Simplified Echocardiography Screening Criteria for Diagnosing and Predicting Progression of Latent Rheumatic Heart Disease.

BACKGROUND: The 2012 World Heart Federation Criteria are the current gold standard for the diagnosis of latent rheumatic heart disease (RHD). Because data and experience using these criteria have grown, there is opportunity to simplify and develop outcome prediction tools. We aimed to develop a simple echocardiographic score applicable for RHD screening with potential to predict disease progression. METHODS: This study included 3 cohorts used for score derivation (n=9501), score validation (n=7312), and assessment of outcomes prediction (n=227). In the derivation cohort, variables independently associated with definite RHD were assigned point values proportional to their regression coefficients. The sum of these values was stratified into low (0-6), intermediate (7-9), and high (≥10) risk. RESULTS: Five components were selected for score development, including mitral valve anterior leaflet thickening, excessive leaflet tip motion, and regurgitation jet length ≥2 cm, and aortic valve focal thickening and any regurgitation. The score showed optimal discrimination and calibration for RHD diagnosis in the derivation and validation cohorts (C statistic, 0.998 and 0.994, respectively), with good discrimination for predicting disease progression (C statistic, 0.811). Progression-free survival rate in the low-risk children at 1-, 2-, and 3-year follow-up was 100%, 100%, and 93%, respectively, compared with 90%, 60%, and 47% in high-risk group. The point-based score was strongly associated with disease progression (hazard ratio, 1.270; 95% CI, 1.188-1.358; P<0.001). CONCLUSIONS: This simplified score, based on components of the World Heart Federation criteria, is highly accurate to recognize definite RHD and provides the first tool for risk stratification, assigning children with latent RHD to low, intermediate, or high risk based on echocardiographic features at diagnosis.

Integration of echocardiographic screening by non-physicians with remote reading in primary care.

INTRODUCTION: Heart disease (HD) accounts for high morbidity and mortality in Brazil. Underserved populations often suffer long delays in diagnosis. We aimed to evaluate the feasibility of integrating screening echocardiography (echo) with remote interpretation in the established primary care system (PC) in Brazil and to assess HD prevalence. METHODS: Over 11 months, 20 healthcare workers (four physicians, four nurses, and 12 technicians) at 16 PC centres were trained on simplified handheld echo protocols. Three screening (SC) groups, including all consented patients aged 17-20, 35-40 and 60-65 years, and patients referred (RF) for clinical indications underwent focused echo. Studies were remotely interpreted through telemedicine. Significant HD was defined as moderate/severe valve disease, ventricular dysfunction/hypertrophy, pericardial effusion, wall-motion abnormalities and congenital heart disease. RESULTS: Total 1004 patients underwent echo; 299 (29.8%) in the SC group. Median age was 51±18 years, 63.9% females; 42.7% had cardiovascular symptoms. Significant HD was found in 354 (35.3%) patients (23.4% in SC vs 40.3% in RF group, p<0.001). Prevalence was higher in patients in the SC group aged >60 years (29.2%), compared with 35-40 (14.9%) and under 20 (16.5%), p=0.012. Comparing SC to RF groups, moderate/severe left ventricular dysfunction was observed in 4.1% vs 8.1%, p=0.03, mitral regurgitation in 8.9% vs 20.3%, p<0.001 and aortic stenosis in 5.4% vs 4.3%, p=0.51. CONCLUSIONS: Integration focused echo into PC is feasible in Brazil as a strategy to deliver cardiovascular care to low-resourced areas through task shifting. The burden of HD observed suggests this tool may improve early diagnosis and referral.

Cardiac Involvement by Yellow Fever(from the PROVAR+ Study).

Incidence of Yellow Fever (YF) has increased in Brazil, and cardiac findings such as bradyarrhythmias and conduction abnormalities have been described. We aimed to perform a comprehensive cardiac evaluation of patients with YF, and to assess the association between cardiac involvement and disease severity. Patients hospitalized with YF from February to March 2018 underwent clinical and laboratory evaluation, focused bedside echocardiography (GE Vivid IQ), electrocardiogram and, in case of alterations, 24-hours Holter. Patients were divided into 2 groups according to YF severity. Five patients underwent magnetic resonance imaging and 3 had necropsy. Seventy patients had confirmed YF, 69% with severe form. Mean age was 48 ± 14 years, 63 (90%) were males and 5 (7%) died. Significant electrocardiogram abnormalities were present in 52% of patients with mild/moderate form of YF (G1) and 77% of those with severe form (G2), p = 0.046. Sinus bradycardia was observed in 24% (N = 17): G1 23% versus G2 25%, p = 0.67. Among 32 patients who underwent Holter, 14 (44%) had mean HR <60 beats per minute, being 8 from G2. Echocardiogram revealed left ventricular dysfunction in 4 (6%) patients, from G2. Left ventricular wall thickening with a hyper-refringent myocardial texture suggesting infiltration was observed in 17 patients (G1 18% vs G2 27%, p = 0.55). One magnetic resonance (G2) was suggestive of myocarditis, and one necropsy revealed areas of myocardial necrosis and acute myocarditis. In conclusion, cardiac involvement was observed in patients with YF, most commonly bradycardia and myocardial hyper-refringent texture suggestive of infiltration.

Comparison Between Different Strategies of Rheumatic Heart Disease Echocardiographic Screening in Brazil: Data From the PROVAR (Rheumatic Valve Disease Screening Program) Study.

BACKGROUND: Considering the limited accuracy of clinical examination for early diagnosis of rheumatic heart disease (RHD), echocardiography has emerged as an important epidemiological tool. The ideal setting for screening is yet to be defined. We aimed to evaluate the prevalence and pattern of latent RHD in schoolchildren (aged 5-18 years) and to compare effectiveness of screening between public schools, private schools, and primary care centers in Minas Gerais, Brazil. METHODS AND RESULTS: The PROVAR (Rheumatic Valve Disease Screening Program) study uses nonexperts and portable and handheld devices for RHD echocardiographic screening, with remote interpretation by telemedicine, according to the 2012 World Heart Federation criteria. Compliance with study consent and prevalence were compared between different screening settings, and variables associated with RHD were analyzed. In 26 months, 12 048 students were screened in 52 public schools (n=10 901), 2 private schools (n=589), and 3 primary care centers (n=558). Median age was 12.9 years, and 55.4% were girls. Overall RHD prevalence was 4.0% borderline (n=486) and 0.5% definite (n=63), with statistically similar rates between public schools (4.6%), private schools (3.5%), and primary care centers (4.8%) (P=0.24). The percentage of informed consents signed was higher in primary care centers (84.4%) and private schools (66.9%) compared with public schools (38.7%) (P<0.001). Prevalence was higher in children ≥12 years (5.3% versus 3.1%; P<0.001) and girls (4.9% versus 4.0%; P=0.02). Only age (odds ratio, 1.12; 95% confidence interval, 1.09-1.17; P<0.001) was independently associated with RHD. CONCLUSIONS: RHD screening in primary care centers seems to achieve higher coverage rates. Prevalence among schoolchildren is significantly high, with rates higher than expected in private schools of high-income areas. These data are important for the formulation of public policies to confront RHD.

A focussed single-view hand-held echocardiography protocol for the detection of rheumatic heart disease.

BACKGROUND: Echocardiographic screening represents an opportunity for reduction in the global burden of rheumatic heart disease. A focussed single-view screening protocol could allow for the rapid training of healthcare providers and screening of patients. OBJECTIVE: The aim of this study was to determine the sensitivity and specificity of a focussed single-view hand-held echocardiographic protocol for the diagnosis of rheumatic heart disease in children. METHODS: A total of nine readers were divided into three reading groups; each interpreted 200 hand-held echocardiography studies retrospectively as screen-positive, if mitral regurgitation ⩾1.5 cm and/or any aortic insufficiency were observed, or screen-negative from a pooled study library. The performance of experts receiving focussed hand-held protocols, non-experts receiving focussed hand-held protocols, and experts receiving complete hand-held protocols were determined in comparison with consensus interpretations on fully functional echocardiography machines. RESULTS: In all, 587 studies including 76 on definite rheumatic heart disease, 122 on borderline rheumatic heart disease, and 389 on normal cases were available for analysis. The focussed single-view protocol had a sensitivity of 81.1%, specificity of 75.5%, negative predictive value of 88.5%, and a positive predictive value of 63.2%; expert readers had higher specificity (86.1 versus 64.8%, p<0.01) but equal sensitivity. Sensitivity - experts, 96% and non-experts, 95% - and negative predictive value - experts, 99% and non-experts, 98% - were better for definite rheumatic heart disease. False-positive screening studies resulting from erroneous identification of mitral regurgitation and aortic insufficiency colour jets increased with shortened protocols and less experience (p<0.01). CONCLUSION: Our data support a focussed screening protocol limited to parasternal long-axis images. This holds promise in making echocardiographic screening more practical in regions where rheumatic heart disease remains endemic.

Telehealth solutions to enable global collaboration in rheumatic heart disease screening.

Background The global burden of rheumatic heart disease is nearly 33 million people. Telemedicine, using cloud-server technology, provides an ideal solution for sharing images performed by non-physicians with cardiologists who are experts in rheumatic heart disease. Objective We describe our experience in using telemedicine to support a large rheumatic heart disease outreach screening programme in the Brazilian state of Minas Gerais. Methods The Programa de Rastreamento da Valvopatia Reumática (PROVAR) is a prospective cross-sectional study aimed at gathering epidemiological data on the burden of rheumatic heart disease in Minas Gerais and testing of a non-expert, telemedicine-supported model of outreach rheumatic heart disease screening. The primary goal is to enable expert support of remote rheumatic heart disease outreach through cloud-based sharing of echocardiographic images between Minas Gerais and Washington. Secondary goals include (a) developing and sharing online training modules for non-physicians in echocardiography performance and interpretation and (b) utilising a secure web-based system to share clinical and research data. Results PROVAR included 4615 studies that were performed by non-experts at 21 schools and shared via cloud-telemedicine technology. Latent rheumatic heart disease was found in 251 subjects (4.2% of subjects: 3.7% borderline and 0.5% definite disease). Of the studies, 50% were preformed on full functional echocardiography machines and transmitted via Digital Imaging and Communications in Medicine (DICOM) and 50% were performed on handheld echocardiography machines and transferred via a secure Dropbox connection. The average time between study performance date and interpretation was 10 days. There was 100% success in initial image transfer. Less than 1% of studies performed by non-experts could not be interpreted. Discussion A sustainable, low-cost telehealth model, using task-shifting with non-medical personal in low and middle income countries can improve access to echocardiography for rheumatic heart disease.

Echocardiographic prevalence of rheumatic heart disease in Brazilian schoolchildren: Data from the PROVAR study.

BACKGROUND: Accurate estimates of Rheumatic Heart Disease (RHD) burden are needed to justify improved integration of RHD prevention and screening into the public health systems, but data from Latin America are still sparse. OBJECTIVE: To determine the prevalence of RHD among socioeconomically disadvantaged youth (5-18years) in Brazil and examine risk factors for the disease. METHODS: The PROVAR program utilizes non-expert screeners, telemedicine, and handheld and standard portable echocardiography to conduct echocardiographic screening in socioeconomically disadvantaged schools in Minas Gerais, Brazil. Cardiologists in the US and Brazil provide expert interpretation according to the 2012 World Heart Federation Guidelines. Here we report prevalence data from the first 14months of screening, and examine risk factors for RHD. RESULTS: 5996 students were screened across 21 schools. Median age was 11.9 [9.0/15.0] years, 59% females. RHD prevalence was 42/1000 (n=251): 37/1000 borderline (n=221) and 5/1000 definite (n=30). Pathologic mitral regurgitation was observed in 203 (80.9%), pathologic aortic regurgitation in 38 (15.1%), and mixed mitral/aortic valve disease in 10 (4.0%) children. Older children had higher prevalence (50/1000 vs. 28/1000, p<0.001), but no difference was observed between northern (lower resourced) and central areas (34/1000 vs. 44/1000, p=0.31). Females had higher prevalence (48/1000 vs. 35/1000, p=0.016). Age (OR=1.15, 95% CI:1.10-1.21, p<0.001) was the only variable independently associated with RHD findings. CONCLUSIONS: RHD continues to be an important and under recognized condition among socioeconomically disadvantaged Brazilian schoolchildren. Our data adds to the compelling case for renewed investment in RHD prevention and early detection in Latin America.