Parasite DNA and Markers of Decreased Immune Activation Associate Prospectively with Cardiac Functional Decline over 10 Years among Trypanosoma cruzi Seropositive Individuals in Brazil.

Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and São Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.

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.

Global, Regional, and National Burden of Rheumatic Heart Disease, 1990-2015.

BACKGROUND: Rheumatic heart disease remains an important preventable cause of cardiovascular death and disability, particularly in low-income and middle-income countries. We estimated global, regional, and national trends in the prevalence of and mortality due to rheumatic heart disease as part of the 2015 Global Burden of Disease study. METHODS: We systematically reviewed data on fatal and nonfatal rheumatic heart disease for the period from 1990 through 2015. Two Global Burden of Disease analytic tools, the Cause of Death Ensemble model and DisMod-MR 2.1, were used to produce estimates of mortality and prevalence, including estimates of uncertainty. RESULTS: We estimated that there were 319,400 (95% uncertainty interval, 297,300 to 337,300) deaths due to rheumatic heart disease in 2015. Global age-standardized mortality due to rheumatic heart disease decreased by 47.8% (95% uncertainty interval, 44.7 to 50.9) from 1990 to 2015, but large differences were observed across regions. In 2015, the highest age-standardized mortality due to and prevalence of rheumatic heart disease were observed in Oceania, South Asia, and central sub-Saharan Africa. We estimated that in 2015 there were 33.4 million (95% uncertainty interval, 29.7 million to 43.1 million) cases of rheumatic heart disease and 10.5 million (95% uncertainty interval, 9.6 million to 11.5 million) disability-adjusted life-years due to rheumatic heart disease globally. CONCLUSIONS: We estimated the global disease prevalence of and mortality due to rheumatic heart disease over a 25-year period. The health-related burden of rheumatic heart disease has declined worldwide, but high rates of disease persist in some of the poorest regions in the world. (Funded by the Bill and Melinda Gates Foundation and the Medtronic Foundation.).

Short-term diuretic withdrawal in stable outpatients with mild heart failure and no fluid retention receiving optimal therapy: a double-blind, multicentre, randomized trial.

AIMS: Although loop diuretics are widely used to treat heart failure (HF), there is scarce contemporary data to guide diuretic adjustments in the outpatient setting. METHODS AND RESULTS: In a prospective, randomized and double-blind protocol, we tested the safety and tolerability of withdrawing low-dose furosemide in stable HF outpatients at 11 HF clinics in Brazil. The trial had two blindly adjudicated co-primary outcomes: (i) symptoms assessment quantified as the area under the curve (AUC) of a dyspnoea score on a visual-analogue scale evaluated at 4 time-points (baseline, Day 15, Day 45, and Day 90) and (ii) the proportion of patients maintained without diuretic reuse during follow-up. We enrolled 188 patients (25% females; 59 ± 13 years old; left ventricular ejection fraction = 32 ± 8%) that were randomized to furosemide withdrawal (n = 95) or maintenance (n = 93). For the first co-primary endpoint, no significant difference in patients' assessment of dyspnoea was observed in the comparison of furosemide withdrawal with continuous administration [median AUC 1875 (interquartile range, IQR 383-3360) and 1541 (IQR 474-3124), respectively; P = 0.94]. For the second co-primary endpoint, 70 patients (75.3%) in the withdrawal group and 77 patients (83.7%) in the maintenance group were free of furosemide reuse during follow-up (odds ratio for additional furosemide use with withdrawal 1.69, 95% confidence interval 0.82-3.49; P = 0.16). Heart failure-related events (hospitalizations, emergency room visits, and deaths) were infrequent and similar between groups (P = 1.0). CONCLUSIONS: Diuretic withdrawal did not result in neither increased self-perception of dyspnoea nor increased need of furosemide reuse. Diuretic discontinuation may deserve consideration in stable outpatients with no signs of fluid retention receiving optimal medical therapy. CLINICALTRIALS.GOV IDENTIFIER: NCT02689180.

Percutaneous closure of ostium secundum atrial septal defect using left internal jugular vein access in a child with situs inversus and absence of inferior caval vein.

Femoral vein access is the first choice for percutaneous atrial septal defect closure, and when it cannot be used due to anatomic reasons, the alternative sites should be considered, frequently increasing the complexity of the procedure. Here we report the case of a 3-year-old boy, with situs inversus and dextrocardia, electively referred for percutaneous closure of an ostium secundum atrial septal defect. During the procedure, agenesis of the infra-hepatic segment of the inferior caval vein was diagnosed, and no double inferior caval vein or right superior caval vein were identified by ultrasound or angiography. Therefore, we opted to perform the procedure through the left internal jugular vein, with fluoroscopy and transesophageal echocardiographic guidance. Catheters were navigated through a hydrophilic guidewire, and a Stiff guidewire was positioned in the left ventricle for better support. An Amplatzer septa occluder 19 was successfully deployed without major difficulties and the patient was discharged after 24 hours in good clinical condition. Percutaneous atrial septal defect closure through alternative access sites, especially in the presence of situs inversus, may pose significant challenges to the interventional team. In this case, the left internal jugular vein has shown to be a feasible option, allowing the navigation and manipulation of devices without complications. Provided the expertise of the interventional team, and awareness of the risks involved, alternative access sites can be successfully used for paediatric structural interventions.

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.

Rational and design of a randomized, double-blind, multicenter trial to evaluate the safety and tolerability of furosemide withdrawal in stable chronic outpatients with heart failure: The ReBIC-1 trial.

AIMS: Furosemide is commonly prescribed for symptom relief in heart failure (HF) patients. Although few data support the continuous use of loop diuretics in apparently euvolemic HF patients with mild symptoms, there is concern about safety of diuretic withdrawal in these patients. The ReBIC-1 trial was designed to evaluate the safety and tolerability of withdrawing furosemide in stable, euvolemic, chronic HF outpatients. This multicenter initiative is part of the Brazilian Research Network in Heart Failure (ReBIC) created to develop clinical studies in HF and composed predominantly by university tertiary care hospitals. METHODS: The ReBIC-1 trial is currently enrolling HF patients in NYHA functional class I-II, left ventricular ejection fraction ≤45%, without a HF-related hospital admission within the last 6 months, receiving a stable dose of furosemide (40 or 80 mg per day) for at least 6 months. Eligible patients will be randomized to maintain or withdraw furosemide in a double-blinded protocol. The trial has two co-primary outcomes: (1) dyspnea assessment using a visual-analogue scale evaluated at 4 time points and (2) the proportion of patients maintained without diuretics during the follow-up period. Total sample size was calculated to be 220 patients. Enrolled patients will be followed up to 90 days after randomization, and diuretic will be restarted if clinical deterioration or signs of congestion are detected. Pre-defined sub-group analysis based on NT-proBNP levels at baseline is planned. PERSPECTIVE: Evidence-based strategies aiming to simplify HF pharmacotherapy are needed in clinical practice. The ReBIC-1 trial will determine the safety of withdrawing furosemide in stable chronic HF patients.

Normal limits of the electrocardiogram derived from a large database of Brazilian primary care patients.

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.

Race and Resting-State Heart Rate Variability in Brazilian Civil Servants and the Mediating Effects of Discrimination: An ELSA-Brasil Cohort Study.

OBJECTIVES: African Americans are characterized by higher heart rate variability (HRV), a finding ostensibly associated with beneficial health outcomes. However, these findings are at odds with other evidence that blacks have worse cardiovascular outcomes. Here, we examine associations in a large cohort from the ELSA-Brasil study and determined whether these effects are mediated by discrimination. METHODS: Three groups were compared on the basis of self-declared race: "black" (n = 2,020), "brown" (n = 3,502), and "white" (n = 6,467). Perceived discrimination was measured using a modified version of the Everyday Discrimination Scale. Resting-state HRV was extracted from 10-minute resting-state electrocardiograms. Racial differences in HRV were determined by regression analyses weighted by propensity scores, which controlled for potentially confounding variables including age, sex, education, and other health-related information. Nonlinear mediation analysis quantified the average total effect, comprising direct (race-HRV) and indirect (race-discrimination-HRV) pathways. RESULTS: Black participants displayed higher HRV relative to brown (Cohen's d = 0.20) and white participants (Cohen's d = 0.31). Brown relative to white participants also displayed a small but significantly higher HRV (Cohen's d = 0.14). Discrimination indirectly contributed to the effects of race on HRV. CONCLUSIONS: This large cohort from the Brazilian population shows that HRV is greatest in black, followed by brown, relative to white participants. The presence of higher HRV in these groups may reflect a sustained compensatory psychophysiological response to the adverse effects of discrimination. Additional research is needed to determine the health consequences of these differences in HRV across racial and ethnic groups.

Differential Associations of Specific Selective Serotonin Reuptake Inhibitors With Resting-State Heart Rate and Heart Rate Variability: Implications for Health and Well-Being.

OBJECTIVE: Debate has focused on the effects of the selective serotonin reuptake inhibitor (SSRI) antidepressants on heart rate (HR) and HR variability (HRV), both of which are predictors of adverse cardiovascular events. Here, we examine the associations between specific SSRI antidepressants and resting state HR (and HRV) after accounting for a host of potential confounding factors using propensity score techniques. METHODS: Participants included 10,466 not taking antidepressants, 46 participants taking escitalopram, 86 taking citalopram, 66 taking fluoxetine, 103 taking paroxetine, and 139 taking sertraline. HR and HRV (root mean square of successive squared differences, high frequency) were extracted from 10-minute resting-state ECGs. Analyses including propensity score weighting and matching were conducted using R-statistics to control for potentially confounding variables. RESULTS: Major findings indicated that users of all SSRI medications-except fluoxetine-displayed lower HRV relative to nonusers. Users of paroxetine also displayed significantly lower HRV relative to users of citalopram (Cohen's d = 0.42), fluoxetine (Cohen's d = 0.54), and sertraline (Cohen's d = 0.35), but not escitalopram. Although associations were also observed for HR, these were less robust than those for HRV. CONCLUSIONS: Although paroxetine is associated with decreases in HRV relative to nonusers, as well as users of other SSRI medications, fluoxetine was the only medication not to display significant alterations in HR or HRV. These conclusions are limited by the cross-sectional design and nonrandomized nature of medication prescriptions. Findings highlight the importance of focusing on specific medications, rather than more heterogeneous groupings according to antidepressant action, and may have implications for health and well-being for the longer term.

Trends in Procedure Type, Morbidity and In-Hospital Outcomes of Patients with Peripheral Artery Disease: Data from the Brazilian Public Health System.

BACKGROUND: The prevalence of peripheral artery disease (PAD) is rising worldwide, with considerable impact on health care systems. METHODS: We aimed to characterize the trends in therapeutic procedures and outcomes of PAD in the Brazilian Public Health System Database (DataSUS) between 2008 and 2012. RESULTS: The number of hospitalizations remained stable from 2008 to 2012, although there was a significant change in the proportions of treatment modalities. In 2008, surgical revascularization (SR) = 8,001 (29%), endovascular revascularization (EVR) = 3,207 (11%), and clinical treatment (CT) = 16,887 (60%); and in 2012, SR = 7,882 (28%), EVR = 5,044 (18%), and CT = 15,225 (54%); P < 0.001, a 57% increase in EVR, and 9.8% decrease in CT. Total costs raised 37% (US $18.2-24.9 million, P < 0.001), with a marked 92% increase in EVR costs (US $5.1-9.8 million), compared with SR (11%) and CT (30%). Mortality decreased for EVR (2.0-1.4%, P = 0.048), increased for CT (5.1-5.8%, P = 0.002) and remained stable for SR. A nonsignificant increase was observed in total mortality (5.7-5.9%, P = NS). CONCLUSIONS: Our analysis depicts the high-PAD mortality in Brazil emphasizing the need of preventing and controlling cardiovascular risk factors. The impact of PAD in costs increased, mainly because of costs related to EVR.

In-hospital mortality risk prediction after percutaneous coronary interventions: Validating and updating the Toronto score in Brazil.

OBJECTIVES: We aimed to assess the accuracy of the simple, contemporary and well-designed Toronto PCI mortality risk score in ICP-BR registry, the first Brazilian PCI multicenter registry with follow-up information. BACKGROUND: Estimating percutaneous coronary intervention (PCI) mortality risk by a clinical prediction model is imperative to help physicians, patients and family members make informed clinical decisions and optimize participation in the consent process, reducing anxiety and improving quality of care. At a healthcare system level, risk prediction scores are essential to measure and benchmark performance. METHODS: Between 2009 and 2013, a cohort of 4,806 patients from the ICP-BR registry, treated with PCI in eight tertiary referral medical centers, was included in the analysis. This population was compared to 10,694 patients of the derivation dataset from the Toronto study. To assess predictive performance, an update of the model was performed by three different methods, which were compared by discrimination, calculating the area under the receiver operating characteristic curve (AUC), and by calibration, assessed through Hosmer-Lemeshow (H-L) test and graphical analysis. RESULTS: Death occurred in 2.6% of patients in the ICP-BR registry and in 1.3% in the Toronto cohort. The median age was 64 and 63 years, 23.8 and 32.8% were female, 28.6 and 32.3% were diabetics, respectively. Through recalibration of intercept and slope (AUC = 0.8790; H-L P value = 0.3132), we achieved a well-calibrated and well-discriminative model. CONCLUSIONS: After updating to our dataset, we demonstrated that the Toronto PCI in-hospital mortality risk score performed well in Brazilian hospitals.

Diagnostic accuracy of intravascular ultrasound-derived minimal lumen area compared with fractional flow reserve--meta-analysis: pooled accuracy of IVUS luminal area versus FFR.

INTRODUCTION: Although intravascular ultrasound minimal luminal area (IVUS-MLA) is one of many anatomic determinants of lesion severity, it has been proposed as an alternative to fractional flow reserve (FFR) to assess severity of coronary artery disease. OBJECTIVE: Pool the diagnostic performance of IVUS-MLA and determine its overall accuracy to predict the functional significance of coronary disease using FFR (0.75 or 0.80) as the gold standard. METHODS: Studies comparing IVUS and FFR to establish the best MLA cutoff value that correlates with significant coronary stenosis were reviewed from a Medline search using the terms "fractional flow reserve" and "ultrasound." DerSimonian Laird method was applied to obtain pooled accuracy. RESULTS: Eleven clinical trials, including two left main (LM) trials (total N = 1,759 patients, 1,953 lesions) were included. The weighted overall mean MLA cutoff was 2.61 mm(2) in non-LM trials and 5.35 mm(2) in LM trials. For non-LM lesions, the pooled sensitivity of MLA was 0.79 (95% CI = 0.76-0.83) and specificity was 0.65 (95% CI = 0.62-0.67). Positive likelihood ratio (LR) was 2.26 (95% CI = 1.98-2.57) and LR- was 0.32 (95% CI = 0.24-0.44). Area under the summary receiver operator curve for all trials was 0.848. Pooled LM trials had better accuracy: sensitivity = 0.90, specificity = 0.90, LR+ = 8.79, and LR- = 0.120. CONCLUSION: Given its limited pooled accuracy, IVUS-MLA's impact on clinical decision in this scenario is low and may lead to misclassification in up to 20% of the lesions. Pooled analysis points toward lower MLA cutoffs than the ones used in current practice.

Agreement among four drug information sources for the occurrence of warfarin drug interactions in Brazilian heart disease patients with a high prevalence of Trypanosoma cruzi infection.

PURPOSE: The aim of this study was to assess the agreement of four renowned interaction lists on potentially severe warfarin drug interactions (DI) in outpatients at a university hospital in Brazil, specifically in subgroups of Trypanosoma cruzi-infected and non-infected patients and those with previous bleeding episodes. METHODS: This was a cross-sectional study in which adult outpatients with heart disease and indications for chronic warfarin use were enrolled. The occurrence of potentially severe warfarin DI was evaluated based on the lists provided by three compendia, i.e., Drug Interaction Facts (DIF), Drug Interactions: Analysis and Management (DIAM) and DRUG-REAX, and by the World Health Organization (WHO) Model Formulary. A kappa coefficient was used to calculate the agreement among the sources. RESULTS: A total of 280 patients were studied. Most patients were female (54.6 %) with an average age of 56.8 (standard deviation 13.1) years. The agreement among the four sources was fair (Fleiss' kappa coefficient = 0.295). T. cruzi-infected individuals were less likely to have severe warfarin DI than non-infected patients (p < 0.05 for DIAM, DRUG-REAX and the WHO Model Formulary). Potentially severe DI were more frequent in patients with previous bleeding episodes, based on the DIF compendia (p = 0.007). CONCLUSIONS: This evaluation of warfarin DI revealed that the disagreement between compendia is also observed in clinical practice. T. cruzi infection is associated with a lower prevalence of potentially severe warfarin DI, but with a wider variation in its detection. Our results suggest a wide spectrum of discrepancies in detecting heart disease patients at higher risk for severe warfarin DI and a possible heterogeneity in clinical guidance.

Associations Between Coronary Artery Calcification and Left Ventricular Global Longitudinal Strain and Diastolic Parameters: the ELSA-Brasil Study.

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.

Association of lifestyle with deep learning predicted electrocardiographic age.

Background: People age at different rates. Biological age is a risk factor for many chronic diseases independent of chronological age. A good lifestyle is known to improve overall health, but its association with biological age is unclear. Methods: This study included participants from the UK Biobank who had undergone 12-lead resting electrocardiography (ECG). Biological age was estimated by a deep learning model (defined as ECG-age), and the difference between ECG-age and chronological age was defined as Δage. Participants were further categorized into an ideal (score 4), intermediate (scores 2 and 3) or unfavorable lifestyle (score 0 or 1). Four lifestyle factors were investigated, including diet, alcohol consumption, physical activity, and smoking. Linear regression models were used to examine the association between lifestyle factors and Δage, and the models were adjusted for sex and chronological age. Results: This study included 44,094 individuals (mean age 64 ± 8, 51.4% females). A significant correlation was observed between predicted biological age and chronological age (correlation coefficient = 0.54, P < 0.001) and the mean Δage (absolute error of biological age and chronological age) was 9.8 ± 7.4 years. Δage was significantly associated with all of the four lifestyle factors, with the effect size ranging from 0.41 ± 0.11 for the healthy diet to 2.37 ± 0.30 for non-smoking. Compared with an ideal lifestyle, an unfavorable lifestyle was associated with an average of 2.50 ± 0.29 years of older predicted ECG-age. Conclusion: In this large contemporary population, a strong association was observed between all four studied healthy lifestyle factors and deaccelerated aging. Our study underscores the importance of a healthy lifestyle to reduce the burden of aging-related diseases.

Screening for Chagas disease from the electrocardiogram using a deep neural network.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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.

Association Between Electrocardiographic Age and Cardiovascular Events in Community Settings: The Framingham Heart Study.

BACKGROUND: Deep neural networks have been used to estimate age from ECGs, the electrocardiographic age (ECG-age), which predicts adverse outcomes. However, this prediction ability has been restricted to clinical settings or relatively short periods. We hypothesized that ECG-age is associated with death and cardiovascular outcomes in the long-standing community-based FHS (Framingham Heart Study). METHODS: We tested the association of ECG-age with chronological age in the FHS cohorts in ECGs from 1986 to 2021. We calculated the gap between chronological and ECG-age (Δage) and classified individuals as having normal, accelerated, or decelerated aging, if Δage was within, higher, or lower than the mean absolute error of the model, respectively. We assessed the associations of Δage, accelerated and decelerated aging with death or cardiovascular outcomes (atrial fibrillation, myocardial infarction, and heart failure) using Cox proportional hazards models adjusted for age, sex, and clinical factors. RESULTS: The study population included 9877 FHS participants (mean age, 55±13 years; 54.9% women) with 34 948 ECGs. ECG-age was correlated to chronological age (r=0.81; mean absolute error, 9±7 years). After 17±8 years of follow-up, every 10-year increase of Δage was associated with 18% increase in all-cause mortality (hazard ratio [HR], 1.18 [95% CI, 1.12-1.23]), 23% increase in atrial fibrillation risk (HR, 1.23 [95% CI, 1.17-1.29]), 14% increase in myocardial infarction risk (HR, 1.14 [95% CI, 1.05-1.23]), and 40% increase in heart failure risk (HR, 1.40 [95% CI, 1.30-1.52]), in multivariable models. In addition, accelerated aging was associated with a 28% increase in all-cause mortality (HR, 1.28 [95% CI, 1.14-1.45]), whereas decelerated aging was associated with a 16% decrease (HR, 0.84 [95% CI, 0.74-0.95]). CONCLUSIONS: ECG-age was highly correlated with chronological age in FHS. The difference between ECG-age and chronological age was associated with death, myocardial infarction, atrial fibrillation, and heart failure. Given the wide availability and low cost of ECG, ECG-age could be a scalable biomarker of cardiovascular risk.

Cardiovascular Mortality During the COVID-19 Pandemics in a Large Brazilian City: A Comprehensive Analysis.

Introduction: The impact of COVID-19 pandemics on cardiovascular diseases (CVD) may be caused by health system reorganization and/or collapse, or from changes in the behaviour of individuals. In Brazil, municipalities were empowered to define regulatory measures, potentially resulting in diverse effects on CVD morbimortality. Objective: To analyse the impact of COVID-19 pandemics on CVD outcomes in Belo Horizonte (BH), the sixth greater capital city in Brazil, including: mortality, mortality at home, hospitalizations, intensive care unit utilization, and in-hospital mortality; and the differential effect according to sex, age range, social vulnerability, and pandemic's phase. Methods: Ecological study analysing data from the Mortality and Hospital Information System of BH residents aged ≥30 years. CVD was defined as in Chapter IX from ICD-10. Social vulnerability was classified by a composite socioeconomic index as high, medium and low. The observed age-standardized rates for epidemiological weeks 10-48, 2020, were compared to the expected rates (mean of 2015-2019). Risk ratios (RiR) were analysed and 95% confidence intervals were calculated for all estimates. Population projected to 2020 for BH and its census tracts were used to calculate rates. Results: We found no changes in CVD mortality rates (RiR 1.01, 95%CI 0.96-1.06). However, CVD deaths occurred more at homes (RiR 1.32, 95%CI 1.20-1.46) than in hospitals (RiR 0.89, 95%CI 0.79-0.99), as a result of a substantial decline in hospitalization rates, even though proportional in-hospital deaths increased. The rise in home deaths was greater in older adults and in had an increasing gradient in those more socially vulnerable (RiR 1.45); for high (RiR 1.45), medium (RiR 1.32) and low vulnerability (RiR 1.21). Conclusion: The greater occurrence of CVD deaths at home, in parallel with lower hospitalization rates, suggests that CVD care was disrupted during the COVID-19 pandemics, which more adversely affected older and more socially vulnerable individuals, exacerbating health inequities in BH.