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4.
Lipids Health Dis ; 17(1): 242, 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30342531

RESUMO

BACKGROUND: Heart failure (HF) courses with chronic inflammatory process and alterations in lipid metabolism may aggravate the disease. The aim was to test whether the severity of HF, using brain natriuretic peptide (BNP) as a marker, is associated with alterations in functional aspects of HDL, such as lipid transfer, cholesterol ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT) concentration. METHODS: Twenty-five HF patients in NYHA class I/II and 23 in class III/IV were enrolled. Plasma lipids, apolipoproteins, CETP, LCAT, oxidized-LDL (oxLDL) and paraoxonase-1 (PON-1) activity were determined. Lipid transfer from a donor artificial nanoparticle to HDL was measured by in vitro assay. RESULTS: Total cholesterol (p = 0.049), LDL-C (p = 0.023), non-HDL-C (p = 0.029) and CETP, that promotes lipid transfer among lipoproteins (p = 0.013), were lower in III/IV than in I/II group. Triglycerides, HDL-C, apo A-I, apo B, oxLDL, LCAT, enzyme that catalyzes serum cholesterol esterification, PON-1 activity, and in vitro transfers of cholesterol, triglycerides and phospholipids to HDL, important steps in HDL metabolism, were equal. IL-8 was higher in III/IV (p = 0.025), but TNFα, IL-1ß, IL-6 and MCP-1 were equal. BNP was negatively correlated with CETP (r = - 0.294; p = 0.042) and positively correlated with IL-8 (r = 0.299; p = 0.039). CONCLUSIONS: Our results disclosed the relationship between CETP levels and HF severity, by comparing two HF groups and by correlation analysis. Lower CETP levels may be a marker of HF aggravation and possibly of worse prognosis. Practical applications of this initial finding, as the issue whether CETP could be protective against HF aggravation, should be explored in larger experimental and clinical studies.


Assuntos
Proteínas de Transferência de Ésteres de Colesterol/sangue , Insuficiência Cardíaca/sangue , Peptídeo Natriurético Encefálico/sangue , Fosfatidilcolina-Esterol O-Aciltransferase/sangue , Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Colesterol/sangue , HDL-Colesterol/sangue , Citocinas/sangue , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Interleucina-8/sangue , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Triglicerídeos/sangue
5.
Cardiol Rev ; 26(4): 196-200, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29369824

RESUMO

Heart failure (HF) is a common clinical syndrome associated with significant morbidity and mortality, and there remains a clear need for innovative therapies that can modify disease progression. Sacubitril/valsartan (LCZ696) is a novel complex that combines simultaneous neprilysin inhibition and angiotensin II receptor blockade, that has demonstrated significant cardiovascular death or HF hospitalization reduction in the Prospective Comparison of Angiotensin Receptor/Neprilysin Inhibitor (ARNI) With Angiotensin-Converting Enzyme (ACE) Inhibitors to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial when compared with evidence-based doses of the gold standard ACE inhibitor enalapril. In this comprehensive review, the authors discuss historical trials that have investigated clinical outcomes utilizing variable dosing levels of ACE inhibitors or angiotensin receptor blockers in patients with HF with reduced ejection fraction. A critical analysis of the highlighted studies is proposed in the context of current HF management guidelines and HF clinical practice. In conclusion, based on current evidence, it is unclear whether a maximum recommended enalapril dose would promote improved patient outcomes compared with an intermediate dose. However, no prospective study to date comparing ACE inhibitor doses has documented that higher doses result in significant mortality reduction, although the data suggest that there may be a decrease in HF hospitalizations when compared with lower doses.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Ensaios Clínicos como Assunto , Humanos , Resultado do Tratamento
6.
Am J Cardiovasc Drugs ; 16(2): 93-101, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26817946

RESUMO

We reviewed clinical evidence for the use of ivabradine in systolic heart failure (HF), in which it appears to improve symptoms, improve quality of life, prevent hospitalization, and prolong survival, thereby addressing unmet needs in the management of HF. Ivabradine provides symptomatic benefits in HF on top of standard therapies, in terms of functional parameters and exercise capacity, and there is some evidence that this leads to improvements in quality of life in symptomatic HF patients, who may have dyspnea, altered exercise capacity, and fatigue. The SHIFT trial demonstrated that ivabradine has significant beneficial effects on major outcomes in HF. Ivabradine had a significant effect on pump failure death, which was reduced by 26 % (p = 0.014), with no effect on sudden cardiac death. This is an important result since pump failure death is currently the main cause of death in HF, and also because the reductions in mortality obtained with beta-blockers and spironolactone in the last 20 years appear to be mainly due to reduction in sudden death rather than reduction in pump failure death. Ivabradine also has a beneficial effect on hospital admissions (-26 %, p < 0.0001), which is clinically relevant since a quarter of HF patients can expect to be readmitted to hospital for HF within 1 month of discharge. Ivabradine-treated patients are also at significantly lower risk of experiencing a second or third hospitalization for worsening HF. Ivabradine clearly has a key role to play in the management of HF by covering the main therapeutic objectives of symptoms, quality of life, and outcomes.


Assuntos
Benzazepinas/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Hospitalização , Humanos , Ivabradina , Qualidade de Vida , Resultado do Tratamento
7.
Adv Ther ; 32(10): 906-19, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26521191

RESUMO

Heart failure has seen a number of therapeutic advances in recent years. Despite this, heart failure is still related to increasing rates of morbidity, repeated hospitalizations, and mortality. Ivabradine is a recent treatment option for heart failure. It has a mode of action that includes reduction in heart rate, and leads to improvement in outcomes related to heart failure mortality and morbidity, as demonstrated by the results of the SHIFT trial in patients with systolic heart failure, functional classes II and III on the New York Heart Association classification, and left ventricular ejection fraction ≤ 35%. These results are intriguing since many heart failure drugs reduce heart rate without such benefits, or with quite different effects, making it more difficult to understand the novelty of ivabradine in this setting. Many of the drugs used in heart failure modify heart rate, but most have other pathophysiological effects beyond their chronotropic action, which affect their efficacy in preventing morbidity and mortality outcomes. For instance, heart rate reduction at rest or exercise with ivabradine prolongs diastolic perfusion time, improves coronary blood flow, and increases exercise capacity. Another major difference is the increase in stroke volume observed with ivabradine, which may underlie its beneficial cardiac effects. Finally, there is mounting evidence from both preclinical and clinical studies that ivabradine has an anti-remodeling effect, improving left ventricular structures and functions. All together, these mechanisms have a positive impact on the prognosis of ivabradine-treated patients with heart failure, making a compelling argument for use of ivabradine in combination with other treatments.


Assuntos
Benzazepinas/farmacologia , Fármacos Cardiovasculares/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Benzazepinas/uso terapêutico , Fármacos Cardiovasculares/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Humanos , Ivabradina , Volume Sistólico/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
8.
Am J Cardiovasc Drugs ; 15(6): 387-93, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26239259

RESUMO

Careful review of the literature of the last 20 years since the appearance of the first positive trials in heart failure indicates an evolution in the mode of death moving from sudden death to a predominance of pump failure death (i.e., death due to progression of heart failure). Pump failure is becoming a leading cause of mortality in a range of patient profiles, including patients with newly diagnosed or severe heart failure, patients with devices, and patients with heart failure associated with Chagas' disease. Indeed, the evidence suggests that modern management strategies, such as beta-blockers and devices, are successful in preventing sudden death. However, this means that optimally treated patients are at greater risk for the consequences of pump failure (death, hospitalization, and reduced quality of life). This highlights a new important unmet need in heart failure, and a priority for current research should be therapies that reduce pump failure death and hospitalization for more cost-effective management of the disease. Insofar as one-third of heart failure patients do not survive more than 3 years after diagnosis, properly addressing pump failure is an essential target in heart failure.


Assuntos
Causas de Morte , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Antagonistas Adrenérgicos beta/uso terapêutico , Terapia de Ressincronização Cardíaca , Ensaios Clínicos como Assunto , Desfibriladores Implantáveis , Insuficiência Cardíaca/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Estudos Observacionais como Assunto , Qualidade de Vida , Fatores de Risco
9.
Arq Bras Cardiol ; 104(6): 502-6, 2015 Jun.
Artigo em Inglês, Português | MEDLINE | ID: mdl-26131706

RESUMO

In heart failure syndrome, myocardial dysfunction causes an increase in neurohormonal activity, which is an adaptive and compensatory mechanism in response to the reduction in cardiac output. Neurohormonal activity is initially stimulated in an attempt to maintain compensation; however, when it remains increased, it contributes to the intensification of clinical manifestations and myocardial damage. Cardiac remodeling comprises changes in ventricular volume as well as the thickness and shape of the myocardial wall. With optimized treatment, such remodeling can be reversed, causing gradual improvement in cardiac function and consequently improved prognosis.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Remodelação Ventricular/efeitos dos fármacos , Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Insuficiência Cardíaca/fisiopatologia , Humanos , Prognóstico , Volume Sistólico/fisiologia , Fatores de Tempo , Remodelação Ventricular/fisiologia
10.
Arq. bras. cardiol ; 104(6): 502-506, 06/2015. graf
Artigo em Inglês | LILACS | ID: lil-750701

RESUMO

In heart failure syndrome, myocardial dysfunction causes an increase in neurohormonal activity, which is an adaptive and compensatory mechanism in response to the reduction in cardiac output. Neurohormonal activity is initially stimulated in an attempt to maintain compensation; however, when it remains increased, it contributes to the intensification of clinical manifestations and myocardial damage. Cardiac remodeling comprises changes in ventricular volume as well as the thickness and shape of the myocardial wall. With optimized treatment, such remodeling can be reversed, causing gradual improvement in cardiac function and consequently improved prognosis.


Na síndrome da insuficiência cardíaca, a disfunção do miocárdio gera um aumento da atividade neuro-hormonal, que é um mecanismo adaptativo e compensatório em resposta à redução do débito cardíaco. A atividade neuro-hormonal é estimulada inicialmente na tentativa de manter o paciente compensado, mas quando permanece aumentada, contribui para a intensificação das manifestações clínicas e do dano miocárdico. A remodelação cardíaca consiste nas alterações no volume do ventrículo bem como na espessura e forma da parede do miocárdio. Com o tratamento otimizado, pode ocorrer a reversão da remodelação, com melhora gradual da função cardíaca e consequente melhora do prognóstico.


Assuntos
Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adiposidade/genética , Peso Corporal/genética , Predisposição Genética para Doença , Variação Genética , Obesidade/genética , /genética , Alelos , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , /genética , Genoma Humano , Desequilíbrio de Ligação , Metanálise como Assunto , Obesidade/epidemiologia , Obesidade/patologia , Polimorfismo de Nucleotídeo Único , Proteínas , Locos de Características Quantitativas , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Arq. bras. cardiol ; 102(5): 495-504, 10/06/2014. tab, graf
Artigo em Português | LILACS | ID: lil-711091

RESUMO

Fundamento: O tratamento da insuficiência cardíaca evoluiu nas últimas décadas, sugerindo que sua sobrevida tem aumentado. Objetivo: Verificar se houve melhora na sobrevida dos pacientes com insuficiência cardíaca avançada. Métodos: Comparamos retrospectivamente os dados de seguimento e tratamento de duas coortes de pacientes com insuficiência cardíaca sistólica admitidos para compensação até o ano 2000 (n = 353) e após 2000 (n = 279). Foram analisados: morte hospitalar, re-hospitalizações e morte no seguimento de 1 ano. Utilizamos os testes U de Mann-Whitney e qui-quadrado para comparação entre os grupos. Os preditores de mortalidade foram identificados pela análise de regressão por meio do método dos riscos proporcionais de Cox e análise de sobrevida pelo método de Kaplan-Meier. Resultados: Os pacientes internados até o ano 2000 eram mais jovens, tinham menor comprometimento ventricular esquerdo e receberam menor proporção de betabloqueadores na alta. A sobrevida dos pacientes hospitalizados antes de 2000 foi menor do que a dos hospitalizados após 2000 (40,1% vs. 67,4%; p < 0,001). Os preditores independentes de mortalidade na análise de regressão foram: a etiologia chagásica (hazard ratio: 1,9; intervalo de confiança de 95%: 1,3-3,0), inibidores da enzima conversora da angiotensina (hazard ratio: 0,6; intervalo de confiança de 95%: 0,4-0,9), betabloqueador (hazard ratio: 0,3; intervalo de confiança de 95%: 0,2-0,5), creatinina ≥ 1,4 mg/dL (hazard ratio: 2,0; intervalo de confiança de 95%: 1,3-3,0), sódio sérico ≤ 135 mEq/L (hazard ratio: 1,8; intervalo de confiança de 95%: 1,2-2,7). Conclusões: Pacientes com insuficiência cardíaca avançada apresentaram melhora significativa na sobrevida e redução ...


Background: The treatment of heart failure has evolved in recent decades suggesting that survival is increasing. Objective: To verify whether there has been improvement in the survival of patients with advanced heart failure. Methods: We retrospectively compared the treatment and follow-up data from two cohorts of patients with systolic heart failure admitted for compensation up to 2000 (n = 353) and after 2000 (n = 279). We analyzed in-hospital death, re-hospitalization and death in 1 year of follow-up. We used Mann-Whitney U test and chi-square test for comparison between groups. The predictors of mortality were identified by regression analysis through Cox proportional hazards model and survival analysis by the Kaplan-Meier survival analysis. Results: The patients admitted until 2000 were younger, had lower left ventricular impairment and received a lower proportion of beta-blockers at discharge. The survival of patients hospitalized before 2000 was lower than those hospitalized after 2000 (40.1% vs. 67.4%; p<0.001). The independent predictors of mortality in the regression analysis were: Chagas disease (hazard ratio: 1.9; 95% confidence interval: 1.3-3.0), angiotensin-converting-enzyme inhibitors (hazard ratio: 0.6; 95% confidence interval: 0.4-0.9), beta-blockers (hazard ratio: 0.3; 95% confidence interval: 0.2-0.5), creatinine ≥ 1.4 mg/dL (hazard ratio: 2.0; 95% confidence interval: 1.3-3.0), serum sodium ≤ 135 mEq/L (hazard ratio: 1.8; 95% confidence interval: 1.2-2.7). Conclusions: Patients with advanced heart failure showed a significant improvement in survival and reduction in re-hospitalizations. The neurohormonal blockade, with angiotensin-converting-enzyme inhibitors and beta-blockers, had an important role in increasing survival of these patients with advanced heart failure. .


Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Hospitalização/estatística & dados numéricos , Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Brasil , Pressão Sanguínea/fisiologia , Métodos Epidemiológicos , Mortalidade Hospitalar , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
12.
Arq Bras Cardiol ; 102(5): 495-504, 2014 May.
Artigo em Inglês, Português | MEDLINE | ID: mdl-24759950

RESUMO

BACKGROUND: The treatment of heart failure has evolved in recent decades suggesting that survival is increasing. OBJECTIVE: To verify whether there has been improvement in the survival of patients with advanced heart failure. METHODS: We retrospectively compared the treatment and follow-up data from two cohorts of patients with systolic heart failure admitted for compensation up to 2000 (n = 353) and after 2000 (n = 279). We analyzed in-hospital death, re-hospitalization and death in 1 year of follow-up. We used Mann-Whitney U test and chi-square test for comparison between groups. The predictors of mortality were identified by regression analysis through Cox proportional hazards model and survival analysis by the Kaplan-Meier survival analysis. RESULTS: The patients admitted until 2000 were younger, had lower left ventricular impairment and received a lower proportion of beta-blockers at discharge. The survival of patients hospitalized before 2000 was lower than those hospitalized after 2000 (40.1% vs. 67.4%; p<0.001). The independent predictors of mortality in the regression analysis were: Chagas disease (hazard ratio: 1.9; 95% confidence interval: 1.3-3.0), angiotensin-converting-enzyme inhibitors (hazard ratio: 0.6; 95% confidence interval: 0.4-0.9), beta-blockers (hazard ratio: 0.3; 95% confidence interval: 0.2-0.5), creatinine ≥ 1.4 mg/dL (hazard ratio: 2.0; 95% confidence interval: 1.3-3.0), serum sodium ≤ 135 mEq/L (hazard ratio: 1.8; 95% confidence interval: 1.2-2.7). CONCLUSIONS: Patients with advanced heart failure showed a significant improvement in survival and reduction in re-hospitalizations. The neurohormonal blockade, with angiotensin-converting-enzyme inhibitors and beta-blockers, had an important role in increasing survival of these patients with advanced heart failure.


Assuntos
Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Hospitalização/estatística & dados numéricos , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea/fisiologia , Brasil , Métodos Epidemiológicos , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo
13.
Arq. bras. cardiol ; 101(5): 442-448, nov. 2013. ilus, tab
Artigo em Português | LILACS | ID: lil-696887

RESUMO

FUNDAMENTO: A Insuficiência Cardíaca (IC) é uma síndrome que cursa com má evolução nas formas avançadas. O bloqueio neuro-hormonal modifica essa história natural; no entanto, ele com frequência é subotimizado. OBJETIVO: Neste estudo procuramos verificar em qual percentual médicos cardiologistas habituados no tratamento da IC conseguem prescrever as doses-alvo dos medicamentos de comprovada eficácia. MÉTODOS: Foram selecionados consecutivamente 104 pacientes ambulatoriais com disfunção sistólica, todos sob tratamento estabilizado. Avaliaram-se dados demográficos e o tratamento verificando-se as doses atingidas. Os achados são apresentados em percentual e fizeram-se correlações entre as diferentes variáveis. RESULTADOS: A idade média dos pac. foi de 64,1 ± 14,2 anos, com PAS 115,4 ± 15,3 mmHg, FC de 67,8 ± 9,4 bpm, peso 76,0 ± 17,0 kg e em ritmo sinusal (90,4%). Quanto ao tratamento, 93,3% estavam recebendo um bloqueador do SRA (52,9% IECA), todos recebiam betabloqueador (BB), sendo o carvedilol o mais prescrito (92,3%). Quanto às doses: 97,1% dos que recebiam um BRA estavam com dose abaixo da ideal; os que recebiam IECA 52,7% receberam dose otimizada. Quanto ao BB, em 76,0% foi possível prescrever as doses alvos. Nesse grupo de pac. a maioria com dose alvo do BB, pode-se observar que 36,5% apresentavam frequência cardíaca igual ou maior que 70 bpm em ritmo sinusal. CONCLUSÕES: Médicos cardiologistas habituados no tratamento da IC conseguem prescrever as doses-alvo de inibidores da ECA e BB para a maioria dos pac. Mesmo recebendo as doses preconizadas, cerca de um terço dos pac. persiste com FC acima de 70 bpm e deveria ter seu tratamento otimizado.


BACKGROUND: Heart failure (HF) is a syndrome that leads to poor outcome in advanced forms. The neurohormonal blockade modifies this natural history; however, it is often suboptimal. OBJECTIVE: The aim of this study is to assess at what percentage cardiologists used to treating HF can prescribe target doses of drugs of proven efficacy. METHODS: A total of 104 outpatients with systolic dysfunction were consecutively enrolled, all under stabilized treatment. Demographic and treatment data were evaluated and the doses achieved were verified. The findings are shown as percentages and correlations are made between different variables. RESULTS: The mean age of patients was 64.1 ± 14.2 years, with SBP =115.4 ± 15.3, HR = 67.8 ± 9.4 bpm, weight = 76.0 ± 17.0 kg and sinus rhythm (90.4%). As for treatment, 93.3% received a RAS blocker (ACEI 52.9%), all received beta-blockers (BB), the most often prescribed being carvedilol (92.3%). As for the doses: 97.1% of those receiving an ARB were below the optimal dose and of those who received ACEI, 52.7% received an optimized dose. As for the BB, target doses were prescribed to 76.0% of them. In this group of patients, most with BB target dose, it can be seen that 36.5% had HR > 70 bpm in sinus rhythm. CONCLUSION: Cardiologists used to treating HF can prescribe target doses of ACEI and BB to most patients. Even though they receive the recommended doses, about one third of patients persists with HR > 70 bpm and should have their treatment optimized.


Assuntos
Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Adrenérgicos beta/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Doença Crônica , Estudos de Coortes , Estudos Transversais , Pacientes Ambulatoriais , Estatísticas não Paramétricas
14.
Arq Bras Cardiol ; 101(5): 442-8, 2013 Nov.
Artigo em Inglês, Português | MEDLINE | ID: mdl-24100693

RESUMO

BACKGROUND: Heart failure (HF) is a syndrome that leads to poor outcome in advanced forms. The neurohormonal blockade modifies this natural history; however, it is often suboptimal. OBJECTIVE: The aim of this study is to assess at what percentage cardiologists used to treating HF can prescribe target doses of drugs of proven efficacy. METHODS: A total of 104 outpatients with systolic dysfunction were consecutively enrolled, all under stabilized treatment. Demographic and treatment data were evaluated and the doses achieved were verified. The findings are shown as percentages and correlations are made between different variables. RESULTS: The mean age of patients was 64.1 ± 14.2 years, with SBP =115.4 ± 15.3, HR = 67.8 ± 9.4 bpm, weight = 76.0 ± 17.0 kg and sinus rhythm (90.4%). As for treatment, 93.3% received a RAS blocker (ACEI 52.9%), all received beta-blockers (BB), the most often prescribed being carvedilol (92.3%). As for the doses: 97.1% of those receiving an ARB were below the optimal dose and of those who received ACEI, 52.7% received an optimized dose. As for the BB, target doses were prescribed to 76.0% of them. In this group of patients, most with BB target dose, it can be seen that 36.5% had HR > 70 bpm in sinus rhythm. CONCLUSION: Cardiologists used to treating HF can prescribe target doses of ACEI and BB to most patients. Even though they receive the recommended doses, about one third of patients persists with HR > 70 bpm and should have their treatment optimized.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Idoso , Doença Crônica , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estatísticas não Paramétricas
15.
Int J Cardiol ; 168(4): 3439-42, 2013 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-23680589

RESUMO

BACKGROUND: Anemia in heart failure patients and has been associated with increased morbi-mortality. Previous studies have treated anemia in heart failure patients with either erythropoietin alone or combination of erythropoietin and intravenous (i.v.) iron. However, the effect of i.v. or oral (p.o.) iron supplementation alone in heart failure patients with anemia was virtually unknown. AIM: To compare, in a double-blind design, the effects of i.v. iron versus p.o. iron in anemic heart failure patients. METHODS: IRON-HF study was a multicenter, investigator initiated, randomized, double-blind, placebo controlled trial that enrolled anemic heart failure patients with preserved renal function, low transferrin saturation (TSat) and low-to-moderately elevated ferritin levels. Interventions were Iron Sucrose i.v. 200 mg, once a week, for 5 weeks, ferrous sulfate 200 mg p.o. TID, for 8 weeks, or placebo. Primary endpoint was variation of peak oxygen consumption (peak VO2) assessed by ergospirometry over 3 month follow-up. RESULTS: Eighteen patients had full follow-up data. There was an increment of 3.5 ml/kg/min in peak VO2 in the i.v. iron group. There was no increment in peak VO2 in the p.o. iron group. Patients' ferritin and TSat increased significantly in both treated groups. Hemoglobin increased similarly in all groups. CONCLUSION: I.v. iron seems to be superior in improving functional capacity of heart failure patients. However, correction of anemia seems to be at least similar between p.o. iron and i.v. iron supplementation.


Assuntos
Anemia Ferropriva/sangue , Anemia Ferropriva/tratamento farmacológico , Compostos Férricos/administração & dosagem , Compostos Ferrosos/administração & dosagem , Ácido Glucárico/administração & dosagem , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/tratamento farmacológico , Idoso , Anemia Ferropriva/epidemiologia , Método Duplo-Cego , Feminino , Óxido de Ferro Sacarado , Insuficiência Cardíaca/epidemiologia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
16.
Clin Ther ; 35(5): 702-10, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23623755

RESUMO

BACKGROUND: Fixed-dose combinations of antihypertensive agents demonstrate advantages in terms of efficacy, tolerability, and treatment adherence. OBJECTIVE: This study was designed to compare the efficacy and safety of 2 ramipril and hydrochlorothiazide (HCTZ) fixed-dose combinations in patients with hypertension stage 1 or 2. Patients' blood pressure (BP) profiles were evaluated by using 24-hour ambulatory BP monitoring (ABPM). METHODS: This was a multicenter, prospective, randomized, open-label, parallel-group, noninferiority trial of adult patients (age ≥18 years) with hypertension stage 1 or 2 and systolic blood pressure (SBP) within 140 to 179 mm Hg or diastolic blood pressure (DBP) 90 to 109 mm Hg. After a 2-week washout period, eligible patients were randomized to receive 1 of 2 ramipril/HCTZ fixed-dose combination formulations (5/25 mg/d) for 8 weeks. The primary end point was the difference in 24-hour ABPM SBP/DBP mean reductions between groups after 8 weeks of treatment. The secondary end points were the changes in daytime and nighttime ABPM and in office BP. Safety profile and tolerability assessments included monitoring of adverse events. RESULTS: A total of 102 patients with hypertension (54 in group A [test formulation] and 48 in group B [reference formulation]), aged 27 to 85 years, completed the 8-week treatment period. The decreases in SBP and DBP according to 24-hour ABPM from baseline to week 8 were significant and similar in both groups. SBP decreased from 149.1 to 133.0 mm Hg (-16.1 mm Hg) in group A and from 146.2 to 130.6 mm Hg in group B (-15.6 mm Hg) (P = 0.8537); DBP was reduced by 8.8 mm Hg in group A and by 8.5 mm Hg in group B (P = 0.8748). Because the lower 95% CI limit for the difference between groups A and B of 3.96 mm Hg in SBP and 3.54 mm Hg in DBP was lower than that preestablished by the trial protocol (4 mm Hg), noninferiority of the test formulation was demonstrated compared with the reference formulation. For the secondary end points, there was no significant difference between groups in SBP and DBP during daytime or nighttime at the end of week 8. Office BP was significantly reduced in both treatment groups, with no significant differences between groups. The incidence of adverse events was 23.7% in group A and 21.7% in group B. CONCLUSIONS: Both treatment options were well tolerated and equally reduced BP. The results support the conclusion that group A (new fixed-dose combination of ramipril/HCTZ) was noninferior to group B (reference medication in Brazil). ISRCTN Register: ISRCTN05051235.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Ramipril/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Brasil , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/efeitos adversos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ramipril/administração & dosagem , Ramipril/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
17.
Arq Bras Cardiol ; 100(3): 281-7, 2013 Mar.
Artigo em Inglês, Português | MEDLINE | ID: mdl-23598583

RESUMO

BACKGROUND: Heart failure (HF) is a condition with poor outcome, especially in advanced cases. Determination of B-type natriuretic peptide (BNP) levels is useful in the diagnosis of cardiac decompensation and has also been proving useful in the prognostic evaluation. OBJECTIVES: To verify whether BNP levels are able to identify patients with a poorer outcome and whether it is an independent prognostic factor considering age, gender, cardiac and renal functions, as well as the cause of heart disease. METHODS: 189 patients in functional class III/IV advanced HF were studied. All had systolic dysfunction and had their BNP levels determined during hospitalization. Variables related to mortality were studied using univariate and multivariate analyses. RESULTS: BNP levels were higher in patients who died in the first year of follow-up (1,861.9 versus 1,408.1 pg/dL; p = 0.044) and in chagasic patients (1,985 versus 1,452 pg/mL; p = 0.001); the latter had a higher mortality rate in the first year of follow-up (56% versus 35%; p = 0.010). The ROC curve analysis showed that the BNP level of 1,400 pg/mL was the best predictor of events; high levels were associated with lower LVEF (0.23 versus 0.28; p = 0.002) and more severe degree of renal dysfunction (mean urea 92 versus 74.5 mg/dL; p = 0.002). CONCLUSION: In advanced HF, high BNP levels identified patients at higher risk of a poorer outcome. Chagasic patients showed higher BNP levels than those with heart diseases of other causes, and have poorer prognosis.


Assuntos
Cardiomiopatia Chagásica/sangue , Insuficiência Cardíaca/sangue , Peptídeo Natriurético Encefálico/sangue , Biomarcadores/sangue , Cardiomiopatia Chagásica/mortalidade , Métodos Epidemiológicos , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Volume Sistólico/fisiologia , Ureia/sangue
18.
Arq. bras. cardiol ; 100(3): 281-287, mar. 2013. ilus, tab
Artigo em Português | LILACS | ID: lil-670870

RESUMO

FUNDAMENTO: A insuficiência cardíaca (IC) é doença que cursa com má evolução, especialmente naqueles com IC avançada. A dosagem de peptídeo natriurético tipo B(BNP), ao lado da utilidade no diagnóstico da descompensação cardíaca, vem se mostrando útil na avaliação prognóstica. OBJETIVOS: Verificar se os níveis de BNP identificam quais pacientes evoluiriam pior e se o BNP seria fator independente de mortalidade considerando-se idade, sexo, funções cardíaca e renal e etiologia da cardiopatia. MÉTODOS: 189 pacientes com IC avançada em classe funcional III/IV foram estudados. Todos tinham disfunção sistólica e dosaram-se os níveis de BNP na hospitalização. Analisaram-se as variáveis relacionadas com a mortalidade através de análises univariada e multivariada. RESULTADOS: Os níveis de BNP foram mais elevados nos pacientes que morreram no primeiro ano de seguimento (1.861,9 versus 1.408,1 pg/dL; p = 0,044) e nos chagásicos (1.985 versus 1.452 pg/mL; p = 0,001), e esses pacientes chagásicos tiveram maior mortalidade no primeiro ano de seguimento (56% versus 35%; p = 0,010). Pela curva ROC, o valor de BNP de 1.400 pg/mL foi o melhor preditor de eventos, estando os valores elevados associados a FEVE mais baixa (0,23 versus 0,28; p = 0,002) e maior grau de disfunção renal (ureia média 92 versus 74,5 mg/dL; p = 0,002). CONCLUSÃO: Na IC avançada, os níveis elevados de BNP identificam pacientes com maior potencial de pior evolução. Os pacientes chagásicos apresentam níveis mais elevados de BNP do que as outras etiologias e têm pior evolução.


BACKGROUND: Heart failure (HF) is a condition with poor outcome, especially in advanced cases. Determination of B-type natriuretic peptide (BNP) levels is useful in the diagnosis of cardiac decompensation and has also been proving useful in the prognostic evaluation. OBJECTIVES: To verify whether BNP levels are able to identify patients with a poorer outcome and whether it is an independent prognostic factor considering age, gender, cardiac and renal functions, as well as the cause of heart disease. METHODS: 189 patients in functional class III/IV advanced HF were studied. All had systolic dysfunction and had their BNP levels determined during hospitalization. Variables related to mortality were studied using univariate and multivariate analyses. RESULTS: BNP levels were higher in patients who died in the first year of follow-up (1,861.9 versus 1,408.1 pg/dL; p = 0.044) and in chagasic patients (1,985 versus 1,452 pg/mL; p = 0.001); the latter had a higher mortality rate in the first year of follow-up (56% versus 35%; p = 0.010). The ROC curve analysis showed that the BNP level of 1,400 pg/mL was the best predictor of events; high levels were associated with lower LVEF (0.23 versus 0.28; p = 0.002) and more severe degree of renal dysfunction (mean urea 92 versus 74.5 mg/dL; p = 0.002). CONCLUSION: In advanced HF, high BNP levels identified patients at higher risk of a poorer outcome. Chagasic patients showed higher BNP levels than those with heart diseases of other causes, and have poorer prognosis.


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cardiomiopatia Chagásica/sangue , Insuficiência Cardíaca/sangue , Peptídeo Natriurético Encefálico/sangue , Biomarcadores/sangue , Cardiomiopatia Chagásica/mortalidade , Métodos Epidemiológicos , Insuficiência Cardíaca/mortalidade , Prognóstico , Volume Sistólico/fisiologia , Ureia/sangue
19.
Hypertension ; 60(3): 669-76, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22802226

RESUMO

We described recently that systemic hypoxia provokes vasoconstriction in heart failure (HF) patients. We hypothesized that either the exaggerated muscle sympathetic nerve activity and/or endothelial dysfunction mediate the blunted vasodilatation during hypoxia in HF patients. Twenty-seven HF patients and 23 age-matched controls were studied. Muscle sympathetic nerve activity was assessed by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. Peripheral chemoreflex control was evaluated through the inhaling of a hypoxic gas mixture (10% O(2) and 90% N(2)). Basal muscle sympathetic nerve activity was greater and basal FBF was lower in HF patients versus controls. During hypoxia, muscle sympathetic nerve activity responses were greater in HF patients, and forearm vasodilatation in HF was blunted versus controls. Phentolamine increased FBF responses in both groups, but the increase was lower in HF patients. Phentolamine and N(G)-monomethyl-l-arginine infusion did not change FBF responses in HF but markedly blunted the vasodilatation in controls. FBF responses to hypoxia in the presence of vitamin C were unchanged and remained lower in HF patients versus controls. In conclusion, muscle vasoconstriction in response to hypoxia in HF patients is attributed to exaggerated reflex sympathetic nerve activation and blunted endothelial function (NO activity). We were unable to identify a role for oxidative stress in these studies.


Assuntos
Células Quimiorreceptoras/fisiologia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Músculo Liso Vascular/inervação , Músculo Liso Vascular/fisiologia , Fluxo Sanguíneo Regional/fisiologia , Vasodilatação/fisiologia , Adulto , Ácido Ascórbico/farmacologia , Estudos de Casos e Controles , Antebraço/irrigação sanguínea , Hemodinâmica/fisiologia , Humanos , Hipóxia/fisiopatologia , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Fentolamina/farmacologia , Sistema Nervoso Simpático/fisiopatologia , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologia , Vasodilatação/efeitos dos fármacos , ômega-N-Metilarginina/farmacologia
20.
Arq. bras. cardiol ; 95(6): 732-737, dez. 2010. graf, tab
Artigo em Português | LILACS | ID: lil-572196

RESUMO

FUNDAMENTO: A depressão é uma comorbidade frequente na insuficiência cardíaca (IC), mas os mecanismos relacionados a pior evolução de pacientes deprimidos com IC ainda não estão esclarecidos. OBJETIVO: Avaliar o papel da depressão grave na evolução dos pacientes com IC descompensada. MÉTODOS: Estudamos consecutivamente 43 pacientes com IC avançada e FE < 40,0 por cento, hospitalizados para compensação cardíaca. Os pacientes, após história e exame físico, foram submetidos a exames laboratoriais, incluindo a dosagem de BNP. Após o diagnóstico de depressão, aplicou-se a escala de Hamilton-D. Depressão grave foi definida por escore igual ou maior que 18. As variáveis clínico-laboratoriais, segundo a presença ou não de depressão grave, foram analisadas pela regressão logística. A curva ROC definiu o ponto de corte para o BNP. RESULTADOS: Depressão grave ou muito grave foi identificada em 24 (55,8 por cento) pacientes. Os pacientes deprimidos graves não diferiram dos não deprimidos quanto à idade, sexo e função renal, mas apresentaram menor comprometimento cardíaco (FE 23,4 ± 7,2 por cento vs 19,5 ± 5,2 por cento; p = 0,046) e valores mais elevados do BNP (2.582,8 ± 1.596,6 pg/ml vs 1.206,6 ± 587,0 pg/ml; p < 0,001). Entretanto, os pacientes com BNP maior que 1.100 pg/ml tiveram 12,0 (odds ratio [IC 95 por cento] = 2,61 - 55,26) vezes mais chance de desenvolverem quadros de depressão grave. CONCLUSÃO: Os pacientes com depressão grave apresentaram maior grau de estimulação neuro-hormonal, apesar do grau de disfunção ventricular ser menor. As alterações fisiopatológicas relacionadas à depressão, aumentando a estimulação neuro-hormonal e as citocinas, provavelmente contribuíram para essa maior manifestação clínica, mesmo em presença de menor dano cardíaco.


BACKGROUND: Depression is a common comorbidity in heart failure (HF); however, the mechanisms related to a poorer outcome of depressed patients with HF remain unclear. OBJECTIVE: To evaluate the role of severe depression in the outcome of patients with decompensated HF. METHODS: A total of 43 patients with advanced HF, EF < 40.0 percent, and hospitalized for cardiac compensation were consecutively studied. After history taking and physical examination, the patients underwent laboratory tests including BNP determination. After the diagnosis of depression was made, the Hamilton-D scale was applied. Severe depression was defined by a score equal to or greater than 18. The clinical and laboratory variables according to the presence or absence of severe depression were analyzed using logistic regression. The ROC curve defined the cut-off point for BNP. RESULTS: Severe or very severe depression was identified in 24 (55.8 percent) patients. Severely depressed patients did not differ from non-depressed patients as regards age, gender and renal function, but showed less cardiac impairment (EF 23.4 ± 7.2 percent vs 19.5 ± 5.2 percent; p = 0.046) and higher BNP levels (2,582.8 ± 1,596.6 pg/ml vs 1,206.6 ± 587.0 pg/ml; p < 0.001). However, patients with BNP levels higher than 1,100 pg/ml had a 12.0-fold higher chance (odds ratio [95 percent CI] = 2.61 - 55.26) of developing severe depression. CONCLUSION: Patients with severe depression showed a higher degree of neurohormonal stimulation despite their lower degree of ventricular dysfunction. The pathophysiological changes related to depression, leading to increased neurohormonal stimulation and cytokines, probably contributed to this more intense clinical manifestation even in the presence of less cardiac damage.


FUNDAMENTO: La depresión es una comorbilidad frecuente en la insuficiencia cardíaca (IC), pero los mecanismos relacionados a peor evolución de pacientes deprimidos con IC aun no están aclarados. OBJETIVO: Evaluar el papel de la depresión grave en la evolución de los pacientes con IC descompensada. MÉTODOS: Estudiamos consecutivamente 43 pacientes con IC avanzada y FE < 40,0 por ciento, hospitalizados para compensación cardíaca. Los pacientes, después de historia y examen físico, fueron sometidos a exámenes de laboratorio, incluyendo el dosaje de BNP. Después del diagnóstico de depresión, se aplicó la escala de Hamilton-D. Depresión grave fue definida por escore igual o mayor que 18. Las variables clínicas-de laboratorio, según la presencia o no de depresión grave, fueron analizadas por la regresión logística. La curva ROC definió el punto de corte para el BNP. RESULTADOS: Depresión grave o muy grave fue identificada en 24 (55,8 por ciento) pacientes. Los pacientes deprimidos graves no difirieron de los no deprimidos en cuanto a la edad, sexo y función renal, pero presentaron menor compromiso cardíaco (FE 23,4 ± 7,2 por ciento vs. 19,5 ± 5,2 por ciento; p = 0,046) y valores más elevados del BNP (2.582,8 ± 1.596,6 pg/ml vs. 1.206,6 ± 587,0 pg/ml; p < 0,001). Mientras tanto, los pacientes con BNP mayor que 1.100 pg/ml tuvieron 12,0 (odds ratio [IC 95 por ciento] = 2,61 - 55,26) veces más chance de desarrollar cuadros de depresión grave. CONCLUSÍON: Los pacientes con depresión grave presentaron mayor grado de estimulación neurohormonal, a pesar del grado de disfunción ventricular ser menor. Las alteraciones fisiopatológicas relacionadas a la depresión, aumentando la estimulación neurohormonal y las citocinas, probablemente contribuyeron a esa mayor manifestación clínica, aun en presencia de menor daño cardíaco.


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Depressão/epidemiologia , Insuficiência Cardíaca/epidemiologia , Peptídeo Natriurético Encefálico/sangue , Disfunção Ventricular/epidemiologia , Biomarcadores/sangue , Depressão/diagnóstico , Métodos Epidemiológicos , Valores de Referência
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