Clinical Characteristics and Outcomes of Chagas Disease in the United States: A Multicenter Retrospective Analysis.

Chagas disease affects approximately 300,000 patients in the United States. We evaluated a multicenter U.S.-based network to obtain clinical characteristics and outcomes of chronic Chagas disease by disease forms. This was a U.S.-based, multicenter, population-based, retrospective cohort study. We queried TriNetX, a global research network, to identify patients with dual-positive IgG serology for Trypanosoma cruzi. We captured outcomes of interest for up to 5 years. We found 429 patients with evidence of dual-positive T. cruzi IgG out of 19,831 patients with an available test result from 31 U.S. medical centers. The positive proportion for those tested was 2.2%, up to 4.6% among Hispanics. We found a prevalence of a positive Chagas serology of 0.02% among Hispanics. Cardiomyopathy risk reached an annual rate of 1.3% during the initial 5 years of follow-up among patients with the indeterminate form. We found no new events for pulmonary embolism, sudden death, or left ventricular aneurysms at 5 years. Annual risks for arrhythmias and stroke for chronic Chagas cardiomyopathy (CCC) were 1.6% and 0.8%, respectively. The yearly mortality and hospitalization rates for CCC were 2.7% and 17.1%, respectively. Only 13 patients had a documented antitrypanosomal therapy course within 6 months after diagnosis. Of those receiving treatment, 10 patients received benznidazole and three nifurtimox. Chagas disease screening in patients from endemic areas living in the United States remains crucial. Chronic Chagas cardiomyopathy carries a considerable disease burden, translating into increased morbidity and mortality and an enlarging medical health service utilization.

Defibrillation Threshold Testing and Long-term Follow-up in Chagas Disease. / Teste de Limiar de Desfibrilação e Seguimento a Longo Prazo de Pacientes com Cardiopatia Crônica da Doença de Chagas.

BACKGROUND: Sudden cardiac death is the most common cause of death in chronic Chagas cardiomyopathy (CCC). Because most CCC patients who are candidates for implantable cardioverter-defibrillators (ICD) meet criteria for high defibrillation threshold values, a defibrillator threshold test (DTT) is suggested. OBJECTIVES: We investigated the use of DTT in CCC patients, focusing on deaths related to ICD and arrhythmic events, as well as treatment during long-term follow-up. METHODS: We retrospectively evaluated 133 CCC patients who received an ICD mainly for secondary prevention. Demographic, clinical, laboratory data, Rassi score, and DTT data were collected, with p < 0.05 considered significant. RESULTS: The mean patient age was 61 (SD, 13) years and 72% were men. The baseline left ventricular ejection fraction was 40 (SD, 15%) and the mean Rassi score was 10 (SD, 4). No deaths occurred during DTT and no ICD failures were documented. There was a relationship between higher baseline Rassi scores and higher DTT scores (ANOVA = 0.007). The mean time to first shock was 474 (SD, 628) days, although shock was only necessary for 28 (35%) patients with ventricular tachycardia, since most cases resolved spontaneously or through antitachycardia pacing. After a mean clinical follow-up of 1728 (SD, 1189) days, 43 deaths occurred, mainly related to progressive heart failure and sepsis. CONCLUSIONS: A routine DTT may not be necessary for CCC patients who receive an ICD for secondary prevention. High DTT values seem to be unusual and may be related to high Rassi scores.

FUNDAMENTO: A morte súbita cardíaca (MSC) é a causa mais comum de óbito na cardiomiopatia crônica da doença de Chagas (CCDC). Visto que muitos pacientes com CCDC que são candidatos a receber um cardioversor desfibrilador implantável (CDI) atendem a critérios que sugerem alto risco de apresentarem limiares de desfibrilação elevados, sugere-se realizar um teste de limite de desfibrilação (LDF). OBJETIVOS: Investigamos o uso do teste de LDF em pacientes com CCDC, com enfoque nos óbitos relacionados ao implante do CDI e na ocorrência de eventos arrítmicos e o tratamento oferecido durante o seguimento de longo prazo. MÉTODOS: Avaliações retrospectivas de 133 pacientes com CCDC que receberam CDI, principalmente para prevenção secundária. Foram coletados dados demográficos, clínicos e laboratoriais, escore de Rassi e dados do teste de LDF. Adotou-se p<0,05 como estatisticamente significativo. RESULTADOS: A média de idade foi 61±13 anos, e 72% da amostra era do sexo masculino. A fração de ejeção basal do ventrículo esquerdo foi 40±15%, e o escore de Rassi médio foi 10±4 pontos. Não ocorreram óbitos durante o teste de LDF, e não foram documentadas falhas do CDI. Foi identificada relação entre escore de Rassi basal mais elevado e LDFs mais elevados (ANOVA =0,007). O tempo médio até o primeiro choque foi de 474±628 dias, mas a aplicação de choque foi necessária em apenas 28 (35%) pacientes com TV, visto que a maioria dos casos se resolveu espontaneamente ou através da programação de ATP. Após seguimento clínico de 1728±1189 dias, em média, ocorreram 43 óbitos, relacionados principalmente a insuficiência cardíaca progressiva e sepse. CONCLUSÕES: Um teste de LDF de rotina pode não ser necessário para pacientes com CCDCs que receberam CDI para prevenção secundária. LDFs elevados parecem ser incomuns e podem estar relacionados a escore de Rassi elevado.

Heart rate variability as a biomarker in patients with Chronic Chagas Cardiomyopathy with or without concomitant digestive involvement and its relationship with the Rassi score.

BACKGROUND: Dysautonomia plays an ancillary role in the pathogenesis of Chronic Chagas Cardiomyopathy (CCC), but is the key factor causing digestive organic involvement. We investigated the ability of heart rate variability (HRV) for death risk stratification in CCC and compared alterations of HRV in patients with isolated CCC and in those with the mixed form (CCC + digestive involvement). Thirty-one patients with CCC were classified into three risk groups (low, intermediate and high) according to their Rassi score. A single-lead ECG was recorded for a period of 10-20 min, RR series were generated and 31 HRV indices were calculated. The HRV was compared among the three risk groups and regarding the associated digestive involvement. Four machine learning models were created to predict the risk class of patients. RESULTS: Phase entropy is decreased and the percentage of inflection points is increased in patients from the high-, compared to the low-risk group. Fourteen patients had the mixed form, showing decreased triangular interpolation of the RR histogram and absolute power at the low-frequency band. The best predictive risk model was obtained by the support vector machine algorithm (overall F1-score of 0.61). CONCLUSIONS: The mixed form of Chagas' disease showed a decrease in the slow HRV components. The worst prognosis in CCC is associated with increased heart rate fragmentation. The combination of HRV indices enhanced the accuracy of risk stratification. In patients with the mixed form of Chagas disease, a higher degree of sympathetic autonomic denervation may be associated with parasympathetic impairment.

Mortality risk in chronic Chagas cardiomyopathy: a systematic review and meta-analysis.

AIMS: This study aimed to estimate the annual mortality risk and its determinants in chronic Chagas cardiomyopathy. METHODS AND RESULTS: We conducted a systematic search in MEDLINE, Web of Science Core Collection, Embase, Cochrane Library, and LILACS. Longitudinal studies published between 1 January 1946 and 24 October 2018 were included. A random-effects meta-analysis using the death rate over the mean follow-up period in years was used to obtain pooled estimated annual mortality rates. Main outcomes were defined as all-cause mortality, including cardiovascular, non-cardiovascular, heart failure, stroke, and sudden cardiac deaths. A total of 5005 studies were screened for eligibility. A total of 52 longitudinal studies for chronic Chagas cardiomyopathy including 9569 patients and 2250 deaths were selected. The meta-analysis revealed an annual all-cause mortality rate of 7.9% [95% confidence interval (CI): 6.3-10.1; I2  = 97.74%; T2  = 0.70] among patients with chronic Chagas cardiomyopathy. The pooled estimated annual cardiovascular death rate was 6.3% (95% CI: 4.9-8.0; I2  = 96.32%; T2  = 0.52). The annual mortality rates for heart failure, sudden death, and stroke were 3.5%, 2.6%, and 0.4%, respectively. Meta-regression showed that low left ventricular ejection fraction (coefficient = -0.04; 95% CI: -0.07, -0.02; P = 0.001) was associated with an increased mortality risk. Subgroup analysis based on American Heart Association (AHA) classification revealed pooled estimate rates of 4.8%, 8.7%, 13.9%, and 22.4% (P < 0.001) for B1/B2, B2/C, C, and C/D stages of cardiomyopathy, respectively. CONCLUSIONS: The annual mortality risk in chronic Chagas cardiomyopathy is substantial and primarily attributable to cardiovascular causes. This risk significantly increases in patients with low left ventricular ejection fraction and those classified as AHA stages C and C/D.

Experiences with Diagnosis and Treatment of Chagas Disease at a United States Teaching Hospital-Clinical Features of Patients with Positive Screening Serologic Testing.

Chagas disease (CD) is the third most common parasitic infection globally and can cause cardiac and gastrointestinal complications. Around 300,000 carriers of CD live in the U.S., with about 3000 of those in Colorado. We described our experience in diagnosing CD at a Colorado teaching hospital to revise screening eligibility criteria. From 2006 to 2020, we reviewed Trypanosoma cruzi (TC) IgG serology results for 1156 patients in our institution. We identified 23 patients (1.99%) who had a positive test. A total of 14/23 (60%) of positive serologies never had confirmatory testing, and 7 of them were lost to follow up. Confirmatory testing, performed in 9 patients, resulted in being positive in 3. One additional case of CD was identified by positive tissue pathology. All four confirmed cases were among patients born in Latin America. While most of the testing for CD at our institution is part of the pretransplant screening, no confirmed cases of CD derived from this strategy. Exposure risk in this population is not always documented, and initial positive results from screening are not always confirmed. The lack of standardized screening protocols for CD in our institution contributes to underdiagnosis locally and in health systems nationwide. Given a large number of individuals in the U.S. with chronic CD, improved screening is warranted.

Chagas disease. The use of serology to establish drug efficacy. Value and limitations

Presented at the "Consultative Meeting on the Strategic and Operational Aspects for the Clinical Development of Trypanocidal Drugs for Chagas Disease, 23-24 April 2007, Buenos Aires, Argentina.", sponsored by TDR, WHO.

Risk of Chronic Cardiomyopathy Among Patients With the Acute Phase or Indeterminate Form of Chagas Disease: A Systematic Review and Meta-analysis.

Importance: Chagas cardiomyopathy is associated with substantial morbidity and mortality. Precise estimates of the risk of developing cardiomyopathy among patients with the acute or indeterminate chronic forms of Chagas disease are lacking. Objective: To estimate the risk of developing chronic cardiomyopathy in patients with acute and indeterminate chronic forms of Chagas disease. Data Sources: A systematic search in the Cochrane Library, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), Medline, and Web of Science Core Collection databases was conducted from October 8 to October 24, 2018. Studies published between January 1, 1946, and October 24, 2018, that were written in the English, Spanish, and Portuguese languages were included. Search terms included Chagas disease; development of cardiomyopathy; latency duration; and determinants of the Chagas latency period. Study Selection: Longitudinal observational studies of participants diagnosed with the acute phase of Chagas infection or the indeterminate chronic form of Chagas disease who were followed up until the development of cardiomyopathy were included. Studies were excluded if they did not provide sufficient outcome data. Of 10 761 records initially screened, 32 studies met the criteria for analysis. Data Extraction and Synthesis: Critical appraisals of studies were performed using checklists from the Joanna Briggs Institute Reviewer's Manual, and data were collected from published studies. A random-effects meta-analysis was used to obtain pooled estimated annual rates. Data were analyzed from September 11 to December 4, 2019. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline for the registration of the protocol, data collection and integrity, assessment of bias, and sensitivity analyses. Main Outcomes and Measures: Main outcomes were defined as the composite of the development of any new arrhythmias or changes in electrocardiogram results, dilated cardiomyopathy and segmental wall motion abnormalities in echocardiogram results, and mortality associated with Chagas disease. Results: A total of 5005 records were screened for eligibility. Of those, 298 full-text articles were reviewed, and 178 of those articles were considered for inclusion in the quantitative synthesis. After exclusions, 32 studies that included longitudinal observational outcomes were selected for the analysis; 23 of those studies comprised patients with the indeterminate chronic form of Chagas disease, and 9 of those studies comprised patients in the acute phase of Chagas infection. The analysis indicated that the pooled estimated annual rate of cardiomyopathy development was 1.9% (95% CI, 1.3%-3.0%; I2 = 98.0%; τ2 [ln scale] = 0.9992) in patients with indeterminate chronic Chagas disease and 4.6% (95% CI, 2.7%-7.9%; I2 = 86.6%; τ2 [ln scale] = 0.4946) in patients with acute Chagas infection. Conclusions and Relevance: Patients with the indeterminate chronic form of Chagas disease had a significant annual risk of developing cardiomyopathy. The annual risk was more than double among patients in the acute phase of Chagas infection.

A deadly feast: Elucidating the burden of orally acquired acute Chagas disease in Latin America - Public health and travel medicine importance.

Over the past two decades, several countries in Latin American, particularly Brazil, Venezuela, and Colombia, have experienced multiple outbreaks of oral Chagas disease. Transmission occurs secondary to contamination of food or beverages by triatomine (kissing bug) feces containing infective Trypanosoma cruzi metacyclic trypomastigotes. Orally transmitted infections are acute and potentially fatal. Oral Chagas transmission carries important clinical implications from management to public health policies compared to vector-borne transmission. This review aims to discuss the contemporary situation of orally acquired Chagas disease, and its eco-epidemiology, pathogenesis, and clinical management. We also propose preventive public health interventions to reduce the burden of disease and provide important perspectives for travel medicine. Travel health advisors need to counsel intending travellers to South America on avoidance of "deadly feasts" - risky beverages such as fruit juices including guava juice, bacaba, babaçu and palm wine (vino de palma), açai pulp, sugar cane juice and foodstuffs such as wild animal meats that may be contaminated with T. cruzi.

Systematic Review and Meta-Analysis of Clinical Outcome After Implantable Cardioverter-Defibrillator Therapy in Patients With Chagas Heart Disease.

OBJECTIVES: The goal of this analysis was to pool data from published studies on outcomes after implantable cardioverter-defibrillator (ICD) therapy in patients with Chagas heart disease (CHD). BACKGROUND: CHD is characterized by a high burden of ventricular arrhythmias and an increased risk of sudden cardiac death. The indications for ICD are not well established. METHODS: An extensive literature search without language restrictions was performed to identify all studies on ICD therapy in patients with CHD. A random effects model was used to calculate percentages and 95% confidence intervals (CIs). RESULTS: Of 397 articles screened, 13 studies (all observational) were included. There were 1,041 patients (mean age at implantation 57 ± 11 years; 64% men), most of whom (92%) received an ICD for secondary prevention. Antiarrhythmic medication consisted of amiodarone (79%) and beta-blockers (44%). Overall, the annual all-cause mortality rate was 9.0% (95% CI: 6.9 to 11.7) in 2.8 ± 1.9 years of follow-up, and the annual sudden cardiac death rate was 2.0% (95% CI: 1.3 to 3.3) in 2.6 ± 1.9 years. In addition, 24.8% (95% CI: 15.7 to 37.0) of patients received 1 or more appropriate interventions (shocks or antitachycardia pacing), 4.7% (95% CI: 3.2 to 6.9) received inappropriate shocks, and 9.1% (95% CI: 5.5 to 14.7) had electric storms annually. CONCLUSIONS: In patients with an ICD, annual all-cause mortality rate was 9%. Appropriate ICD interventions and electric storms were frequent, occurring at a rate of 25% and 9% per year, respectively. Inappropriate ICD shocks were not infrequent (5% per year). The benefits and risks of ICD therapy in patients with CHD should be carefully weighed until data from better studies become available.

Duration and determinants of Chagas latency: an etiology and risk systematic review protocol.

OBJECTIVE: The objective of this systematic review is to explore and discuss the latency duration among asymptomatic people with chronic Chagas disease. INTRODUCTION: Studies estimate the latency period of Chagas disease to be approximately 10-30 years. However, new findings may indicate that this latency period is shorter and depends on the presence of clinical factors. This systematic review protocol will explore the duration and factors affecting this latency period to inform treatment, with the potential of improving outcomes. INCLUSION CRITERIA: Eligible studies will include asymptomatic people with indeterminate Chagas disease confirmed through positive serologic testing and the absence of structural cardiomyopathy with no heart failure symptoms and normal electrocardiography results. Studies that involve a longitudinal observation period of participants will be considered. This period must start from the acute acquisition of the infection or an already established indeterminate form of the disease until the development of a primary or secondary cardiac outcome. METHODS: The following electronic databases will be searched: MEDLINE, Embase, Cochrane Library, Web of Science Core Collection and LILACS. The search will include the following concepts: Chagas disease, latency duration and determinants of the Chagas latency period. The languages will be restricted to English, Spanish and Portuguese. Two reviewers will review the selected studies for methodological quality using critical appraisal tools and conduct data extraction. Studies will, where possible, be pooled in a statistical meta-analysis. All data will be presented and synthesized through tables, summaries, figures and charts. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019118019.

Effects of trypanocidal treatment on echocardiographic parameters in chagas cardiomyopathy and prognostic value of wall motion score index: A BENEFIT trial echocardiographic substudy

Serial echocardiographic studies in chronic Chagas cardiomyopathy are scarce. The aims of this study were to evaluate whether therapy with benznidazole modifies the progression of cardiac impairment and to identify baseline echocardiographic parameters related to prognosis. METHODS: A prospective sub study was conducted in 1,508 patients with chronic Chagas cardiomyopathy randomized to benznidazole or placebo, who underwent two-dimensional echocardiography at enrollment, 2 years, and final follow-up (5.4 years). Left ventricular (LV) ejection fraction, LV wall motion score index (WMSI), indexed left atrial volume, and chamber dimensions were collected and correlated to all-cause death and a composite hard outcome using univariate and multivariate analyses. RESULTS: At enrollment, most patients had normal chamber dimensions, and 70.5% had preserved LV ejection fractions. During follow-up, all chamber dimensions increased similarly in both treatment arms. LV ejection fraction was comparably reduced (55.7 ± 12.7% to 52.1 ± 14.6% vs 56.3 ± 12.7% to 52.8 ± 14.1%) and LV WMSI similarly increased (1.31 ± 0.41 to 1.49 ± 0.03 and 1.27 ± 0.38 to 1.51 ± 0.03) for the benznidazole and placebo groups, respectively (P > .05). A higher baseline LV WMSI was identified in subjects who died compared with those alive at final echocardiography (1.76 ± 0.517 vs 1.271 ± 0.393, P < .0001). There was a significant (P < .0001) graded increase in the risk for the composite outcome with worsening LV WMSI (hazard ratios, 2.27 [95% CI, 1.69-3.06] and 6.42 [95% CI, 4.94-8.33]) and also of death (hazard ratios, 2.45 [95% CI, 1.62-3.71] and 8.99 [95% CI, 6.3-12.82]) for 1 < LV WMSI < 1.5 and LV WMSI > 1.5, respectively. Both LV WMSI and indexed left atrial volume remained independent predictors in multivariate analysis. CONCLUSIONS: Trypanocidal treatment had no effect on echocardiographic progression of chronic Chagas cardiomyopathy over 5.4 years. Despite normal global LV systolic function, regional wall motion abnormalities and indexed left atrial volume identified patients at higher risk for hard adverse clinical outcomes. Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved. KEYWORDS: Chagas cardiomyopathy; Echocardiography; Prognosis; Trypanocidal therapy. (AU)

Effects of Trypanocidal Treatment on Echocardiographic Parameters in Chagas Cardiomyopathy and Prognostic Value of Wall Motion Score Index: A BENEFIT Trial Echocardiographic Substudy.

BACKGROUND: Serial echocardiographic studies in chronic Chagas cardiomyopathy are scarce. The aims of this study were to evaluate whether therapy with benznidazole modifies the progression of cardiac impairment and to identify baseline echocardiographic parameters related to prognosis. METHODS: A prospective substudy was conducted in 1,508 patients with chronic Chagas cardiomyopathy randomized to benznidazole or placebo, who underwent two-dimensional echocardiography at enrollment, 2 years, and final follow-up (5.4 years). Left ventricular (LV) ejection fraction, LV wall motion score index (WMSI), indexed left atrial volume, and chamber dimensions were collected and correlated to all-cause death and a composite hard outcome using univariate and multivariate analyses. RESULTS: At enrollment, most patients had normal chamber dimensions, and 70.5% had preserved LV ejection fractions. During follow-up, all chamber dimensions increased similarly in both treatment arms. LV ejection fraction was comparably reduced (55.7 ± 12.7% to 52.1 ± 14.6% vs 56.3 ± 12.7% to 52.8 ± 14.1%) and LV WMSI similarly increased (1.31 ± 0.41 to 1.49 ± 0.03 and 1.27 ± 0.38 to 1.51 ± 0.03) for the benznidazole and placebo groups, respectively (P > .05). A higher baseline LV WMSI was identified in subjects who died compared with those alive at final echocardiography (1.76 ± 0.517 vs 1.271 ± 0.393, P < .0001). There was a significant (P < .0001) graded increase in the risk for the composite outcome with worsening LV WMSI (hazard ratios, 2.27 [95% CI, 1.69-3.06] and 6.42 [95% CI, 4.94-8.33]) and also of death (hazard ratios, 2.45 [95% CI, 1.62-3.71] and 8.99 [95% CI, 6.3-12.82]) for 1 < LV WMSI < 1.5 and LV WMSI > 1.5, respectively. Both LV WMSI and indexed left atrial volume remained independent predictors in multivariate analysis. CONCLUSIONS: Trypanocidal treatment had no effect on echocardiographic progression of chronic Chagas cardiomyopathy over 5.4 years. Despite normal global LV systolic function, regional wall motion abnormalities and indexed left atrial volume identified patients at higher risk for hard adverse clinical outcomes.

Stem-cell therapy in ST-segment elevation myocardial infarction with reduced ejection fraction: A multicenter, double-blind randomized trial.

BACKGROUND: Left ventricular ejection fraction (LVEF) is a major determinant of long-term prognosis after ST-segment elevation myocardial infarction (STEMI). STEMI patients with reduced LVEF have a poor prognosis, despite successful reperfusion and the use of renin-angiotensin-aldosterone inhibitors. HYPOTHESIS: Intracoronary infusion of bone marrow-derived mononuclear cells (BMMC) may improve LVEF in STEMI patients successfully reperfused. METHODS: The main inclusion criteria for this double-blind, randomized, multicenter study were patient age 30 to 80 years, LVEF ≤50%, successful angioplasty of infarct-related artery, and regional dysfunction in the infarct-related area analyzed before cell injection. Cardiac magnetic resonance imaging was used to assess LVEF, left ventricular volumes, and infarct size at 7 to 9 days and 6 months post-myocardial infarction. RESULTS: One hundred and twenty-one patients were included (66 patients in the BMMC group and 55 patients in the placebo group). The primary endpoint, mean LVEF, was similar between both groups at baseline (44.63% ± 10.74% vs 42.23% ± 10.33%; P = 0.21) and at 6 months (44.74% ± 12.95 % vs 43.50 ± 12.43%; P = 0.59). The groups were also similar regarding the difference between baseline and 6 months (0.11% ± 8.5% vs 1.27% ± 8.93%; P = 0.46). Other parameters of left ventricular remodeling, such as systolic and diastolic volumes, as well as infarct size, were also similar between groups. CONCLUSIONS: In this randomized, multicenter, double-blind trial, BMMC intracoronary infusion did not improve left ventricular remodeling or decrease infarct size.

Long-term follow-up of Chagas heart disease patients receiving an implantable cardioverter-defibrillator for secondary prevention.

BACKGROUND: Chagas heart disease (CHD) is a dilated cardiomyopathy characterized by malignant ventricular arrhythmias and increased risk of sudden cardiac death (SCD). Much controversy exists concerning the efficacy of implantable cardioverter-defibrillator (ICDs) in CHD because of mixed results observed. We report our long-term experience with ICDs for secondary prevention in CHD, with the specific aim of assessing the results in groups with preserved or depressed global left ventricular function. METHODS: 111 patients (75 males; 60 ± 12 years) were followed for 1,948 ± 1,275 days after ICD. Time to death was the primary outcome; LVEF ≤ 45% the exposure; and age, gender, and ICD therapy delivery the potential confounders. We used time-to-event methods and Cox proportional models for analysis, censoring observations at time of death or at 5-year follow-up in survivors. RESULTS: Seventy-two percent of the patients presented at least one sustained ventricular arrhythmia requiring appropriate therapy, and only three patients received inappropriate therapy. Death occurred in 50 (45%) patients, with an annual mortality rate of 8.4%, mostly due to refractory heart failure or noncardiac causes. Unadjusted survival rates were significantly distinct between patients with left ventricular ejection fraction (LVEF) ≤ 45% (26 deaths), 50.5% (95% confidence interval [CI]: 36.2%-63.2%) when compared to patients with LVEF > 45% (10 deaths), 77.6% (95% CI: 62.3%-87.3%, P < 0.01). After adjusting for confounders, low LVEF (hazard ratio [HR]: 5.2, 95% CI: 2.3-11.6), age (HR: 1.04, 95% CI: 1.01-1.07), and female gender (HR: 3.97, 95% CI: 1.85-8.54) were independently associated with the outcome. CONCLUSIONS: ICDs successfully aborted life-threatening arrhythmias in CHD patients. Impaired left ventricular function predicted higher mortality in CHD patients with an ICD for secondary prevention of SCD.

'Choosing Wisely' culture among Brazilian cardiologists.

OBJECTIVE: (i) To describe how aligned the 'Choosing Wisely' concept is with the medical culture among Brazilian cardiologists and (ii) to identify predictors for physicians' preference for avoiding wasteful care. DESIGN: Cross-sectional study. SETTING: Brazilian Society of Cardiology. PARTICIPANTS: Cardiologists who agree to fill a web questionary. INTERVENTION: A task force of 12 Brazilian cardiologists prepared a list of 13 'do not do' recommendations, which were made available on the Brazilian Society of Cardiology website for affiliates to assign a supported score of 1 to 10 to each recommendation. MAIN OUTCOME MEASUREMENT: Score average for supporting recommendations. RESULTS: Of 14 579 Brazilian cardiologists, 621 (4.3%) answered the questionnaire. The top recommendation was 'do not perform routine percutaneous coronary intervention in asymptomatic individuals' (mean score = 8.0 ± 2.9) while the one with the lowest support was 'do not use an intra-aortic balloon pump in infarction with cardiogenic shock' (5.8 ± 3.2). None of the 13 recommendations presented a mean grade >9 (strong support); 7 recommendations averaged 7-8 (moderate support) followed by 6 recommendations with an average of 5-7 (modest support). Multivariate analysis independently identified predictors of the score attributed to the top recommendation; being an interventionist and time since graduation were both negatively associated with support. CONCLUSIONS: (i) The support of Brazilian cardiologists for the 'Choosing Wisely' concept is modest to moderate, and (ii) older generations and enthusiasm towards the procedure one performs may be factors against the 'Choosing Wisely' philosophy.

Chronic Chagas cardiomyopathy: a review of the main pathogenic mechanisms and the efficacy of aetiological treatment following the BENznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial

Chagas cardiomyopathy is the most frequent and most severe manifestation of chronic Chagas disease, and is one of the leading causes of morbidity and death in Latin America. Although the pathogenesis of Chagas cardiomyopathy is incompletely understood, it may involve several mechanisms, including parasite-dependent myocardial damage, immune-mediated myocardial injury (induced by the parasite itself and by self-antigens), and microvascular and neurogenic disturbances. In the past three decades, a consensus has emerged that parasite persistence is crucial to the development and progression of Chagas cardiomyopathy. In this context, antiparasitic treatment in the chronic phase of Chagas disease could prevent complications related to the disease. However, according to the results of the BENEFIT trial, benznidazole seems to have no benefit for arresting disease progression in patients with chronic Chagas cardiomyopathy. In this review, we give an update on the main pathogenic mechanisms of Chagas disease, and re-examine and discuss the results of the BENEFIT trial, together with its limitations and implications.