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1.
Oncotarget ; 8(4): 6994-7002, 2017 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-28052002

RESUMO

Cardiotoxicity is associated with the chronic use of doxorubicin leading to cardiomyopathy and heart failure. Identification of cardiotoxicity-specific miRNA biomarkers could provide clinicians with a valuable prognostic tool. The aim of the study was to evaluate circulating levels of miRNAs in breast cancer patients receiving doxorubicin treatment and to correlate with cardiac function. This is an ancillary study from "Carvedilol Effect on Chemotherapy-induced Cardiotoxicity" (CECCY trial), which included 56 female patients (49.9±3.3 years of age) from the placebo arm. Enrolled patients were treated with doxorubicin followed by taxanes. cTnI, LVEF, and miRNAs were measured periodically. Circulating levels of miR-1, -133b, -146a, and -423-5p increased during the treatment whereas miR-208a and -208b were undetectable. cTnI increased from 6.6±0.3 to 46.7±5.5 pg/mL (p<0.001), while overall LVEF tended to decrease from 65.3±0.5 to 63.8±0.9 (p=0.053) over 12 months. Ten patients (17.9%) developed cardiotoxicity showing a decrease in LVEF from 67.2±1.0 to 58.8±2.7 (p=0.005). miR-1 was associated with changes in LVEF (r=-0.531, p<0.001). In a ROC curve analysis miR-1 showed an AUC greater than cTnI to discriminate between patients who did and did not develop cardiotoxicity (AUC = 0.851 and 0.544, p= 0.0016). Our data suggest that circulating miR-1 might be a potential new biomarker of doxorubicin-induced cardiotoxicity in breast cancer patients.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/genética , Doxorrubicina/efeitos adversos , MicroRNAs/sangue , Biomarcadores , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Carbazóis , Cardiotoxicidade/sangue , Cardiotoxicidade/fisiopatologia , Carvedilol , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Propanolaminas , Curva ROC , Volume Sistólico/efeitos dos fármacos , Troponina C/metabolismo , Função Ventricular Esquerda/efeitos dos fármacos
2.
PLoS One ; 11(12): e0168790, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28030609

RESUMO

BACKGROUND: The identification of new biomarkers of heart failure (HF) could help in its treatment. Previously, our group studied 89 patients with HF and showed that exhaled breath acetone (EBA) is a new noninvasive biomarker of HF diagnosis. However, there is no data about the relevance of EBA as a biomarker of prognosis. OBJECTIVES: To evaluate whether EBA could give prognostic information in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: After breath collection and analysis by gas chromatography-mass spectrometry and by spectrophotometry, the 89 patients referred before were followed by one year. Study physicians, blind to the results of cardiac biomarker testing, ascertained vital status of each study participant at 12 months. RESULTS: The composite endpoint death and heart transplantation (HT) were observed in 35 patients (39.3%): 29 patients (32.6%) died and 6 (6.7%) were submitted to HT within 12 months after study enrollment. High levels of EBA (≥3.7µg/L, 50th percentile) were associated with a progressively worse prognosis in 12-month follow-up (log-rank = 11.06, p = 0.001). Concentrations of EBA above 3.7µg/L increased the risk of death or HT in 3.26 times (HR = 3.26, 95%CI = 1.56-6.80, p = 0.002) within 12 months. In a multivariable cox regression model, the independent predictors of all-cause mortality were systolic blood pressure, respiratory rate and EBA levels. CONCLUSIONS: High EBA levels could be associated to poor prognosis in HFrEF patients.


Assuntos
Acetona/metabolismo , Expiração , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/metabolismo , Adulto , Testes Respiratórios , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
3.
PLoS Negl Trop Dis ; 7(4): e2176, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23638197

RESUMO

BACKGROUND: Sudden death has been considered the main cause of death in patients with Chagas heart disease. Nevertheless, this information comes from a period before the introduction of drugs that changed the natural history of heart failure. We sought to study the mode of death of patients with heart failure caused by Chagas heart disease, comparing with non-Chagas cardiomyopathy. METHODS AND RESULTS: We examined the REMADHE trial and grouped patients according to etiology (Chagas vs non-Chagas) and mode of death. The primary end-point was all-cause, heart failure and sudden death mortality; 342 patients were analyzed and 185 (54.1%) died. Death occurred in 56.4% Chagas patients and 53.7% non-Chagas patients. The cumulative incidence of all-cause mortality and heart failure mortality was significantly higher in Chagas patients compared to non-Chagas. There was no difference in the cumulative incidence of sudden death mortality between the two groups. In the Cox regression model, Chagas etiology (HR 2.76; CI 1.34-5.69; p = 0.006), LVEDD (left ventricular end diastolic diameter) (HR 1.07; CI 1.04-1.10; p<0.001), creatinine clearance (HR 0.98; CI 0.97-0.99; p = 0.006) and use of amiodarone (HR 3.05; CI 1.47-6.34; p = 0.003) were independently associated with heart failure mortality. LVEDD (HR 1.04; CI 1.01-1.07; p = 0.005) and use of beta-blocker (HR 0.52; CI 0.34-0.94; p = 0.014) were independently associated with sudden death mortality. CONCLUSIONS: In severe Chagas heart disease, progressive heart failure is the most important mode of death. These data challenge the current understanding of Chagas heart disease and may have implications in the selection of treatment choices, considering the mode of death. TRIAL REGISTRATION: ClinicalTrials.gov NCT00505050 (REMADHE).


Assuntos
Cardiomiopatia Chagásica/mortalidade , Adulto , Morte Súbita Cardíaca , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Int J Cardiol ; 167(1): 34-40, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-22243938

RESUMO

BACKGROUND: Renal dysfunction is associated with increased mortality in patients with decompensated heart failure. However, interventions targeted to prevention in this setting have been disappointing. We investigated the effects of hypertonic saline solution (HSS) for prevention of renal dysfunction in decompensated heart failure. METHODS: In a double-blind randomized trial, patients with decompensated heart failure were assigned to receive three-day course of 100mL HSS (NaCl 7.5%) twice daily or placebo. Primary end point was an increase in serum creatinine of 0.3mg/dL or more. Main secondary end point was change in biomarkers of renal function, including serum levels of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin-NGAL and the urinary excretion of aquaporin 2 (AQP2), urea transporter (UT-A1), and sodium/hydrogen exchanger 3 (NHE3). RESULTS: Twenty-two patients were assigned to HSS and 12 to placebo. Primary end point occurred in two (10%) patients in HSS group and six (50%) in placebo group (relative risk 0.3; 95% CI 0.09-0.98; P=0.01). Relative to baseline, serum creatinine and cystatin C levels were lower in HSS as compared to placebo (P=0.004 and 0.03, respectively). NGAL level was not statistically different between groups, however the urinary expression of AQP2, UT-A1 and NHE3 was significantly higher in HSS than in placebo. CONCLUSIONS: HSS administration attenuated heart failure-induced kidney dysfunction as indicated by improvement in both glomerular and tubular defects, a finding with important clinical implications. HSS modulated the expression of tubular proteins involved in regulation of water and electrolyte homeostasis.


Assuntos
Hidratação/métodos , Insuficiência Cardíaca/terapia , Nefropatias/prevenção & controle , Nefropatias/fisiopatologia , Solução Salina Hipertônica/administração & dosagem , Adulto , Idoso , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade
5.
Chest ; 142(2): 457-466, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22345382

RESUMO

BACKGROUND: Heart failure (HF) is associated with poor prognosis, and the identification of biomarkers of its severity could help in its treatment. In a pilot study, we observed high levels of acetone in the exhaled breath of patients with HF. The present study was designed to evaluate exhaled acetone as a biomarker of HF diagnosis and HF severity. METHODS: Of 235 patients with systolic dysfunction evaluated between May 2009 and September 2010, 89 patients (HF group) fulfilled inclusion criteria and were compared with sex- and age-matched healthy subjects (control group, n = 20). Patients with HF were grouped according to clinical stability (acute decompensated HF [ADHF], n = 59; chronic HF, n = 30) and submitted to exhaled breath collection. Identification of chemical species was done by gas chromatography-mass spectrometry and quantification by spectrophotometry. Patients with diabetes were excluded. RESULTS: The concentration of exhaled breath acetone (EBA) was higher in the HF group (median, 3.7 µg/L; interquartile range [IQR], 1.69-10.45 µg/L) than in the control group (median, 0.39 µg/L; IQR, 0.30-0.79 µg/L; P < .001) and higher in the ADHF group (median, 7.8 µg/L; IQR, 3.6-15.2 µg/L) than in the chronic HF group (median, 1.22 µg/L; IQR, 0.68-2.19 µg/L; P < .001). The accuracy and sensitivity of this method in the diagnosis of HF and ADHF were about 85%, a value similar to that obtained with B-type natriuretic peptide (BNP). EBA levels differed significantly as a function of severity of HF (New York Heart Association classification, P < .001). There was a positive correlation between EBA and BNP (r = 0.772, P < .001). CONCLUSIONS: EBA not only is a promising noninvasive diagnostic method of HF with an accuracy equivalent to BNP but also a new biomarker of HF severity.


Assuntos
Acetona/metabolismo , Expiração/fisiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/metabolismo , Adulto , Biomarcadores/metabolismo , Testes Respiratórios , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Projetos Piloto , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença
6.
Am Heart J ; 159(1): 90-7, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20102872

RESUMO

BACKGROUND: Heart failure and diabetes often occur simultaneously in patients, but the prognostic value of glycemia in chronic heart failure is debatable. We evaluated the role of glycemia on prognosis of heart failure. METHODS: Outpatients with chronic heart failure from the Long-term Prospective Randomized Controlled Study Using Repetitive Education at Six-Month Intervals and Monitoring for Adherence in Heart Failure Outpatients (REMADHE) trial were grouped according to the presence of diabetes and level of glycemia. All-cause mortality/heart transplantation and unplanned hospital admission were evaluated. RESULTS: Four hundred fifty-six patients were included (135 [29.5%] female, 124 [27.2%] with diabetes mellitus, age of 50.2 +/- 11.4 years, and left-ventricle ejection fraction of 34.7% +/- 10.5%). During follow-up (3.6 +/- 2.2 years), 27 (5.9%) patients were submitted to heart transplantation and 202 (44.2%) died; survival was similar in patients with and without diabetes mellitus. When patients with and without diabetes were categorized according to glucose range (glycemia < or = 100 mg/dL [5.5 mmol/L]), as well as when distributed in quintiles of glucose, the survival was significantly worse among patients with lower levels of glycemia. This finding persisted in Cox proportional hazards regression model that included gender, etiology, left ventricle ejection fraction, left ventricle diastolic diameter, creatinine level and beta-blocker therapy, and functional status (hazard ratio 1.45, 95% CI 1.09-1.69, P = .039). No difference regarding unplanned hospital admission was found. CONCLUSION: We report on an inverse association between glycemia and mortality in outpatients with chronic heart failure. These results point to a new pathophysiologic understanding of the interactions between diabetes mellitus, hyperglycemia, and heart disease.


Assuntos
Glicemia/análise , Causas de Morte , Diabetes Mellitus/mortalidade , Insuficiência Cardíaca/mortalidade , Hiperglicemia/mortalidade , Adulto , Fatores Etários , Doença Crônica , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/tratamento farmacológico , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Análise Multivariada , Pacientes Ambulatoriais/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Educação de Pacientes como Assunto , Probabilidade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Estatísticas não Paramétricas , Análise de Sobrevida , Fatores de Tempo
7.
Circ Heart Fail ; 3(1): 82-8, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19933408

RESUMO

BACKGROUND: Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of beta-blockers in patients with Chagas cardiomyopathy. METHODS AND RESULTS: We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and beta-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1+/-4.1 versus 26.3+/-5.1, P=0.001), smaller end-diastolic left ventricle diameter (6.7+/-1.0 mm versus 7.0+/-0.9 mm, P=0.001), smaller proportion of beta-blocker therapy (35.8% versus 68%, P<0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P=0.003). Twenty-four (35.8%) patients with Chagas disease were under beta-blocker therapy and had lower serum sodium (136.6+/-3.1 versus 138.4+/-3.1 mEqs, P=0.05) and lower body mass index (22.5+/-3.3 versus 24.9+/-4.3, P=0.03) compared with those who received beta-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under beta-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with beta-blockers was higher than that of patients without beta-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P=0.009) and beta-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P=0.044) were associated with better survival. CONCLUSIONS: Our study suggests that beta-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial. Clinical Trial Registration- clinicaltrials.gov. Identifier: NCT00505050.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Cardiomiopatia Chagásica/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Índice de Massa Corporal , Cardiomiopatia Chagásica/mortalidade , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Resultado do Tratamento
8.
Eur J Heart Fail ; 7(5): 869-73, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16043406

RESUMO

Patients with Chagas' cardiomyopathy have the worst prognosis when compared to other aetiologies. It has been suggested that a more intense inflammatory activation could be responsible for this excessive mortality. We studied 35 patients with idiopathic dilated cardiomyopathy (IDC group) and 28 patients with Chagas' heart disease (Chagas' group) and 12 control subjects. We compared plasma tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptor type 1 (sTNF-R1), soluble Fas (sFas), interleukin 6 (IL-6), and brain natriuretic peptide type B (BNP) concentrations between the groups. TNF-alpha and IL-6 concentrations were higher in the IDC and Chagas groups as compared to controls (p<0.001 and p=0.001, respectively). sTNF-R1 concentration was higher in IDC after stratification for functional class (p=0.039), and there was a trend toward higher plasma TNF-alpha concentration in the Chagas' group (p=0.092). IL-6 concentration was higher in Chagas than in IDC (p=0.005). Higher IL-6 levels were associated with worse outcome (p=0.03 for Chagas; p=0.003 for IDC). sFas concentration was similar among groups. BNP concentrations were higher in IDC (350 pg/ml) and in Chagas (444.6 pg/ml) as compared to the controls (20.3 pg/ml; p<0.01). Higher BNP levels were associated with death and heart transplantation in both aetiologies. Inflammatory activation in Chagas heart disease differs from IDC and is associated with heart failure severity.


Assuntos
Cardiomiopatia Dilatada/sangue , Cardiomiopatia Chagásica/sangue , Interleucina-6/sangue , Peptídeo Natriurético Encefálico/sangue , Receptores do Fator de Necrose Tumoral/sangue , Fator de Necrose Tumoral alfa/análise , Receptor fas/sangue , Adulto , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Chagásica/mortalidade , Cardiomiopatia Chagásica/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurotransmissores/sangue , Estudos Prospectivos , Análise de Sobrevida
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