Chagas Cardiomyopathy in Latin America Review.

PURPOSE OF REVIEW: Chagas cardiomyopathy is a major public health disease in Latin America and, due to migration, is becoming a worldwide health and economic burden. This review sought to present the clinical and epidemiological aspects of Chagas cardiomyopathy, as well as some specific features and principles of treatment. We also retrospectively assessed our institutional experience with mechanical circulatory support in refractory heart failure due to Chagas cardiomyopathy over a 10-year period. RECENT FINDINGS: The role of antiparasitic treatment in patients with heart failure due to Chagas cardiomyopathy is controversial. Heart transplantation, although formerly contraindicated, is currently established as an important therapeutic option. Also, the favorable characteristics of Chagas patients, such as younger age, little comorbidity, and no reoperations or severe pulmonary hypertension, could be an advantage for a mechanical circulatory support indication in advanced heart failure due to Chagas cardiomyopathy. Despite the absence of large evidence-based data, much has been accomplished since Carlos Chagas' discovery one century ago. Our institutional experience shows that mechanical circulatory support in Chagas patients is associated with more successful bridging to heart transplantation when compared to non-Chagas patients.

Enhancing risk assessment in Chagas cardiomyopathy: Electrophysiology study stratified by Rassi score.

BACKGROUND: Chagas cardiomyopathy (CCM) is increasingly prevalent in developed countries due to migration from endemic areas. Accurate risk stratification is crucial due to the variable clinical course of CCM. OBJECTIVE: To analyze the association between Rassi score progression and electrophysiology study (EPS) changes in CCM patients. METHODS: This prospective, observational cohort study involved CCM patients from two tertiary hospitals. Patients were classified as low, intermediate, or high risk based on the Rassi score. Data collected included demographics, clinical history, and diagnostic tests. EPS assessed AH, HH, and HV intervals, and inducibility of ventricular arrhythmias. Follow-ups were at 30 days and six-month intervals, with individualized discussions for cardiac implantable electric devices (CIED) based on EPS results. RESULTS: Of 67 screened CCM patients, 59 underwent EPS. The mean Rassi score was 8.7 ± 4.5 points, with 33.8 % low, 38.9 % intermediate, and 27.1 % high risk. EPS abnormalities were found in 57.6 % of patients, mainly VT/VF (52.5 %). Most induced ventricular arrhythmias were monomorphic VT (80.7 %). A significant association was found between Rassi score risk classification and EPS changes (OR = 1.88 95 %CI: 1.15-3.06 p = 0.02). Higher Rassi scores correlated with VT presence on EPS (p = 0.0036). Syncope/pre-syncope had an OR 2.45 95 %CI:1.21-4.94; p = 0.012, independent of Rassi risk. Decreased ejection fraction was linked to EPS changes (p = 0.04). CONCLUSION: EPS changes among CCM was associated with progression of the Rassi score, indicating its utility as a stratification tool. Factors such as the presence of syncope/pre-syncope, decreased LVEF and wall motion abnormalities emerged as independent predictors within Rassi scores for changes in EPS.

The effects of METhotrexate therapy on the physical capacity of patients with ISchemic heart failure: a randomized double-blind, placebo-controlled trial (METIS trial).

BACKGROUND: The cytokine hypothesis suggests that there is an association between chronic heart failure (CHF) and inflammation. Methotrexate could improve CHF patients' clinical status, especially those with ischemic etiology. METHODS AND RESULTS: METIS is a randomized, double-blinded trial studying 50 patients with ischemic CHF given methotrexate (7.5mg) or placebo, plus folic acid (5mg), for 12 weeks. The primary end point was the difference in 6-minute walk test (6MWT) distance before and after treatment. We also evaluated functional class (NYHA), Short-Form 36 protocol quality of life, C-reactive protein (CRP), incidence of adverse effects, and the combined incidence of death, myocardial infarction, stroke, hospitalization, and need for myocardial revascularization. There was no significant difference between groups in distance covered in the 6MWT: the methotrexate group improved by 24.5+/-39.5m, the placebo group by 21.3+/-43.7m (P=.80). The NYHA scores improved in 66.7% of the methotrexate group patients and in 50.0% of the placebo group (P=.2). SF-36 scores indicated improved mental health in the placebo group. There were no significant differences in CRP levels, the combined outcome, or adverse events. CONCLUSIONS: These results show that the methotrexate group tended toward improved NYHA scores and that there were no significant changes in 6MWT results or secondary assessments.

Systemic effects of controlled exposure to diesel exhaust: a meta-analysis from randomized controlled trials.

INTRODUCTION: Ambient air pollution is associated with adverse cardiovascular events. This meta-analysis aimed to investigate the short-term association between air pollution and cardiovascular effects on healthy volunteers. METHODS: We searched databases to identify randomized trials with controlled human exposures to either of two models for studying ambient particulate matter: diesel-exhaust or concentrated ambient particles. Estimates of size effect were performed using standardized mean difference (SMD). Heterogeneity was assessed with I2 statistics. Outcomes were vascular function estimated by forearm blood flow (FBF), blood pressure, heart rate, and blood analysis. RESULTS: Database searches yielded 17 articles (n = 342) with sufficient information for meta-analyses. High levels of heterogeneity for the some outcomes were analyzed using random-effects model. The pooled effect estimate showed that short-term exposure to air pollution impaired FBF response from 2.7 to 2.5 mL/100 mL tissue/min (SMD 0.404; p = .006). There was an increase in 5000 platelet/mm3 following pollution exposure (SMD 0.390; p = .050) but no significant differences for other outcomes. CONCLUSION: Controlled human exposures to air pollution are associated with the surrogates of vascular dysfunction and increase in platelet count, which might be related to adverse cardiovascular events. Given the worldwide prevalence of exposure to air pollution, these findings are relevant for public health. KEY MESSAGES Controlled exposure to air pollution impairs vasomotor response, which is a surrogate for adverse cardiovascular events. This is the first meta-analysis from randomized clinical trials showing short-term association between air pollution and cardiovascular effects on healthy volunteers. Given the worldwide prevalence of exposure to air pollution, this finding is important for public health.

Role of vascular inflammation in coronary artery disease: potential of anti-inflammatory drugs in the prevention of atherothrombosis. Inflammation and anti-inflammatory drugs in coronary artery disease.

Coronary artery disease (CAD) and acute myocardial infarction (AMI) are inflammatory pathologies, involving interleukins (ILs), such as IL-1ß, IL-6 and tumor necrosis factor (TNF)-α, and acute phase proteins production, such as for C reactive protein (CRP). The process begins with retention of low-density lipoprotein (LDL) and its oxidation inside the intima, with the formation of the "foam cells." Toll-like receptors and inflamassomes participate in atherosclerosis formation, as well as in the activation of the complement system. In addition to innate immunity, adaptive immunity is also associated with atherosclerosis through antigen-presenting cells, T and B lymphocytes. AMI also increases the expression of some ILs and promotes macrophage and lymphocyte accumulation. Reperfusion increases the expression of anti-inflammatory ILs (such as IL-10) and generates oxygen free radicals. Although CAD and AMI are inflammatory disorders, the only drugs with anti-inflammatory effect so far widely used in ischemic heart disease are aspirin and statins. Some immunomodulatory or immunosuppressive promising therapies, such as cyclosporine and colchicine, may have benefits in CAD. Methotrexate also has potential cardioprotective anti-inflammatory effects, through increased adenosine levels. The TETHYS trial (The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS trial) will evaluate low-dose methotrexate in ST elevation AMI. The CIRT (Cardiovascular Inflammation Reduction Trial), in turn, will evaluate low-dose methotrexate in patients with a high prevalence of subclinical vascular inflammation. The CANTOS (The Canakinumab Antiinflammatory Thrombosis Outcomes Study) will evaluate canakinumab in patients with CAD and persistently elevated CRP. The blockage of other potential targets, such as the IL-6 receptor, CC2 chemokine receptor and CD20, could bring benefits in CAD.

The effect of maternal hypercholesterolemia on the placenta and fetal arteries in rabbits.

PURPOSE: To investigate the degree of placental permeability in dyslipidemic rabbits and the consequent vascular dysfunction in fetuses of female rabbits with high lipoprotein levels. METHODS: Fifteen adult females New Zealand White rabbits were divided into two groups. Group 1(n=5) - hypercholesterolemic diet with 0.5% cholesterol, and Group 2 (n=10) - control. On day 30, the levels of plasma lipoproteins and triglycerides were analyzed in the mothers, and the presence of collagen was analyzed in the placenta as well as in fetal coronary and aorta. Statistical analyses used the Student's t and the Mann-Whitney tests. RESULTS: Lipoprotein levels were significantly different (p=0.02 to p<0.001) in experimental and control groups. In the hypercholesterolemic group, total cholesterol levels were in average 793 mg/dl; triglycerides were in average 257 mg/dl; HDL-C was 48 mg/dl, and LDL-C was in average 692 mg/dl. The amount of collagen per micrometers square (mµ²) in samples from hypercholesterolemic animals was significantly higher than in the control group. CONCLUSIONS: The study confirmed placental permeability to lipoproteins, shown by increased amounts of collagen in fetal tissues. This alteration results in increased susceptibility to atherosclerosis in adult life, representing a risk factor for the early development of disease, which may appear even in the prenatal period.

Docinhos e ensaios de não inferioridade: uma experiência pedagógica criativa / Candies in the study of non-inferiority trials: a creative pedagogic experiment

Os novos desafios na área da educação surgem com o próprio desenvolvimento do conhecimento. Novas técnicas de pesquisa possibilitaram grandes descobertas na ciência e, com isso, uma crescente complexificação dos temas estudados. Os alunos, inseridos no universo dinâmico da internet, também evoluíram e não se encaixam mais nas prescrições da pedagogia tradicional. Para essas novas realidades, a forma de educar no século XXI exige dos educadores um esforço de criatividade para transmitir um conhecimento cada vez mais complexo. Para ilustrar essa nova situação, relatamos uma experiência pedagógica que buscou, com a criatividade de uma intervenção fictícia, favorecer o ensino dos ensaios clínicos de não inferioridade. A experiência demonstra a utilidade de tais ensaios clínicos quando se necessita testar a eficácia de tratamentos. A utilização dos docinhos e a participação dos alunos como sujeitos do ensaio configuraram-se como uma metodologia ativa, de aproximação entre os educandos e seu objeto de estudo. O exercício realizado está de acordo com os modelos pedagógicos sugeridos pela teoria da aprendizagem significativa e pode servir de referência para iniciativas semelhantes.

New challenges in education parallel with knowledge expansion. New research techniques have enabled major discoveries in science, together with a growing complexity of the studied themes. Students, part of the dynamic universe of the Internet, have also evolved and no longer fit the requirements of traditional pedagogy. For these new realities the way to educate in the twenty-first century requires a creative effort from educators, in order to convey knowledge that is increasingly complex. As an illustration of this new situation, we bring the report of a pedagogical experiment that sought, with the creativity of a fictitious intervention, to support the teaching of non-inferiority clinical trials. The experiment managed to show the usefulness of such clinical trials when there is the need to test the efficacy of treatments. The use of sweets and the participation of students as the test subjects constitute an active methodology, bringing students closer to their subject of study. The exercise conducted is in line with the pedagogical models suggested by the meaningful learning theory and can be used as a benchmark for similar initiatives.

The effect of maternal hypercholesterolemia on the placenta and fetal arteries in rabbits / Efeito da hipercolesterolemia maternal sobre a placenta e as artérias fetais em coelhos

PURPOSE: To investigate the degree of placental permeability in dyslipidemic rabbits and the consequent vascular dysfunction in fetuses of female rabbits with high lipoprotein levels. METHODS: Fifteen adult females New Zealand White rabbits were divided into two groups. Group 1(n=5) - hypercholesterolemic diet with 0.5 percent cholesterol, and Group 2 (n=10) - control. On day 30, the levels of plasma lipoproteins and triglycerides were analyzed in the mothers, and the presence of collagen was analyzed in the placenta as well as in fetal coronary and aorta. Statistical analyses used the Student's t and the Mann-Whitney tests. RESULTS: Lipoprotein levels were significantly different (p=0.02 to p<0.001) in experimental and control groups. In the hypercholesterolemic group, total cholesterol levels were in average 793mg/dl; triglycerides were in average 257mg/dl; HDL-C was 48mg/dl, and LDL-C was in average 692mg/dl. The amount of collagen per micrometers square (mµ²) in samples from hypercholesterolemic animals was significantly higher than in the control group. CONCLUSIONS: The study confirmed placental permeability to lipoproteins, shown by increased amounts of collagen in fetal tissues. This alteration results in increased susceptibility to atherosclerosis in adult life, representing a risk factor for the early development of disease, which may appear even in the prenatal period.

OBJETIVO: Investigar a permeabilidade placentária em coelhos adultos fêmeas dislipidêmicas e a consequente disfunção vascular em seus fetos. MÉTODOS: Quinze coelhos adultos fêmeas Nova Zelândia Brancas foram distribuídas em grupo dislipidêmico e grupo controle. No trigésimo dia de gestação foram medidos os triglicerídeos e as lipoproteínas nas coelhas e verificada a presença de colágeno na placenta e coronárias fetais. Análise estatística foi feita com teste t de Student´s e Mann-Whitney. RESULTADOS: Os níveis de lipoproteínas foram diferentes estatisticamente entre os grupos (p=0,02 a p<0,001). A quantidade de colágeno por micrômetro quadrado foi significantemente maior no grupo hipercolesterolêmico em comparação ao grupo controle. CONCLUSÕES: O estudo confirmou a permeabilidade placentária para lipoproteínas demonstrando aumento de colágeno nos tecidos fetais. Esta alteração induz ao aumento da suscetibilidade para aterosclerose na vida adulta, representando um fator de risco para desenvolvimento precoce da doença aterosclerótica a qual pode estar presente mesmo no período pré-natal.

Filtro respiratório reduz efeitos cardiovasculares associados à poluição: estudo randomizado, duplo-cego, controlado e cruzado em pacientes com insuficiência cardíaca (FILTER-HF trial) / Respiratory filter reduces the cardiovascular effects associated with diesel exhaust exposure: a randomized, prospective, double-blind, controlled study of heart failure

A poluição do ar é um fator de risco associado com descompensação e mortalidade em pacientes com insuficiência cardíaca (IC). Objetivo Avaliar o impacto de um filtro de polipropileno sobre desfechos cardiovasculares em pacientes com IC e voluntários saudáveis durante exposição controlada à poluição. Métodos Ensaio clínico duplocego, controlado e cruzado, incluindo 26 pacientes com IC e 15 voluntários saudáveis, expostos a três protocolos diferentes de inalação randomizados por ordem: Ar Limpo; Exposição à Partículas de Exaustão do Diesel (ED); e ED filtrada. Os desfechos estudados foram função endotelial por índice de hiperemia reativa (RHi) e índice de aumento (Aix), biomarcadores séricos, variáveis de teste cardiopulmonar submáximo (caminhada de seis-minutos [tc6m]; consumo de oxigênio [VO2]; equivalente ventilatório de gás carbônico [VE/VCO2 slope]; consumo de O2 por batida [PulsoO2]) e variabilidade da frequência cardíaca (VFC). Resultados No grupo IC, a ED piorou o RHi [de 2,17 (IQR: 1,8-2,5) para 1,72 (IQR: 1,5-2,2); p=0,002], reduziu o VO2 [de 11.0 ± 3.9 para 8.4±2.8ml/Kg/min; p < 0.001], o tc6m [de 243,3±13 para 220,8 ± 14m; p=0,030] e o PulsoO2 [de 8.9 ± 1.0 para 7.8±0.7ml/bpm; p < 0.001]; e aumentou o BNP [de 47,0pg/ml (IQR: 17,3-118,0) para 66,5pg/ml (IQR: 26,5-155,5); p=0,004]. O filtro foi capaz de reduzir a concentração de poluição de 325±31 para 25±6?g/m3 (p < 0,001 vs. ED). No grupo IC, o filtro foi associado com melhora no RHi [2,06 (IQR: 1,5-2,6); p=0,019 vs. ED); aumento no VO2 (10.4 ± 3.8ml/Kg/min; p < 0.001 vs. ED) e PulsoO2 (9.7±1.1ml/bpm; p < 0.001 vs. ED); e redução no BNP [44,0pg/ml (IQR: 20,0-110,0); p=0,015 vs. ED]. Em ambos os grupos, a ED reduziu o Aix, sem efeito do filtro. O uso do filtro foi associado com maior ventilação e reinalação de CO2. Outras variáveis pesquisadas como VE/VCO2 slope e VFC não sofreram influências entre os protocolos. Conclusão A poluição do ar afetou adversamente o desempenho...

Air pollution is considered a risk factor for heart failure (HF) decompensation and mortality. The effects of respiratory filters on patients with HF exposed to air pollution have not been established. Objective To test the effects of a respiratory filter intervention (filter) during controlled pollution exposure Methods Double-blind, randomized to order and 3-way crossover study with 26 HF patients and 15 control volunteers. Participants were exposed in three separate sessions to: clean air, diesel exhaust exposure (DE) or filtered-DE. Endpoints were endothelial function via reactive hyperemia index (RHi), and arterial stiffness (Aix), serum biomarkers, variables from submaximal cardiopulmonary exercise test (sixminute walk test [6mwt]; oxygen uptake [VO2]; ventilation and carbon dioxide production ratio [VE/VCO2 slope]; oxygen uptake per heart beat [O2Pulse]), and heart rate variability (HRV). Results In patients with HF, DE was associated with a worsening in RHi [from 2.17 (IQR: 1.8-2.5) to 1.72 (IQR: 1.5-2.2); p=0.002]; a decline in VO2 [from 11.0±3.9 to 8.4±2.8ml/Kg/min; 0.001], 6mwt [from 243.3 +- 13.0 to 220.8±13.7m; p=0.030] and O2Pulse [from 8.9±1.0 to 7.8±0.7ml/beat; 0.001] and a rise in BNP [from 47.0pg/ml (IQR: 17.3-118.0) to 66.5pg/ml (IQR: 26.5-155.5); p=0.004]. Filtration reduced the particulate concentration (from 325±31 to 25±6?g/m3; 0.001 vs. DE). In the HF group, filter was associated with an improvement in RHi [2.06 (IQR: 1.5-2.6); p=0.019 vs. DE]; an increase in VO2 (10.4 ± 3.8ml/Kg/min; p < 0.001 vs. DE) and O2Pulse (9.7 ± 1.1ml/beat; p < 0.001 vs. DE); and also a decrease in BNP [44.0pg/ml (IQR: 20.0-110.0); p=0.015 vs. DE]. In both groups DE decreased Aix, however filtration did not change these responses. In both groups, filtration was associated with higher pulmonary ventilation and CO2 rebreathing. Other variables as VE/VCO2 slope and HRV did not differ between exposure protocols. Conclusion Air pollution adversely...

Contribuições e limitações dos biomarcadores no diagnóstico e prognóstico da insuficiência cardíaca com fração de ejeção preservada / Contributions and limitations of biomarkers in the diagnosis of heart failure with preserved ejection fraction

A insuficiência cardíaca é uma síndrome clínica de prevalência crescente. Aproximadamente 30-50% dos pacientes com insuficiência cardíaca congestiva têm disfunção diastólica como causa de seus sintomas. No entanto, o diagnóstico de insuficiência cardíaca de fração de ejeção preservada não é tão simples. Neste contexto, cresce o interesse em encontrarmos biomarcadores que possam auxiliar no diagnóstico e na avaliação prognóstica da insuficiência cardíaca de fração de ejeção preservada. As evidências atuais são provenientes de estudos que avaliaram pacientes com disfunção sistólica e diastólica. No entanto, alguns biomarcadores parecem promissores na avaliação de pacientes com disfunção diastólica. Os peptídeos natriuréticos são os biomarcadores mais amplamente estudados. Níveis de peptídeo natriurético do tipo B e da fração N-terminal do peptídeo natriurético do tipo B são mais elevados entre pacientes com disfunção diastólica quando comparados a indivíduos saudáveis e parecem estar relacionados a maior mortalidade intra-hospitalar e maior risco de evento combinado de morte e re-hospitalização. Assim como entre pacientes com disfunção sistólica, pacientes com insuficiência cardíaca de fração de ejeção preservada com troponina elevada também parecem apresentar maior risco de morte e re-hospitalização. Mais recentemente, tem sido descritos biomarcadores de fibrose como galectina-3 e ST2 solúvel e dados da literatura sugerem que quando elevados podem refletir pior prognóstico. De forma geral, biomarcadores que identificam injúria miocárdica; alterações no turnover celular e marcadores de fibrose parecem promissores por refletirem mecanismos fisiopatológicos da insuficiência cardíaca de fração de ejeção preservada. Assim, estudos prospectivos envolvendo especificamente esta população ainda são necessários para que o real papel destes biomarcadores seja estabelecido.

Heart Failure is a disease whose prevalence has been increasing in the last years. About 30-50% of patients with congestive heart failure have heart failure with preserved ejection fraction (HF-pEF) as the cause of their symptoms. However, the diagnosis of HF-pEF is not so easy to be established. In this context, multiple biomarkers of heart failure have emerged recently and have been used to help in the diagnosis and prognosis of HF-pEF. Current evidence about biomarkers in heart failure comes from trials that involved patients with systolic and diastolic dysfunction. There are few studies involving exclusively patients with HF-pEF. Nevertheless, some biomarkers seem to be promising in patients with HF-pEF. Natriuretic peptides are the most common biomarkers of heart failure, B-type natriuretic peptide and N-terminal B-type natriuretic peptide are higher in patient with diastolic dysfunction when compared to healthy people and seem to be related with higher in-hospital mortality and higher risk of death and re-hospitalization. Patients with HF-pEF, who have high levels of troponin, have also higher risk of death and re-hospitalization. Recently, new biomarkers of fibrosis as 3-galectin and soluble ST2 have been described and data suggest that high levels of these biomarkers should reflect worse prognosis. In summary, biomarkers of myocardial injury; cellular turnover changes and fibrosis seem to be promising biomarkers of the heart failure with preserved ejection fraction since they could reflect their physiopathological mechanisms. So, we believe that prospective thats involving patients with heart failure with preserved ejection fraction are still necessary to establish the importance of these biomarkers.

Inflamação na insuficiência cardíaca / Inflammation in heart failure

A insuficiência cardíaca (IC) é um problema de saúde pública que acomete 2,5% da população com mais de 20 anos. Apesar da evolução terapêutica das últimas décadas, a mortalidade e o número de internações persistem elevados. Existe uma ativação inflamatória na IC, com aumento dos níveis plasmáticos de fator de necrose tumoral a (TNF-a), interleucina 1b (IL-1b), IL-2, IL-6, IL-8, receptor solúvel de IL-6, cluster de diferenciação 14 (CD14), endotelinas 1A e 1B. Esta ativação inflamatória ficou conhecida como a ?hipótese das citocinas?. A magnitude do aumento das citocinas está relacionado à gravidade do quadro, sendo que a IC isquêmica apresenta níveis plasmáticos mais elevados. A hipótese das citocinas promoveu uma procura por potenciais alvos terapêuticos: as tentativas de antagonizar o TNF-a, endotelina A e matriz metaloproteinase, todavia, mostraram-se inefetivas ou prejudiciais. Apesar do insucesso dos grandes ensaios clínicos, pequenos estudos mostraram resultados promissores com anti-inflamatórios inespecíficos, como a talidomida, pentoxifilina e o metotrexato.