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1.
PLoS One ; 14(10): e0223838, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31603935

RESUMO

BACKGROUND: Heart failure is associated with exercise intolerance and sleep- disordered breathing; however, studies in patients with chronic constrictive pericarditis are scarce. The purpose of our study was to assess exercise capacity and sleep in patients with chronic constrictive pericarditis (CCP) undergoing a pericardiectomy. METHODS: We studied consecutive patients scheduled for pericardiectomy due to symptomatic CCP. Were performed quality of life (Minnesota Living with Heart Failure Questionnaire-MLHFQ) and sleep questionnaires (Epworth, Pittsburgh Sleep Quality Index-PSQI), serum B-type natriuretic peptide (BNP), serum C-reactive protein, transthoracic echocardiography, cardiopulmonary exercise test and overnight polysomnography immediately before and six months after pericardiectomy. RESULTS: Twenty-five patients (76% males, age: 45.5±13.8 years, body mass index: 24.9±3.7 kg/m2, left ventricular ejection fraction: 60±6%) with CCP (76% idiopathic, 12% tuberculosis) were studied. As compared to the preoperative period, pericardiectomy resulted in reduction in BNP (143 (83.5-209.5) vs 76 (40-117.5) pg/mL, p = 0.011), improvement in VO2 peak (18.7±5.6 vs. 25.2±6.3 mL/kg/min, p<0.001), quality of life (MLHFQ score 62 (43,5-77,5) vs. 18 (8,5-22), p<0,001) and sleep (PSQI score 7.8±4.1 vs. 4.7±3.7, p<0.001) and no significant change in sleep disordered breathing (apnea hypopnea index-AHI 15.6 (8.3-31.7) vs. 14.6 (5.75-29.9) events/h, p = 0.253). CONCLUSION: Patients with symptomatic CCP showed reduced exercise capacity and sleep-disordered breathing. After pericardiectomy, there was improvement in exercise capacity and neutral effect on sleep-disordered breathing.

2.
J Card Surg ; 34(9): 796-802, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31269267

RESUMO

OBJECTIVE: The purpose of this study was to analyze the learning curve effect on hospital mortality, postoperative outcomes, freedom from reintervention in the aorta and long-term survival after frozen elephant trunk (FET) operation. METHODS: From July 2009 to June 2018, 79 patients underwent surgery with the FET technique. They had type A aortic dissection (acute 7.6%, chronic 33%), type B aortic dissection (acute 1.26%, chronic 34.2%), and complex thoracic aortic aneurysm (24%). 27.8% were reoperations and 43% received concomitant cardiac procedures. To compare the results, the sample was divided into group 1 (G1) (first half of the sample - operations from 2009 to 2014) and group 2 (G2) (first half of the sample - operations from 2015 to 2018). RESULTS: The in-hospital mortality was 20.25%, 30.7% for G1 and 10% for G2 (P = .02). The mean cardiopulmonary bypass time, myocardial ischemia time, and selective cerebral perfusion at 25°C time were 154 ± 31, 118 ± 32, and 59 ± 12 minutes, respectively, similar for both groups. Stroke and spinal cord injury occurred in four and two patients, with no difference between groups (P = .61 and P = .24). The necessity for secondary intervention on the downstream aorta for both groups was also similar (P = .136). Five of sixty-three surviving patients died during the follow-up period and the estimated survival rate was different between groups 49% vs 88% (P = .007). CONCLUSION: The learning curve with the FET procedure had a significant impact on hospital mortality and midterm survival over the follow-up period, albeit did not influence the freedom from reintervention on the downstream aorta.

3.
Can J Physiol Pharmacol ; 97(2): 140-145, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30557036

RESUMO

Metabolic, inflammatory, and autonomic nervous system (ANS) dysfunction are present in patients with heart failure. However, whether these changes are due to left ventricular dysfunction or heart failure etiology is unknown. We evaluated metabolism and inflammatory activity in patients with idiopathic dilated cardiomyopathy (IDC) and Chagas cardiomyopathy (CHG) and their correlation with the ANS. Forty-six patients were divided into 3 groups: IDC, CHG, and control. We evaluated adiponectin, leptin, insulin, interleukin-6, and tumor necrosis factor-alpha. ANS were analyzed by heart rate variability in time and frequency domains on a 24-hour Holter monitor. Levels of glucose, cholesterol, leptin, and adiponectin did not show differences between groups. Insulin levels were lower in CHG group (5.4 ± 3.3 µU/mL) when compared with control (8.0 ± 4.9 µU/mL) and IDC (9.9 ± 5.0 µU/mL) groups (p = 0.007). Insulin was positively associated with LFr/HFr ratio (r = 0.562; p = 0.029) and with the LFr component (r = 0.562; p = 0.029) and negatively associated with adiponectin (r = -0.603; p = 0.017) in CHG group. The addition of an adiponectin unit reduced average insulin by 0.332 µg/mL. Insulin levels were decreased in the CHG group when compared with the IDC group and were associated with ANS indexes and adiponectin levels.


Assuntos
Adipocinas/sangue , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Chagásica/metabolismo , Insulina/sangue , Adipocinas/metabolismo , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Chagásica/sangue , Cardiomiopatia Chagásica/diagnóstico , Cardiomiopatia Chagásica/fisiopatologia , Ecocardiografia Doppler , Eletrocardiografia , Feminino , Coração , Frequência Cardíaca/fisiologia , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade
4.
Arq Bras Cardiol ; 111(3): 436-539, 2018 09.
Artigo em Português | MEDLINE | ID: mdl-30379264
6.
Rev. Soc. Cardiol. Estado de Säo Paulo ; 28(4): 428-433, out.-dez. 2018. tab, ilus, graf
Artigo em Português | LILACS | ID: biblio-970626

RESUMO

A Insuficiência cardíaca é uma síndrome clínica cuja prevalência vem aumentado nos últimos anos, sendo uma das principais causas de internação no Brasil e no mundo. A apresentação da insuficiência cardíaca aguda compreende dois espectros, quais sejam, insuficiência cardíaca crônica agudizada e insuficiência cardíaca nova e ambas estão associadas a alta morbidade e mortalidade. A primeira abordagem desses pacientes deve ser realizada de maneira sistemática para estabelecer o diagnóstico, classificação hemodinâmica e estratificação de risco para orientar adequadamente as condutas iniciais. A decisão terapêutica imediata é essencial para otimizar o manejo desses pacientes, visando a melhor evolução prognóstica intra e extra-hospitalar


Heart failure is a clinical syndrome that has been increasing over the last few years and is currently one of the main causes of hospitalization in Brazil and in the world. Acute heart failure has two forms of presentation - chronic acute decompensated heart failure and new heart failure, both conditions being associated with high morbidity and mortality. The first approach to these patients should be conducted systematically in order to establish the diagnosis, the hemodynamic classification, and the risk stratification in order to adequately guide the initial conducts. An immediate therapeutic decision is essential to optimize the intra- and extra-hospital management of these patients for better prognostic evolution


Assuntos
Humanos , Masculino , Feminino , Terapêutica , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Hemodinâmica , Espectroscopia de Ressonância Magnética/métodos , Comorbidade , Doença Aguda , Doença Crônica , Epidemiologia , Guias como Assunto/normas , Diagnóstico , Eletrocardiografia/métodos
7.
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
8.
Can J Physiol Pharmacol ; 96(6): 541-549, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29120671

RESUMO

Myocardial remodeling includes inappropriate collagen deposition in the interstitium. Erythropoietin (EPO) may have cardioprotective effects. We aimed to assess the role of EPO on myocardial remodeling during the chronic phase. We studied 60 Wistar rats divided into the following groups: control (CT), control + EPO (CT + EPO), myocardial infarction + EPO (MI + EPO), and myocardial infarction (MI). The interstitial collagen volume fraction (ICVF) was quantified and echocardiography was performed. We quantified asymmetric dimethylarginine and glutathione by ELISA, and used real-time PCR to assess apoptosis and inflammation. Western blotting was used to evaluate inflammatory proteins and tissue inhibitors of metalloproteinases (TIMPs), and TUNEL staining was used to detect apoptosis. For matrix metalloproteinases (MMPs), we performed zymography. Parametric and nonparametric analyses were performed according to normality testing. ICVF was greater in MI groups (p < 0.001) and was attenuated by EPO (p = 0.05). The MMP-2 did not show any difference between groups. The TIMP-1 and TIMP-2 did not have difference between groups. The MI groups had worse fraction shortening (p < 0.001), without EPO protection (p = 0.666). The MI groups had increased left ventricle diastolic dimension (p < 0.001) without EPO attenuation (p = 0.79). EPO did not act on oxidative stress. Apoptosis and inflammation were not modulated by EPO. We concluded that EPO attenuated interstitial collagen accumulation, but did not protect from heart dilation or dysfunction.


Assuntos
Colágeno/metabolismo , Eritropoetina/farmacologia , Coração/efeitos dos fármacos , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Animais , Apoptose/efeitos dos fármacos , Arginina/análogos & derivados , Arginina/metabolismo , Diástole/efeitos dos fármacos , Glutationa/metabolismo , Coração/fisiopatologia , Hematócrito , Hemoglobinas/metabolismo , Masculino , Infarto do Miocárdio/patologia , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos
9.
Eur J Heart Fail ; 20(3): 514-522, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29193563

RESUMO

AIMS: Elevated serum uric acid concentration (SUA) has been associated with an increased risk of cardiovascular disease, but this may be due to unmeasured confounders. We examined the association between SUA and outcomes as well as the effect of sacubitril/valsartan on SUA in patients with heart failure with reduced ejection fraction (HFrEF) in PARADIGM-HF. METHODS AND RESULTS: The association between SUA and the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization, its components, and all-cause mortality was examined using Cox regression analyses among 8213 patients using quintiles (Q1-Q5) of SUA adjusted for baseline prognostic variables including estimated glomerular filtration rate (eGFR), diuretic dose, and log N-terminal pro-brain natriuretic peptide. Change in SUA from baseline over 12 months was also evaluated in each treatment group. Patients in Q5 (SUA ≥8.6 mg/dL) compared with Q1 (<5.4 mg/dL) were younger (62.8 vs. 64.2 years), more often male (88.7% vs. 63.1%), had lower systolic blood pressure (119 vs. 123 mmHg), lower eGFR (57.4 vs. 76.6 mL/min/1.73 m2 ), and greater diuretic use. Higher SUA was associated with a higher risk of the primary outcome (adjusted hazard ratios) Q5 vs. Q1 = 1.28 [95% confidence intervals (1.09-1.50), P = 0.003], cardiovascular death [1.44 (1.11-1.77), P = 0.001], HF hospitalization [1.37 (1.11-1.70), P = 0.004], and all-cause mortality [1.36 (1.13-1.64), P = 0.001]. Compared with enalapril, sacubitril/valsartan reduced SUA by 0.24 (0.17-0.32) mg/dL over 12 months (P < 0.0001). Sacubitril/valsartan improved outcomes, irrespective of SUA concentration. CONCLUSION: Serum uric acid concentration was an independent predictor of worse outcomes after multivariable adjustment in patients with HFrEF. Compared with enalapril, sacubitril/valsartan reduced SUA and improved outcomes irrespective of SUA.


Assuntos
Aminobutiratos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico/efeitos dos fármacos , Tetrazóis/uso terapêutico , Ácido Úrico/sangue , Antagonistas de Receptores de Angiotensina/uso terapêutico , Biomarcadores/sangue , Método Duplo-Cego , Feminino , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Neprilisina , Prognóstico , Resultado do Tratamento
10.
Circ Heart Fail ; 10(11)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29141857

RESUMO

BACKGROUND: Chagas' disease is an important cause of cardiomyopathy in Latin America. We aimed to compare clinical characteristics and outcomes in patients with heart failure (HF) with reduced ejection fraction caused by Chagas' disease, with other etiologies, in the era of modern HF therapies. METHODS AND RESULTS: This study included 2552 Latin American patients randomized in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure) trials. The investigator-reported etiology was categorized as Chagasic, other nonischemic, or ischemic cardiomyopathy. The outcomes of interest included the composite of cardiovascular death or HF hospitalization and its components and death from any cause. Unadjusted and adjusted Cox proportional hazards models were performed to compare outcomes by pathogenesis. There were 195 patients with Chagasic HF with reduced ejection fraction, 1300 with other nonischemic cardiomyopathy, and 1057 with ischemic cardiomyopathy. Compared with other etiologies, Chagasic patients were more often female, younger, and had lower prevalence of hypertension, diabetes mellitus, and renal impairment (but had higher prevalence of stroke and pacemaker implantation) and had worse health-related quality of life. The rates of the composite outcome were 17.2, 12.5, and 11.4 per 100 person-years for Chagasic, other nonischemic, and ischemic patients, respectively-adjusted hazard ratio for Chagasic versus other nonischemic: 1.49 (95% confidence interval, 1.15-1.94; P=0.003) and Chagasic versus ischemic: 1.55 (1.18-2.04; P=0.002). The rates of all-cause mortality were also higher. CONCLUSIONS: Despite younger age, less comorbidity, and comprehensive use of conventional HF therapies, patients with Chagasic HF with reduced ejection fraction continue to have worse quality of life and higher hospitalization and mortality rates compared with other etiologies. CLINICAL TRIAL REGISTRATION: PARADIGM-HF: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255; ATMOSPHERE: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00853658.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Cardiomiopatia Chagásica/complicações , Insuficiência Cardíaca/tratamento farmacológico , Idoso , Amidas/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Fármacos Cardiovasculares/efeitos adversos , Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/virologia , Feminino , Fumaratos/uso terapêutico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/virologia , Hospitalização , Humanos , Estimativa de Kaplan-Meier , América Latina , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Volume Sistólico/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos
11.
Arq. bras. cardiol ; 109(5): 457-465, Nov. 2017. tab
Artigo em Inglês | LILACS-Express | ID: biblio-887962

RESUMO

Abstract Background: International studies have reported the value of the clinical profile and laboratory findings in the diagnosis of constrictive pericarditis. However, Brazilian population data are scarce. Objective: To assess the clinical characteristics, sensitivity of imaging tests and factors related to the death of patients with constrictive pericarditis undergoing pericardiectomy. Methods: Patients with constrictive pericarditis surgically confirmed were retrospectively assessed regarding their clinical and laboratory variables. Two methods were used: transthoracic echocardiography and cardiac magnetic resonance imaging. Mortality predictors were determined by use of univariate analysis with Cox proportional hazards model and hazard ratio. All tests were two-tailed, and an alpha error ≤ 5% was considered statically significant. Results: We studied 84 patients (mean age, 44 ± 17.9 years; 67% male). Signs and symptoms of predominantly right heart failure were present with jugular venous distention, edema and ascites in 89%, 89% and 62% of the cases, respectively. Idiopathic etiology was present in 69.1%, followed by tuberculosis (21%). Despite the advanced heart failure degree, low BNP levels (median, 157 pg/mL) were found. The diagnostic sensitivities for constriction of echocardiography and magnetic resonance imaging were 53.6% and 95.9%, respectively. There were 9 deaths (10.7%), and the risk factors were: anemia, BNP and C reactive protein levels, pulmonary hypertension >55 mm Hg, and atrial fibrillation. Conclusions: Magnetic resonance imaging had better diagnostic sensitivity. Clinical, laboratory and imaging markers were associated with death.


Resumo Fundamento: Estudos internacionais têm relatado o valor de perfil clínico e exames de imagem no diagnóstico e prognóstico da pericardite constritiva. Entretanto, dados da população brasileira são escassos. Objetivo: Avaliar as características clínicas, sensibilidade de exames de imagem e fatores relacionados ao óbito em uma série de casos de pericardite constritiva submetidos à pericardiectomia. Métodos: Pacientes com pericardite constritiva confirmada por cirurgia foram avaliados retrospectivamente quanto a variáveis clínicas e laboratoriais. Dois métodos diagnósticos foram utilizados: ecocardiograma transtorácico e ressonância cardíaca. Preditores de mortalidade foram determinados por análise univariada usando metodologia das proporções de Cox e hazard ratio. Todos os testes foram considerados bicaudais e um erro alfa ≤ 5% foi considerado como significante. Resultados: Foram estudados 84 pacientes com idade média de 44 ± 17,9 anos, sendo 67% do sexo masculino. Sinais e sintomas de insuficiência cardíaca (IC) predominantemente direita estiveram presentes com estase jugular, edema e ascite em 89%, 89% e 62% dos casos, respectivamente. Etiologia idiopática foi observada em 69% dos casos, seguida por tuberculose em 21%. Apesar do grau de IC, encontramos baixos níveis de BNP (mediana de 157 pg/mL). As sensibilidades diagnósticas para constrição do ecocardiograma e da ressonância foram 53,6% e 95,9%, respectivamente. Durante a evolução clínica, houve 9 óbitos (10,7%) e os fatores de risco foram: anemia, elevações de BNP, PCR, hipertensão pulmonar > 55 mmHg e fibrilação atrial. Conclusões: Pericardite constritiva manifesta-se com sinais e sintomas de IC biventricular com predomínio à direita e baixos níveis de BNP. A ressonância magnética apresenta melhor sensibilidade para diagnóstico. Marcadores clínicos, laboratoriais e de imagem estiveram associados ao óbito.

12.
Arq Bras Cardiol ; 109(5): 457-465, 2017 Nov.
Artigo em Inglês, Português | MEDLINE | ID: mdl-28977057

RESUMO

BACKGROUND: International studies have reported the value of the clinical profile and laboratory findings in the diagnosis of constrictive pericarditis. However, Brazilian population data are scarce. OBJECTIVE: To assess the clinical characteristics, sensitivity of imaging tests and factors related to the death of patients with constrictive pericarditis undergoing pericardiectomy. METHODS: Patients with constrictive pericarditis surgically confirmed were retrospectively assessed regarding their clinical and laboratory variables. Two methods were used: transthoracic echocardiography and cardiac magnetic resonance imaging. Mortality predictors were determined by use of univariate analysis with Cox proportional hazards model and hazard ratio. All tests were two-tailed, and an alpha error ≤ 5% was considered statically significant. RESULTS: We studied 84 patients (mean age, 44 ± 17.9 years; 67% male). Signs and symptoms of predominantly right heart failure were present with jugular venous distention, edema and ascites in 89%, 89% and 62% of the cases, respectively. Idiopathic etiology was present in 69.1%, followed by tuberculosis (21%). Despite the advanced heart failure degree, low BNP levels (median, 157 pg/mL) were found. The diagnostic sensitivities for constriction of echocardiography and magnetic resonance imaging were 53.6% and 95.9%, respectively. There were 9 deaths (10.7%), and the risk factors were: anemia, BNP and C reactive protein levels, pulmonary hypertension >55 mm Hg, and atrial fibrillation. CONCLUSIONS: Magnetic resonance imaging had better diagnostic sensitivity. Clinical, laboratory and imaging markers were associated with death.


Assuntos
Pericardite Constritiva/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Feminino , Humanos , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pericardiectomia , Pericardite Constritiva/diagnóstico , Pericardite Constritiva/mortalidade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
14.
J Am Coll Cardiol ; 66(19): 2059-2071, 2015 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-26541915

RESUMO

BACKGROUND: Although most patients in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial had mild symptoms, there is a poor correlation between reported functional limitation and prognosis in heart failure. OBJECTIVES: The aim of this study was to examine the spectrum of risk in PARADIGM-HF and the effect of LCZ696 across that spectrum. METHODS: This study analyzed rates of the primary composite outcome of cardiovascular death or heart failure hospitalization, its components, and all-cause mortality using the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) risk scores to categorize patients. The authors determined whether risk, on the basis of these scores, modified the treatment effect of LCZ696. RESULTS: The complete MAGGIC risk score was available for 8,375 of the 8,399 patients in PARADIGM-HF. The median MAGGIC score was 20 (IQR: 16 to 24). An increase of 1 point was associated with a 6% increased risk for the primary endpoint (p < 0.001) and a 7% increased risk for cardiovascular death (p < 0.001). The benefit of LCZ696 over enalapril for the primary endpoint was similar across the spectrum of risk (p = 0.159). Treating 100 patients for 2 years with LCZ696 instead of enalapril led to 7 fewer patients in the highest quintile of risk experiencing primary outcomes, compared with 3 in the lowest quintile. Analyses using the EMPHASIS-HF risk score gave similar findings. CONCLUSIONS: Although most PARADIGM-HF patients had mild symptoms, many were at high risk for adverse outcomes and obtained a large absolute benefit from LCZ696, compared with enalapril, over a relatively short treatment period. LCZ696's benefit was consistent across the spectrum of risk. (PARADIGM-HF trial [Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure]; NCT01035255).


Assuntos
Aminobutiratos/uso terapêutico , Enalapril/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Medição de Risco/métodos , Tetrazóis/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Feminino , Saúde Global , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Neprilisina/antagonistas & inibidores , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida/tendências , Adulto Jovem
15.
PLoS One ; 10(7): e0131447, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26147101

RESUMO

BACKGROUND: Chagas disease (CD) induces autonomic dysfunction and inflammatory activity, which may promote metabolic abnormalities. We studied metabolism and his correlation with Autonomic Nervous System (ANS) and inflammation in CD. METHODS AND RESULTS: Sixty subjects were divided into 4 groups: control group (CG), IF (indeterminate form) group; ECG group (ECG abnormalities and normal left ventricular systolic function), and LVD group (left ventricular sistolic dysfunction). Levels of adiponectin, leptin, insulin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were assayed in serum samples by ELISA. ANS was assessed by heart rate variability in frequency domain in 24-hour Holter and postural tilt test (rest and orthostatic position). High frequency (HFr) component values were used to estimate parasympathetic activity and low frequency (LFr) component, sympathetic activity. Analyzes were made of the correlations of each of the metabolic parameters (leptin and adiponectin) with the inflammatory cytokines (interleukin-6 and TNF- alpha) and with the ANS assessment measurements. No significant differences were observed in leptin and insulin levels. Adiponectin was higher in ECG and LVD groups: [CG = 4766.5 (5529.5), IF = 4003.5 (2482.5), ECG = 8376.5 (8388.5), LVD = 8798 (4188.0) ng/mL, p<0.001)]. IL-6 and TNF-alpha were higher in LVD group: [IL-6: CG = 1.85 (6.41); IF = 1.58 (1.91); ECG = 1.0 (1.57); LVD= 31.44 (72.19) pg/ml; p = 0.001. TNF-alpha: CG = 22.57 (88.2); IF = 19.31 (33.16); ECG = 12.45 (3.07); LVD = 75.15 (278.57) pg/ml; p = 0.04]. Adiponectin levels had a positive association with the HFr component (r = 0.539; p = 0.038) and an inverse association with the LFr component (r = - 0.539; p = 0.038) in ECG group. Leptin levels had a negative association with the HFr component (r= - 0.632; p = 0.011) and a positive association with the LFr component (r = 0.632; p = 0.011) in LVD group. CONCLUSIONS: We found increased adiponectin levels in Chagas' heart disease with systolic dysfunction and in patients with ECG abnormalities and normal systolic function at rest. Adipocytokines levels (adiponectin and leptin) were associated with ANS parameters in Chagas' heart disease.


Assuntos
Adipocinas/sangue , Sistema Nervoso Autônomo/fisiopatologia , Cardiomiopatia Chagásica/fisiopatologia , Inflamação/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adiponectina/sangue , Adulto , Cardiomiopatia Chagásica/sangue , Eletrocardiografia , Feminino , Coração/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Inflamação/sangue , Insulina/sangue , Interleucina-6/sangue , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/sangue , Disfunção Ventricular Esquerda/sangue
16.
Arq. bras. cardiol ; 105(1): 28-36, July 2015. tab
Artigo em Inglês | LILACS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: lil-755004

RESUMO

Background:

Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks.

Objective:

To assess the different LA functions (reservoir, conduit and pump functions) and their correlation with the echocardiographic parameters of left ventricular (LV) systolic and diastolic functions.

Methods:

10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging.

Results:

Reservoir function (Total Emptying Fraction: TEF): (p <0.0001), lower in GIII as compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p<0.0001) and GII (p = 0.002). There was a negative correlation of E/e’average with the reservoir and pump functions (TEF and AEF), and a positive correlation of e’average with s’ wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions.

Conclusion:

An impairment of LA functions in Chagas cardiomyopathy was observed.

.

Fundamento:

A doença de Chagas é uma causa de miocardiopatia dilatada, sendo ainda pouco conhecida a função do átrio esquerdo (AE) nessa doença.

Objetivo:

Avaliar as diferenças nas funções do AE (reservatório, conduto e bomba) e sua correlação com os parâmetros ecocardiográficos das funções sistólica e diastólica do ventrículo esquerdo (VE).

Método:

10 controles (GC) e os seguintes pacientes com doença de Chagas: 26 com a forma indeterminada (GI); 30 com alterações eletrocardiográficas (GII); e 19 com disfunção de VE (GIII). Todos os pacientes foram submetidos a ecocardiografia bidimensional e em modo M, Doppler pulsado e Doppler tecidual.

Resultados:

Função de reservatório (fração de esvaziamento total: FET) (p < 0,0001), mais baixa no GIII do que no GC (p = 0,003), GI (p < 0,001) e GII (p < 0,001). Função de conduto (fração de esvaziamento passivo: FEP) (p = 0,004), mais baixa no GIII (GIII e GC, p = 0.06; GI e GII, p = 0.06; e GII e GIII, p = 0,07). Função de bomba (fração de esvaziamento ativo: FEA) (p = 0,0001), mais baixa no GIII do que no CG (p = 0,05), GI (p<0,0001) e GII (p = 0,002). Observou-se uma correlação negativa entre E/e’média e as funções de reservatório e de bomba (FET e FEA), e uma correlação positiva entre as ondas e’média e s’ (paredes septal e lateral) e as funções de reservatório, conduto e bomba.

Conclusão:

Observou-se comprometimento das funções do AE na miocardiopatia chagásica.

.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Função do Átrio Esquerdo/fisiologia , Cardiomiopatia Chagásica/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Cardiomiopatia Chagásica , Ecocardiografia Doppler , Contração Miocárdica/fisiologia , Valores de Referência , Estatísticas não Paramétricas , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda
17.
Arq Bras Cardiol ; 105(1): 28-36, 2015 Jul.
Artigo em Inglês, Português | MEDLINE | ID: mdl-25993486

RESUMO

BACKGROUND: Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks. OBJECTIVE: To assess the different LA functions (reservoir, conduit and pump functions) and their correlation with the echocardiographic parameters of left ventricular (LV) systolic and diastolic functions. METHODS: 10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging. RESULTS: Reservoir function (Total Emptying Fraction: TEF): (p <0.0001), lower in GIII as compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p<0.0001) and GII (p = 0.002). There was a negative correlation of E/e' (average) with the reservoir and pump functions (TEF and AEF), and a positive correlation of e' (average) with s' wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions. CONCLUSION: An impairment of LA functions in Chagas cardiomyopathy was observed.


Assuntos
Função do Átrio Esquerdo/fisiologia , Cardiomiopatia Chagásica/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Cardiomiopatia Chagásica/diagnóstico por imagem , Ecocardiografia Doppler , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Valores de Referência , Estatísticas não Paramétricas , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem
18.
Circulation ; 131(1): 54-61, 2015 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-25403646

RESUMO

BACKGROUND: Clinical trials in heart failure have focused on the improvement in symptoms or decreases in the risk of death and other cardiovascular events. Little is known about the effect of drugs on the risk of clinical deterioration in surviving patients. METHODS AND RESULTS: We compared the angiotensin-neprilysin inhibitor LCZ696 (400 mg daily) with the angiotensin-converting enzyme inhibitor enalapril (20 mg daily) in 8399 patients with heart failure and reduced ejection fraction in a double-blind trial. The analyses focused on prespecified measures of nonfatal clinical deterioration. In comparison with the enalapril group, fewer LCZ696-treated patients required intensification of medical treatment for heart failure (520 versus 604; hazard ratio, 0.84; 95% confidence interval, 0.74-0.94; P=0.003) or an emergency department visit for worsening heart failure (hazard ratio, 0.66; 95% confidence interval, 0.52-0.85; P=0.001). The patients in the LCZ696 group had 23% fewer hospitalizations for worsening heart failure (851 versus 1079; P<0.001) and were less likely to require intensive care (768 versus 879; 18% rate reduction, P=0.005), to receive intravenous positive inotropic agents (31% risk reduction, P<0.001), and to have implantation of a heart failure device or cardiac transplantation (22% risk reduction, P=0.07). The reduction in heart failure hospitalization with LCZ696 was evident within the first 30 days after randomization. Worsening of symptom scores in surviving patients was consistently more common in the enalapril group. LCZ696 led to an early and sustained reduction in biomarkers of myocardial wall stress and injury (N-terminal pro-B-type natriuretic peptide and troponin) versus enalapril. CONCLUSIONS: Angiotensin-neprilysin inhibition prevents the clinical progression of surviving patients with heart failure more effectively than angiotensin-converting enzyme inhibition. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255.


Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Progressão da Doença , Enalapril/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina/antagonistas & inibidores , Tetrazóis/uso terapêutico , Biomarcadores/sangue , Método Duplo-Cego , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Fatores de Risco , Volume Sistólico/fisiologia , Sobreviventes , Resultado do Tratamento , Troponina/sangue
19.
Eur Heart J ; 36(7): 434-9, 2015 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-25416329

RESUMO

AIMS: Although active-controlled trials with renin­angiotensin inhibitors are ethically mandated in heart failure with reduced ejection fraction, clinicians and regulators often want to know how the experimental therapy would perform compared with placebo. The angiotensin receptor-neprilysin inhibitor LCZ696 was compared with enalapril in PARADIGM-HF. We made indirect comparisons of the effects of LCZ696 with putative placebos. METHODS AND RESULTS: We used the treatment-arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) as the reference trial for comparison of an ACE inhibitor to placebo and the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity-Alternative trial (CHARM-Alternative) as the reference trial for comparison of an ARB to placebo. The hazard ratio of LCZ696 vs. a putative placebo was estimated through the product of the hazard ratio of LCZ696 vs. enalapril (active-control) and that of the historical active-control (enalapril or candesartan) vs. placebo. For the primary composite outcome of cardiovascular death or heart failure hospitalization in PARADIGM-HF, the relative risk reduction with LCZ696 vs. a putative placebo from SOLVD-T was 43% (95%CI 34­50%; P < 0.0001) with similarly large effects on cardiovascular death (34%, 21­44%; P < 0.0001) and heart failure hospitalization (49%, 39­58%; P < 0.0001). For all-cause mortality, the reduction compared with a putative placebo was 28% (95%CI 15­39%; P < 0.0001). Putative placebo analyses based on CHARM-Alternative gave relative risk reductions of 39% (95%CI 27­48%; P < 0.0001) for the composite outcome of cardiovascular death or heart failure hospitalization, 32% (95%CI 16­45%; P < 0.0001) for cardiovascular death, 46% (33­56%; P < 0.0001) for heart failure hospitalization, and 26% (95%CI 11­39%; P < 0.0001) for all-cause mortality. CONCLUSION: These indirect comparisons of LCZ696 with a putative placebo show that the strategy of combined angiotensin receptor blockade and neprilysin inhibition led to striking reductions in cardiovascular and all-cause mortality, as well as heart failure hospitalization. These benefits were obtained even though LCZ696 was added to comprehensive background beta-blocker and mineralocorticoid receptor antagonist therapy.


Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Tetrazóis/uso terapêutico , Idoso , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Benzimidazóis/uso terapêutico , Enalapril/uso terapêutico , Feminino , Insuficiência Cardíaca/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Efeito Placebo , Resultado do Tratamento
20.
Arq. bras. cardiol ; 105(1): 28-36, 2015. tab
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-32565

RESUMO

Background: Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function inthis disease still lacks.Objective: To assess the different LA functions (reservoir, conduit and pump functions) and their correlation withthe echocardiographic parameters of left ventricular (LV) systolic and diastolic functions.Methods: 10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI);30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging. Results: Reservoir function (Total Emptying Fraction: TEF): (p < 0.0001), lower in GIII as compared to CG (p = 0.003),GI (p < 0.001) and GII (p < 0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIIIand CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF):(p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p < 0.0001) and GII (p = 0.002). There was a negative correlation of E/e’average with the reservoir and pump functions (TEF and AEF), and a positive correlation of e’average with s’wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions. Conclusion: An impairment of LA functions in Chagas cardiomyopathy was observed. (Arq Bras Cardiol. 2015;105(1):28-36). (AU)


Assuntos
Doença de Chagas , Cardiomiopatia Chagásica , Disfunção Ventricular , Ecocardiografia
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