RESUMEN
OBJECTIVE: The aim of this work was to assess the prognostic value of absolute N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration in combination with changes during admission because of acute heart failure (AHF) and early after hospital discharge. BACKGROUND: In AHF, readmission and mortality rates are high. Identifying those at highest risk for events early after hospital discharge might help to select patients in need of intensive outpatient monitoring. METHODS AND RESULTS: We evaluated the prognostic value of NT-proBNP concentration on admission, at discharge, 1 month after hospital discharge and change over time in 309 patients included in the PRIMA (Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study. Primary outcome measures were mortality and the combined end point of heart failure (HF) readmission or mortality. In a multivariate Cox regression analysis, change in NT-proBNP concentration during admission, change from discharge to 1 month after discharge, and the absolute NT-proBNP concentration at 1 month after discharge were of independent prognostic value for both end points (hazard ratios for HF readmission or mortality: 1.71, 95% confidence interval [CI] 1.13-2.60, Wald 6.4 [P = .011] versus 2.71, 95% CI 1.76-4.17, Wald 20.5 [P < .001] versus 1.81, 95% CI 1.13-2.89, Wald 6.1 [P = .014], respectively. CONCLUSIONS: Knowledge of change in NT-proBNP concentration during admission because of AHF in combination with change early after discharge and the absolute NT-proBNP concentration at 1 month after discharge allows accurate risk stratification.
Asunto(s)
Causas de Muerte , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Insuficiencia Cardíaca/fisiopatología , Mortalidad Hospitalaria/tendencias , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Admisión del Paciente , Alta del Paciente , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores Sexuales , Análisis de SupervivenciaRESUMEN
OBJECTIVES: The purpose of this study was to assess whether management of heart failure (HF) guided by an individualized N-terminal pro-B-type natriuretic peptide (NT-proBNP) target would lead to improved outcome compared with HF management guided by clinical assessment alone. BACKGROUND: Natriuretic peptides may be attractive biomarkers to guide management of heart failure (HF) and help select patients in need of more aggressive therapy. The PRIMA (Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study is, to our knowledge, the first large, prospective randomized study to address whether management of HF guided by an individualized target NT-proBNP level improves outcome. METHODS: A total of 345 patients hospitalized for decompensated, symptomatic HF with elevated NT-proBNP levels at admission were included. After discharge, patients were randomized to either clinically-guided outpatient management (n = 171), or management guided by an individually set NT-proBNP (n = 174) defined by the lowest level at discharge or 2 weeks thereafter. The primary end point was defined as number of days alive outside the hospital after index admission. RESULTS: HF management guided by this individualized NT-proBNP target increased the use of HF medication (p = 0.006), and 64% of HF-related events were preceded by an increase in NT-proBNP. Nevertheless, HF management guided by this individualized NT-proBNP target did not significantly improve the primary end point (685 vs. 664 days, p = 0.49), nor did it significantly improve any of the secondary end points. In the NT-proBNP-guided group mortality was lower, as 46 patients died (26.5%) versus 57 (33.3%) in the clinically-guided group, but this was not statistically significant (p = 0.206). CONCLUSIONS: Serial NT-proBNP measurement and targeting to an individual NT-proBNP value did result in advanced detection of HF-related events and importantly influenced HF-therapy, but failed to provide significant clinical improvement in terms of mortality and morbidity. (Effect of NT-proBNP Guided Treatment of Chronic Heart Failure [PRIMA]; NCT00149422).
Asunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Diuréticos/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Anciano , Anciano de 80 o más Años , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Antiarrítmicos/administración & dosificación , Biomarcadores Farmacológicos/sangre , Digoxina/administración & dosificación , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Estudios ProspectivosRESUMEN
The implementation of molecular biological approaches has led to the discovery of single genetic variations that contribute to the development of cardiac failure. In the present review, the characteristics that are invariably associated with the development of failure in experimental animals and clinical studies are discussed, which may provide attractive biological targets in the treatment of human heart failure. Findings from the Framingham studies have provided evidence that the presence of left ventricular hypertrophy is the main risk factor for subsequent development of heart failure in man. Conventional views identify myocardial hypertrophy as a compensatory response to increased workload, prone to evoke disease. Recent findings in genetic models of myocardial hypertrophy and human studies have provided the molecular basis for a novel concept, which favours the existence of either compensatory or maladaptive forms of hypertrophy, of which only the latter leads the way to cardiac failure. Furthermore, the concept that hypertrophy compensates for augmented wall stress is probably outdated. In this article, we provide the molecular pathways that can distinguish beneficial from maladaptive hypertrophy.
Asunto(s)
Insuficiencia Cardíaca/genética , Hipertrofia Ventricular Izquierda/genética , Apoptosis , Calcio/metabolismo , Femenino , Fibrosis/patología , Insuficiencia Cardíaca/patología , Humanos , Hipertrofia Ventricular Izquierda/patología , Líquido Intracelular/química , Masculino , Células Musculares/patología , Mutación/genética , Factores de Riesgo , Factores SexualesRESUMEN
BACKGROUND: In heart failure patients, diuretics cause renin-angiotensin-aldosterone system (RAS) activation, which may lead to increased morbidity and mortality despite short-term symptomatic improvement. AIM: To determine changes in RAS activation and clinical correlates following furosemide withdrawal in elderly heart failure patients without left ventricular systolic dysfunction. METHODS AND RESULTS: We performed clinical assessments and laboratory determinations of aldosterone, plasma renin activity (PRA), atrial natriuretic peptide (ANP), norepinephrine, and endothelin in 29 heart failure patients [aged 75.1+/-0.7 (mean+/-S.E.M.) years], before, 1 and 3 months after placebo-controlled furosemide withdrawal. Recurrent congestion occurred in 2 of 19 patients withdrawn, and in 1 of 10 patients continuing on furosemide. Three months after withdrawal, PRA had decreased -1.61+/-0.71 nmol/l/h (P<0.05). Decreases in aldosterone levels did not reach significance (-0.17+/-0.38 nmol/l). The decreases in PRA after withdrawal correlated with decreases in systolic (r(s)=0.61, P=0.020) and diastolic blood pressure (r(s)=0.80, P=0.01). Successful withdrawal was associated with increases in norepinephrine (+0.58+/-0.22 nmol/l) and ANP (+3.5+/-1.3 pmol/l) (P<0.05) after 1 month, but these changes did not persist after 3 months. Endothelin levels did not change in both groups. CONCLUSION: Successful furosemide withdrawal in elderly heart failure patients causes persistent decreases in RAS activation.