Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 64
Filtrar
2.
Eur Heart J ; 40(44): 3605-3612, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31424503

RESUMO

AIMS: Although loop diuretics are widely used to treat heart failure (HF), there is scarce contemporary data to guide diuretic adjustments in the outpatient setting. METHODS AND RESULTS: In a prospective, randomized and double-blind protocol, we tested the safety and tolerability of withdrawing low-dose furosemide in stable HF outpatients at 11 HF clinics in Brazil. The trial had two blindly adjudicated co-primary outcomes: (i) symptoms assessment quantified as the area under the curve (AUC) of a dyspnoea score on a visual-analogue scale evaluated at 4 time-points (baseline, Day 15, Day 45, and Day 90) and (ii) the proportion of patients maintained without diuretic reuse during follow-up. We enrolled 188 patients (25% females; 59 ± 13 years old; left ventricular ejection fraction = 32 ± 8%) that were randomized to furosemide withdrawal (n = 95) or maintenance (n = 93). For the first co-primary endpoint, no significant difference in patients' assessment of dyspnoea was observed in the comparison of furosemide withdrawal with continuous administration [median AUC 1875 (interquartile range, IQR 383-3360) and 1541 (IQR 474-3124), respectively; P = 0.94]. For the second co-primary endpoint, 70 patients (75.3%) in the withdrawal group and 77 patients (83.7%) in the maintenance group were free of furosemide reuse during follow-up (odds ratio for additional furosemide use with withdrawal 1.69, 95% confidence interval 0.82-3.49; P = 0.16). Heart failure-related events (hospitalizations, emergency room visits, and deaths) were infrequent and similar between groups (P = 1.0). CONCLUSIONS: Diuretic withdrawal did not result in neither increased self-perception of dyspnoea nor increased need of furosemide reuse. Diuretic discontinuation may deserve consideration in stable outpatients with no signs of fluid retention receiving optimal medical therapy. CLINICALTRIALS.GOV IDENTIFIER: NCT02689180.

3.
Am J Physiol Regul Integr Comp Physiol ; 316(6): R776-R782, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042418

RESUMO

Exercise promotes physiological cardiac hypertrophy and activates the renin-angiotensin system (RAS), which plays an important role in cardiac physiology, both through the classical axis [angiotensin II type 1 receptor (AT1R) activated by angiotensin II (ANG II)] and the alternative axis [proto-oncogene Mas receptor (MASR) activated by angiotensin-(1-7)]. However, very intense exercise could have deleterious effects on the cardiovascular system. We aimed to analyze the cardiac hypertrophy phenotype and the classical and alternative RAS axes in the myocardium of mice submitted to swimming exercises of varying volume and intensity for the development of cardiac hypertrophy. Male Balb/c mice were divided into three groups, sedentary, swimming twice a day without overload (T2), and swimming three times a day with a 2% body weight overload (T3), totaling 6 wk of training. Both training groups developed similar cardiac hypertrophy, but only T3 mice improved their oxidative capacity. We observed that T2 had increased levels of MASR, which was followed by the activation of its main downstream protein AKT; meanwhile, AT1R and its main downstream protein ERK remained unchanged. Furthermore, no change was observed regarding the levels of angiotensin peptides, in either group. In addition, we observed no change in the ratio of expression of the myosin heavy chain ß-isoform to that of the α-isoform. Fibrosis was not observed in any of the groups. In conclusion, our results suggest that increasing exercise volume and intensity did not induce a pathological hypertrophy phenotype, but instead improved the oxidative capacity, and this process might have the participation of the RAS alternative axis.

4.
Gene ; 698: 157-169, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-30844478

RESUMO

Pathological cardiac hypertrophy (CH) is associated with increased heart failure risk and sudden cardiac death. Several transcription factors (TFs) and miRNAs were implicated in CH, and their high combinatorial action in gene expression regulation is becoming more clear. We adopted a systems biology approach to construct a comprehensive TF-miRNA co-regulatory network in CH and systematically characterize its structure, from node- to systems-level properties. Parallel expression profiles for miRNAs and messenger RNA (mRNA) from an in vitro model of CH were integrated with experimentally validated interactions from seven curated databases to build the CH-related TF-miRNA regulatory network. To leverage this network, we proposed a completely unsupervised approach to identify core regulatory elements, based on Borda count aggregation of distinct network-based properties. By combining node scores derived from motif-based centrality, active pathways, and k-shell index, our approach was able to prioritize biologically meaningful TFs (e.g., MYC, SP1, AKR1B1, EGR1, NFKB1, and ETS1) and miRNAs (e.g., hsa-let-7i-5p, hsa-let-7e-5p, hsa-miR-21a-5p, and hsa-miR-27b-5p) as central nodes in the network and point potential active regulatory pathways in CH. Our findings suggest distinct roles of TFs and miRNAs, which tend to act mostly as network bottlenecks and hubs, respectively. Moreover, we identified feed-forward loop motifs and recurrent associations in the crosstalk between TFs and miRNAs, observing extensive synergistic regulation of common targets and cascade signaling among regulators. Interestingly, most TFs and miRNAs were engaged in specific regulatory roles or interconnection patterns (i.e., master regulator, intermediate regulator, co-regulation of a common target gene, reciprocal regulation, or downstream target) within this network, while few had multiplicity observed in their network function. The constructed CH-related regulatory network has the potential to provide new insights about key regulators, molecular mechanisms, and the interplay between miRNAs and TFs in the pathogenesis of CH, which after proper experimental validation may contribute to the search for new therapeutic approaches.


Assuntos
Cardiomegalia/metabolismo , Cardiomegalia/fisiopatologia , Biologia de Sistemas/métodos , Biologia Computacional/métodos , Bases de Dados Genéticas , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Humanos , MicroRNAs/metabolismo , MicroRNAs/fisiologia , RNA Mensageiro , Transdução de Sinais , Fatores de Transcrição/metabolismo , Fatores de Transcrição/fisiologia , Transcriptoma/genética
5.
PLoS One ; 14(1): e0209964, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30633750

RESUMO

Circulating advanced glycation end products (AGE) and their receptor, RAGE, are increased after a myocardial infarction (MI) episode and seem to be associated with worse prognosis in patients. Despite the increasing importance of these molecules in the course of cardiac diseases, they have never been characterized in an animal model of MI. Thus, the aim of this study was to characterize AGE formation and RAGE expression in plasma and cardiac tissue during cardiac remodeling after MI in rats. Adult male Wistar rats were randomized to receive sham surgery (n = 15) or MI induction (n = 14) by left anterior descending coronary artery ligation. The MI group was stratified into two subgroups based on postoperative left ventricular ejection fraction: low (MIlowEF) and intermediate (MIintermEF). Echocardiography findings and plasma levels of AGEs, protein carbonyl, and free amines were assessed at baseline and 2, 30, and 120 days postoperatively. At the end of follow-up, the heart was harvested for AGE and RAGE evaluation. No differences were observed in AGE formation in plasma, except for a decrease in absorbance in MIlowEF at the end of follow-up. A decrease in yellowish-brown AGEs in heart homogenate was found, which was confirmed by immunodetection of N-ε-carboxymethyl-lysine. No differences could be seen in plasma RAGE levels among the groups, despite an increase in MI groups over the time. However, MI animals presented an increase of 50% in heart RAGE at the end of the follow-up. Despite the inflammatory and oxidative profile of experimental MI in rats, there was no increase in plasma AGE or RAGE levels. However, AGE levels in cardiac tissue declined. Thus, we suggest that the rat MI model should be employed with caution when studying the AGE-RAGE signaling axis or anti-AGE drugs for not reflecting previous clinical findings.


Assuntos
Produtos Finais de Glicação Avançada/sangue , Infarto do Miocárdio/sangue , Miocárdio/metabolismo , Receptor para Produtos Finais de Glicação Avançada/sangue , Animais , Modelos Animais de Doenças , Ecocardiografia , Masculino , Infarto do Miocárdio/diagnóstico por imagem , Distribuição Aleatória , Ratos , Ratos Wistar
6.
Arq Bras Cardiol ; 111(3): 436-539, 2018 Sep.
Artigo em Português | MEDLINE | ID: mdl-30379264
7.
Int. j. cardiovasc. sci. (Impr.) ; 31(5)set.-out. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-914718

RESUMO

Background: The SAMe-TT2R2 score was introduced to identify atrial fibrillation patients with a high risk of not achieving a good time in therapeutic range (TTR) during vitamin K antagonists (VKA) therapy. Objective: The aim of this study was to evaluate this score in venous thromboembolism (VTE) patients. Patients and methods: A retrospective cohort study of patients receiving care at the outpatient anticoagulation clinic of a tertiary care teaching hospital. Patients were classified as having low (score 0-1) or high risk (score ≥2) of not achieving a good TTR. The area under the ROC curve was calculated to assess the ability of the score to predict a TTR ≥ 65%. Adverse event-free survival curves according to the SAMe-TT2 R2 score were calculated by the Kaplan-Meier method and compared by the log-rank test. A p-value < 0.05 was considered statistically significant. Results: We investigated 111 patients during a median follow-up of 2.3 (0.7-6.4) years. Mean age was 54.1 ± 15.7 years and 71 (64.0%) were women. Low- and high-risk groups had similar mean TTR (51.9 vs. 49.6%; p = 0.593). The two groups did not differ significantly in the percentage of patients achieving a TTR ≥ 65% (35.6 vs. 25.8%; p =0.370). The c-statistic was 0.595 (p = 0.113) for TTR ≥ 65%. Adverse event-free survival during anticoagulation was also similar in both groups (p = 0.136).Conclusions: The SAMe-TT2R2 score does not seem to be a useful tool in oral anticoagulation decision-making for patients with VTE and should not be used in this setting


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Anticoagulantes , Técnicas de Apoio para a Decisão , Tromboembolia Venosa/complicações , Tromboembolia Venosa/fisiopatologia , Fibrilação Atrial , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Comorbidade , Infarto do Miocárdio/mortalidade , Análise Estatística , Acidente Vascular Cerebral
8.
Trials ; 19(1): 405, 2018 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-30055633

RESUMO

BACKGROUND: Current therapies for heart failure (HF) are followed by strategies to improve quality of life and exercise tolerance, besides reducing morbidity and mortality. Some HF patients present changes in the musculoskeletal system and inspiratory muscle weakness, which may be restored by inspiratory muscle training, thus increasing respiratory muscle strength and endurance, maximal oxygen uptake (VO2), functional capacity, respiratory responses to exercise, and quality of life. Yoga therapies have been shown to improve quality of life, inflammatory markers, and peak VO2 mostly in HF patients with a reduced ejection fraction. However, the effect of different yoga breathing techniques in patients showing HF with a preserved ejection fraction (HFpEF) remain to be assessed. METHODS/DESIGN: A PROBE (prospective randomized open blinded end-point) parallel-group trial will be conducted at two specialized HF clinics. Adult patients previously diagnosed with HFpEF will be included. After signing informed consent and performing a pre-test intervention, patients will be randomized into three groups and provided with either (1) active yoga breathing techniques; (2) passive yoga breathing techniques (pranayama); or and (3) control (standard pharmacological treatment). Follow-up will last 8 weeks (16 sessions). The post-intervention tests will be performed at the end of the intervention period for analysis of outcomes. Interventions will occur continuously according to patients' enrollment. The main outcome is respiratory muscular resistance. A total of 33 enrolled patients are expected. The present protocol followed the SPIRIT guidelines and fulfilled the SPIRIT checklist. DISCUSSION: This trial is probably the first to assess the effects of a non-pharmacological intervention, namely yoga and specific breathing techniques, to improve cardiorespiratory function, autonomic system, and quality of life in patients with HFpEF. TRIAL REGISTRATION: REBEC Identifier: RBR-64mbnx (August 19, 2012). Clinical Trials Register: NCT03028168 . Registered on 16 January 2017).

9.
Sci Rep ; 8(1): 9446, 2018 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-29930267

RESUMO

Dysregulated expression of tissue inhibitors of matrix metalloproteinases (TIMPs) is associated with systolic dysfunction and worsening heart failure (HF). However, no study has assessed the relationship between TIMP polymorphisms and chronic HF. In this study, 300 HF outpatients with reduced left ventricular ejection fraction and 304 healthy blood donors were genotyped for the 372 T > C polymorphism (Phe124Phe; rs4898) in the TIMP-1 gene and the -418 G > C polymorphism (rs8179090) in the TIMP-2 gene to investigate whether these polymorphisms are associated with HF susceptibility and prognosis. The genotype and allele frequencies of the 372 T > C polymorphism in HF patients were not significantly different from those observed among healthy subjects, and the C allele of the -418 G > C polymorphism was very rare in our population (frequency < 1%). After a median follow-up duration of 5.5 years, 121 patients (40.3%) died (67 of them from HF). Survival analysis did not show statistically significant differences in all-cause death and HF-related death between patients with and without the T allele (P > 0.05 for all comparisons). Thus, our findings do not support the hypothesis that the 372 T > C (Phe124Phe) polymorphism in the TIMP-1 gene and the -418 G > C polymorphism in the TIMP-2 gene are associated with HF susceptibility and prognosis in Southern Brazilians.

10.
Nutrition ; 54: 111-117, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29793053

RESUMO

OBJECTIVES: Sodium and fluid restriction is commonly prescribed for heart failure patients. However, its role in the treatment of heart failure with preserved ejection fraction (HFpEF) remains unclear. The aim of this study was to compare the effect of a diet with sodium and fluid restriction with an unrestricted diet in patients admitted for decompensated HFpEF. METHODS: Patients were randomized to a diet with sodium (0.8 g/d) and fluid (800 mL/d) restriction (intervention group [IG]) or an unrestricted diet (control group [CG]) and followed for 7 d or hospital discharge. The primary outcome was weight loss. Secondary outcomes included clinical stability, perception of thirst, neurohormonal activation, nutrient intake, readmission, and mortality rate after 30 d. RESULTS: Fifty-three patients were included (30, IG; 23, CG). The mean ejection fraction was 62% ± 8% for IG and 60% ± 7% for CG (P = 0.44). Weight loss was similar in both groups, being 1.6 ± 2.2 kg in the IG and 1.8 ± 2.1 kg in CG (P = 0.49) as well as the reduction in the congestion score (IG = 3.4 ± 3.5; CG = 3.8 ± 3.4; P = 0.70). The daily perception of thirst was higher in the IG (P = 0.03). Lower energy consumption was seen in the IG (P <0.001). No significant between-group differences at 30 d were found. CONCLUSIONS: Aggressive sodium and fluid restriction does not provide symptomatic or prognosis benefits, but does produce greater perception of thirst, may impair the patient's food intake, and does not seem to have an important neurohormonal effect in patients admitted for decompensated HFpEF.

11.
Mol Med Rep ; 17(3): 4736-4746, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29344661

RESUMO

MicroRNAs are associated with myocardial damage and heart failure (HF). The present study investigated whether the plasma levels of microRNA (miR)­21, ­126 and ­423­5p alter according to the (de)compensated state of patients with HF and are associated with all­cause mortality. In 48 patients with HF admitted to the emergency room for an episode of acute decompensation, blood samples were collected to measure miR and B­type natriuretic peptide levels within 24 h of hospital admission, at the time of hospital discharge, and a number of weeks post­discharge (chronic stable compensated state). Levels of miR­21, miR­126 and miR­423­5p increased between admission and discharge, and decreased following clinical compensation. During follow­up (up to 48 months), 38 patients (79%) were rehospitalized at least once and 21 patients (44%) succumbed. Patients who had increased levels of miR­21 and miR­126 at the time of clinical compensation exhibited better 24­month survival and remained rehospitalization­free for a longer period compared with those with low levels. Additionally, patients whose levels of miR­423­5p increased between admission and clinical compensation experienced fewer hospital readmissions in the 24 months following the time of clinical compensation compared with those who had decreased levels. It was concluded that the plasma levels of miR­21, miR­126 and miR­423­5p altered during clinical improvement and were associated with the prognosis of acute decompensated HF.


Assuntos
Insuficiência Cardíaca/diagnóstico , MicroRNAs/sangue , Doença Aguda , Idoso , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Hospitalização , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Prognóstico
12.
Am Heart J ; 194: 125-131, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29223430

RESUMO

AIMS: Furosemide is commonly prescribed for symptom relief in heart failure (HF) patients. Although few data support the continuous use of loop diuretics in apparently euvolemic HF patients with mild symptoms, there is concern about safety of diuretic withdrawal in these patients. The ReBIC-1 trial was designed to evaluate the safety and tolerability of withdrawing furosemide in stable, euvolemic, chronic HF outpatients. This multicenter initiative is part of the Brazilian Research Network in Heart Failure (ReBIC) created to develop clinical studies in HF and composed predominantly by university tertiary care hospitals. METHODS: The ReBIC-1 trial is currently enrolling HF patients in NYHA functional class I-II, left ventricular ejection fraction ≤45%, without a HF-related hospital admission within the last 6 months, receiving a stable dose of furosemide (40 or 80 mg per day) for at least 6 months. Eligible patients will be randomized to maintain or withdraw furosemide in a double-blinded protocol. The trial has two co-primary outcomes: (1) dyspnea assessment using a visual-analogue scale evaluated at 4 time points and (2) the proportion of patients maintained without diuretics during the follow-up period. Total sample size was calculated to be 220 patients. Enrolled patients will be followed up to 90 days after randomization, and diuretic will be restarted if clinical deterioration or signs of congestion are detected. Pre-defined sub-group analysis based on NT-proBNP levels at baseline is planned. PERSPECTIVE: Evidence-based strategies aiming to simplify HF pharmacotherapy are needed in clinical practice. The ReBIC-1 trial will determine the safety of withdrawing furosemide in stable chronic HF patients.


Assuntos
Tolerância a Medicamentos , Furosemida/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Pacientes Ambulatoriais , Idoso , Biomarcadores/sangue , Deterioração Clínica , Diuréticos/administração & dosagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Resultado do Tratamento
14.
Arq Bras Cardiol ; 108(4): 290-296, 2017 04.
Artigo em Inglês, Português | MEDLINE | ID: mdl-28538758

RESUMO

Background: The SAMe-TT2R2 score was developed to predict which patients on oral anticoagulation with vitamin K antagonists (VKAs) will reach an adequate time in therapeutic range (TTR) (> 65%-70%). Studies have reported a relationship between this score and the occurrence of adverse events. Objective: To describe the TTR according to the score, in addition to relating the score obtained with the occurrence of adverse events in patients with nonvalvular atrial fibrillation (AF) on oral anticoagulation with VKAs. Methods: Retrospective cohort study including patients with nonvalvular AF attending an outpatient anticoagulation clinic of a tertiary hospital. Visits to the outpatient clinic and emergency, as well as hospital admissions to the institution, during 2014 were evaluated. The TTR was calculated through the Rosendaal´s method. Results: We analyzed 263 patients (median TTR, 62.5%). The low-risk group (score 0-1) had a better median TTR as compared with the high-risk group (score ≥ 2): 69.2% vs. 56.3%, p = 0.002. Similarly, the percentage of patients with TTR ≥ 60%, 65% or 70% was higher in the low-risk group (p < 0.001, p = 0.001 and p = 0.003, respectively). The high-risk group had a higher percentage of adverse events (11.2% vs. 7.2%), although not significant (p = 0.369). Conclusions: The SAMe-TT2R2 score proved to be effective to predict patients with a better TTR, but was not associated with adverse events. Fundamento: O escore SAMe-TT2R2 foi desenvolvido visando predizer quais pacientes em anticoagulação oral com antagonistas da vitamina K (AVKs) atingirão um tempo na faixa terapêutica (TFT) adequado (> 65%-70%) no seguimento. Estudos também o relacionaram com a ocorrência de eventos adversos. Objetivos: Descrever o TFT de acordo com o escore, além de relacionar a pontuação obtida com a ocorrência de eventos adversos adversos em pacientes com fibrilação atrial (FA) não valvar em anticoagulação oral com AVKs. Métodos: Estudo de coorte retrospectivo incluindo pacientes com FA não valvar em acompanhamento em ambulatório de anticoagulação de um hospital terciário. Foi realizada uma avaliação retrospectiva de consultas ambulatoriais, visitas a emergência e internações hospitalares na instituição no período de janeiro-dezembro/2014. O TFT foi calculado aplicando-se o método de Rosendaal. Resultados: Foram analisados 263 pacientes com TFT mediano de 62,5%. O grupo de baixo risco (0-1 ponto) obteve um TFT mediano maior em comparação com o grupo de alto risco (≥ 2 pontos): 69,2% vs. 56,3%, p = 0,002. Da mesma forma, o percentual de pacientes com TFT ≥ 60%, 65% ou 70% foi superior nos pacientes de baixo risco (p < 0,001, p = 0,001 e p = 0,003, respectivamente). Os pacientes de alto risco tiveram um percentual maior de eventos adversos (11,2% vs. 7,2%), embora não significativo (p = 0,369). Conclusões: O escore SAMe-TT2R2 foi uma ferramenta eficaz na predição do TFT em pacientes com FA em uso de AVKs para anticoagulação, porém não se associou à ocorrência de eventos adversos.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Hemorragia/induzido quimicamente , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/prevenção & controle , Vitamina K/antagonistas & inibidores , Varfarina/uso terapêutico , Idoso , Anticoagulantes/efeitos adversos , Técnicas de Apoio para a Decisão , Intervalo Livre de Doença , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Tempo de Protrombina , Estudos Retrospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/etiologia , Tromboembolia/etiologia , Varfarina/efeitos adversos
15.
Arq. bras. cardiol ; 108(4): 290-296, Apr. 2017. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-838729

RESUMO

Abstract Background: The SAMe-TT2R2 score was developed to predict which patients on oral anticoagulation with vitamin K antagonists (VKAs) will reach an adequate time in therapeutic range (TTR) (> 65%-70%). Studies have reported a relationship between this score and the occurrence of adverse events. Objective: To describe the TTR according to the score, in addition to relating the score obtained with the occurrence of adverse events in patients with nonvalvular atrial fibrillation (AF) on oral anticoagulation with VKAs. Methods: Retrospective cohort study including patients with nonvalvular AF attending an outpatient anticoagulation clinic of a tertiary hospital. Visits to the outpatient clinic and emergency, as well as hospital admissions to the institution, during 2014 were evaluated. The TTR was calculated through the Rosendaal´s method. Results: We analyzed 263 patients (median TTR, 62.5%). The low-risk group (score 0-1) had a better median TTR as compared with the high-risk group (score ≥ 2): 69.2% vs. 56.3%, p = 0.002. Similarly, the percentage of patients with TTR ≥ 60%, 65% or 70% was higher in the low-risk group (p < 0.001, p = 0.001 and p = 0.003, respectively). The high-risk group had a higher percentage of adverse events (11.2% vs. 7.2%), although not significant (p = 0.369). Conclusions: The SAMe-TT2R2 score proved to be effective to predict patients with a better TTR, but was not associated with adverse events.


Resumo Fundamento: O escore SAMe-TT2R2 foi desenvolvido visando predizer quais pacientes em anticoagulação oral com antagonistas da vitamina K (AVKs) atingirão um tempo na faixa terapêutica (TFT) adequado (> 65%-70%) no seguimento. Estudos também o relacionaram com a ocorrência de eventos adversos. Objetivos: Descrever o TFT de acordo com o escore, além de relacionar a pontuação obtida com a ocorrência de eventos adversos adversos em pacientes com fibrilação atrial (FA) não valvar em anticoagulação oral com AVKs. Métodos: Estudo de coorte retrospectivo incluindo pacientes com FA não valvar em acompanhamento em ambulatório de anticoagulação de um hospital terciário. Foi realizada uma avaliação retrospectiva de consultas ambulatoriais, visitas a emergência e internações hospitalares na instituição no período de janeiro-dezembro/2014. O TFT foi calculado aplicando-se o método de Rosendaal. Resultados: Foram analisados 263 pacientes com TFT mediano de 62,5%. O grupo de baixo risco (0-1 ponto) obteve um TFT mediano maior em comparação com o grupo de alto risco (≥ 2 pontos): 69,2% vs. 56,3%, p = 0,002. Da mesma forma, o percentual de pacientes com TFT ≥ 60%, 65% ou 70% foi superior nos pacientes de baixo risco (p < 0,001, p = 0,001 e p = 0,003, respectivamente). Os pacientes de alto risco tiveram um percentual maior de eventos adversos (11,2% vs. 7,2%), embora não significativo (p = 0,369). Conclusões: O escore SAMe-TT2R2 foi uma ferramenta eficaz na predição do TFT em pacientes com FA em uso de AVKs para anticoagulação, porém não se associou à ocorrência de eventos adversos.

16.
Nutr Rev ; 74(11): 659-669, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27753623

RESUMO

CONTEXT: Ghrelin is a hormone that stimulates weight gain and increases appetite. For these reasons, it has been used for treatment of cachexia syndrome. OBJECTIVE: The aim of this systematic review was to examine the use of ghrelin in cachexia patients to better understand the most prevalent clinical outcomes, particularly since the type and dosage of hormone used and the route and duration of administration often varies. DATA SOURCES: A search of electronic databases (MEDLINE, SciELO, Embase, Cochrane Library, and Clinical Trials.gov) was limited to original articles describing interventions in adult humans, with no limits for publication date or language. STUDY SELECTION: Articles were searched independently by 2 reviewers, from October 2013 to April 2015. Studies were eligible for inclusion if they were conducted in adult patients with a diagnosis of cachexia and provided information on type of ghrelin or analogue used, route of administration and dose administered, duration of intervention, outcomes, and clinical trial study design. DATA EXTRACTION: Data were extracted independently by 2 reviewers using a preconstructed spreadsheet. Initially, 573 references were identified. Seven articles describing 379 participants were selected for review. RESULTS: Ghrelin was found to have a predominantly positive effect on growth hormone plasma levels, weight gain, increases in lean mass, and reductions in loss of adipose tissue. CONCLUSIONS: Although the studies reviewed here report positive results, there is still little evidence available on the use of ghrelin to treat cachexia. Further research is required to determine conclusively whether the use of ghrelin in patients with cachexia is a viable therapy.


Assuntos
Caquexia/tratamento farmacológico , Grelina/administração & dosagem , Tecido Adiposo/efeitos dos fármacos , Apetite , Composição Corporal/efeitos dos fármacos , Hormônio do Crescimento Humano/sangue , Humanos , MEDLINE , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Ganho de Peso/efeitos dos fármacos
17.
PLoS One ; 11(8): e0161666, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27551966

RESUMO

Circulating levels of matrix metalloproteinase-2 (MMP-2) predict mortality and hospital admission in heart failure (HF) patients. However, the role of MMP-2 gene polymorphisms in the susceptibility and prognosis of HF remains elusive. In this study, 308 HF outpatients (216 Caucasian- and 92 African-Brazilians) and 333 healthy subjects (256 Caucasian- and 77 African-Brazilians) were genotyped for the -1575G>A (rs243866), -1059G>A (rs17859821), and -790G>T (rs243864) polymorphisms in the MMP-2 gene. Polymorphisms were analyzed individually and in combination (haplotype), and positive associations were adjusted for clinical covariates. Although allele frequencies were similar in HF patients and controls in both ethnic groups, homozygotes for the minor alleles were not found among African-Brazilian patients. After a median follow-up of 5.3 years, 124 patients (40.3%) died (54.8% of them for HF). In Caucasian-Brazilians, the TT genotype of the -790G>T polymorphism was associated with a decreased risk of HF-related death as compared with GT genotype (hazard ratio [HR] = 0.512, 95% confidence interval [CI] 0.285-0.920). However, this association was lost after adjusting for clinical covariates (HR = 0.703, 95% CI 0.365-1.353). Haplotype analysis revealed similar findings, as patients homozygous for the -1575G/-1059G/-790T haplotype had a lower rate of HF-related death than those with any other haplotype combination (12.9% versus 28.5%, respectively; P = 0.010). Again, this association did not remain after adjusting for clinical covariates (HR = 0.521, 95% CI 0.248-1.093). Our study does not exclude the possibility that polymorphisms in MMP-2 gene, particularly the -790G>T polymorphism, might be related to HF prognosis. However, due to the limitations of the study, our findings need to be confirmed in further larger studies.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/mortalidade , Metaloproteinase 2 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Idoso , Alelos , Biomarcadores , Brasil , Comorbidade , Feminino , Frequência do Gene , Genótipo , Haplótipos , Insuficiência Cardíaca/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco
18.
Clin Nutr ; 35(6): 1530-1534, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27118274

RESUMO

BACKGROUND & AIMS: Patients with acute decompensated heart failure (ADHF) have exacerbation of symptoms and fluid retention, and high risk of re-hospitalizations and mortality. The aim of this study was to evaluate the role of phase angle at hospital admission as a prognostic marker of mortality in patients with ADHF. METHODS: Patients hospitalized for ADHF, with left ventricular ejection fraction (LVEF) <45% and BOSTON criteria ≥8 points were included. The patients were evaluated at hospital admission (first 36 h) and then followed up for assessment of outcomes. Phase angle was measured with tetra polar bioelectrical impedance device. Mortality data was obtained from an average of 24 months after discharge, from the medical records of the hospital and outpatient or telephone contact with patients or family members. The best-discriminatory level of phase angle was selected based on the ROC curve for mortality. RESULTS: Seventy-one patients were included and the majority was male (63%), with a mean age of 61 ± 12 years, ischemic etiology being the most prevalent (48%) and LVEF average of 26 ± 8%. Mortality was 49% at an average of 24 months after hospital discharge. The average phase angle at hospital admission was 5.6 ± 2°, and lower values were associated with higher mortality. Survivors were compared to died patients in the risk factor variables for mortality. In multivariate analysis adjusting for age, LVEF and urea, phase angle <4.8° was independently associated with increased mortality (HR 2.67; p = 0.015). CONCLUSIONS: Phase angle seems to be a prognostic marker in patients with ADHF independently of other known risk factors.


Assuntos
Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Hospitalização , Doença Aguda , Idoso , Composição Corporal , Brasil , Proteína C-Reativa/metabolismo , Creatinina/sangue , Impedância Elétrica , Feminino , Seguimentos , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Volume Sistólico , Resultado do Tratamento
19.
Gene ; 574(1): 1-10, 2015 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-26211628

RESUMO

AIMS: MicroRNAs (miRs) regulate processes involved in both cardiac remodeling and obesity. We investigated if the expression of selected miRs in patients with heart failure (HF) is influenced by the presence of obesity. METHODS: In this case-control study, we compared plasma levels of miR-21, -130b, -221, -423-5p, and the -221/-130b ratio in 57 age- and gender-matched subjects: 40 HF patients (20 obese HF and 20 lean HF) and 17 lean healthy controls. Body composition was estimated by bioelectrical impedance analysis. MiRs were measured by quantitative reverse transcription-PCR. Bioinformatics analysis was performed based on miRs findings to predict their putative targets and investigate their biological function. RESULTS: HF was associated with increased miR-423-5p levels in both lean and obese patients (P<0.05 vs. controls) without differences between HF groups. MiR-130b levels were reduced in obese HF patients compared with HF lean (P=0.036) and controls (P=0.025). MiR-221 levels were non-significantly increased in obese HF patients. MiR-21 levels were not different among the groups. MiR-221/-130b ratio was increased in obese HF patients, and was positively associated with body fat percentage (r=0.43; P=0.002), body mass index (r=0.44; P=0.002), and waist circumference (r=0.40; P=0.020). Computational prediction of target genes followed by functional enrichment analysis indicated a relevant role of miR-130b and miR-221 in modulating the expression of genes associated to cardiovascular and endocrine diseases, and suggested their influence in important signaling mechanisms and in numerous processes related to the circulatory and endocrine systems. CONCLUSIONS: In HF patients, the presence of obesity is associated with a differential expression of selected miRs and the miR-221/-130b ratio had significant correlations with adiposity parameters. Computational target prediction analysis identified several interrelated pathways targeted by miR-130b and miR-221 with a known relationship with endocrine and cardiovascular diseases, representing potential mechanisms to be further validated.


Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/genética , MicroRNAs/sangue , Obesidade/sangue , Obesidade/genética , Magreza/sangue , Magreza/genética , Composição Corporal/genética , Índice de Massa Corporal , Estudos de Casos e Controles , Biologia Computacional/métodos , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Circunferência da Cintura/genética
20.
J Cardiovasc Transl Res ; 8(5): 328-37, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26085187

RESUMO

The antioxidant N-acetycysteine can turn into a prooxidant molecule in presence of iron ions. Thus, our goal was to test if the association of N-acetylcysteine (NAC) and an iron chelator (deferoxamine--DFX) in a rodent model of acute myocardial infarction (AMI) improves cardiac function. Male Wistar rats were subjected to a SHAM surgery or AMI. The animals were randomized: vehicle, NAC (25 mg/kg for 28 days), DFX (40 mg/kg for 7 days), or NAC plus DFX (NAC plus DFX, respectively). Animals were killed 28 days after the AMI. Animals treated with NAC/DFX showed an increase in left ventricular ejection fraction at 28 days when compared with vehicle group (45.2 ± 10.9 % vs. 34.7 ± 8.7 %, p = 0.03). Antioxidant effect of NAC/DFX treatment decreased 4-hydroxynonenal when compared to AMI group (p = 0.06). In conclusion, we showed beneficial effect of NAC/DFX association in improving left ventricle function in an experimental AMI.


Assuntos
Acetilcisteína/administração & dosagem , Antioxidantes/administração & dosagem , Desferroxamina/administração & dosagem , Quelantes de Ferro/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Função Ventricular/efeitos dos fármacos , Aldeídos , Animais , Ecocardiografia , Imuno-Histoquímica , Ferro/sangue , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Ratos , Ratos Wistar , Volume Sistólico/fisiologia , Compostos de Sulfidrila/sangue , Troponina I/sangue
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA