New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19.

PURPOSE: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated. METHODS: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. RESULTS: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. CONCLUSION: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial.

Importance: It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Objective: To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days. Design, Setting, and Participants: A randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020). Interventions: Discontinuation (n = 334) or continuation (n = 325) of ACEIs or ARBs. Main Outcomes and Measures: The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression. Results: Among 659 patients, the median age was 55.1 years (interquartile range [IQR], 46.1-65.0 years), 14.7% were aged 70 years or older, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days [SD, 8 days]) vs patients in the continuation group (mean, 22.9 days [SD, 7.1 days]) and the mean ratio was 0.95 (95% CI, 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs 2.8% for the continuation group; odds ratio [OR], 0.97 [95% CI, 0.38-2.52]), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95 [95% CI, 0.19-42.12]), or COVID-19 progression (38.3% vs 32.3%; OR, 1.30 [95% CI, 0.95-1.80]). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%). Conclusions and Relevance: Among patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04364893.

Quality of life and associated factors in patients with chronic Chagas disease.

OBJECTIVES: To evaluate the quality of life (QoL) of patients with Chagas disease (CD) and the association between QoL domains and several clinical, socioeconomic and lifestyle characteristics of this population. METHODS: Cross-sectional observational study conducted from March 2014 to March 2017 including a total of 361 outpatients followed at Evandro Chagas National Institute of Infectious Disease, Brazil. QoL was assessed using the Portuguese shorter version of the original WHO Quality of Life questionnaire (WHOQOL-BREF). Information about clinical CD presentation, presence of comorbidities, functional class, previous benznidazole treatment, socioeconomic profile and lifestyle was also obtained. RESULTS: Environment and physical domains presented the worst QoL scores, while the social relationship domain presented the highest score. Multivariate regression analysis demonstrated that variables independently associated with QoL were functional class, sex, clinical presentation of CD, sleep duration, schooling, physical activity level, smoking, income per capita and residents by domicile. CONCLUSIONS: The low socioeconomic status and the physical limitations imposed by the disease presented an important impact on the QoL reduction among CD patients, especially on environment and physical domains. Strategies to improve QoL among CD patients should be tailored and consider many different variables to maximise improvements not only of patients' physical but also of their mental health.

Lack of Anticoagulant Use in Patients with Atrial Fibrillation and Increased Risk of Thromboembolic Events According to Sex: Insights from a Multicentric Brazilian Study. / Falta de Uso de Anticoagulantes em Pacientes com Fibrilação Atrial e Risco Aumentado de Eventos Tromboembólicos de Acordo com o Sexo: Insights de um Estudo Multicêntrico Brasileiro.

BACKGROUND: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and its presentation differs according to age and sex. Recent studies have revealed differences in AF among various demographic groups, including the Latin American population. OBJECTIVES: To better understand potential disparities in AF prevalence and treatment strategies in the Brazilian population through data from a large multicentric prospective registry. METHODS: The Rede D'Or AF registry is a multicenter prospective observational study including patients aged ≥ 18 years with AF who were seen in the emergency department of 32 tertiary hospitals in Brazil. Patients were characterized according to sex and other baseline characteristics and were classified according to previous anticoagulant use. The lack of anticoagulant use in patients with previous indications was analyzed. Statistical significance was set at 5%. RESULTS: The study data were from a total of 1955 patients enrolled. Male sex was more prevalent, and men were younger than the women. Due to an increased prevalence of previous AF episode and a higher CHA2DS2-VASc score, more women had indications for anticoagulant therapy; however, a significant proportion was not receiving this treatment. From 29 in-hospital deaths, 15 patients had previous indication for anticoagulation, but only 3 were using anticoagulants. CONCLUSION: This study revealed sex-related differences in the Brazilian population of patients with AF that are consistent with trends in high-income countries. The promotion of better implementation of anticoagulant and antithrombotic therapies to reduce the risk of death and thromboembolic events among women with AF in Brazil is crucial.

FUNDAMENTO: A fibrilação atrial (FA) é a arritmia cardíaca mais prevalente e sua apresentação difere de acordo com a idade e o sexo. Estudos recentes revelaram diferenças na FA entre vários grupos demográficos, incluindo a população latino-americana. OBJETIVOS: Melhor compreender as possíveis disparidades na prevalência da FA e nas estratégias de tratamento na população brasileira por meio de dados de um registro prospectivo multicêntrico de grande escala. MÉTODOS: O registro de FA da Rede D'Or é um estudo observacional prospectivo multicêntrico que incluiu pacientes com idade ≥ 18 anos com FA atendidos no pronto-socorro de 32 hospitais terciários no Brasil. Os pacientes foram caracterizados de acordo com o sexo e outras características basais e classificados de acordo com o uso prévio de anticoagulantes. Foi analisada a falta de uso de anticoagulantes em pacientes com indicações prévias. A significância estatística foi estabelecida em 5%. RESULTADOS: Os dados do estudo foram provenientes de um total de 1.955 pacientes inscritos. O sexo masculino foi mais prevalente e os homens eram mais jovens que as mulheres. Devido ao aumento da prevalência de episódios anteriores de FA e a um escore CHA2DS2-VASc mais elevado, mais mulheres tiveram indicação de terapia anticoagulante; no entanto, uma proporção significativa não estava recebendo esse tratamento. Dos 29 óbitos intra-hospitalares, 15 pacientes tinham indicação prévia para anticoagulação, mas apenas 3 estavam em uso de anticoagulantes. CONCLUSÃO: O presente estudo revelou diferenças relacionadas ao sexo na população brasileira de pacientes com FA que são consistentes com tendências em países de alta renda. A promoção de uma melhor implementação de terapias anticoagulantes e antitrombóticas para reduzir o risco de óbito e eventos tromboembólicos entre mulheres com FA no Brasil é crucial.

Corrigendum: Home-based exercise program in the indeterminate form of Chagas disease (PEDI-CHAGAS study): a study protocol for a randomized clinical trial.

[This corrects the article DOI: 10.3389/fmed.2022.1087188.].

Biomarkers and Echocardiographic Predictors of Cardiovascular Outcome in Patients With Chronic Chagas Disease.

Background Chagas disease (CD) presents an ominous prognosis. The predictive value of biomarkers and new echocardiogram parameters in adjusted models have not been well studied. Methods and Results There were 361 patients with chronic CD (57.6% men, 61±11 years of age, clinical forms: indeterminate 27.1%, cardiac 56.6%, digestive 3.6%, cardiodigestive 12.7%) included in this single-center, observational, prospective longitudinal study. Echocardiographic evaluation included strain analyses of left atrial, left ventricular (LV), and right ventricular and 3-dimensional analyses of left atrial and LV volumes. Biomarkers included cardiac troponin I, brain natriuretic peptide, transforming growth factor ß1, tumor necrosis factor, matrix metalloproteinases, and Trypanosoma cruzi polymerase chain reaction. The studied end point was a composite of CD-related mortality, heart transplant, hospital admission due to worsening heart failure, or new cardiac device insertion. Event-free survival was analyzed by multivariable regression analyses adjusted for competing risks. P values <0.05 were considered significant. The composite event occurred in 79 patients after 4.9±2.0 years follow-up. LV end-diastolic volume (hazard ratio [HR], 1.01 [95% CI, 1.00-1.02]; P=0.02), peak negative global atrial strain (HR, 1.08 [95% CI, 1.00-1.17]; P=0.04), LV global circumferential strain (HR, 1.12 [95% CI, 1.04-1.21]; P=0.003), LV torsion (HR, 0.55 [95% CI, 0.35-0.81]; P=0.003), brain natriuretic peptide (HR, 2.03 [95% CI, 1.23-3.34]; P=0.005), and positive T cruzi polymerase chain reaction (HR, 1.80 [95% CI, 1.12-2.91]; P=0.01) were end point predictors independent from age, sex, 2-dimensional echocardiographic indexes, hypertension, previous cardiac device, and CD cardiac form. Conclusions Two-dimensional strain- and 3-dimensional-derived parameters, brain natriuretic peptide, and positive T cruzi polymerase chain reaction can be useful for prediction of CD cardiovascular events.

Safety of benznidazole use in the treatment of chronic Chagas' disease.

OBJECTIVES: To assess the safety of benznidazole use in adult patients with chronic Chagas' disease. METHODS: The Naranjo algorithm was applied to classify the causality of adverse drug reactions (ADRs). RESULTS: In total, 190 patients were treated with benznidazole over a period of 4-180 days (mean 58.90 ± 36.54 days) with a dose of 50-500 mg/day (221.33 ± 57.16 mg/day). Of the 190 patients treated, 93 had ADRs and 59 of these interrupted treatment. There was a higher incidence of ADRs among female and young adult patients. There was a higher incidence of ADRs during the first 30 days of treatment. Interruption of treatment was more frequent in women. Among the patients who interrupted treatment, 39 had mild ADRs, 19 had moderate ADRs and 1 had a severe ADR. There were no interruptions in treatment for 97 patients without ADRs. The survival curves indicated that the time until interruption of treatment in patients with moderate and severe ADRs was lower than in patients with mild or no ADRs. The most frequent disorders were in the skin (26.3%), gastrointestinal system (9.5%) and nervous system (5.3%). CONCLUSIONS: The Naranjo algorithm was a useful tool to reduce the underreporting of ADRs. Events were common, but were associated with low morbidity and were reversible upon discontinuation of drug treatment. Moreover, there were no fatal events; therefore, benznidazole treatment was considered safe.

Two-dimensional strain derived parameters provide independent predictors of progression to Chagas cardiomyopathy and mortality in patients with Chagas disease.

BACKGROUND: Patients with chronic Chagas disease (CD) cardiomyopathy have a high mortality. We evaluated if two-dimensional (2D) strain (ε) parameters provide independent predictors of progression to CD cardiomyopathy and all-cause mortality. METHODS: A total of 408 patients with chronic CD (58.6% women; 53 ± 11 years; clinical forms: indeterminate 34.1%, cardiac 57.6%, digestive 1.2%, cardiodigestive 7.1%) were consecutively included in this single-center prospective longitudinal study. Echocardiographic evaluation included left atrial and left ventricular (LV) function on ε analyses. Primary end-point was a composite of all-cause mortality or heart transplant. Secondary end-point was CD progression defined as the occurrence of changes typical of CD in electrocardiogram, sustained ventricular tachycardia, wall motion abnormalities, or heart failure among patients with the indeterminate form at baseline. Multivariable Cox-proportional-hazards regression analyses were performed to test if 2D ε parameters were associated with the studied end-points. P values < 0.05 were considered significant. RESULTS: The primary end-point occurred in 91 patients after a follow-up of 6.5 ± 2.7 years. CD progression occurred in 26 out of 144 patients without cardiac form at baseline (2.88 cases/100 patient-years). Peak LV circumferential (HR 1.09, 95% CI 1.01-1.18, P = .02) and radial (HR 0.97, 95% CI 0.95-0.99, P = .007) ε, and LV torsion (HR 0.51, 95% CI 0.35-0.74, P = .0004) were independent predictors of the primary end-point. Peak LV radial ε (HR 0.96, 95% CI 0.93-0.99, P = .03) was an independent predictor of CD progression. CONCLUSIONS: Therefore, 2D ε derived parameters can be useful for CD progression and mortality prediction.

The association of exercise test variables with long-term mortality in patients with chronic Chagas disease.

Background: The identification of variables obtained in the exercise test (ET) associated with increased risk of death is clinically relevant and would provide additional information for the management of Chagas disease (CD). The objective of the present study was to evaluate the association of ET variables with mortality in patients with chronic CD. Methods: This retrospective longitudinal observational study included 232 patients (median age 46.0 years; 50% women) with CD that were followed at the Evandro Chagas National Institute of Infectious Diseases (Rio de Janeiro, Brazil) and performed an ET between 1989 and 2000. The outcome of interest was all-cause mortality. Results: There were 103 deaths (44.4%) during a median follow-up of 21.5 years (IQR 25-75% 8.0-27.8), resulting in 24.5 per 1,000 patients/year incidence rate. The ET variables associated with mortality after adjustments for potential confounders were increased maximal (HR 1.02; 95% CI 1.00-1.03 per mmHg) and change (HR 1.03; 95% CI 1.01-1.06 per mmHg) of diastolic blood pressure (DBP) during ET, ventricular tachycardia at rest (HR 3.95; 95% CI 1.14-13.74), during exercise (HR 2.73; 95% CI 1.44-5.20), and recovery (HR 2.60; 95% CI 1.14-5.91), and premature ventricular complexes during recovery (HR 2.06; 1.33-3.21). Conclusion: Our findings suggest that ET provides important prognostic value for mortality risk assessment in patients with CD, with hemodynamic (increased DBP during exercise) and electrocardiographic (presence of ventricular arrhythmias) variables independently associated with an increased mortality risk in patients with CD. The identification of individuals at higher mortality risk can facilitate the development of intervention strategies (e.g., close follow-up) that may potentially have an impact on the longevity of patients with CD.

Troponin in COVID-19: To Measure or Not to Measure? Insights from a Prospective Cohort Study.

Myocardial injury (MI), defined by troponin elevation, has been associated with increased mortality and adverse outcomes in patients with coronavirus disease 2019 (COVID-19), but the role of this biomarker as a risk predictor remains unclear. Data from adult patients hospitalized with COVID-19 were recorded prospectively. A multiple logistic regression model was used to quantify associations of all variables with in-hospital mortality, including the calculation of odds ratios (ORs) and confidence intervals (CI). Troponin measurement was performed in 1476 of 4628 included patients, and MI was detected in 353 patients, with a prevalence of 23.9%; [95% CI, 21.8-26.1%]. The total in-hospital mortality rate was 10.9% [95% CI, 9.8-12.0%]. The mortality was much higher among patients with MI than among those without MI, with a prevalence of 22.7% [95% CI, 18.5-27.3%] vs. 5.5% [95% CI, 4.3-7.0%] and increased with each troponin level. After adjustment for age and comorbidities, the model revealed that the mortality risk was greater for patients with MI [OR = 2.99; 95% CI, 2.06-4.36%], and for those who did not undergo troponin measurement [OR = 2.2; 95% CI, 1.62-2.97%], compared to those without MI. Our data support the role of troponin as an important risk predictor for these patients, capable of discriminating between those with a low or increased mortality rate. In addition, our findings suggest that this biomarker has a remarkable negative predictive value in COVID-19.

Home-based exercise program in the indeterminate form of Chagas disease (PEDI-CHAGAS study): A study protocol for a randomized clinical trial.

Background: Chagas disease (CD) is a neglected endemic disease with worldwide impact due to migration. Approximately 50-70% of individuals in the chronic phase of CD present the indeterminate form, characterized by parasitological and/or serological evidence of Trypanosoma cruzi infection, but without clinical signs and symptoms. Subclinical abnormalities have been reported in indeterminate form of CD, including pro-inflammatory states and alterations in cardiac function, biomarkers and autonomic modulation. Moreover, individuals with CD are usually impacted on their personal and professional life, making social insertion difficult and impacting their mental health and quality of life (QoL). Physical exercise has been acknowledged as an important strategy to prevent and control numerous chronic-degenerative diseases, but unexplored in individuals with the indeterminate form of CD. The PEDI-CHAGAS study (which stands for "Home-Based Exercise Program in the Indeterminate Form of Chagas Disease" in Portuguese) aims to evaluate the effects of a home-based exercise program on physical and mental health outcomes in individuals with indeterminate form of CD. Methods and design: The PEDI-CHAGAS is a two-arm (exercise and control) phase 3 superiority randomized clinical trial including patients with indeterminate form of CD. The exclusion criteria are <18 years old, evidence of non-Chagasic cardiomyopathy, musculoskeletal or cognitive limitations that preclude the realization of exercise protocol, clinical contraindication for regular exercise, and regular physical exercise (≥1 × per week). Participants will be assessed at baseline, and after three and 6 months of follow-up. The primary outcome will be QoL. Secondary outcomes will include blood pressure, physical fitness components, nutritional status, fatigability, autonomic modulation, cardiac morphology and function, low back pain, depression and anxiety, stress, sleep quality, medication use and adherence, and biochemical, inflammatory and cardiac biomarkers. Participants in the intervention group will undergo a home-based exercise program whilst those in the control group will receive only general information regarding the benefits of physical activity. Both groups will receive the same general nutritional counseling consisting of general orientations about healthy diets. Conclusion: The findings from the present study may support public health intervention strategies to improve physical and mental health parameters to be implemented more effectively in this population. Clinical trial registration: [https://ensaiosclinicos.gov.br/rg/RBR-10yxgcr9/], identifier [U1111-1263-0153].

NKG2A Expression among CD8 Cells Is Associated with COVID-19 Progression in Hypertensive Patients: Insights from the BRACE CORONA Randomized Trial.

Cardiovascular comorbidities and immune-response dysregulation are associated with COVID-19 severity. We aimed to explore the key immune cell profile and understand its association with disease progression in 156 patients with hypertension that were hospitalized due to COVID-19. The primary outcome was progression to severe disease. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and immune cell subsets associated with the primary outcome. Obesity; diabetes; oxygen saturation; lung involvement on computed tomography (CT) examination; the C-reactive protein concentration; total lymphocyte count; proportions of CD4+ and CD8+ T cells; CD4/CD8 ratio; CD8+ HLA-DR MFI; and CD8+ NKG2A MFI on admission were all associated with progression to severe COVID-19. This study demonstrated that increased CD8+ NKG2A MFI at hospital admission, in combination with some clinical variables, is associated with a high risk of COVID-19 progression in hypertensive patients. These findings reinforce the hypothesis of the functional exhaustion of T cells with the increased expression of NKG2A in patients with severe COVID-19, elucidating how severe acute respiratory syndrome coronavirus 2 infection may break down the innate antiviral immune response at an early stage of the disease, with future potential therapeutic implications.

Chagas heart disease: An overview of diagnosis, manifestations, treatment, and care.

Chagas heart disease (CHD) affects approximately 30% of patients chronically infected with the protozoa Trypanosoma cruzi. CHD is classified into four stages of increasing severity according to electrocardiographic, echocardiographic, and clinical criteria. CHD presents with a myriad of clinical manifestations, but its main complications are sudden cardiac death, heart failure, and stroke. Importantly, CHD has a higher incidence of sudden cardiac death and stroke than most other cardiopathies, and patients with CHD complicated by heart failure have a higher mortality than patients with heart failure caused by other etiologies. Among patients with CHD, approximately 90% of deaths can be attributed to complications of Chagas disease. Sudden cardiac death is the most common cause of death (55%-60%), followed by heart failure (25%-30%) and stroke (10%-15%). The high morbimortality and the unique characteristics of CHD demand an individualized approach according to the stage of the disease and associated complications the patient presents with. Therefore, the management of CHD is challenging, and in this review, we present the most updated available data to help clinicians and cardiologists in the care of these patients. We describe the clinical manifestations, diagnosis and classification criteria, risk stratification, and approach to the different clinical aspects of CHD using diagnostic tools and pharmacological and non-pharmacological treatments.

Benznidazole decreases the risk of chronic Chagas disease progression and cardiovascular events: A long-term follow up study.

BACKGROUND: Chagas disease (CD) remains an important endemic disease in Latin America. However, CD became globalized in recent decades. The majority of the chronically infected individuals did not receive etiologic treatment for several reasons, among them the most conspicuous is the lack of access to diagnosis. The impact of trypanocidal treatment on CD chronic phase, without cardiac involvement (indeterminate form ICF), is yet to be determined. We aimed to evaluate the effect of trypanocidal treatment with benznidazole (BZN) on the rate of progression to Chagas heart disease in patients with ICF. METHODS: This is a retrospective cohort observational study including patients with ICF treated with BZN and compared to a group of non-treated patients matched for age, sex, region of origin, and the year of cohort entry. We reviewed the medical charts of all patients followed from May 1987 to June 2020 at the outpatient center of the Evandro Chagas National Institute of Infectious Diseases (INI) of the Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil. Patients' follow-up included at least one annual medical visit and one annual electrocardiogram (ECG). Echocardiographic exams were performed at baseline and during the follow-up. Disease progression from ICF to cardiac form was defined by changes in baseline ECG. Cumulative incidence and the incidence rate were described in the incidence analysis. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association between BZN and CD progression, cardiovascular events or death. FINDINGS: One hundred and fourteen treated patients met the study inclusion criteria. A comparison group of 114 non-treated patients matched for age, sex, region of origin, and the year of cohort entry was also included, totalizing 228 patients. Most patients included in the study were male (70.2%), and their mean age was 31.3 (+7.4) years. Over a median follow-up of 15.1 years (ranging from 1.0 to 32.4), the cumulative CD progression incidence in treated patients was 7.9% vs. 21.1% in the non-treated group (p = 0.04) and the CD progression rate was 0.49 per 1.000 patients/year in treated patients vs. 1.10 per 1.000 patients/year for non-treated patients (p = 0.02). BZN treatment was associated with a decreased risk of CD progression in both unadjusted (HR 0.46; 95%CI 0.21 to 0.98) and adjusted (HR 0.43; 95%CI 0.19 to 0.96) models and with a decreased risk of occurrence of the composite of cardiovascular events only in the adjusted (HR 0.15; 95%CI 0.03 to 0.80) model. No association was observed between BZN treatment and mortality. INTERPRETATION: In a long-term follow-up, BZN treatment was associated with a decreased incidence of CD progression from ICF to the cardiac form and also with a decreased risk of cardiovascular events. Therefore, our results indicate that BZN treatment for CD patients with ICF should be implemented into clinical practice.

Effects of Selenium treatment on cardiac function in Chagas heart disease: Results from the STCC randomized Trial.

BACKGROUND: Chagas disease (caused by Trypanosoma cruzi infection) evolves to chronic chagasic cardiomyopathy (CCC) affecting 1.8 million people worldwide. This is the first randomized, placebo-controlled, double-blinded, clinical trial designed to estimate efficacy and safety of selenium (Se) treatment in CCC. METHODS: 66 patients with CCC stages B1 (left ventricular ejection fraction [LVEF] > 45% and no heart failure; n = 54) or B2 (LVEF < 45% and no heart failure; n = 12) were randomly assigned to receive 100 mcg/day sodium selenite (Se, n = 32) or placebo (Pla, n = 34) for one year (study period: May 2014-September 2018). LVEF changes over time and adverse effects were investigated. Trial registration number: NCT00875173 (clinicaltrials.gov). FINDINGS: No significant differences between the two groups were observed for the primary outcome: mean LVEF after 6 (ß= +1.1 p = 0.51 for Se vs Pla) and 12 months (ß= +2.1; p = 0.23). In a subgroup analysis, statistically significant longitudinal changes were observed for mean LVEF in the stage B2 subgroup (ß= +10.1; p = 0.02 for Se [n = 4] vs Pla [n = 8]). Se treatment was safe for CCC patients, and the few adverse effects observed were similarly distributed across the two groups. INTERPRETATION: Se treatment did not improve cardiac function (evaluated from LVEF) in CCC. However, in the subgroup of patients at B2 stage, a potential beneficial influence of Se was observed. Complementary studies are necessary to explore diverse Se dose and/or associations in different CCC stages (B2 and C), as well as in A and B1 stages with longer follow-up. FUNDING: Brazilian Ministry of Health, Fiocruz, CNPq, FAPERJ.

Left Atrial Structure and Function Predictors of New-Onset Atrial Fibrillation in Patients with Chagas Disease.

BACKGROUND: Atrial fibrillation (AF) carries ominous consequences in patients with Chagas disease. The aim of this study was to determine whether left atrial (LA) volume and function assessed using three-dimensional echocardiographic (3DE) imaging and two-dimensional speckle-tracking echocardiographic deformation analysis of strain (ε) could predict new-onset AF in patients with Chagas disease. METHODS: A total of 392 adult patients with chronic Chagas disease (59% women; mean age, 53 ± 11 years) who underwent echocardiography were consecutively enrolled in this prospective longitudinal study. Echocardiographic evaluation included two-dimensional (2D) Doppler echocardiography, with evaluation of left ventricular systolic and diastolic function, LA size, and LA and left ventricular function on 3DE and ε analyses. Multivariate Cox proportional-hazards regression analysis models adjusting for age, sex, hypertension, presence of a pacemaker, and 2D Doppler echocardiographic parameters were used to test if the variables of interest had independent prognostic value for AF prediction. RESULTS: Patients with Chagas disease were followed for 5.6 ± 2.7 years. Among these, 139 (35.5%) had the indeterminate form, 224 (57.1%) had the cardiac form, five (1.3%) had the digestive form, and 24 (6.1%) had the cardiodigestive form. The study end point of AF occurred in 45 patients. Total LA emptying fraction (hazard ratio, 0.93; 95% CI, 0.89-0.98; P = .002), passive LA emptying fraction (HR, 0.95; 95% CI, 0.91-0.99; P = .02), and peak negative global LA ε (HR, 1.22; 95% CI, 1.05-1.41; P = .01) were predictors of new-onset AF independent of clinical and 2D Doppler echocardiographic parameters. CONCLUSIONS: LA function assessed on 3DE and ε analyses predicts new-onset AF in patients with Chagas disease independent of clinical and 2D Doppler echocardiographic indexes.

Acute Chagas disease in Brazil from 2001 to 2018: A nationwide spatiotemporal analysis.

BACKGROUND: In Brazil, acute Chagas disease (ACD) surveillance involves mandatory notification, which allows for population-based epidemiological studies. We conducted a nationwide population-based ecological analysis of the spatiotemporal patterns of ACD notifications in Brazil using secondary surveillance data obtained from the Notifiable Diseases Information System (SINAN) maintained by Brazilian Ministry of Health. METHODOLOGY/PRINCIPAL FINDINGS: In this nationwide population-based ecological all cases of ACD reported in Brazil between 2001 and 2018 were included. Epidemiological characteristics and time trends were analyzed through joinpoint regression models and spatial distribution using microregions as the unit of analysis. A total of 5,184 cases of ACD were recorded during the period under study. The annual incidence rate in Brazil was 0.16 per 100,000 inhabitants/year. Three statistically significant changes in time trends were identified: a rapid increase prior to 2005 (Period 1), a stable drop from 2005 to 2009 (Period 2), followed by another increasing trend after 2009 (Period 3). Higher frequencies were noted in males and females in the North (all three periods) and in females in Northeast (Periods 1 and 2) macroregions, as well as in individuals aged between 20-64 years in the Northeast, and children, adolescents and the elderly in the North macroregion. Vectorial transmission was the main route reported during Period 1, while oral transmission was found to increase significantly in the North during the other periods. Spatiotemporal distribution was heterogeneous in Brazil over time. Despite regional differences, over time cases of ACD decreased significantly nationwide. An increasing trend was noted in the North (especially after 2007), and significant decreases occurred after 2008 among all microregions other than those in the North, especially those in the Northeast and Central-West macroregions. CONCLUSIONS/SIGNIFICANCE: In light of the newly identified epidemiological profile of CD transmission in Brazil, we emphasize the need for strategically integrated entomological and health surveillance actions.

Development and validation of a risk score for predicting death in Chagas' heart disease.

BACKGROUND: Chagas' disease is an important health problem in Latin America, and cardiac involvement is associated with substantial morbidity and mortality. We developed a model to predict the risk of death in patients with Chagas' heart disease. METHODS: We retrospectively evaluated 424 outpatients from a regional Brazilian cohort. The association of potential risk factors with death was tested by Cox proportional-hazards analysis, and a risk score was created. The model was validated in 153 patients from a separate community hospital. RESULTS: During a mean follow-up of 7.9 years, 130 patients in the development cohort died. Six independent prognostic factors were identified, and each was assigned a number of points proportional to its regression coefficient: New York Heart Association class III or IV (5 points), evidence of cardiomegaly on radiography (5 points), left ventricular systolic dysfunction on echocardiography (3 points), nonsustained ventricular tachycardia on 24-hour Holter monitoring (3 points), low QRS voltage on electrocardiography (2 points), and male sex (2 points). We calculated risk scores for each patient and defined three risk groups: low risk (0 to 6 points), intermediate risk (7 to 11 points), and high risk (12 to 20 points). In the development cohort, the 10-year mortality rates for these three groups were 10 percent, 44 percent, and 84 percent, respectively. In the validation cohort, the corresponding mortality rates were 9 percent, 37 percent, and 85 percent. The C statistic for the point system was 0.84 in the development cohort and 0.81 in the validation cohort. CONCLUSIONS: A simple risk score was developed to predict death in Chagas' heart disease and was validated in an independent cohort.

Falta de Uso de Anticoagulantes em Pacientes com Fibrilação Atrial e Risco Aumentado de Eventos Tromboembólicos de Acordo com o Sexo: Insights de um Estudo Multicêntrico Brasileiro / Lack of Anticoagulant Use in Patients with Atrial Fibrillation and Increased Risk of Thromboembolic Events According to Sex: Insights from a Multicentric Brazilian Study

Resumo Fundamento A fibrilação atrial (FA) é a arritmia cardíaca mais prevalente e sua apresentação difere de acordo com a idade e o sexo. Estudos recentes revelaram diferenças na FA entre vários grupos demográficos, incluindo a população latino-americana. Objetivos Melhor compreender as possíveis disparidades na prevalência da FA e nas estratégias de tratamento na população brasileira por meio de dados de um registro prospectivo multicêntrico de grande escala. Métodos O registro de FA da Rede D'Or é um estudo observacional prospectivo multicêntrico que incluiu pacientes com idade ≥ 18 anos com FA atendidos no pronto-socorro de 32 hospitais terciários no Brasil. Os pacientes foram caracterizados de acordo com o sexo e outras características basais e classificados de acordo com o uso prévio de anticoagulantes. Foi analisada a falta de uso de anticoagulantes em pacientes com indicações prévias. A significância estatística foi estabelecida em 5%. Resultados Os dados do estudo foram provenientes de um total de 1.955 pacientes inscritos. O sexo masculino foi mais prevalente e os homens eram mais jovens que as mulheres. Devido ao aumento da prevalência de episódios anteriores de FA e a um escore CHA2DS2-VASc mais elevado, mais mulheres tiveram indicação de terapia anticoagulante; no entanto, uma proporção significativa não estava recebendo esse tratamento. Dos 29 óbitos intra-hospitalares, 15 pacientes tinham indicação prévia para anticoagulação, mas apenas 3 estavam em uso de anticoagulantes. Conclusão O presente estudo revelou diferenças relacionadas ao sexo na população brasileira de pacientes com FA que são consistentes com tendências em países de alta renda. A promoção de uma melhor implementação de terapias anticoagulantes e antitrombóticas para reduzir o risco de óbito e eventos tromboembólicos entre mulheres com FA no Brasil é crucial.

Abstract Background Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and its presentation differs according to age and sex. Recent studies have revealed differences in AF among various demographic groups, including the Latin American population. Objectives To better understand potential disparities in AF prevalence and treatment strategies in the Brazilian population through data from a large multicentric prospective registry. Methods The Rede D'Or AF registry is a multicenter prospective observational study including patients aged ≥ 18 years with AF who were seen in the emergency department of 32 tertiary hospitals in Brazil. Patients were characterized according to sex and other baseline characteristics and were classified according to previous anticoagulant use. The lack of anticoagulant use in patients with previous indications was analyzed. Statistical significance was set at 5%. Results The study data were from a total of 1955 patients enrolled. Male sex was more prevalent, and men were younger than the women. Due to an increased prevalence of previous AF episode and a higher CHA2DS2-VASc score, more women had indications for anticoagulant therapy; however, a significant proportion was not receiving this treatment. From 29 in-hospital deaths, 15 patients had previous indication for anticoagulation, but only 3 were using anticoagulants. Conclusion This study revealed sex-related differences in the Brazilian population of patients with AF that are consistent with trends in high-income countries. The promotion of better implementation of anticoagulant and antithrombotic therapies to reduce the risk of death and thromboembolic events among women with AF in Brazil is crucial.