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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.

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INTRODUCTION: Most patients with chronic cardiomyopathy of Chagas disease (CCCD) harbor a secondary cause of coronary microvascular dysfunction (CMD), for which there is no evidence-based therapy. We evaluated the impact of verapamil plus aspirin on symptoms and perfusion abnormalities in patients with CCCD and CMD. METHODS: Consecutive patients with angina pectoris, who had neither coronary artery obstructions nor moderate-severe left ventricular dysfunction (left ventricular ejection fraction > 40%) despite showing wall motion abnormalities on ventriculography, were referred for invasive angiography and tested for Chagas disease. Thirty-two patients with confirmed CCCD and ischemia on stress-rest SPECT myocardial perfusion scintigraphy (MPS) were included. Clinical evaluation, quality of life (EQ-5D/ Seattle Angina Questionnaire), and MPS were assessed before and after 3 months of treatment with oral verapamil plus aspirin (n=26) or placebo (n=6). RESULTS: The mean patient age was 64 years, and 18 (56%) were female. The ischemic index summed difference score (SDS) in MPS was significantly reduced by 55.6% after aspirin+verapamil treatment. A decrease in SDS was observed in 20 (77%) participants, and in 10 participants, no more ischemia could be detected. Enhancements in quality of life were also detected. No change in symptoms or MPS was observed in the placebo group. CONCLUSIONS: This low-cost 3-month treatment for patients diagnosed with CCCD and CMD was safe and resulted in a 55.6% reduction in ischemic burden, symptomatic improvement, and better quality of life.

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Background: Trypanosoma cruzi has a high rate of biological and genetic variability, and its population structure is divided into seven distinct genetic groups (TcI-TcVI and Tcbat). Due to immigration, Chagas disease (ChD), caused by T. cruzi, has become a serious global health problem including in Europe. Therefore, the aim of this study was to evaluate the existence of genetic variability within discrete typing unit (DTU) TcV of T. cruzi in Bolivian patients with chronic ChD residing in Barcelona, Spain. Methods: The DNA was extracted from the peripheral blood of 27 patients infected with T. cruzi DTU TcV and the fragments of the genetic material were amplificated through the low stringency single primer-polymerase chain reaction (LSSP-PCR). The data generated after amplification were submitted to bioinformatics analysis. Results: Of the 27 patients evaluated in the study, 8/27 (29.6%) were male and 19/27 (70.4%) female, 17/27 (62.9%) were previously classified with the indeterminate clinical form of Chagas disease and 10/27 (37.1%) with Chagas cardiomyopathy. The LSSP-PCR detected 432 band fragments from 80 to 1,500 bp. The unweighted pair-group method analysis and principal coordinated analysis data demonstrated the existence of three distinct genetic groups with moderate-high rates of intraspecific genetic variability/diversity that had shared parasite's alleles in patients with the indeterminate and cardiomyopathy forms of ChD. Conclusions: This study demonstrated the existence of a moderate to high rate of intra-DTU TcV variability in T. cruzi. Certain alleles of the parasite were associated with the absence of clinical manifestations in patients harboring the indeterminate form of ChD. These results support the need to search for increasingly specific targets in the genome of T. cruzi to be correlated with its main biological properties and clinical features in patients with chronic ChD.

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Abstract INTRODUCTION: Most patients with chronic cardiomyopathy of Chagas disease (CCCD) harbor a secondary cause of coronary microvascular dysfunction (CMD), for which there is no evidence-based therapy. We evaluated the impact of verapamil plus aspirin on symptoms and perfusion abnormalities in patients with CCCD and CMD. METHODS: Consecutive patients with angina pectoris, who had neither coronary artery obstructions nor moderate-severe left ventricular dysfunction (left ventricular ejection fraction > 40%) despite showing wall motion abnormalities on ventriculography, were referred for invasive angiography and tested for Chagas disease. Thirty-two patients with confirmed CCCD and ischemia on stress-rest SPECT myocardial perfusion scintigraphy (MPS) were included. Clinical evaluation, quality of life (EQ-5D/ Seattle Angina Questionnaire), and MPS were assessed before and after 3 months of treatment with oral verapamil plus aspirin (n=26) or placebo (n=6). RESULTS: The mean patient age was 64 years, and 18 (56%) were female. The ischemic index summed difference score (SDS) in MPS was significantly reduced by 55.6% after aspirin+verapamil treatment. A decrease in SDS was observed in 20 (77%) participants, and in 10 participants, no more ischemia could be detected. Enhancements in quality of life were also detected. No change in symptoms or MPS was observed in the placebo group. CONCLUSIONS: This low-cost 3-month treatment for patients diagnosed with CCCD and CMD was safe and resulted in a 55.6% reduction in ischemic burden, symptomatic improvement, and better quality of life.

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BACKGROUND: Trypanosoma cruzi has a high genetic and biological diversity and has been subdivided into seven genetic lineages, named TcI-TcVI and TcBat. DTUs TcI-TcII-TcV and TcVI are agents of ChD in different regions of Latin America. Due to population movements, the disease is an emergent global public health problem. Thus, the aim of this study was to quantify the parasitic load and identify the presence of T. cruzi DTUs in 101 Latin American immigrants with chronic ChD, residing in Barcelona, Spain. METHODOLOGY / PRINCIPAL FINDINGS: 5ml of peripheral blood were collected in guanidine/EDTA from each patient for DNA extraction, quantification of the parasitic load and genotyping. A great variation of the parasitic load of the patients was verified: from 0.001 to 22.2 T. cruzi DNA (fg) / Blood DNA (ng). In patients from Bolivia the parasitic load was 3.76±4.43 T. cruzi DNA (fg) / Blood DNA (ng) (mean ± SD), in patients of other countries was 0.95±1.38 T. cruzi DNA (fg) / Blood DNA (ng). No statistically significant difference was observed in the parasitic load between patients with the indeterminate and cardiac forms of ChD (p = 0,57). Parasite genotyping was performed by multilocus conventional PCR. In patients from Bolivia there was a nearly equal prevalence of DTUs TcV (27/77), TcII/TcV/TcVI (26/77), and TcII/TcVI (22/77). TcVI was detected in only 2 samples (2/77). A higher prevalence of TcII/TcVI (19/24) was verified in patients of other countries, with low prevalence of TcII/TcV/TcVI (4/24) and TcV (1/24). CONCLUSIONS/SIGNIFICANCE: In this study, low/medium parasitic load was found in all patients evaluated. Our data corroborate previous conclusions indicating that patients from the Bolivia, living in Spain, are predominantly infected by TcV, and TcVI DTUs. On the other hand, in Non-Bolivians patients TcII/TcVI predominated. Surprisingly, in our cohort of 101 patients no infection by TcI DTU was observed.

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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.

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Aims: To develop a document by Brazilian Cardiovascular Imaging Department (DIC) and the European Association of Cardiovascular Imaging (EACVI) to review and summarize the most recent evidences about the non-invasive assessment of patients with Chagas disease, with the intent to set up a framework for standardized cardiovascular imaging to assess cardiovascular morphologic and functional disturbances, as well as to guide the subsequent process of clinical decision-making. Methods and results: Chagas disease remains one of the most prevalent infectious diseases in Latin America, and has become a health problem in non-endemic countries. Dilated cardiomyopathy is the most severe manifestation of Chagas disease, which causes substantial disability and early mortality in the socially most productive population leading to a significant economical burden. Prompt and correct diagnosis of Chagas disease requires specialized clinical expertise to recognize the unique features of this disease. The appropriate and efficient use of cardiac imaging is pivotal for diagnosing the cardiac involvement in Chagas disease, to stage the disease, assess patients' prognosis and address management. Echocardiography is the most common imaging modality used to assess, and follow-up patients with Chagas disease. The presence of echocardiographic abnormalities is of utmost importance, since it allows to stage patients according to disease progression. In early stages of cardiac involvement, echocardiography may demonstrate segmental left ventricuar wall motion abnormalities, mainly in the basal segments of inferior, inferolateral walls, and the apex, which cannot be attributed to obstructive coronary artery arteries. The prevalence of segmental wall motion abnormalities varies according to the stage of the disease, reaching about 50% in patients with left ventricular dilatation and dysfunction. Speckle tracking echocardiography allows a more precise and quantitative measurement of the regional myocardial function. Since segmental wall motion abnormalities are frequent in Chagas disease, speckle tracking echocardiography may have an important clinical application in these patients, particularly in the indeterminate forms when abnormalities are more subtle. Speckle tracking echocardiography can also quantify the heterogeneity of systolic contraction, which is associated with the risk of arrhythmic events. Three-dimensional (3D) echocardiography is superior to conventional two-dimensional (2D) echocardiography for assessing more accurately the left ventricular apex and thus to detect apical aneurysms and thrombus in patients in whom ventricular foreshortening is suspected by 2D echocardiography. In addition, 3D echocardiography is more accurate than 2D Simpson s biplane rule for assessing left ventricular volumes and function in patients with significant wall motion abnormalities, including aneurysms with distorted ventricular geometry. Contrast echocardiography has the advantage to enhancement of left ventricular endocardial border, allowing for more accurate detection of ventricular aneurysms and thrombus in Chagas disease. Diastolic dysfunction is an important hallmark of Chagas disease even in its early phases. In general, left ventricular diastolic and systolic dysfunction coexist and isolated diastolic dysfunction is uncommon but may be present in patients with the indeterminate form. Right ventricular dysfunction may be detected early in the disease course, but in general, the clinical manifestations occur late at advanced stages of Chagas cardiomyopathy. Several echocardiographic parameters have been used to assess right ventricular function in Chagas disease, including qualitative evaluation, myocardial performance index, tissue Doppler imaging, tricuspid annular plane systolic excursion, and speckle tracking strain. Cardiac magnetic resonance (CMR) is useful to assess global and regional left ventricular function in patients with Chagas diseases. Myocardial fibrosis is a striking feature of Chagas cardiomyopathy and late gadolinium enhancement (LGE) is used to detect and quantify the extension of myocardial fibrosis. Myocardial fibrosis might have a role in risk stratification of patients with Chagas disease. Limited data are available regarding right ventricular function assessed by CMR in Chagas disease. Radionuclide ventriculography is used for global biventricular function assessment in patients with suspected or definite cardiac involvement in Chagas disease with suboptimal acoustic window and contraindication to CMR. Myocardial perfusion scintigraphy may improve risk stratification to define cardiac involvement in Chagas disease, especially in the patients with devices who cannot be submitted to CMR and in the clinical setting of Chagas patients whose main complaint is atypical chest pain. Detection of reversible ischemic defects predicts further deterioration of left ventricular systolic function and helps to avoid unnecessary cardiac catheterization and coronary angiography. Conclusion: Cardiac imaging is crucial to detect the cardiac involvement in patients with Chagas disease, stage the disease and stratify patient risk and address management. Unfortunately, most patients live in regions with limited access to imaging methods and point-of-care, simplified protocols, could improve the access of these remote populations to important information that could impact in the clinical management of the disease. Therefore, there are many fields for further research in cardiac imaging in Chagas disease. How to better provide an earlier diagnosis of cardiac involvement and improve patients risk stratification remains to be addressed using different images modalities.

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Introdução: A possibilidade de ocorrer liberação de níquel na corrente sanguínea após implante de dispositivos oclusores de comunicação interatrial de última geração (Cocoon Septal Occluder®), cujo principal componente é o nitinol (55% de níquel e 45% de titânio), ainda permanece controversa, principalmente em determinados grupos de pacientes, como crianças e mulheres em idade fértil. Dessa maneira, o objetivo do presente estudo foi avaliar a correlação entre o implante da prótese e os níveis séricos de níquel. Métodos: Estudo prospectivo de coorte, longitudinal e observacional, realizado em um hospital público. Pacientes submetidos à oclusão percutânea de comunicação interatrial foram avaliados clinicamente, por meio de ecocardiograma transtorácico, e foi feita coleta de amostras de sangue em veia periférica, para a dosagem do níquel antes e após (1 dia, 1 e 3 meses) o implante. Resultados: O procedimento e os exames subsequentes foram realizados com sucesso em dez pacientes, com média de idade de 34,4 anos (variação de 5 a 60 anos). O ecocardiograma seriado comprovou a manutenção dos resultados adequados do implante dos dispositivos. Os pacientes não apresentaram manifestações que pudessem sugerir reação ao metal, como rash cutâneo, dispneia, desconforto torácico, palpitações ou migrânea. Níveis séricos de níquel não apresentaram variação significativa e se mantiveram dentro dos limites de normalidade populacional dos métodos de dosagem até os 3 meses decorridos do procedimento. Conclusões: Os resultados preliminares desta investigação com a prótese Cocoon demonstraram que, durante o período inicial de endotelização após o procedimento, não ocorreu liberação apreciável de níquel para a corrente sanguínea...

Background: The possibility of nickel release to the bloodstream after implantation of latest generation atrial septal defect occlusion devices (Cocoon Septal OccluderTM), whose main component is nitinol (55% nickel and 45% titanium), remains controversial, especially in certain groups of patients such as children and women of childbearing age. Thus, the aim of this study was to evaluate the correlation between the device implantation and serum levels of nickel. Methods: This was a prospective longitudinal observational study conducted at a public hospital. Patients undergoing percutaneous atrial septal defect occlusion were clinically evaluated using transthoracic echocardiography and peripheral vein blood sampling for serum nickel before and after (1 day, 1 and 3 months) implantation. Results: The procedure and subsequent examinations were successfully performed in ten patients, with mean age of 34.4 years (range 5 to 60 years). Serial echocardiography confirmed the maintenance of adequate results of the procedure. Patients did not show manifestations that might suggest a reaction to metal, such as skin rash, dyspnea, thoracic discomfort, palpitations or migraine. Serum nickel levels did not show any significant changes and remained within the normal range for the population, according to the dosing methods within 3 months of the procedure. Conclusions: Preliminary results of this investigation with the Cocoon device have shown that during the initial period of endothelization after the procedure there was no significant nickel release into the bloodstream...

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Introdução: A despeito de suas reconhecidas limitações, a angiografia coronária invasiva é o método mais usado (muitas vezes único) para a adoção de estratégias terapêuticas em pacientes submetidos a cateterismo cardíaco diagnóstico. A mensuração de reserva de fluxo fracionada (FFR) tem sido empregada em diversos estudos, fundamentalmente no contexto de pacientes em que a avaliação angiográfica per se indica a necessidade de intervenção sobre as lesões coronárias. No entanto, o método praticamente não foi ainda testado em condições opostas, no cenário clínico em que as obstruções, angiograficamente, não indicariam intervenções. O propósito deste trabalho, a ser realizado de forma piloto em dois centros, é testar a hipótese de que também para lesões intermediárias, nas quais a angiografia não demonstra necessidade de intervenção coronária, a medida de FFR resultaria em alteração da conduta terapêutica baseada em angiografia. Métodos: Serão incluídos pacientes consecutivos e clinicamente estáveis, com doença coronária em segmento proximal e/ou médio de um ou mais vasos epicárdicos (diâmetro > 2,5 mm), apresentando obstruções entre 40 e 70%, por estimativa visual. Em seguida, a conduta terapêutica (clínica ou intervencionista) baseada em angiografia, relativamente a essas lesões, será ...

Background: Despite its well-known limitations, invasive coronary angiography remains the most used, and often times the only method used to define treatment strategies in patients undergoing diagnostic cardiac catheterization. Measurement of coronary fractional flow reserve (FFR) has been used in several studies in patients for whom an interventional the rapy strategy was determined based on angiography. However, this method has not been tested in the opposite scenario, in which the angiographic evaluation does not indicate the need for interventions. The purpose of this pilot study, to be performed in two sites, is to test the hypothesis that for intermediate injuries, in which angiography does not indicate the need for coronary intervention, measurement of FFR might change the therapeutic approach based on angiography. Methods: Consecutive clinically stable patients, with coronary disease in the proximal or middle segment of one or more epicardial vessels (diameter > 2.5 mm), with injuries between 40 and 70% by visual estimation will be enrolled in this trial. The treatment approach (clinical or interventional) based on angiography will be defined independently and by consensus of two observers. Thereafter, patients in both groups will be randomized into two subgroups: (1) maintenance of the angiography-based therapeutic strategy; and (2) use of FFR to define therapeutic strategy. Patients with FFR < 0.80 will be treated by percutaneous or surgical revascularization, whereas patients with FFR ≥ 0.80 ...