Intestinal fatty acid binding protein is associated with cardiac function and gut dysbiosis in chronic heart failure.

Background: The gut microbiota in patients with chronic heart failure (HF) is characterized by low bacterial diversity and reduced ability to synthesize beneficial metabolites. These changes may facilitate leakage of whole bacteria or bacterial products from the gut into the bloodstream, which may activate the innate immune system and contribute to the low-grade inflammation seen in HF. In this exploratory cross-sectional study, we aimed to investigate relationships between gut microbiota diversity, markers of gut barrier dysfunction, inflammatory markers, and cardiac function in chronic HF patients. Methods: In total, 151 adult patients with stable HF and left ventricular ejection fraction (LVEF) < 40% were enrolled. We measured lipopolysaccharide (LPS), LPS-binding protein (LBP), intestinal fatty acid binding protein (I-FABP), and soluble cluster of differentiation 14 (sCD14) as markers of gut barrier dysfunction. N-terminal pro-B-type natriuretic peptide (NT-proBNP) level above median was used as a marker of severe HF. LVEF was measured by 2D-echocardiography. Stool samples were sequenced using 16S ribosomal RNA gene amplification. Shannon diversity index was used as a measure of microbiota diversity. Results: Patients with severe HF (NT-proBNP > 895 pg/ml) had increased I-FABP (p < 0.001) and LBP (p = 0.03) levels. ROC analysis for I-FABP yielded an AUC of 0.70 (95% CI 0.61-0.79, p < 0.001) for predicting severe HF. A multivariate logistic regression model showed increasing I-FABP levels across quartiles of NT-proBNP (OR 2.09, 95% CI 1.28-3.41, p = 0.003). I-FABP was negatively correlated with Shannon diversity index (rho = -0.30, p = <0.001), and the bacterial genera Ruminococcus gauvreauii group, Bifidobacterium, Clostridium sensu stricto, and Parasutterella, which were depleted in patients with severe HF. Conclusions: In patients with HF, I-FABP, a marker of enterocyte damage, is associated with HF severity and low microbial diversity as part of an altered gut microbiota composition. I-FABP may reflect dysbiosis and may be a marker of gut involvement in patients with HF.

Rifaximin or Saccharomyces boulardii in heart failure with reduced ejection fraction: Results from the randomized GutHeart trial.

BACKGROUND: The gut microbiota represents a potential treatment target in heart failure (HF) through microbial metabolites such as trimethylamine N-oxide (TMAO) and systemic inflammation. Treatment with the probiotic yeast Saccharomyces boulardii have been suggested to improve left ventricular ejection fraction (LVEF). METHODS: In a multicentre, prospective randomized open label, blinded end-point trial, we randomized patients with LVEF <40% and New York Heart Association functional class II or III, despite optimal medical therapy, to treatment (1:1:1) with the probiotic yeast Saccharomyces boulardii, the antibiotic rifaximin, or standard of care (SoC) only. The primary endpoint, the baseline-adjusted LVEF at three months, was assessed in an intention-to-treat analysis. FINDINGS: We enrolled a total of 151 patients. After three months' treatment, the LVEF did not differ significantly between the SoC arm and the rifaximin arm (mean difference was -1•2 percentage points; 95% CI -3•2 - 0•7; p=0•22) or between the SoC arm and the Saccharomyces boulardii arm (mean difference -0•2 percentage points; 95% CI -2•2 - 1•9; p=0•87). We observed no significant between-group differences in changes in microbiota diversity, TMAO, or C-reactive protein. INTERPRETATION: Three months' treatment with Saccharomyces boulardii or rifaximin on top of SoC had no significant effect on LVEF, microbiota diversity, or the measured biomarkers in our population with HF. FUNDING: The trial was funded by the Norwegian Association for Public Health, the Blix foundation, Stein Erik Hagen's Foundation for Clinical Heart Research, Ada og Hagbart Waages humanitære og veldedige stiftelse, Alfasigma, and Biocodex.

The Use of Two-Dimensional Strain Measured by Speckle Tracking in the Identification of Incipient Ventricular Dysfunction in HIV-Infected Patients on Antiretroviral Therapy, Untreated HIV Patients and Healthy Controls / O Uso do Strain Bidimensional Obtido pelo Speckle Tracking na Identificação da Disfunção Ventricular Incipiente em Pacientes Infectados pelo HIV em Uso de Terapia Antirretroviral, Pacientes HIV não Tratados e Controles Saudáveis

Abstract Background: Most cardiovascular abnormalities in patients infected with the human immunodeficiency virus (HIV) have been associated with myocardial damage directly caused by the virus. Some cases, however, may be associated with adverse effects from antiretroviral therapy (ART). New ventricular function assessment techniques are capable of detecting early changes in the cardiac function of HIV-infected patients using or not using ART. The usefulness of these techniques has been little employed in these patients. Objectives: To investigate the potential influence of antiretroviral therapy (ART) on the occurrence of subclinical left ventricular systolic dysfunction evaluated by myocardial strain rate analysis using two-dimensional speckle tracking echocardiography (2-D Echo) in treated HIV patients compared to untreated patients and healthy individuals. Methods: Sixty-eight HIV-infected patients with no cardiovascular symptoms, normal left ventricular (LV) ejection fraction (> 0.55 on 2-D Echo) were divided into three groups: 11 patients not using antiretroviral therapy (NT), 24 using protease inhibitor (PI) and 33 using non-nucleoside reverse transcriptase inhibitor (NNRTI). We also studied 30 normal non-HIV infected individuals (Ctrl). Demographic, clinical, biochemical and anthropometric data were collected. Preliminary transthoracic echocardiography included study of myocardial strain using two-dimensional speckle tracking. We studied strain and strain rate in the seventeen left ventricular (LV) myocardial segments in the longitudinal, circumferential and radial axes. Statistical analysis of the data was done with IBM SPSS - version 20 for Windows. Upon analysis of the data, namely the normality of independent variables in the different groups and the homogeneity of the variances between the groups, Kruskal-Wallis' non-parametric test was done, followed by Dunn's multiple comparison tests to test the significance of the differences between the values measured in the study groups. A significance level of 5% was adopted for decision-making on statistical tests. Results: The mean age of HIV patients was 40 ± 8.65 years and the mean age of controls was 50 ± 11.6 years (p < 0.001). Median LV global longitudinal strain (GLS) of NT patients (-17.70%), PI patients (-18.27%) and NNRTIs (-18.47%) were significantly lower than that of the Ctrl group (-20.77%; p = 0.001). There was no significant difference in mean SLG between treated patients (PI, NNRTI) and untreated (NT) patients. No significant differences were observed in mean circumferential and radial strain, nor on circumferential and radial strain rates between the NT, PI, NNRTI and Ctrl groups. Conclusion: The data suggest that HIV patients present, on myocardial strain measured by speckle tracking, signs of early LV systolic dysfunction that seem to be unrelated to the presence of ART. The prognostic significance of this condition in these patients deserves further studies.

Resumo Fundamento: A maior parte das alterações cardiovasculares dos pacientes infectados pelo vírus da imunodeficiência humana (HIV) tem sido associada ao dano miocárdico causado diretamente pelo vírus. Alguns casos, porém, podem estar associados a efeitos adversos da terapia antirretroviral (TARV). Novas técnicas de avaliação da função ventricular são capazes de detectar modificações precoces na função cardíaca do paciente infectado pelo HIV em uso ou não de TARV. A utilidade dessas técnicas tem sido pouco empregada nesses pacientes. Objetivos: Investigar possível influência da terapia antirretroviral (TARV) na ocorrência de disfunção sistólica ventricular esquerda subclínica avaliada pela análise da taxa de deformação miocárdica (strain) por meio do speckle tracking ao ecocardiograma bidimensional (E2D) em pacientes portadores do HIV tratados, comparados com pacientes não tratados e indivíduos saudáveis. Métodos: Sessenta e oito pacientes infectados pelo HIV assintomáticos do ponto de vista cardiovascular, com fração de ejeção do ventrículo esquerdo (VE) normal (>0,55 pelo E2D) foram divididos em três grupos: 11 pacientes sem tratamento antirretroviral (ST), 24 em uso de inibidor de protease (IP) e 33 em uso de inibidor de transcriptase reversa não nucleosídeo (ITRNN). Foram estudados também 30 indivíduos normais não infectados pelo HIV (Ctrl). Foram coletados dados demográficos, clínicos, bioquímicos e antropométricos. A ecocardiografia transtorácica foi realizada incluindo no estudo inicial o estudo da deformação miocárdica pela técnica bidimensional (speckle tracking). Estudamos o strain e a sua taxa de deformação (strain rate) nos dezessete segmentos miocárdicos do ventrículo esquerdo (VE) nos eixos longitudinal, circunferencial e radial. A análise estatística dos dados foi feita com o programa IBM SPSS - versão 20 para Windows. Depois de analisados os dados, nomeadamente a normalidade das variáveis independentes nos diferentes grupos e a homogeneidade das variâncias entre os grupos, decidiu-se utilizar o teste não paramétrico de Kruskal-Wallis seguido dos testes de comparações múltiplas pelo procedimento de Dunn, para testar a significância das diferenças entre os valores medidos nos grupos em estudo. Foi considerado o nível de significância de 5% para a tomada de decisão nos testes estatísticos realizados. Resultados: A média das idades dos pacientes com HIV foi de 40 ± 8,65 anos e a idade média dos controles foi de 50 ± 11,6 anos (p < 0,001). Os valores medianos do strain longitudinal global do VE (SLG) dos pacientes ST (-17.70%), dos pacientes IP (-18.27%) e ITRNN (-18.47%) foram significativamente menores do que o grupo Ctrl (-20,77%; p = 0,001). Não houve diferença significante nos valores médios do SLGentre os pacientes tratados (IP, ITRNN) e não tratados (ST). Não foram observadas diferenças significantes nos valores médios do strain circunferencial e radial, nem nas taxas de deformação circunferencial e radial entre os grupos ST, IP, ITRNN e Ctrl. Conclusão: Os dados sugerem que pacientes com HIV apresentam, à análise da deformação miocárdica ao speckle tracking, sinais de disfunção sistólica incipiente do VE que parece não ter relação com a presença de TARV. O significado prognóstico dessa alteração nesses pacientes merece estudos futuros.

The Use of Two-Dimensional Strain Measured by Speckle Tracking in the Identification of Incipient Ventricular Dysfunction in HIV-Infected Patients on Antiretroviral Therapy, Untreated HIV Patients and Healthy Controls.

BACKGROUND: Most cardiovascular abnormalities in patients infected with the human immunodeficiency virus (HIV) have been associated with myocardial damage directly caused by the virus. Some cases, however, may be associated with adverse effects from antiretroviral therapy (ART). New ventricular function assessment techniques are capable of detecting early changes in the cardiac function of HIV-infected patients using or not using ART. The usefulness of these techniques has been little employed in these patients. OBJECTIVES: To investigate the potential influence of antiretroviral therapy (ART) on the occurrence of subclinical left ventricular systolic dysfunction evaluated by myocardial strain rate analysis using two-dimensional speckle tracking echocardiography (2-D Echo) in treated HIV patients compared to untreated patients and healthy individuals. METHODS: Sixty-eight HIV-infected patients with no cardiovascular symptoms, normal left ventricular (LV) ejection fraction (> 0.55 on 2-D Echo) were divided into three groups: 11 patients not using antiretroviral therapy (NT), 24 using protease inhibitor (PI) and 33 using non-nucleoside reverse transcriptase inhibitor (NNRTI). We also studied 30 normal non-HIV infected individuals (Ctrl). Demographic, clinical, biochemical and anthropometric data were collected. Preliminary transthoracic echocardiography included study of myocardial strain using two-dimensional speckle tracking. We studied strain and strain rate in the seventeen left ventricular (LV) myocardial segments in the longitudinal, circumferential and radial axes. Statistical analysis of the data was done with IBM SPSS - version 20 for Windows. Upon analysis of the data, namely the normality of independent variables in the different groups and the homogeneity of the variances between the groups, Kruskal-Wallis' non-parametric test was done, followed by Dunn's multiple comparison tests to test the significance of the differences between the values measured in the study groups. A significance level of 5% was adopted for decision-making on statistical tests. RESULTS: The mean age of HIV patients was 40 ± 8.65 years and the mean age of controls was 50 ± 11.6 years (p < 0.001). Median LV global longitudinal strain (GLS) of NT patients (-17.70%), PI patients (-18.27%) and NNRTIs (-18.47%) were significantly lower than that of the Ctrl group (-20.77%; p = 0.001). There was no significant difference in mean SLG between treated patients (PI, NNRTI) and untreated (NT) patients. No significant differences were observed in mean circumferential and radial strain, nor on circumferential and radial strain rates between the NT, PI, NNRTI and Ctrl groups. CONCLUSION: The data suggest that HIV patients present, on myocardial strain measured by speckle tracking, signs of early LV systolic dysfunction that seem to be unrelated to the presence of ART. The prognostic significance of this condition in these patients deserves further studies.

Design of the GutHeart-targeting gut microbiota to treat heart failure-trial: a Phase II, randomized clinical trial.

AIMS: Heart failure (HF) is a multifactorial disease. Current treatments target only a fraction of the putative pathophysiological pathways. In patients with HF, reduced cardiac output and congestion cause increased gut wall permeability. It has been suggested that leakage of microbial products is detrimental to the heart, at least partly through activation of systemic inflammatory pathways, which again could promote gut leakage. Whether manipulating the gut microbiota can improve cardiac function in patients with HF remains unknown. We aim to evaluate the effect of drugs targeting the gut microbiota on left ventricular function, quality of life, and functional capacity, as well as on markers of gut leakage and inflammation, in stable patients with HF with reduced ejection fraction. METHODS AND RESULTS: GutHeart is a randomized, open-label, controlled trial. Four centres will randomize 150 patients with stable HF and a left ventricular ejection fraction <40% to receive the antibiotic rifaximin, the probiotic yeast Saccharomyces boulardii (ATCC 74012), or no treatment (control) in a 1:1:1 fashion. Treatment will last for 3 months. The primary endpoint is baseline-adjusted left ventricular ejection fraction as measured by echocardiography after 3 months. A further follow-up 6 months after randomization will be undertaken. CONCLUSIONS: This trial is likely to give new insights into important disease processes involving the gut microbiota in HF patients, hereby leading to new potential therapeutic strategies to prevent and down-regulate the inflammation seen in these patients.

Evaluation of Quality of Life in Patients with and without Heart Failure in Primary Care / Avaliação da Qualidade de Vida em Pacientes com e sem Insuficiência Cardíaca na Atenção Primária

Abstract Background: Heart failure (HF) is a major public health issue with implications on health-related quality of life (HRQL). Objective: To compare HRQL, estimated by the Short-Form Health Survey (SF-36), in patients with and without HF in the community. Methods: Cross-sectional study including 633 consecutive individuals aged 45 years or older, registered in primary care. The subjects were selected from a random sample representative of the population studied. They were divided into two groups: group I, HF patients (n = 59); and group II, patients without HF (n = 574). The HF group was divided into HF with preserved ejection fraction (HFpEF - n = 35) and HF with reduced ejection fraction (HFrEF - n = 24). Results: Patients without HF had a mean SF-36 score significantly greater than those with HF (499.8 ± 139.1 vs 445.4 ± 123.8; p = 0.008). Functional capacity - ability and difficulty to perform common activities of everyday life - was significantly worse (p < 0.0001) in patients with HF independently of sex and age. There was no difference between HFpEF and HFrEF. Conclusion: Patients with HF had low quality of life regardless of the syndrome presentation (HFpEF or HFrEF phenotype). Quality of life evaluation in primary care could help identify patients who would benefit from a proactive care program with more emphasis on multidisciplinary and social support. (Arq Bras Cardiol. 2017; [online].ahead print, PP.0-0)

Resumo Fundamento: A insuficiência cardíaca (IC) é um importante problema de saúde pública, com implicações na qualidade de vida relacionada à saúde (QVRS). Objetivo: Comparar a QVRS, estimada através do Questionário SF-36 (Short-Form Health Survey), em pacientes com e sem IC na comunidade. Métodos: Estudo transversal incluindo 633 indivíduos consecutivos com idade igual ou superior a 45 anos, registrados na atenção primária e selecionados de uma amostra aleatória representativa da população estudada. Foram divididos em dois grupos: grupo I, pacientes com IC (n = 59); e grupo II, pacientes sem IC (n = 574). O grupo I foi dividido em pacientes com IC com fração de ejeção preservada (ICFEP - n = 35) e pacientes com IC com fração de ejeção reduzida (ICFER - n = 24). Resultados: Pacientes sem IC tiveram um escore médio do SF-36 significativamente maior do que aqueles com IC (499,8 ± 139,1 vs 445,4 ± 123,8; p = 0,008). A capacidade funcional - habilidade e dificuldade para realizar atividades comuns da vida diária - foi significativamente pior (p < 0,0001) nos pacientes com IC independentemente de sexo e idade. Não houve diferença entre ICFEP e ICFER. Conclusão: Pacientes com IC mostraram baixa qualidade de vida a despeito da apresentação da síndrome (fenótipo ICFEP ou ICFER). A avaliação da qualidade de vida na atenção primária poderia auxiliar a identificar pacientes que se beneficiariam de um programa de atenção à saúde pró-ativo com maior ênfase em suporte multidisciplinar e social. (Arq Bras Cardiol. 2017; [online].ahead print, PP.0-0)

Evaluation of Quality of Life in Patients with and without Heart Failure in Primary Care.

BACKGROUND: Heart failure (HF) is a major public health issue with implications on health-related quality of life (HRQL). OBJECTIVE: To compare HRQL, estimated by the Short-Form Health Survey (SF-36), in patients with and without HF in the community. METHODS: Cross-sectional study including 633 consecutive individuals aged 45 years or older, registered in primary care. The subjects were selected from a random sample representative of the population studied. They were divided into two groups: group I, HF patients (n = 59); and group II, patients without HF (n = 574). The HF group was divided into HF with preserved ejection fraction (HFpEF - n = 35) and HF with reduced ejection fraction (HFrEF - n = 24). RESULTS: Patients without HF had a mean SF-36 score significantly greater than those with HF (499.8 ± 139.1 vs 445.4 ± 123.8; p = 0.008). Functional capacity - ability and difficulty to perform common activities of everyday life - was significantly worse (p < 0.0001) in patients with HF independently of sex and age. There was no difference between HFpEF and HFrEF. CONCLUSION: Patients with HF had low quality of life regardless of the syndrome presentation (HFpEF or HFrEF phenotype). Quality of life evaluation in primary care could help identify patients who would benefit from a proactive care program with more emphasis on multidisciplinary and social support. (Arq Bras Cardiol. 2017; [online].ahead print, PP.0-0).

Gender and obesity interaction in quality of life in adults assisted by family doctor program in Niterói, Brazil.

Obesity impacts the quality of life (HRQL). Studies about the effects of a possible interaction between gender and body mass are rare. The objective of the present paper is to estimate the biological interaction between gender and obesity on HRQL. This was a cross-sectional study based on data from CAMELIA study with population assisted by the Family Doctor Program of Niteroi visited between June 2006 and December 2007. HRQL was assessed by the SF-36. The exposure categories were: obese women, non-obese women, obese men and non-obese men, the reference category. Obese women showed higher percentages of low overall, physical and mental quality of life with the largest associations in the physical component. The excess risk due to interaction was statistically significant in physical dimension: RERI = 1.97 (0.40-3.52) and RERIa = 1,97 (0.40-1.7). Among the Brazilian population aged 20-64 years, obesity was independently associated with low HRQL. This association differed by gender, being significant for women. The possibility of the combined effect takes greater importance in the context of increasing incidence of obesity globally. Healthcare professionals in primary care settings should pay attention to gender differences in the impact of obesity on HRQL.

Gender and obesity interaction in quality of life in adults assisted by family doctor program in Niterói, Brazil / Interação entre gênero e obesidade na qualidade de vida de adultos assistidos pelo programa médico de família de Niterói, Brasil

Abstract Obesity impacts the quality of life (HRQL). Studies about the effects of a possible interaction between gender and body mass are rare. The objective of the present paper is to estimate the biological interaction between gender and obesity on HRQL. This was a cross-sectional study based on data from CAMELIA study with population assisted by the Family Doctor Program of Niteroi visited between June 2006 and December 2007. HRQL was assessed by the SF-36. The exposure categories were: obese women, non-obese women, obese men and non-obese men, the reference category. Obese women showed higher percentages of low overall, physical and mental quality of life with the largest associations in the physical component. The excess risk due to interaction was statistically significant in physical dimension: RERI = 1.97 (0.40-3.52) and RERIa = 1,97 (0.40-1.7). Among the Brazilian population aged 20–64 years, obesity was independently associated with low HRQL. This association differed by gender, being significant for women. The possibility of the combined effect takes greater importance in the context of increasing incidence of obesity globally. Healthcare professionals in primary care settings should pay attention to gender differences in the impact of obesity on HRQL.

Resumo A obesidade causa impacto na qualidade de vida relacionada à saúde (QVRS). Estudos sobre os efeitos de uma possível interação entre sexo e obesidade são escassos. O objetivo do presente trabalho é estimar a interação biológica entre gênero e obesidade na QVRS. Trata-se de um estudo transversal com base em dados do estudo CAMELIA da população atendida pelo Programa Médico de Família de Niterói que ocorreu entre junho de 2006 e dezembro de 2007. A QVRS foi avaliada pelo SF-36. As variáveis de exposição foram: mulheres obesas, mulheres não obesas, homens obesos e homens não obesos, a categoria de referência. As mulheres obesas apresentaram maiores percentuais de baixa qualidade de vida global, física e mental com as maiores associações no componente físico. O excesso de risco devido à interação foi estatisticamente significativo na dimensão física: RERI = 1,97 (0,40-3,52) e RERIa = 1,97 (0,40-1,7). A obesidade na população brasileira com idade entre 20-64 anos foi associada com baixa QVRS. Esta associação difere por sexo, sendo significativa para as mulheres. A possibilidade de um efeito combinado assume maior importância no contexto da crescente incidência de obesidade no mundo. Os profissionais de saúde de atenção primária devem considerar as diferenças de gênero no impacto da obesidade sobre a QVRS.

Remodelamento reverso do átrio esquerdo após terapia com carvedilolem pacientes com ICFER / Reverse left atrial remodeling after treatment with carvedilol in patients with HFREF

Fundamentos: Metade dos pacientes com fração de ejeção reduzida tem disfunção diastólica associada e os dados relacionados ao impacto da terapia com carvedilol nesses pacientes ainda são conflitantes.Objetivo: Avaliar o comportamento dos índices ecocardiográficos, cintilográficos e do volume do átrio esquerdo(VAE) antes e após três meses de terapia com carvedilol em pacientes com ICFER, classe funcional (CF) II e III da New York Heart Association (NYHA).Métodos: Selecionados 19 pacientes com IC, CF II e III, fração de ejeção <45% (método de Simpson) e sem terapiaprévia com carvedilol. Para análise estatística, utilizados os testes de Wilcoxon e McNemar, coeficiente de Spearmane regressão linear múltipla. Resultados: Houve melhora significativa dos parâmetros de função sistólica do ventrículo esquerdo (VE): DSF,VSF, FEJ Simpson, FEVI. Não houve melhora significativa dos parâmetros de função diastólica derivados do Doppler: E’, E/E’, VP, E/VP. O comportamento da função diastólica através VAE apresentou significativa melhora:VAE (83,2±33,4mL vs. 73,7±29,8mL, p=0,009), índice de VAE (44,8±15,8mL/m² vs. 39,7±14,5mL/m², p=0,014). Conclusões: A regressão do VAE após terapia em curto prazo com carvedilol não se associou à melhora dos demais índices de função diastólica, entretanto houve associação com a melhora da função sistólica do VE. Estes achados sugerem que a redução do VAE seja secundária à melhora da performance sistólica.

Background: Half of the patients with reduced ejection fraction have diastolic dysfunction associated and the data related to the impact of carvedilol therapy in these patients are still conflicting.Objective: To evaluate the behavior of echocardiographic, scintigraphic and left atrial volume (LAV) indexes before and after three months of therapy with carvedilol in patients with HFREF, New York Heart Association (NYHA) functional class (FC) II and III. Methods: Nineteen patients with HF, CF II and III, ejection fraction <45% (Simpson method) without previous therapy with carvedilol were selected. For statistical analysis, Wilcoxon and McNemar tests, Spearman coefficient and multiple linear regression were used. Results: There was significant improvement in the left ventricular (LV) systolic function parameters: DSF, ESV, Simpson EF,EFVI. There was no significant improvement in the diastolic function parameters derived from Doppler: E’, E/E’, VP, E/VP. Diastolic function behavior through VAE showed significant improvement: LAV (83.2±33.4 mL vs. 73.7±29.8 mL, p=0.009), LAV index(44.8±15.8mL/m2 vs. 39.7±14.5mL/m2, p=0.014). Conclusions: LAV regression after short-term therapy with carvedilol was not associated with improvement in other diastolic function indexes, but was associated with improved LV systolic function. These findings suggest that LAV reduction is secondary to improvement in systolic performance.

Comparison of adipokines in a cross-sectional study with healthy overweight, insulin-sensitive and healthy lean, insulin-resistant subjects, assisted by a family doctor primary care program.

BACKGROUND: In most individuals, obesity and insulin resistance coexist. However, some individuals have excessive adipose tissue mass but remain insulin sensitive. Moreover, lean individuals can develop acute inflammation-induced insulin resistance, even without excess adipose tissue mass. OBJECTIVE: Our aim was to compare inflammatory markers in overweight, insulin-sensitive and lean, insulin-resistant healthy subjects. METHODS: A cross-sectional study with 1098 participants (CAMELIA project) was conducted in family doctor primary care program at Niteroi, RJ, Brazil. In the present substudy, we have selected non-obese healthy subjects (n = 203). Insulin resistance was defined by a homeostatic model assessment (HOMA-IR) >2.6, and overweight subject BMIs were 25< BMI <30 kg/m2. Associations were estimated through binary logistic regression with generalized estimation equation models. RESULTS: We compared overweight, insulin-sensitive healthy individuals (n = 74) with a mean age of 39.2 ± 1.3 and lean, insulin-resistant healthy individuals (n = 18) with a mean age of 31.9 ± 3.6. C-reactive protein levels were positively correlated with body mass index in the lean, insulin-resistant group. In the multiple regression model, a positive association was observed with MCP-1 and IL-6 expression after adjustment for age, waist circumference, glycated hemoglobin, resistin, adiponectin, C-reactive protein and PAI-1 levels. CONCLUSION: Our findings suggest that a lean, insulin-resistant subject may have higher pro-inflammatory marker levels (MCP-1, IL-6 and resistin) than an overweight, insulin-sensitive subject. This suggest an early risk phenotype that should further be investigated for possible prognostic implications.

The Prevalence of Stages of Heart Failure in Primary Care: A Population-Based Study.

BACKGROUND: Planning strategies to prevent heart failure (HF) in developing countries require epidemiologic data in primary care. The purpose of this study was to estimate the prevalence of HF stages and their phenotypes, HF with preserved ejection fraction (HFPEF), and HF with reduced EF (HFREF) and to determine B-type natriuretic peptide (BNP) levels to identify HF in the adult population. METHODS AND RESULTS: This is a cross-sectional study including 633 individuals, aged ≥45 years, who were randomly selected and registered in a primary care program of a medium-sized city in Brazil. All participants were underwent clinical evaluations, BNP measurements, electrocardiograms, and tissue Doppler echocardiography in a single day. The participants were classified as stage 0 (healthy, 11.7%), stage A (risk factors, 36.6%), stage B (structural abnormalities, 42.7%), or stage C (symptomatic HF, 9.3%). Among patients with HF, 59% presented with HFPEF and 41% presented with HFREF. The mean BNP levels were 20 pg/mL(-1) in stage 0, 20 pg/mL(-1) in stage A, 24 pg/mL(-1) in stage B, 93 pg/mL(-1) in HFPEF, and 266 pg/mL(-1) in HFREF. The cutoff BNP level with optimal sensitivity (92%) and specificity (91%) to identify HF was 42 pg/mL(-1). CONCLUSION: The present study demonstrated a high prevalence of individuals at risk for HF and the predominance of HFPEF in a primary care setting. The clinical examination, along with BNP and tissue Doppler echocardiography, may facilitate early detection of stages A and B HF and allow implementation of interventions aimed at preventing progression to symptomatic HF.

Cardiac I123-MIBG correlates better than ejection fraction with symptoms severity in systolic heart failure.

BACKGROUND: The association of autonomic activation, left ventricular ejection fraction (LVEF) and heart failure functional class is poorly understood. OBJECTIVE: Our aim was to correlate symptom severity with cardiac sympathetic activity, through iodine-123-metaiodobenzylguanidine (123I-MIBG) scintigraphy and with LVEF in systolic heart failure (HF) patients without previous beta-blocker treatment. METHODS: Thirty-one patients with systolic HF, class I to IV of the New York Heart Association (NYHA), without previous beta-blocker treatment, were enrolled and submitted to 123I-MIBG scintigraphy and to radionuclide ventriculography for LVEF determination. The early and delayed heart/mediastinum (H/M) ratio and the washout rate (WR) were performed. RESULTS: According with symptom severity, patients were divided into group A, 13 patients in NYHA class I/II, and group B, 18 patients in NYHA class III/IV. Compared with group B patients, group A had a significantly higher LVEF (25% ± 12% in group B vs. 32% ± 7% in group A, p = 0.04). Group B early and delayed H/M ratios were lower than group A ratios (early H/M 1.49 ± 0.15 vs. 1.64 ± 0.14, p = 0.02; delayed H/M 1.39 ± 0.13 vs. 1.58 ± 0.16, p = 0.001, respectively). WR was significantly higher in group B (36% ± 17% vs. 30% ± 12%, p= 0.04). The variable that showed the best correlation with NYHA class was the delayed H/M ratio (r= -0.585; p=0.001), adjusted for age and sex. CONCLUSION: This study showed that cardiac 123I-MIBG correlates better than ejection fraction with symptom severity in systolic heart failure patients without previous beta-blocker treatment.

O I123-MIBG cardíaco se correlaciona melhor do que a fração de ejeção com a gravidade dos sintomas na insuficiência cardíaca sistólica / Cardiac I123-MIBG correlates better than ejection fraction with symptoms severity in systolic heart failure

FUNDAMENTO: A associação da ativação autonômica, fração de ejeção do ventrículo esquerdo (FEVE) e classe funcional da insuficiência cardíaca é mal compreendida. Objetivo: Nosso objetivo foi correlacionar a gravidade dos sintomas com a atividade simpática cardíaca, através do uso de iodo-123-metaiodobenzilguanidina (123I-MIBG); e com FEVE em pacientes com insuficiência cardíaca (IC) sistólica sem tratamento prévio com betabloqueador. MÉTODOS: Trinta e um pacientes com IC sistólica, classe I a IV da New York Heart Association (NYHA), sem tratamento prévio com betabloqueador, foram inscritos e submetidos à cintilografia com 123I-MIBG e ventriculografia radioisotópica para determinação da FEVE. A relação precoce e tardia coração/mediastino (H/M) e a taxa de washout (WO) foram medidas. RESULTADOS: De acordo com a gravidade dos sintomas, os pacientes foram divididos em grupo A, com 13 pacientes em classe funcional NYHA I/II, e grupo B, com 18 pacientes em classe funcional NYHA III/ IV. Em comparação com os pacientes do grupo B, o grupo A apresentou uma FEVE significativamente maior (25% ± 12% para o grupo B vs. 32% ± 7% no grupo A, p = 0,04). As relações precoces e tardias H/M do Grupo B foram menores do que as do grupo A (H/M precoce 1,49 ± 0,15 vs. 1,64 ± 0,14, p = 0,02; H/M tardia 1,39 ± 0,13 vs. 1,58 ± 0,16, p = 0,001, respectivamente). A taxa de WO foi significativamente maior no grupo B (36% ± 17% vs. 30% ± 12%, p = 0,04). A variável que mostrou a melhor correlação com a NYHA foi a relação H/M tardia (r = -0,585, p = 0,001), ajustada para idade e sexo. CONCLUSÃO: Esse estudo mostrou que o 123I-MIBG cardíaco se correlaciona melhor do que a fração de ejeção com a gravidade dos sintomas em pacientes com insuficiência cardíaca sistólica sem tratamento prévio com beta-bloqueador.

BACKGROUND:The association of autonomic activation, left ventricular ejection fraction (LVEF) and heart failure functional class is poorly understood. OBJECTIVE: Our aim was to correlate symptom severity with cardiac sympathetic activity, through iodine-123-metaiodobenzylguanidine (123I-MIBG) scintigraphy and with LVEF in systolic heart failure (HF) patients without previous beta-blocker treatment. METHODS: Thirty-one patients with systolic HF, class I to IV of the New York Heart Association (NYHA), without previous beta-blocker treatment, were enrolled and submitted to 123I-MIBG scintigraphy and to radionuclide ventriculography for LVEF determination. The early and delayed heart/mediastinum (H/M) ratio and the washout rate (WR) were performed. RESULTS: According with symptom severity, patients were divided into group A, 13 patients in NYHA class I/II, and group B, 18 patients in NYHA class III/IV. Compared with group B patients, group A had a significantly higher LVEF (25% ± 12% in group B vs. 32% ± 7% in group A, p = 0.04). Group B early and delayed H/M ratios were lower than group A ratios (early H/M 1.49 ± 0.15 vs. 1.64 ± 0.14, p = 0.02; delayed H/M 1.39 ± 0.13 vs. 1.58 ± 0.16, p = 0.001, respectively). WR was significantly higher in group B (36% ± 17% vs. 30% ± 12%, p= 0.04). The variable that showed the best correlation with NYHA class was the delayed H/M ratio (r= -0.585; p=0.001), adjusted for age and sex. CONCLUSION: This study showed that cardiac 123I-MIBG correlates better than ejection fraction with symptom severity in systolic heart failure patients without previous beta-blocker treatment.

Racial differences in HbA1c: a cross-sectional analysis of a Brazilian public primary care population.

BACKGROUND: Blacks show higher levels of HbA1c in studies with different populations and are disproportionately affected by most diabetes-related complications. AIMS: The study aims to investigate if the prevalence of altered glycated hemoglobin (HbA1c) varies with skin color and if there is a familial aggregation of either skin color and HbA1c. METHODS: The study used the CAMELIA study (Cardio-Metabolic-Renal familiar) population, conducted between June 2006 and December 2007 (cross sectional). Families were recruited from 13 Family Doctor Program Unities of Niteroi, Brazil, a highly miscegenated population. The visits included questionnaire, medical consultation, anthropometric and nutritional assessment. Blood pressure, blood/urine samples were collected. The dosage of HbA1c was performed by immunoturbidimetry in Labmax 240 equipment. RESULTS: We compare data of 241 (25.5%) Blacks, versus 422 (44.7%) Mulattos or 272 (28.8%) Whites. The groups did not differ significantly with regard to most measures. Blacks had the lowest levels of income/education, higher frequency of diabetes and hypertension (p<0.20) as higher levels of HbA1c (p<0.05) that persisted after adjusting for possible confounders. Among blacks, the correlations between siblings of HbA1c were higher than among white/mulatto, reaching 86% versus 50%, respectively. CONCLUSION: Those results indicate that Brazilian Blacks patients must have more attention, focusing on diabetes preventive care. Longitudinal studies are needed to address the question if the altered level of HbA1c has a real clinical impact.

Inadequate request of transthoracic echocardiography according to the guidelines of the Brazilian Society of Cardiology.

BACKGROUND: Guidelines from medical societies suggest recommendations for the appropriate request of tests. In 2009, the Brazilian Society of Cardiology (BSC) published new guidelines for transthoracic echocardiography (TTE) request. OBJECTIVE: To evaluate the prevalence of Class III requests for TTE, as defined by the BSC Guidelines and analyze these requests profile comparing a public university hospital (PUH) with a private cardiology hospital (PCH). METHODS: We prospectively evaluated 779 consecutive outpatient TTE requests: 391 from the PCH and 388 from the PUH between December 2009 and May 2010. The indications studied were classified accordingly to the BSC guidelines. Request distribution was compared by Chi-square test. Statistical significance was set at p < 0.05. RESULTS: Of the 779 requests, 61 (7.8%) were considered Class III. Of these 14 were from the public and 47 from the private hospital. The distribution of requests was statistically different between institutions (p < 0.001). Check-up in asymptomatic patients was the main inadequate indication, with 37 cases (33 in the private institution- 89.18%), followed by evaluation after angioplasty in 9 cases (8 in the private institution - 88.88%); ventricular function monitoring in patients with stable heart failure in 6 cases (4 in the public institution - 66.66%), post-bypass surgery in 5 cases (4 in the private institution- 80%), and evaluation of nonspecific electrocardiographic abnormalities in 4 cases (4 in the public institution - 100%). CONCLUSION: Asymptomatic patients' assessment was the main cause of inadequate TTE requests, which differs between institutions: routine check-up in the private and heart failure in the public hospital.

Immunology, autoimmunity, and autoantibodies in Parkinson's disease.

Recent revelations of immune alterations in Parkinson's disease have led to the convergence that an autoimmune mechanism may play a role in the etiopathogenesis of this neurodegenerative disease. In the current study, 77 Parkinson's disease patients and 77 matched healthy controls were analyzed for the presence of seven autoantibodies previously found to be associated with central nervous system manifestations namely: antineuronal-cells, anti-brain lysate, anti-dsDNA, anti-phosphatidylserine, anti-cardiolipin, anti-serotonin, and anti-melanocytes antibodies. Patients underwent systematic assessments of demographics, clinical, and biochemical manifestations. Three autoantibodies were found to be more prevalent among Parkinson's disease patients (antineuronal cells10.3% vs. 1.3%, p = 0.017; anti-brain lysate 9.1% vs. 1.3%, p = 0.032; anti-dsDNA 10.3% vs. 2.6%, p = 0.049). Clinical manifestations of Parkinson's disease, particularly dyskinesia and depression, were found to be associated with the presence of these autoantibodies.