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Worldwide, it is estimated that over 6 million people are infected with Chagas disease (ChD). It is a neglected disease that can lead to severe heart conditions in its chronic phase. While early treatment can avoid complications, the early-stage detection rate is low. We explore the use of deep neural networks to detect ChD from electrocardiograms (ECGs) to aid in the early detection of the disease. We employ a convolutional neural network model that uses 12-lead ECG data to compute the probability of a ChD diagnosis. Our model is developed using two datasets which jointly comprise over two million entries from Brazilian patients: The SaMi-Trop study focusing on ChD patients, enriched with data from the CODE study from the general population. The model's performance is evaluated on two external datasets: the REDS-II, a study focused on ChD with 631 patients, and the ELSA-Brasil study, with 13,739 civil servant patients. Evaluating our model, we obtain an AUC-ROC of 0.80 (CI 95% 0.79-0.82) for the validation set (samples from CODE and SaMi-Trop), and in external validation datasets: 0.68 (CI 95% 0.63-0.71) for REDS-II and 0.59 (CI 95% 0.56-0.63) for ELSA-Brasil. In the latter, we report a sensitivity of 0.52 (CI 95% 0.47-0.57) and 0.36 (CI 95% 0.30-0.42) and a specificity of 0.77 (CI 95% 0.72-0.81) and 0.76 (CI 95% 0.75-0.77), respectively. Additionally, when considering only patients with Chagas cardiomyopathy as positive, the model achieved an AUC-ROC of 0.82 (CI 95% 0.77-0.86) for REDS-II and 0.77 (CI 95% 0.68-0.85) for ELSA-Brasil. The neural network detects chronic Chagas cardiomyopathy (CCC) from ECG-with weaker performance for early-stage cases. Future work should focus on curating large higher-quality datasets. The CODE dataset, our largest development dataset includes self-reported and therefore less reliable labels, limiting performance for non-CCC patients. Our findings can improve ChD detection and treatment, particularly in high-prevalence areas.

Atherosclerosis burden can be evaluated in asymptomatic patients by measuring coronary artery calcification (CAC), whereas the global longitudinal strain (GLS) and diastolic function parameters (mitral E/e’ ratio, septal e′, and lateral e′) are used to evaluate subclinical left ventricular (LV) dysfunction. We investigated whether subjects with CAC (CAC >0 Agatston units) would present with an impairment in LV functional parameters. Among the participants of the ELSA-Brasil cohort free of clinically prevalent cardiovascular disease who performed cardiac computed tomography and echocardiography within the study protocol, we tested whether those with CAC >0 presented with worse GLS and diastolic function parameters. CAC >0 was present in 203 of the 612 included participants (33.17%; age 51.4 ± 8.6 years, 52.1% women). Absolute CAC values did not correlate with GLS (ro = 0.07, p = 0.105) but did so with E/e′ (ro = 0.19, p <0.001), septal e′ (ro = 0.28, p <0.001), and lateral e′ (ro = 0.30, p <0.001), with stronger correlations in men. Those with CAC >0 had worse mitral E/e’ ratios (7.75 ± 0.13 vs 7.01 ± 0.09; p ≤0.001), septal e′ (8.25 ± 0.15 vs 9.59 ± 0.11 cm/s; p <0.001), and lateral e′ (10.13 ± 0.20 vs 11.99 ± 0.14 cm/s; p ≤0.001), respectively. However, these associations were not independent of diabetes, obesity, hypertension, smoking, and low-density lipoprotein cholesterol, persisting only as significant associations of CAC >0 with mitral E/e’ ratio and septal e’ in men. There is an association between subclinical coronary atherosclerosis and impaired LV functional parameters. These associations are more likely attributed to the presence of common cardiovascular risk factors in the general population. However, in men, it seems to exist as an independent association.

In our previous study of blood donors in the Argentinian Chaco Province, we documented bimodal distributions of anti-Trypanosoma cruzi antibody (Ab) levels, suggesting potential self-cure in donors with low-reactive samples. This study aimed to correlate \"high\" and \"low\" Ab level groups, defined by a mathematical model, with parasitemia and electrocardiogram findings. Ab decline over time was also assessed. We invited T. cruzi Ab reactive blood donors to enroll in the study from October 2018 to November 2019 with a follow up visit two years later. Blood samples were tested for T cruzi Ab by: Chagatest ELISA Lisado and Chagatest ELISA Recombinante v.4.0 (Wiener Lab, Argentina); VITROS Immunodiagnostic Products Anti-T.cruzi (Chagas) (Ortho-Clinical Diagnostics Inc., UK), and Architect Chagas (Abbott Laboratories, Germany). Target capture polymerase chain reaction (PCR) was performed on lysed whole blood samples from enrollment visits and electrocardiograms on second visits. Four hundred fifty donors were recruited, but 68 were excluded due to negative results on all study Ab assays. Ab level distributions were bimodal and classified as \"high\" or \"low\" at a calculated threshold for each of four assays. There were 160 donors with low and 179 with high Ab results on all assays. The remainder 43 were discordant reactive. Ninety-seven percentage of the PCR positive donors were among the concordant high Ab group. During the 2-4 year follow-up interval, relative Ab declines by three assays were significantly greater among those classified as low Ab and with negative PCR results. Ab reactivity is associated with PCR-detectable parasitemia. Greater Ab declines were detected among donors with low and/or discordant Ab reactivity and negative PCR results, suggesting spontaneous parasite clearance in these donors.

Background Knowledge of the normal limits of the electrocardiogram (ECG) is mandatory for establishing which patients have abnormal ECGs. No studies have assessed the reference standards for a Latin American population. Our aim was to establish the normal ranges of the ECG for pediatric and adult Brazilian primary care patients. Methods This retrospective observational study assessed all the consecutive 12-lead digital electrocardiograms of primary care patients at least 1 year old in Minas Gerais state, Brazil, recorded between 2010 and 2015. ECGs were excluded if there were technical problems, selected abnormalities were present or patients with selected self-declared comorbidities or on drug therapy. Only the first ECG from patients with multiple ECGs was accepted. The University of Glasgow ECG analysis program was used to automatically interpret the ECGs. For each variable, the 1st, 2nd, 50th, 98th and 99th percentiles were determined and results were compared to selected studies. Results A total of 1,493,905 ECGs were recorded. 1,007,891 were excluded and 486.014 were analyzed. This large study provided normal values for heart rate, P, QRS and T frontal axis, P and QRS overall duration, PR and QT overall intervals and QTc corrected by Hodges, Bazett, Fridericia and Framingham formulae. Overall, the results were similar to those from other studies performed in different populations but there were differences in extreme ages and specific measurements. Conclusions This study has provided reference values for Latinos of both sexes older than 1 year. Our results are comparable to studies performed in different populations.

No meta-analysis of trial data shows that lowering LDL-C beyond 100 mg/dL in patients with diabetes without pre-existing, clinically evident atherosclerotic cardiovascular disease produces any benefits when considering all causes [2,3]. [...]this benefit is documented, the currently limited trial evidence to support more intensive lipid-lowering coupled is insufficient. [...]in England, only 24% died of ischemic heart disease in 2018 [6]. Despite the limited evidence of all-cause benefits, lipid-lowering treatment, which has become increasingly intensive over time, is a near-universal recommendation for most with diabetes. [...]this issue is of major importance to public health.

Although infection with Trypanosoma cruzi is thought to be lifelong, less than half of those infected develop cardiomyopathy, suggesting greater parasite control or even clearance. Antibody levels appear to correlate with T. cruzi (antigen) load. We test the association between a downwards antibody trajectory, PCR positivity and ECG alterations in untreated individuals with Chagas disease. This is a retrospective cohort of T. cruzi seropositive blood donors. Paired blood samples (index donation and follow-up) were tested using the VITROS Immunodiagnostic Products Anti-T.cruzi (Chagas) assay (Ortho Clinical Diagnostics, Raritan NJ) and PCR performed on the follow-up sample. A 12-lead resting ECG was performed. Significant antibody decline was defined as a reduction of > 1 signal-to-cutoff (S/CO) unit on the VITROS assay. Follow-up S/CO of < 4 was defined as borderline/low. 276 untreated seropositive blood donors were included. The median (IQR) follow-up was 12.7 years (8.5-16.9). 56 (22.1%) subjects had a significant antibody decline and 35 (12.7%) had a low/borderline follow-up result. PCR positivity was lower in the falling (26.8% vs 52.8%, p = 0.001) and low/borderline (17.1% vs 51.9%, p < 0.001) antibody groups, as was the rate of ECG abnormalities. Falling and low/borderline antibody groups were predominantly composed of individuals with negative PCR and normal ECG findings: 64% and 71%, respectively. Low and falling antibody levels define a phenotype of possible spontaneous parasite clearance.

IntroductionGuideline-directed medical therapy (GDMT) for heart failure (HF) reduces adverse events, but is underused. Global barriers to GDMT optimisation include low frequency of visits, clinician inertia and poor patient knowledge, which may be mitigated by digital health interventions (DHI). In Brazil, low digital literacy and reduced access to technology may compromise these potential DHI’s beneficial effects. Our objective is to develop and test the effectiveness of a DHI to optimise GDMT in patients recently hospitalised for HF in the Brazilian public health system (Sistema Único de Saúde (SUS)).Methods and analysisThis is a randomised, controlled, multicentre, parallel-group, clinical trial in which 154 patients being discharged from an HF-related hospitalisation will be randomised. Inclusion criteria are ≥18 years of age, reduced ejection fraction HF (EF<50%) and medication optimisation gaps (at least one GDMT class not started or two among those with prescribed dosage≤50% of the target dose). All participants will receive a written booklet and SUS usual care. Randomisation will be stratified by site. The intervention includes a mobile application (app) to engage patients, developed through a human-centred design. The app’s main features are a check-in page for daily collection of participants’ health status, vital signs and weight; a remote educational programme; a chat function during working hours and longitudinal graphical representations of participants’ data. The participants’ data will be managed daily by a nurse, linked to a cardiologist for teleconsultations. Predefined clinical decision trees will guide actions, including alarm signs and GDMT optimisation. The primary outcome will be changes in GDMT from baseline to end of follow-up in 90 days. Secondary outcomes will include all-cause readmission, HF-related rehospitalisation, change in health status and HF knowledge, and implementation outcomes based on the RE-AIM framework. The analysis of outcomes will follow the intention-to-treat principle.Ethics and disseminationThis study was approved by the Universidade Federal de Minas Gerais. Recruitment started in November 2023, and patients involved will sign an informed consent form. Results will be presented at scientific meetings and published in scientific journals in 2025, and will be disclosed in social media and presented to public health stakeholders.Trial registration numberUniversal Trial Number U1111-1295-1864 Brazilian Clinical Trials Registry (https://ensaiosclinicos.gov.br/rg/RBR-10vpf9bm).

Background/Objectives: Lowering low-density lipoprotein cholesterol (LDL-C) to <70 mg/dL is recommended for most patients with diabetes. However, clinical trials investigating subjects with diabetes who are not at high cardiovascular risk are inconclusive regarding the all-cause mortality benefit of the current target, and real-world studies suggest greater mortality. We aimed to assess the all-cause mortality at different LDL-C levels among subjects with diabetes not at high risk and to examine the potential roles of early deaths and frailty for this greater mortality. Methods: We followed 2098 such participants of the ELSA-Brasil cohort between 2008 and 2019. Results: Over 10.3 (1.4) years of follow-up, 204 (9.7%) individuals died. In the proportional hazards models, participants with LDL-C values < 100 mg/dL and <70 mg/dL had greater adjusted mortality compared to those with LDL-C 100–129 mg/dL (HR = 1.67; 95%CI 1.21–2.30 and HR = 2.27; 95%CI 1.51–3.41, respectively). Increased risk when LDL-C was <100 mg/dL was higher in those >60 years (HR = 2.12; 95%CI 1.35–3.34) and greatest for deaths due to cancer (HR = 2.55; 95%CI 1.10–5.91). Further analyses for those with LDL-C < 100 mg/dL that excluded early deaths and adjusted for the frailty phenotype (HR = 2.01; 1.19–3.41) or frailty index (HR = 1.92; 1.17–3.16) did not materially alter the results. The risk of death across the spectrum of LDL-C was U-shaped, with a nadir at 112.2 mg/dL. Conclusions: The higher risk of all-cause mortality in these subjects with LDL-C within currently recommended levels was not explained by early deaths or frailty. Given the recent decline in cardiovascular mortality and the increased risk of cancer and infections in persons with diabetes, the clinical significance of low LDL-C in diabetes requires reconsideration and the definition of LDL-C treatment targets in diabetes warrants further trial evaluation.

The ability to integrate echocardiographic for rheumatic heart disease (RHD) into RHD prevention programs is limited because of lack of financial and expert human resources in endemic areas. Task shifting to nonexperts is promising; but investigations into workforce composition and training schemes are needed. The objective of this study was to test nonexperts' ability to interpret RHD screening echocardiograms after a brief, standardized, computer-based training course. Six nonexperts completed a 3-week curriculum on image interpretation. Participant performance was tested in a school-screening environment in comparison to the reference approach (cardiologists, standard portable echocardiography machines, and 2012 World Heart Federation criteria). All participants successfully completed the curriculum, and feedback was universally positive. Screening was performed in 1,381 children (5 to 18 years, 60% female), with 397 (47 borderline RHD, 6 definite RHD, 336 normal, and 8 other) referred for handheld echo. Overall sensitivity of the simplified approach was 83% (95% CI 76% to 89%), with an overall specificity of 85% (95% CI 82% to 87%). The most common reasons for false-negative screens (n = 16) were missed mitral regurgitation (MR; 44%) and MR ≤1.5 cm (29%). The most common reasons for false-positive screens (n = 179) included identification of erroneous color jets (25%), incorrect MR measurement (24%), and appropriate application of simplified guidelines (39.4%). In conclusion, a short, independent computer-based curriculum can be successfully used to train a heterogeneous group of nonexperts to interpret RHD screening echocardiograms. This approach helps address prohibitive financial and workforce barriers to widespread RHD screening.

Familial aggregation of Chagas cardiac disease in T. cruzi-infected persons suggests that human genetic variation may be an important determinant of disease progression. To perform a GWAS using a well-characterized cohort to detect single nucleotide polymorphisms (SNPs) and genes associated with cardiac outcomes. A retrospective cohort study was developed by the NHLBI REDS-II program in Brazil. Samples were collected from 499 T. cruzi seropositive blood donors who had donated between 1996 and 2002, and 101 patients with clinically diagnosed Chagas cardiomyopathy. In 2008-2010, all subjects underwent a complete medical examination. After genotype calling, quality control filtering with exclusion of 20 cases, and imputation of 1,000 genomes variants; association analysis was performed for 7 cardiac and parasite related traits, adjusting for population stratification. The cohort showed a wide range of African, European, and modest Native American admixture proportions, consistent with the recent history of Brazil. No SNPs were found to be highly (P<10(-8)) associated with cardiomyopathy. The two mostly highly associated SNPs for cardiomyopathy (rs4149018 and rs12582717; P-values <10(-6)) are located on Chromosome 12p12.2 in the SLCO1B1 gene, a solute carrier family member. We identified 44 additional genic SNPs associated with six traits at P-value <10(-6): Ejection Fraction, PR, QRS, QT intervals, antibody levels by EIA, and parasitemia by PCR. This GWAS identified suggestive SNPs that may impact the risk of progression to cardiomyopathy. Although this Chagas cohort is the largest examined by GWAS to date, (580 subjects), moderate sample size may explain in part the limited number of significant SNP variants. Enlarging the current sample through expanded cohorts and meta-analyses, and targeted studies of candidate genes, will be required to confirm and extend the results reported here. Future studies should also include exposed seronegative controls to investigate genetic associations with susceptibility or resistance to T. cruzi infection and non-Chagas cardiomyopathy.