Safety and efficacy of new potassium binders on hyperkalemia management in patients with heart failure: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hyperkalemia leads to suboptimal use of evidence-based therapies in patients with heart failure (HF). Therefore, we aimed to assess whether new potassium binders are effective and safe to promote medical optimization in patients with HF. METHODS: MEDLINE, Cochrane, and Embase were searched for randomized controlled trials (RCTs) that reported outcomes after initiation of Patiromer or Sodium Zirconium Cyclosilicate (SZC) versus placebo in patients with HF at high risk of hyperkalemia development. Risk ratios (RR) with 95% confidence intervals (CI) were pooled with a random effects model. Quality assessment and risk of bias were performed according to Cochrane recommendations. RESULTS: A total of 1432 patients from 6 RCTs were included, of whom 737 (51.5%) patients received potassium binders. In patients with HF, potassium binders increased the use of renin-angiotensin-aldosterone inhibitors (RR 1.14; 95% CI 1.02-1.28; p = 0.021; I2 = 44%) and reduced the risk of hyperkalemia (RR 0.66; 95% CI 0.52-0.84; p < 0.001; I2 = 46%). The risk of hypokalemia was significantly increased in patients treated with potassium binders (RR 5.61; 95% CI 1.49-21.08; p = 0.011; I2 = 0%). There was no difference between groups in all-cause mortality rates (RR 1.13; 95% CI 0.59-2.16; p = 0.721; I2 = 0%) or in adverse events leading to drug discontinuation (RR 1.08; 95% CI 0.60-1.93; p = 0.801; I2 = 0%). CONCLUSION: The use of new potassium binders Patiromer or SZC in patients with HF at risk for hyperkalemia increased the rates of medical therapy optimization with renin-angiotensin-aldosterone inhibitors and reduced the incidence of hyperkalemia, at the cost of an increased prevalence of hypokalemia.

Modulation of Regulatory T Cells Activity by Distinct CD80 and CD86 Interactions With CD28/CTLA-4 in Chagas Cardiomyopathy.

Chagas cardiomyopathy is the symptomatic cardiac clinical form (CARD) of the chronic phase of Chagas disease caused by Trypanosoma cruzi infection. It was described as the most fibrosing cardiomyopathies, affecting approximately 30% of patients during the chronic phase. Other less frequent symptomatic clinical forms have also been described. However, most patients who progress to the chronic form develop the indeterminate clinical form (IND), may remain asymptomatic for life, or develop some cardiac damage. Some mechanisms involved in the etiology of the clinical forms of Chagas disease have been investigated. To characterize the contribution of CD80 and CD86 co-stimulatory molecules in the activation of different CD4+ (Th1, Th2, Th17, and Treg) and CD8+ T lymphocyte subsets, we used blocking antibodies for CD80 and CD86 receptors of peripheral blood mononuclear cells (PBMC) in cultures with T. cruzi antigens from non-infected (NI), IND, and CARD individuals. We demonstrated a higher frequency of CD8+ CD25+ T lymphocytes and CD8+ Treg cells after anti-CD80 antibody blockade only in the CARD group. In contrast, a lower frequency of CD4+ Treg lymphocytes after anti-CD86 antibody blockade was found only in IND patients. A higher frequency of CD4+ Treg CD28+ lymphocytes, as well as an association between CD4+ Treg lymphocytes and CD28+ expression on CD4+ Treg cells in the CARD group, but not in IND patients, and once again only after anti-CD80 antibody blockade, was observed. We proposed that Treg cells from IND patients could be activated via CD86-CTLA-4 interaction, leading to modulation of the immune response only in asymptomatic patients with Chagas disease, while CD80 may be involved in the proliferation control of T CD8+ lymphocytes, as also in the modulation of regulatory cell activation via CD28 receptor. For the first time, our data highlight the role of CD80 in modulation of Treg lymphocytes activation in patients with CARD, highlighting a key molecule in the development of Chagas cardiomyopathy.

Myocardial fibrosis in chagas disease and molecules related to fibrosis.

Chronic Chagas cardiomyopathy (CCC) is responsible for the disease's greater morbidity and poor prognosis. Although understanding the pathophysiology of CCC and the fundamentals of its clinical management derives from research related to other cardiomyopathies, there are peculiarities that distinguish CCC from the others. CCC is the most fibrous heart disease, and its myocardial involvement is important as it disorganizes or disrupts the extracellular matrix, creating an environment conducive to the formation of arrhythmogenic foci. It is also considered the most arrhythmogenic of the known heart diseases, giving rise to complex arrhythmias, usually associated with varying degrees of stimulus conduction disorders. The central proposal of this review is to describe a possible association between the distribution and degree of myocardial fibrosis and cardiac arrhythmogenicity in patients with Chagas cardiomyopathy, drawing attention to the importance of noninvasive biomarkers for the quantification of myocardial fibrosis.

A focussed single-view hand-held echocardiography protocol for the detection of rheumatic heart disease.

BACKGROUND: Echocardiographic screening represents an opportunity for reduction in the global burden of rheumatic heart disease. A focussed single-view screening protocol could allow for the rapid training of healthcare providers and screening of patients. OBJECTIVE: The aim of this study was to determine the sensitivity and specificity of a focussed single-view hand-held echocardiographic protocol for the diagnosis of rheumatic heart disease in children. METHODS: A total of nine readers were divided into three reading groups; each interpreted 200 hand-held echocardiography studies retrospectively as screen-positive, if mitral regurgitation ⩾1.5 cm and/or any aortic insufficiency were observed, or screen-negative from a pooled study library. The performance of experts receiving focussed hand-held protocols, non-experts receiving focussed hand-held protocols, and experts receiving complete hand-held protocols were determined in comparison with consensus interpretations on fully functional echocardiography machines. RESULTS: In all, 587 studies including 76 on definite rheumatic heart disease, 122 on borderline rheumatic heart disease, and 389 on normal cases were available for analysis. The focussed single-view protocol had a sensitivity of 81.1%, specificity of 75.5%, negative predictive value of 88.5%, and a positive predictive value of 63.2%; expert readers had higher specificity (86.1 versus 64.8%, p<0.01) but equal sensitivity. Sensitivity - experts, 96% and non-experts, 95% - and negative predictive value - experts, 99% and non-experts, 98% - were better for definite rheumatic heart disease. False-positive screening studies resulting from erroneous identification of mitral regurgitation and aortic insufficiency colour jets increased with shortened protocols and less experience (p<0.01). CONCLUSION: Our data support a focussed screening protocol limited to parasternal long-axis images. This holds promise in making echocardiographic screening more practical in regions where rheumatic heart disease remains endemic.

Determinants of prolonged length of hospital stay after cardiac surgery: impact of rheumatic heart disease / Determinantes de internação hospitalar prolongada após cirurgia cardíaca: impacto de cardiopatia reumática

BACKGROUND: Rheumatic heart disease remains a major health problem in developing countries. Several factors contribute to valve-related morbidity after cardiac surgery, but the role of rheumatic etiology of valve disease is not well defined. This study was designed to determine the additional value of rheumatic valve disease in predicting morbidity after cardiac surgery in the current era of heart valve disease treatment. METHOD: This study prospectively included 164 patients for cardiac surgery from June 2010 to June 2011. The outcome was prolonged length of stay, defined as a length of stay greater than or equal to the 75th percentile for length of stay for each operation, including the day of discharge. RESULTS: Rheumatic heart disease was present in 32 patients (20%) and all rheumatic patients underwent valve replacement. Rheumatic heart disease patients were younger with less comorbidities compared to non-rheumatic patients, with most (63%) having had previous surgery. Forty-one patients were classified as having a prolonged hospital length of stay; 11 (34%) patients with rheumatic and 30 (23%) non-rheumatic fever. Rheumatic heart disease was not associated with prolonged hospital stay in the univariate analysis; however, after adjustment for other factors including infectious endocarditis, surgery duration, mechanical ventilation time, EuroSCORE, and postoperative pneumonia, it was found to be a predictor of prolonged hospitalization. CONCLUSION: This study demonstrates that rheumatic heart disease was an important factor associated with prolonged hospital, after adjustment for well-known risk factors of morbidity after cardiac surgery. Rheumatic fever is still prevalent among the patients who underwent to cardiac surgery in the current age, contributing to increase the postoperative morbidity.

OBJETIVO: A doença cardíaca reumática continua a ser um problema grave de saúde nos países em desenvolvimento. Vários fatores contribuem para a morbidade relacionada com a cirurgia valvar cardíaca, mas o papel da etiologia reumática das valvopatias não está bem definido. Este estudo foi desenhado para determinar participação adicional de valvopatias reumáticas na previsão de morbidade após cirurgia cardíaca na era atual de tratamento da doença. MÉTODOS: Este estudo incluiu prospectivamente 164 pacientes submetidos a cirurgia cardíaca, entre junho de 2010 a junho de 2011. O resultado medido foi a duração da estadia prolongada, definido como tempo de permanência maior ou igual ao percentil 75 para a duração da estada para cada operação, incluindo a dia da alta. RESULTADOS: A cardiopatia reumática esteve presente em 32 pacientes (20%) e em todos os pacientes submetidos à substituição da válvula. Pacientes com doenças cardíacas reumáticas eram mais jovens e com menos comorbidades comparados com pacientes não-reumáticos; a maioria deles (63%) tinha tido cirurgia prévia. Quarenta e um pacientes foram classificados como tendo um tempo de permanência hospitalar prolongado; 11 (34%) pacientes com doenças reumáticas e 30 (23%) com doenças não-reumáticas. A doença reumática não se apresentou associada com período de internação prolongado, na análise univariada; No entanto, após o ajuste para outros fatores, incluindo endocardite infecciosa, duração da cirurgia, tempo de ventilação mecânica, EuroSCORE, e pneumonia no pós-operatório, a doença reumática revelou-se um preditor de hospitalização prolongada. CONCLUSÕES: Este estudo demonstra que a doença cardíaca reumática é um importante fator associado com internação prolongada, após o ajuste para fatores de risco bem conhecidos de morbidade após cirurgia cardíaca. A febre reumática ainda é prevalente entre os pacientes que se submeteram à cirurgia cardíaca na época atual, contribuindo para aumentar a morbidade pós-operatória.

Impaired coronary flow reserve in patients with indeterminate form of Chagas' disease.

BACKGROUND: Previous studies suggest that microvascular abnormalities may contribute to the pathogenesis of Chagas' heart disease. Coronary flow reserve (CFR) expressed by the maximum achievable flow relative to baseline flow in the coronary microcirculation, may be useful in identifying patients who may be developing cardiac manifestations of the disease. This study aims to assess the CFR in patients with indeterminate form of Chagas' disease, and also to identify the determinants of CFR. METHODS: Sixty-four asymptomatic patients (37% male; age 49.9 ± 11.5 years) with normal cardiovascular exams classified as in indeterminate form of Chagas' disease underwent transthoracic dipyridamole (0.84 mg/kg in 6 min) stress echocardiography, and were compared with a control group of healthy patients. Coronary flow reserve was assessed on left anterior descending artery using pulsed Doppler as the ratio of maximal peak vasodilation (dipyridamole) to rest diastolic flow velocity. A treadmill exercise test was performed to rule out ischemia. RESULTS: All patients had good functional capacity assessed by exercise testing with peak oxygen consumption (VO2 ) of 28 ± 11 mL/kg per minute, similar to the controls. There were no differences in the echocardiographic parameters of diastolic and systolic left ventricular function and right ventricular function between the patients and controls. Coronary flow reserve was significantly lower in Chagas' disease patients than those in healthy individuals (1.9 ± 0.4 vs. 2.6 ± 0.5; P < 0.001). Several factors were correlated with the CFR, including age, ejection fraction, left ventricular diastolic function, heart rate recovery, and the presence of Chagas' disease. In a multivariate analysis, age and positive serology for Chagas' disease were independent factors associated with the CFR. CONCLUSIONS: Coronary flow reserve was impaired in Chagas' disease patients in the indeterminate form compared with healthy individuals with similar clinical features. Among all variables tested, age and positive serology for Chagas' disease were independent factors associated with the CFR.