Prediction of sudden cardiac death for chagasic patients / Predição de morte súbita cardíaca em pacientes chagásicos / Predicción de muerte súbita cardíaca en pacientes chagásicos federados

Objective: Identify the risk of patients with Chronic Chagas Cardiomyopathy (CCC) to prevent them from having Sudden Cardiac Death (SCD). Methods: We developed an SCD prediction system using a heterogeneous dataset of chagasic patients evaluated in 9 state-of-the-art machine learning algorithms to select the most critical clinical variables and predict SCD in chagasic patients even when the interval between the most recent exams and the SCD event is months or years. Results: 310 patients were analyzed, being 81 (14,7%) suffering from SCD. In the study, Balanced Random Forest showed the best performance, with AUC:80.03 and F1:75.12. Due to their high weights in the machine learning classifiers, we suggest Holter - Non-Sustained Ventricular Tachycardia, Total Ventricular Extrasystoles, Left Ventricular Systolic Diameter, Syncope, and Left Ventricular Diastolic Diameter as essential features to identify SCD. Conclusion: The high-risk pattern of SCD in patients with CCC can be identified and prevented based on clinical and laboratory variables.

Objetivo: Identificar o risco de pacientes com Cardiomiopatia Chagásica Crônica (CCC) para prevenir a Morte Súbita Cardíaca (MSC). Métodos: Desenvolvemos um sistema de MSC usando um conjunto de dados heterogêneo de pacientes chagásicos avaliados em 9 algoritmos de aprendizado de máquina de última geração para selecionar as variáveis clínicas mais críticas e prever MSC em pacientes chagásicos mesmo quando o intervalo mais recente entre os mais recentes exames e o evento MSC é meses ou anos. Resultados: Foram analisados 310 pacientes, sendo 81 (14,7%) portadores de CCC. No estudo, o algoritmo Balanced Random Forest apresentou o melhor desempenho, com AUC:80,03 e F1:75,12. Devido ao seu alto peso nos classificadores de aprendizado de máquina, sugerimos Holter - Taquicardia Ventricular Não Sustentada, Extrassístoles Ventriculares Totais, Diâmetro Sistólico do Ventrículo Esquerdo, Síncope e Diâmetro Diastólico do Ventrículo Esquerdo como características essenciais para identificar a CCC. Conclusão: O padrão de alto risco de MSC em pacientes com CCC pode ser identificado e prevenido com base em variáveis clínicas e laboratoriais.

Objetivo: Identificar el riesgo de los pacientes con Miocardiopatía Chagásica Crónica (MCC) para evitar que presenten Muerte Cardíaca Súbita (MCS). Métodos: Desarrollamos un sistema MCS utilizando un conjunto de datos heterogéneo de pacientes chagásicos evaluados en 9 algoritmos de aprendizaje automático de última generación para seleccionar las variables clínicas más críticas y predecir MCS en pacientes chagásicos incluso cuando el intervalo más reciente entre los más recientes exámenes y el evento MCS es meses o años. Resultados: Se analizaron 310 pacientes, siendo 81 (14,7%) con MSC. En el estudio, Balanced Random Forest mostró el mejor desempeño, con AUC:80.03 y F1:75.12. Debido a su alto peso en los clasificadores de aprendizaje automático, sugerimos Holter - Taquicardia ventricular no sostenida, Extrasístoles ventriculares totales, Diámetro sistólico del ventrículo izquierdo, Síncope y Diámetro diastólico del ventrículo izquierdo como características esenciales para identificar la MSC. Conclusión: El patrón de alto riesgo de MSC en pacientes con MCC se puede identificar y prevenir con base en variables clínicas y de laboratorio.

Desnutrição e Caquexia na Insuficiência Cardíaca Descompensada e Cardiomiopatia Chagásica: Ocorrência e Associação com Desfechos Hospitalares / Undernutrition and Cachexia in Patients with Decompensated Heart Failure and Chagas Cardiomyopathy: Occurrence and Association with Hospital Outcomes

Resumo Fundamento Problemas nutricionais são comuns em pacientes com insuficiência cardíaca (IC) e estão associados a um prognóstico ruim. É relevante mencionar que algumas populações de pacientes, como os com Doença de Chagas, são normalmente excluídas da maioria das análises. Objetivo Buscamos analisar a ocorrência de desnutrição e caquexia em pacientes com Doença de Chagas durante episódios de IC descompensada (ICD) em comparação a outras etiologias, e investigar a influência desses achados em desfechos hospitalares. Método Realizamos um estudo de série de casos consecutivos com pacientes hospitalizados com ICD. Os pacientes foram submetidos à Avaliação Nutricional Subjetiva Global (ASG), além de medidas antropométricas e laboratoriais, e foram avaliados para a ocorrência de caquexia, baixa massa muscular e força. Estudamos a ocorrência de morte e transplante cardíaco de urgência durante a internação. Resultados Ao todo, 131 pacientes foram analisados e 42 (32,1%) tinham Doença de Chagas. Pacientes com Doença de Chagas apresentavam índice de massa corporal (IMC) menor (22,4 kg/m2 [19,9-25,3] vs. 23,6 kg/m2 [20,8-27,3], p=0,03), maior frequência de desnutrição (76,2% vs 55,1%, p=0,015) e mais ocorrências de morte ou transplante (83,3% vs. 41,6%, p<0,001). Observamos que, dentre os pacientes com etiologia da Doença de Chagas, a ocorrência de morte ou transplante cardíaco esteve associada com desnutrição (3 [42,9%] pacientes com alta hospitalar vs. 29 [82,9%] pacientes que morreram ou receberam transplante cardíaco, P=0,043). Conclusões Ao todo, nossos resultados indicam que pacientes com Doença de Chagas internados com ICD costumam apresentar problemas nutricionais, principalmente desnutrição. É importante mencionar que este achado esteve associado à ocorrência de morte e transplante cardíaco durante a internação.

Abstract Background Nutritional disorders are common among patients with heart failure (HF) and associated with poor prognosis. Importantly, some populations of patients, like the ones with Chagas disease, are frequently excluded from most analyses. Objective We sought to study the occurrence of undernutrition and cachexia in patients with Chagas disease during episodes of decompensated HF (DHF) as compared to other etiologies, and to investigate the influence of these findings on hospital outcomes. Methods We performed a consecutive case series study with patients hospitalized with DHF. Patients underwent the Subjective Global Assessment of nutritional status (SGA), besides anthropometric and laboratorial measures, and were evaluated for the occurrence of cachexia, low muscle mass and strength. We studied the occurrence of death or urgent heart transplantation during hospitalization. Results Altogether, 131 patients were analyzed and 42 (32.1%) had Chagas disease. Patients with Chagas disease had lower Body Mass Index (BMI) (22.4 kg/m2[19.9-25.3] vs. 23.6 kg/m2 [20.8-27.3], p=0.03), higher frequency of undernutrition (76.2% vs 55.1%, p=0.015) and higher occurrence of death or transplant (83.3% vs. 41.6%, p<0.001). We found that, in patients with Chagas etiology, the occurrence of death or cardiac transplantation were associated with undernutrition (3 [42.9%] patients with hospital discharge vs 29 [82.9%] patients with death or heart transplant, p=0.043). Conclusions Taken together, our results indicate that patients with Chagas disease hospitalized with DHF often present with nutritional disorders, especially undernutrition; importantly, this finding was associated with the occurrence of death and heart transplant during hospitalization.

Implantable cardioverter-defibrillator prevents sudden death in patients with Chagas cardiomyopathy in the Brazilian Amazon

Abstract Chagas disease (CD), with approximately 10,000 deaths annually, has become a worldwide health problem. Approximately 35% of cases may show cardiac manifestations such as arrhythmias and/or conduction disorders, heart failure, thromboembolic accidents, and sudden death. The Amazon region has long been considered a non-endemic area for CD; however, in the last decades, with an increase in the number of acute and chronic cases, disease evolution has received greater attention. Here, we report the successful implementation of a cardioverter-defibrillator for the prevention of sudden death in a patient with autochthonous Chagas cardiomyopathy in the Brazilian Amazon.

Evaluation of the Autonomic Nervous System in Chronic Chagasic Cardiopathy: A Systematic Review of the Literature

Abstract Background The importance of regional sympathetic denervation in the pathophysiology and prognosis of Chagas disease has been recognized. Objective To conduct a review of studies that have assessed dysautonomia in chronic Chagas heart disease. Methods The search was performed on the Medline, Pubmed, Lilacs and SciELO databases. The inclusion criteria were: original articles published in full; studies on individuals with Chagas disease, that used diagnostic methods for chagasic cardiomyopathy, and had clear inclusion and exclusion criteria. Duplicate studies, studies including children (0 to 10 years old), studies involving animals, in vitro experiments, case reports, editorials, theses, and dissertations were excluded. Results A total of 281 articles were retrieved, and 10 met the inclusion criteria and were analyzed. There was great heterogeneity as to the technique for assessing dysautonomia, groups of patients studied and classification of Chagas disease. The methods used for studying the autonomic system was immunohistochemistry (n=1), Valsalva and tilt-test (n=1), scintigraphy (n=6) and Holter monitoring (n=2). The results indicated dysautonomia in the indeterminate, digestive and cardiac forms of Chagas disease, and sympathetic denervation in the indeterminate and cardiac forms of the disease. There was agreement between areas of denervation, hypoperfusion and fibrosis, but areas of denervation were larger than those of hypoperfusion. The frequency of denervation and its extension increased from the indeterminate to the cardiac form. There was an association between extension of denervation and previous history of malignant ventricular arrhythmia. Conclusions The evidence presented in this review supports that an early diagnosis of autonomic denervation in chronic Chagas' disease allows the identification of patients with an increased risk of sudden death. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0

Prevalence and determinants of depressive symptoms in patients with Chagas cardiomyopathy and predominantly preserved cardiac function

Abstract INTRODUCTION: Chagas cardiomyopathy (ChC) is highly stigmatized, and the presence of depressive symptoms may be a common feature. However, its determinants remain unclear. Therefore, the present study aimed to verify the prevalence of depression and the clinical, echocardiographic, functional, and quality of life factors associated with depressive symptoms in patients with ChC and predominantly preserved cardiac function. METHODS: Thirty-five patients with ChC (aged 40 to 60 years, 66% men, NYHA I-III) were evaluated by echocardiography, cardiopulmonary exercise testing, 6-minute walk test (6MWT), and Mini-Mental State Examination. Physical activity level was assessed using the Human Activity Profile (HAP) and health-related quality of life was assessed using the Short-Form Health Survey (SF-36). Depressive symptoms were evaluated using the Beck Depression Inventory. A cutoff point greater than 9 was indicative of depression. RESULTS: Depression was detected in 13 patients (37%). In the univariate analysis, female sex, NYHA functional class, body mass index, HAP score, mental summary of SF-36, peak oxygen uptake, and 6MWT distance were associated with depressive symptoms. The final model showed that only the HAP score (B = -0.533; 95% confidence interval [CI]: -0.804 to -0.262) and SF-36 mental summary (B = -0.269; 95% CI: -0.386 to -0.153) remained as independent predictors of depressive symptoms in patients with ChC. CONCLUSIONS: Depression was prevalent in patients with ChC and predominantly preserved cardiac function. Physical activity and mental health were independent risk factors for depressive symptoms.

Chagas disease in Virgem da Lapa, Minas Gerais, Brazil: left ventricle aneurysm and the risk of death in the 24-year interval

BACKGROUND Left ventricular aneurysm (LVA) is indicator of high morbidity in Chagas' disease. A cross-sectional study performed identified LVA in 18.8% of the chronic chagasic patients (CCP). OBJECTIVE Determine the risk of death of patients with chronic chagasic cardiopathy (CCC) and LVA in 24-year interval. MATERIAL AND METHODS In 1995 a cohort of 298 CCP was evaluated by anamnesis, physical examination, EKG and ECHO and classified in groups: G0 = 86 without cardiopathy; G1 = 156 with cardiopathy without LVA and G2 = 56 with cardiopathy and LVA. 38 patients of G0 and G1 used benznidazole. Information about the deaths was obtained in the notary, death certificates, hospital records and family members. FINDINGS Were registered 113 deaths (37.9%): 107 (35.9%) attributed to cardiopathy and 6 (2.0%) to other causes (p < 0.05). Amongst these 107 deaths, 10 (11.6%) occurred in G0; 49 (31.4%) occurred in G1 and 48 (85.7%) occurred in G2 (p < 0.05). The risk of death was 2.7 and 7.4 times significantly higher in G2, than in G1 and G0, respectively. CONCLUSION Chronic chagasic patients with LVA and ejection fraction < 45% have a higher risk of death than those without.

Chagas disease is associated with a poor outcome at 1-year follow-up after cardiac resynchronization therapy

SUMMARY BACKGROUND: Cardiac resynchronization therapy (CRT) is a therapeutic modality for patients with heart failure (HF). The effectiveness of this treatment for event reduction is based on clinical trials where the population of patients with Chagas' disease (DC) is underrepresented. OBJECTIVE: To evaluate the prognosis after CRT of a population in which CD is an endemic cause of HF. METHODS: A retrospective cohort conducted between January 2015 and December 2016 that included patients with HF and left ventricular ejection fraction (LVEF) of less than 35% and undergoing CRT. Clinical and demographic data were collected to search for predictors for the combined outcome of death or hospitalization for HF at one year after CRT implantation. RESULTS: Fifty-four patients were evaluated, and 13 (24.1%) presented CD as the etiology of HF. The mean LVEF was 26.2± 6.1%, and 36 (66.7%) patients presented functional class III or IV HF. After the mean follow-up of 15 (±6,9) months, 17 (32.1%) patients presented the combined outcome. In the univariate analysis, CD was associated with the combined event when compared to other etiologies of HF, 8 (47%) vs. 9 (13,5%), RR: 3,91 CI: 1,46-10,45, p=0,007, as well as lower values of LVEF. In the multivariate analysis, CD and LVEF remained independent risk factors for the combined outcome. CONCLUSION: In a population of HF patients undergoing CRT, CD was independently associated with mortality and hospitalization for HF.

RESUMO INTRODUÇÃO: A terapia de ressincronização cardíaca (TRC) é uma modalidade terapêutica para pacientes com insuficiência cardíaca (IC). A eficácia desse tratamento para redução de eventos baseia-se em ensaios clínicos em que a população de pacientes com doença de Chagas (DC) é sub-representada. OBJETIVO: Avaliar o prognóstico após TRC em uma população em que a DC é uma causa frequente de IC. MÉTODOS: Coorte retrospectiva realizada entre janeiro de 2015 e dezembro de 2016, sendo incluídos pacientes portadores de IC com fração de ejeção do ventrículo esquerdo (Feve) menor que 35% e submetidos à TRC. Os dados clínicos e demográficos foram coletados para pesquisa de preditores para o desfecho combinado de morte ou internação por IC após implante da TRC. RESULTADOS: Foram avaliados 54 pacientes, dos quais 13 (24,1%) apresentavam a DC como etiologia da IC. A Feve média foi de 26,2% (±6,1) e 36 (66,7%) pacientes apresentavam classe funcional de IC III ou IV. Após o seguimento médio de 15 meses, 17 (32,1%) pacientes apresentaram o desfecho combinado. Na análise univariada, a DC esteve associada ao evento combinado quando comparada a outras etiologias de IC, 8 (47%) vs 9 (13,5%), RR: 3,91 IC: 1,46-10,45, p=0,007, assim como valores mais baixos da Feve. Na análise multivariada, a DC e a Feve permaneceram como fatores de risco independentes para o desfecho combinado. CONCLUSÃO: Em uma população de pacientes com IC submetidos à TRC, a doença de Chagas esteve independentemente associada à mortalidade e internação por insuficiência cardíaca no seguimento de 15 meses.

Prevenção secundária de morte súbita cardíaca na cardiopatia chagásica crônica e função ventricular quase-normal / Secondary prevention of sudden cardiac death in chronic chagasic cardiopathy and near-normal ventricular function

Introdução: A cardiopatia chagásica crônica (CCC) engloba complexo espectro de apresentações, não sendo incomuns episódios de morte arrítmica em portadores de função ventricular esquerda preservada (FVEP) ou quase normal (FVEQN). Métodos: Avaliação retrospectiva de 7 portadores de CCC por 4 anos, com FVEP, submetidos a implante de cardiodesfibrilador implantável (CDI) devido taquicardia ou fibrilação ventricular (TV/FV). Foram realizadas avaliações clínica, estrutural e eletrocardiográfica. Resultados: Idade média: 57,5±4,45 anos e 71,4% do sexo masculino. Função ventricular esquerda (FVE) inicial foi de 56,14%±4,45, com alterações contrácteis em 100% e hipocinesia inferior em 85,7%. Classe funcional I: 100% sem modificações ao seguimento. Escore de Rassi avaliado previamente ao evento foi de 4,85±0,89. Síncope constituiu a apresentação inicial em 100%, média de 2 episódios por paciente e intervalo de 4 semanas entre os mesmos. Houve alterações em 85,71% dos eletrocardiogramas, sendo bloqueio de ramo direito a principal. TV sustentada foi encontrada em 100%; sítio epicárdico em 71,42% e saída anterolateral do ventrículo esquerdo em 57,14%. A FVE sequencial foi de 54%±3,31; sem alterações contráteis novas. Amiodarona e betabloqueadores foram os fármacos utilizados. Terapias apropriadas aconteceram em 100%; média de 2,1 choques por paciente, com 52,63% dos registros nos primeiros 14 meses. Não foram evidenciados óbitos, terapias inapropriadas ou tempestade elétrica. Conclusão: O elevado número de terapias corrobora o risco arrítmico desta população, ratifica a importância do dispositivo e alerta para a eficácia da terapia clínica. Síncope pode estar associada a maior risco de eventos arrítmicos na CCC

Introduction: Chronic chagasic cardiopathy (CCC) encompasses a complex spectrum of presentations, and episodes of arrhythmic death in patients with preserved left ventricular (PLVF) or near normal (VFNN) are not uncommon. Methods: Retrospective evaluation of 7 patients with PLVF, submitted for implantation of implantable cardioverter defibrillator (ICD) due to tachycardia or ventricular fibrillation (VT / VF). Clinical, structural and electrocardiographic evaluations were performed. Results: Mean age was 57.5±4.45 years. Male sex comprised 71.4%. Left ventricular function (LVF) was 56.14%±4.45 with contractile changes in 100% and lower hypokinesia in 85.7%. Functional class I was evidenced in 100% without changes in follow-up. The Rassi score evaluated before the event was 4.85±0.89. Syncope was the initial presentation in 100%, average of 2 episodes per patient and interval of 4 weeks between them. Electrocardiogram showed alterations in 85.71% being right bundle branch block. Sustained VT was evidenced in 100%; epicardial site in 71.42% and left ventricular anterolateral outlet in 57.14%. The sequential LVF was 54%±3.31; without new contractile changes. Amiodarone and beta-blockers were the drugs used. Appropriate therapies occurred in 100%; average of 2.1 shocks per patient with 52.63% of the records in the first 14 months. There were no deaths, inappropriate therapies or electrical storm. Conclusion: The high number of therapies corroborates the arrhythmic risk of this population, ratifies the importance of the device and disputes the effectiveness of clinical therapy. Syncope may be associated with an increased risk of arrhythmic events in CCC

Obstructive Sleep Apnea is Common and Associated with Heart Remodeling in Patients with Chagas Disease / Apneia Obstrutiva do Sono é Comum e está Associada à Remodelação Cardíaca em Pacientes com Doença de Chagas

Abstract Background: Chagas Disease (CD) is an important cause of morbimortality due to heart failure and malignant arrhythmias worldwide, especially in Latin America. Objective: To investigate the association of obstructive sleep apnea (OSA) with heart remodeling and cardiac arrhythmias in patients CD. Methods: Consecutive patients with CD, aged between 30 to 65 years old were enrolled. Participants underwent clinical evaluation, sleep study, 24-hour Holter monitoring, echocardiogram and ambulatory blood pressure monitoring. Results: We evaluated 135 patients [age: 56 (45-62) years; 30% men; BMI: 26 ± 4 kg/m2, Chagas cardiomyopathy: 70%]. Moderate to severe OSA (apnea-hypopnea index, AHI, ≥ 15 events/h) was present in 21% of the patients. OSA was not associated with arrhythmias in this population. As compared to patients with mild or no OSA, patients with moderate to severe OSA had higher frequency of hypertension (79% vs. 72% vs. 44%, p < 0.01) higher nocturnal systolic blood pressure: 119 ± 17 vs. 113 ± 13 vs. 110 ± 11 mmHg, p = 0.01; larger left atrial diameter [37 (33-42) vs. 35 (33-39) vs. 33 (30-36) mm, p < 0.01]; and a greater proportion of left ventricular dysfunction [LVEF < 50% (39% vs. 28% vs. 11%), p < 0.01], respectively. Predictor of left atrial dimension was Log10 (AHI) (b = 3.86, 95% CI: 1.91 to 5.81; p < 0.01). Predictors of ventricular dysfunction were AHI > 15 events/h (OR = 3.61, 95% CI: 1.31 - 9.98; p = 0.01), systolic blood pressure (OR = 1.06, 95% CI: 1.02 - 1.10; p < 0.01) and male gender (OR = 3.24, 95% CI: 1.31 - 8.01; p = 0.01). Conclusions: OSA is independently associated with atrial and ventricular remodeling in patients with CD.

Resumo Fundamento: A doença de Chagas (DC) é uma causa importante de morbimortalidade por insuficiência cardíaca e arritmias malignas em todo o mundo, especialmente na América Latina. Objetivo: Investigar a associação entre apneia obstrutiva do sono (AOS) com remodelação cardíaca e arritmias cardíacas em pacientes com DC. Métodos: Foram incluídos pacientes consecutivos com DC, com idade entre 30 e 65 anos. Os participantes foram submetidos à avaliação clínica, estudo do sono, Holter de 24 horas, ecocardiograma e monitorização ambulatorial da pressão arterial. Resultados: Foram avaliados 135 pacientes [idade: 56 (45-62) anos; 30% homens; IMC: 26 ± 4 kg/m2, cardiomiopatia chagásica: 70%]. AOS moderada a grave (índice de apneia-hipopneia, IAH, ≥ 15 eventos/h) estava presente em 21% dos pacientes. AOS não estava associada a arritmias nessa população. Em comparação com pacientes com AOS leve ou ausente, pacientes com AOS moderada a grave apresentaram maior frequência de hipertensão (79% vs. 72% vs. 44%, p < 0,01) e pressão arterial sistólica noturna mais alta: 119 ± 17 vs. 113 ± 13 vs. 110 ± 11 mmHg, p = 0,01; diâmetro do átrio esquerdo maior [37 (33‑42) vs. 35 (33-39) vs. 33 (30-36) mm, p < 0,01]; e maior proporção de disfunção ventricular esquerda [FEVE < 50% (39% vs. 28% vs. 11%), p < 0,01], respectivamente. O preditor de dimensão do átrio esquerdo foi Log10 (IAH) (β = 3,86, IC 95%: 1,91 a 5,81; p < 0,01). Os preditores de disfunção ventricular foram IAH >15 eventos/h (OR = 3,61, IC 95%: 1,31 - 9,98; p = 0,01), pressão arterial sistólica (OR = 1,06, IC95%: 1,02 - 1,10; p < 0,01) e sexo masculino (OR = 3,24, IC 95%: 1,31 - 8,01; p = 0,01). Conclusões: A AOS está independentemente associada à remodelação atrial e ventricular em pacientes com DC.

Sympathetic Dysautonomia in Heart Failure by 123I-MIBG: comparison between Chagasic, non-Chagasic and heart transplant patients / Disautonomia Simpática na Insuficiência Cardíaca pela 123I-MIBG: Comparação entre Pacientes Chagásicos, não-Chagásicos e Transplantados Cardíacos

Abstract Background: Heart failure (HF) is a severe public health problem because of its high morbidity and mortality and elevated costs, thus requiring better understanding of its course. In its complex and multifactorial pathogenesis, sympathetic hyperactivity plays a relevant role. Considering that sympathetic dysfunction is already present in the initial phases of chronic Chagas cardiomyopathy (CCC) and frequently associated with a worse prognosis, we assumed it could be more severe in CCC than in cardiomyopathies of other etiologies (non-CCC). Objectives: To assess the cardiac sympathetic dysfunction 123I-MIBG) of HF, comparing individuals with CCC to those with non-CCC, using heart transplant (HT) patients as denervated heart parameters. Methods: We assessed 76 patients with functional class II-VI HF, being 25 CCC (17 men), 25 non-CCC (14 men) and 26 HT (20 men), by use of cardiac 123I-metaiodobenzylguanidine 123I-MIBG) scintigraphy, estimating the early and late heart-to-mediastinum ratio (HMR) of 123I-MIBG uptake and cardiac washout (WO%). The 5% significance level was adopted in the statistical analysis. Results: The early and late HMR values were 1.73 ± 0.24 and 1.58 ± 0.27, respectively, in CCC, and 1.62 ± 0.21 and 1.44 ± 0.16 in non-CCC (p = NS), being, however, higher in HT patients (p < 0.001). The WO% values were 41.65 ± 21.4 (CCC), 47.37 ± 14.19% (non-CCC) and 43.29 ± 23.02 (HT), p = 0.057. The late HMR values showed a positive weak correlation with left ventricular ejection fraction (LVEF) in CCC and non-CCC (r = 0.42 and p = 0.045; and r = 0.49 and p = 0.015, respectively). Conclusion: Sympathetic hyperactivity 123I-MIBG) was evidenced in patients with class II-IV HF, LVEF < 45%, independently of the HF etiology, as compared to HT patients.

Resumo Fundamentos: A insuficiência cardíaca (IC) representa um grave problema de saúde pública pela alta morbimortalidade e custos envolvidos, exigindo uma melhor compreensão de sua evolução. Em sua patogênese, complexa e multifatorial, a hiperatividade simpática ocupa relevante papel. Considerando que a disfunção simpática está presente já nas fases iniciais da cardiopatia chagásica crônica (CCC), frequentemente associando-se a um pior prognóstico, supomos que pudesse ser mais grave na CCC que nas demais etiologias (não-CCC). Objetivos: Avaliar a disfunção simpática cardíaca (123I-MIBG) da IC, comparando-se os portadores de CCC aos não-CCC, utilizando os pacientes transplantados cardíacos (TC) como parâmetro de coração desnervado. Métodos: Estudamos 76 pacientes com IC classe funcional II-VI, sendo 25 CCC (17 homens), 25 não-CCC (14 homens) e 26 TC (20 homens), pela cintilografia cardíaca (123I-MIBG), estimando-se a captação (HMR) precoce e tardia e o washout cardíaco (Wc%). Nas análises estatísticas, o nível de significância foi de 5%. Resultados: Os valores da HMR precoce e da tardia foram 1,73 ± 0,24 e 1,58 ± 0,27, respectivamente, na CCC, e 1,62 ± 0,21 e 1,44 ± 0,16 na não-CCC (p = NS), sendo, porém, mais elevados nos TC (p < 0,001). Os valores de Wc% foram 41,65 ± 21,4 (CCC), 47,37 ± 14,19% (não-CCC) e 43,29 ± 23,02 (TC), p = 0,057. Os valores de HMR tardia apresentaram correlação positiva fraca com a fração de ejeção de ventrículo esquerdo (FEVE) na CCC e na não-CCC (r = 0,42 e p = 0,045; e r = 0,49 e p = 0,015, respectivamente). Conclusão: Evidenciou-se a presença de hiperatividade simpática (123I-MIBG) em pacientes com IC classe II-IV, FEVE < 45%, independentemente da etiologia da IC, quando comparados aos pacientes TC.

Anticoagulation in patients with cardiac manifestations of Chagas disease and cardioembolic ischemic stroke / Anticoagulação nas manifestações cardíacas da doença de Chagas e acidente vascular cerebral isquêmico cardioembólico

ABSTRACT Objectives To describe anticoagulation characteristics in patients with cardiac complications from Chagas disease and compare participants with and without cardioembolic ischemic stroke (CIS). Methods A retrospective cohort of patients with Chagas disease, using anticoagulation, conducted from January 2011 to December 2014. Results Forty-two patients with Chagas disease who were using anticoagulation were studied (age 62.9±12.4 years), 59.5% female and 47.6% with previous CIS, 78.6% with non-valvular atrial fibrillation and 69.7% with dilated cardiomyopathy. Warfarin was used in 78.6% of patients and dabigatran (at different times) in 38%. In the warfarin group, those with CIS had more medical appointments per person-years of follow-up (11.7 vs 7.9), a higher proportion of international normalized ratios within the therapeutic range (57% vs 42% medical appointments, p = 0.025) and an eight times higher frequency of minor bleeding (0.64 vs 0.07 medical appointments). Conclusion Patients with Chagas disease and previous CIS had better control of INR with a higher frequency of minor bleeding.

RESUMO Objetivos descrever as características da anticoagulação em pacientes com manifestações cardíacas da doença de Chagas (MCDC) e comparar os participantes com sem acidente vascular cerebral isquêmico cardioembólico (AVCIC). Resultados 42 pacientes com MCDC em anticoagulação foram estudados (62,9 ± 12,4 anos), 59,5% do sexo feminino e 47,6% com AVCIC prévio, 78,6% portadores de fibrilação atrial não valvar e 69,7% com cardiomiopatia dilatada. Varfarina foi utilizada em 78,6% dos pacientes e dabigatrana em 38% (em momentos diferentes). No grupo da varfarina, aqueles com AVCIC tiveram mais consultas médicas por pessoas-ano de seguimento (11,7 vs 7,9), maior taxa de RNI na faixa terapêutica (57% vs 42% consultas médicas, p = 0,025) e uma frequência oito vezes maior de sangramento menor (0,64 vs. 0,07 consultas médicas). Conclusão pacientes com MCDC e AVCIC prévio têm melhor controle de RNI com maior frequência de sangramento menor.

Chagas disease and systemic autoimmune diseases among Bolivian patients in Switzerland

BACKGROUND Chronic cardiomyopathy occurs in 20-40% of the patients with Chagas disease. Autoimmune mechanisms may contribute to its pathogenesis. We diagnosed several cases of systemic autoimmune diseases among Bolivian migrants in Geneva with a high prevalence of Chagas disease. OBJECTIVES We tested the hypothesis of a clinical association between systemic autoimmune diseases and Chagas disease, particularly with the development of cardiomyopathy. METHODS We retrospectively searched the medical records of all Bolivian patients visiting Geneva University Hospitals between 2012 and 2015 for diagnosis of Chagas disease or systemic autoimmune diseases. FINDINGS Of the 2,189 eligible patients, 28 [1.3%; 95% confidence interval (CI) = 0.9-1.9%] presented with systemic autoimmune disease. The Chagas status was known in 903 (41.3%) patient, of whom 244 (27.0%; 95% CI = 24.2-30.0%) were positive. Eight (28.6%; 95% CI = 15.3-47.1%) of the 28 cases of systemic autoimmune disease had Chagas disease. We found no association between both entities (p = 1.000) or with Chagasic cardiomyopathy (p = 0.729). Moreover, there was no evidence of a temporal relationship between antiparasitic chemotherapy and the development of systemic autoimmune diseases. CONCLUSIONS Our results do not support a clinical association between chronic Chagas disease and systemic autoimmune diseases. However, prospective studies in areas endemic for Chagas disease should better assess the prevalence of systemic autoimmune diseases and thus a possible relationship with this infection.

Single nucleotide polymorphisms of cytokine-related genes and association with clinical outcome in a Chagas disease case-control study from Brazil

BACKGROUND The severity of chronic chagasic cardiomyopathy (CCC), the most frequent clinical outcome of Chagas disease (CD), has been associated with cytokine-enriched heart tissue inflammation, and high serum levels of transforming growth factor (TGFβ), interferon-gamma (IFNγ), and tumour necrosis factor (TNF). Conversely, increased interleukin (IL)-10 serum concentrations have been associated with asymptomatic CD. Cytokines and cytokine-related gene polymorphisms may control cytokine expression and have been proposed to contribute to CCC outcomes. OBJECTIVES We evaluated the association of 13 cytokine-related genes (TGFB: rs8179181, rs8105161, rs1800469; IL10: rs1800890, rs1800871, rs1800896; IFNG: rs2430561; TNF: rs1800629; BAT1: rs3853601; LTA: rs909253, rs2239704; TNFR1: rs767455; TNFR2: rs1061624) with risk and progression of CCC. FINDINGS Four hundred and six seropositive patients from CD endemic areas in the state of Pernambuco, north-eastern Brazil, were classified as non-cardiopathic (A, 110) or cardiopathic (mild, B1, 163; severe, C, 133). We found no evidence of TGFB, IL10, TNF, or TNFR1/2 gene polymorphisms associated with CCC risk or progression. Only BAT1 rs3853601 −22G carriers (B1 vs. C: OR = 0.5; p-value = 0.03) and IFNG rs2430561 +874AT (A vs. C: OR = 0.7; p-value = 0.03; A vs. B1+C: OR = 0.8; p-value = 0.02) showed a significant association with protection from cardiopathy in a logistic regression analysis with adjustment for gender and ethnicity; however, the association disappeared after performing adjustment for multiple testing. A systematic review of TNF rs1800629 −308G>A publications included five studies for meta-analysis (534 CCC and 472 asymptomatic patients) and showed no consensus in pooled odds ratio (OR) estimates for A allele or A carriers (OR = 1.4 and 1.5; p-values = 0.14 and 0.15, respectively). In CD patients, TNF serum levels were increased, but not affected by the TNF rs1800629 −308A allele. MAIN CONCLUSIONS Our data suggest no significant contribution of the analysed gene variants of cytokine-related molecules to development/severity of Chagas' heart disease, reinforcing the idea that parasite/host interplay is critical to CD outcomes.

Angiotensin-Converting Enzyme ID Polymorphism in Patients with Heart Failure Secondary to Chagas Disease / Polimorfismo da Enzima Conversora da Angiotensina (ECA D/I) em Pacientes com Insuficiência Cardíaca de Etiologia Chagásica

Abstract Background: Changes in the angiotensin-converting enzyme (ACE) gene may contribute to the increase in blood pressure and consequently to the onset of heart failure (HF). The role of polymorphism is very controversial, and its identification in patients with HF secondary to Chagas disease in the Brazilian population is required. Objective: To determine ACE polymorphism in patients with HF secondary to Chagas disease and patients with Chagas disease without systolic dysfunction, and to evaluate the relationship of the ACE polymorphism with different clinical variables. Methods: This was a comparative clinical study with 193 participants, 103 of them with HF secondary to Chagas disease and 90 with Chagas disease without systolic dysfunction. All patients attended the outpatient department of the General Hospital of the Federal University of Goias general hospital. Alleles I and D of ACE polymorphism were identified by polymerase chain reaction of the respective intron 16 fragments in the ACE gene and visualized by electrophoresis. Results: In the group of HF patients, 63% were male, whereas 53.6% of patients with Chagas disease without systolic dysfunction were female (p = 0,001). The time from diagnosis varied from 1 to 50 years. Distribution of DD, ID and II genotypes was similar between the two groups, without statistical significance (p = 0,692). There was no difference in clinical characteristics or I/D genotypes between the groups. Age was significantly different between the groups (p = 0,001), and mean age of patients with HF was 62.5 years. Conclusion: No differences were observed in the distribution of (Insertion/Deletion) genotype frequencies of ACE polymorphism between the studied groups. The use of this genetic biomarker was not useful in detecting a possible relationship between ACE polymorphism and clinical manifestations in HF secondary to Chagas disease.

Resumo Fundamento: Alterações no gene da Enzima Conversora de Angiotensina (ECA) podem contribuir para o aumento da pressão arterial e consequentemente para o surgimento de insuficiência cardíaca (IC). O papel do polimorfismo ainda é bastante controverso, sendo necessária sua identificação em pacientes com IC de etiologia chagásica na população brasileira. Objetivo: Determinar o polimorfismo da ECA em portadores de IC com etiologia chagásica e pacientes com doença de Chagas sem disfunção sistólica, e avaliar a relação do polimorfismo ECA com diferentes variáveis clínicas. Métodos: Trata-se um estudo clínico comparativo com 193 participantes, destes, 103 com IC de etiologia chagásica e 90 pacientes com doença de Chagas sem disfunção sistólica, todos em atendimento ambulatorial no Hospital das Clínicas da Universidade Federal de Goiás. Os alelos D e I do polimorfismo da ECA foram identificados por reação em cadeia da polimerase dos respectivos fragmentos provenientes do íntron 16 no gene da ECA e visualizados em eletroforese. Resultados: Dos portadores de IC, 63 % eram do gênero masculino, enquanto nos portadores de doença de Chagas sem disfunção sistólica 53,6% eram do gênero feminino (p = 0,001). O tempo de diagnóstico variou de 1 a 50 anos. A distribuição dos genótipos DD, DI e II foi semelhante entre os dois grupos, não apresentando significância estatística (p = 0,692). Nenhuma interação foi observada em relação às características clínicas e os genótipos D/I entre os grupos. A idade foi significativamente diferente entre os grupos (p = 0,001), e a média de idade dos pacientes com IC foi de 62,5 anos. Conclusão: Não foram observadas diferenças na distribuição das frequências dos genótipos (Deleção/Inserção) do polimorfismo ECA entre os grupos estudados. A utilização deste biomarcador genético não se mostrou útil na tentativa de se conhecer a existência da relação do polimorfismo ECA e as manifestações clínicas da IC de etiologia chagásica.

Prognostic Factors in Severe Chagasic Heart Failure / Fatores Prognósticos na Insuficiência Cardíaca Grave de Etiologia Chagásica

Abstract Background: Prognostic factors are extensively studied in heart failure; however, their role in severe Chagasic heart failure have not been established. Objectives: To identify the association of clinical and laboratory factors with the prognosis of severe Chagasic heart failure, as well as the association of these factors with mortality and survival in a 7.5-year follow-up. Methods: 60 patients with severe Chagasic heart failure were evaluated regarding the following variables: age, blood pressure, ejection fraction, serum sodium, creatinine, 6-minute walk test, non-sustained ventricular tachycardia, QRS width, indexed left atrial volume, and functional class. Results: 53 (88.3%) patients died during follow-up, and 7 (11.7%) remained alive. Cumulative overall survival probability was approximately 11%. Non-sustained ventricular tachycardia (HR = 2.11; 95% CI: 1.04 - 4.31; p<0.05) and indexed left atrial volume ≥ 72 mL/m2 (HR = 3.51; 95% CI: 1.63 - 7.52; p<0.05) were the only variables that remained as independent predictors of mortality. Conclusions: The presence of non-sustained ventricular tachycardia on Holter and indexed left atrial volume > 72 mL/m2 are independent predictors of mortality in severe Chagasic heart failure, with cumulative survival probability of only 11% in 7.5 years.

Resumo Fundamento: Fatores prognósticos são bastante estudados na insuficiência cardíaca (IC), mas ainda não possuem um papel estabelecido na IC grave de etiologia chagásica. Objetivo: Identificar a associação de fatores clínicos e laboratoriais com o prognóstico da IC grave de etiologia chagásica, bem como a associação desses fatores com a taxa de mortalidade e a sobrevida em um seguimento de 7,5 anos. Métodos: 60 pacientes portadores de IC grave de etiologia chagásica foram avaliados com relação às seguintes variáveis: idade, pressão arterial, fração de ejeção, sódio plasmático, creatinina, teste de caminhada de 6 minutos, taquicardia ventricular não sustentada, largura do QRS, volume do átrio esquerdo indexado e classe funcional. Resultados: 53 (88,3%) pacientes foram a óbito durante o período de seguimento e 7 (11,7%) permaneceram vivos. A probabilidade de sobrevida geral acumulada foi de aproximadamente 11%. Taquicardia ventricular não sustentada (HR = 2,11; IC 95%: 1,04 - 4,31; p<0,05) e volume do átrio esquerdo indexado ≥ 72 ml/m2 (HR = 3,51; IC 95%: 1,63 - 7,52; p<0,05) foram as únicas variáveis que permaneceram como preditores independentes de mortalidade. Conclusão: A presença de taquicardia ventricular não sustentada ao Holter e o volume do átrio esquerdo indexado > 72 ml/m2 são preditores independentes de mortalidade na IC chagásica grave, com probabilidade de sobrevida acumulada de apenas 11% em 7,5 anos.

Alterações ao Doppler tecidual em pacientes com a forma aguda da doença de chagas / Alterations to tissue Doppler in patients with acute form of chagas disease

Fundamento: Recentemente tem ocorrido aumento do número de casos agudos de doença de Chagas, principalmente causados por transmissão oral. A maioria dos pacientes mostra boa evolução, apresentando sintomatologia compatívelcom processo infeccioso sistêmico, porém sem alterações cardíacas significativas ao exame físico, eletrocardiograma eecocardiograma transtorácico.Objetivo: Avaliar alterações ecocardiográficas com análise do Doppler tecidual em pacientes com doença de Chagas aguda. Métodos: Foram avaliados pacientes com diagnóstico de doença de Chagas aguda confirmada por exame parasitológico direto. Esses pacientes foram submetidos a exame físico, eletrocardiograma e ecocardiograma transtorácico, sendocomparados com um grupo controle.Resultados: Foram avaliados 12 casos com doença de Chagas aguda e 15 indivíduos no grupo controle. As variáveis que apresentaram diferenças significativas foram: ondas S’ lateral de VE (DCA = 0,09 ± 0,02 m/seg; GC = 0,11 ± 0,02 m/seg; p = 0,024); E’ lateral (DCA = 0,13 ± 0,03 m/seg; GC = 0,18 ± 0,03 m/seg; p = 0,001); E’ septal do VE (DCA = 0,10± 0,03 m/seg; GC = 0,14 ± 0,03 m/seg; p = 0,008), A’ lateral do VE (DCA = 0,08 ± 0,03 m/seg; GC = 0,12 ± 0,01 m/seg;p = 0,003), onda S’ do VD (DCA = 0,12 ± 0,02 m/seg; GC = 0,17 ± 0,02 m/seg; p < 0,001) e TAPSE (DCA = 1,95 ±0,41 cm; GC = 2,37 ± 0,25 cm; p = 0,006). Conclusões: Em pacientes com doença de Chagas aguda, mesmo quando apresentam evolução benigna, podem ocorrer alterações subclínicas detectadas principalmente ao Doppler tecidual. Essas alterações podem ser importantes na avaliação do tratamento da fase aguda e na sua evolução a longo prazo.

Background: Recently there has been an increased number of cases of acute Chagas disease primarily caused by oral transmission. Most patients have a good outcome, presenting symptoms consistent with systemic infectious process, but no significant cardiac abnormalities on physical examination, electrocardiogram and echocardiogram.Objective: To evaluate echocardiographic changes with tissue Doppler analysis in patients with acute Chagas disease.Methods: We evaluated patients with acute Chagas disease confirmed by cytological examination. These patients underwent a physical examination, eletrocardiogram and transthoracic echocardiography, and compared with a control group. Results: We evaluated 12 patients with acute Chagas disease and 15 subjects in the control group. Variables that showed significant diferences were waves S ‘side of LV (DCA = 0.09 ± 0.02m/sec; CG = 0.11 ± 0.02 m/sec; p = 0.024); and ‘side (DCA = 0.13 ± 0.03 m/sec; CG = 0.18 ±0.03 m/sec; p = 0.001); Septal E ‘LV (DCA = 0.10 ± 0.03 m/sec; CG = 0.14 ± 0.03 m/sec; p = 0.008), A’ lateral LV (DCA = 0.08 ± 0.03 m/sec;CG = 0 12 ± 0.01 m/sec; p = 0,003), S wave ‘RV (DCA = 0.12 ± 0.02 m/sec; CG = 0.17 ± 0.02 m/sec; p < 0.001) and TAPSE (DCA = 1,95cm ± 0.41; CG = 2.37 ± 0.25 cm; p = 0.006). Conclusions: In patients with acute Chagas disease, even when present benign, there may be subclinical alterations detected primarilyby tissue Doppler. These changes may be important in the treatment of acute and its long-term evolution.

Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease / Descobertas de Carlos Chagas como Pano de Fundo para a Construção Científica da Cardiopatia Chagásica Crônica

Abstract The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas.

Resumo A construção científica da doença de Chagas crônica (DCC) começou em 1910, quando Carlos Chagas salientou a presença de arritmia cardíaca em exames físicos de pacientes com doença de Chagas crônica, e descreveu um caso de insuficiência cardíaca associada à inflamação do miocárdio e à presença de ninhos de parasitas durante a autópsia. Ele descreveu morte súbita cardíaca associada a arritmias em 1911, e sua associação ao bloqueio AV total detectado com o polígrafo de Jacquet, conforme reportou em 1912. Chagas mostrou a presença de fibrose do miocárdio como subjacente ao quadro clínico da DCC em 1916, e apresentou uma caracterização completa dos aspectos clínicos da DCC em 1922. Em 1928, Chagas detectou fibrose do sistema condutor, e apontou a presença de cardiomegalia acentuada no raio X do tórax, associada a sintomatologia mínima. O uso da reação sorológica no diagnóstico de DCC foi posta em prática clínica em 1936, após a morte de Chagas, e juntamente com o ECG de 12 derivações, revelou a importância epidemiológica da DCC em 1945. Em 1953, ficou comprovado o longo período de tempo entre a infecção inicial e o aparecimento de DCC, enquanto que a incidência anual de DCC na forma indeterminada da doença foi estabelecida em 1956. Os aspectos clínicos fundamentais de DCC descritos por Carlos Chagas foram complementados pelo uso de cateterismo cardíaco em 1965, teste ergométrico em 1973, Holter em 1973, teste eletrofisiológico em 1975, ecocardiografia em 1975, biópsia endomiocárdica em 1981 e ressonância magnética em 1995.