Paulo Bettencourt

N-Terminal–Pro-Brain Natriuretic Peptide Predicts Outcome After Hospital Discharge in Heart Failure Patients

Background—Heart failure (HF) is responsible for a huge burden in hospital care. Our goal was to evaluate the value of N-terminal–pro-brain natriuretic peptide (NT-proBNP) in predicting death or hospital readmission after discharge of HF patients. Methods and Results—We included 182 patients consecutively admitted to hospital because of decompensated HF. Patients were followed up for 6 months. The primary end point was death or readmission. Twenty-six patients died in hospital. The median admission NT-proBNP level was 6778.5 pg/mL, and the median level at discharge was 4137.0 pg/mL (P<0.001). Patients were classified into 3 groups: (1) decreasing NT-proBNP levels by at least 30% (n=82), (2) no significant modifications on NT-proBNP levels (n=49), and (3) increasing NT-proBNP levels by at least 30% (n=25). The primary end point was observed in 42.9% patients. Variables associated with an increased hazard of death and/or hospital readmission in univariate analysis were length of hospitalization, heart rate, signs of volume overload, no use of ACE inhibitors, higher NYHA class at discharge, admission and discharge NT-proBNP, and the change in NT-proBNP levels. The variation in NT-proBNP was the strongest predictor of an adverse outcome. Independent variables associated with an increased risk of readmission or death were signs of volume overload and the change in NT-proBNP levels. Conclusions—Variations in NT-proBNP levels are related to hospital readmission and death within 6 months. NT-proBNP levels are potentially useful in the evaluation of treatment efficacy and might help clinicians in planning discharge of HF patients. Whether therapeutic strategies aimed to lower NT-proBNP levels modify prognosis warrants future investigation.

Preliminary data on the potential usefulness of B-type natriuretic peptide levels in predicting outcome after hospital discharge in patients with heart failure

PURPOSE Among patients admitted for treatment of heart failure, we aimed to evaluate the value of B-type natriuretic peptide levels in predicting subsequent death or hospital readmission. SUBJECTS AND METHODS We observed and followed 50 consecutive patients admitted with decompensated heart failure. B-type natriuretic peptide levels were measured using an immunofluorometric assay at admission and at discharge. We followed patients for 6 months and ascertained readmissions for cardiovascular causes and death. RESULTS Forty-three patients were discharged. There were 20 events during follow-up (15 readmissions and 5 deaths). Mean (+/- SD) B-type natriuretic peptide levels decreased during the initial hospitalization, from 619 +/- 491 pg/mL to 328 +/- 314 pg/mL (P <0.001) among patients who were event free during follow-up, whereas declines were less marked among patients with hospital readmission or death (from 779 +/- 608 pg/mL to 643 +/- 465 pg/mL, P = 0.08). Among the 7 patients with in-hospital increases in B-type natriuretic peptide level, 6 had events, compared with 14 of the 36 patients whose levels declined (P = 0.04). An increase in B-type natriuretic peptide levels during hospital stay was associated with an increased event rate (hazard ratio [HR] = 3.3; 95% confidence interval [CI]: 1.3 to 8.8). Patients whose B-type natriuretic peptide level at discharge was above the median (321 pg/mL) had a somewhat higher rate of dying or being readmitted (HR = 2.3; 95% CI: 0.9 to 5.8). CONCLUSION These preliminary results in a small number of patients suggest that changes in B-type natriuretic peptide levels, as well as predischarge levels, are related to hospital readmission and death within 6 months.

Prognostic Value of High-Sensitivity C-Reactive Protein in Heart Failure: A Systematic Review

BACKGROUND Several studies have suggested that high-sensitivity C-reactive protein (hsCRP) is a strong independent predictor of acute myocardial infarction and cardiovascular death. In the specific heart failure (HF) context, a low-grade inflammatory state can contribute to HF progression. AIMS To perform a systematic review on the current knowledge about low-grade inflammation, as assessed by hsCRP, in the prediction of HF in general and in high-risk populations as well as its prognostic value in established HF. METHODS We used a computerized literature search in the Medline database using the following key words: C-Reactive Protein, Heart Failure, Cardiomyopathy, Cardiac Failure, Prognosis, and Death. Articles were selected if they had measurements of hsCRP in different patient samples and reference to outcomes in terms of morbidity and mortality. RESULTS hsCRP is associated with incident HF in general and high-risk populations and provides prognostic information in HF patients. In almost all studies, the association of hsCRP with clinical events was independent of other baseline variables known to influence morbidity and mortality. Very different cutoffs have been proposed in each context across studies. CONCLUSIONS The prognostic power of hsCRP, whether we consider incident HF or adverse outcomes in established HF, is consistent in different patient populations.

Chronic obstructive pulmonary disease in heart failure. Prevalence, therapeutic and prognostic implications.

BACKGROUND Patients with heart failure (HF) frequently have comorbidities. Frequency, prognostic, and therapeutic implications of chronic obstructive pulmonary disease (COPD) in HF are largely unknown. We aimed to assess the prevalence and prognostic implications of COPD in a sample of stable patients with HF and to determine the frequency of beta-blocker (bB) use and rate of withdrawal according to COPD coexistence. METHODS We conducted a retrospective cohort study including 186 patients followed in an outpatient HF clinic. All patients had left ventricular systolic dysfunction and a spirometry result. Patients were classified according to the GOLD guidelines. Treatment was instituted at the discretion of the attending physicians. Prognosis was compared between groups using Cox proportional hazards regression. The primary end point was death or all-cause hospitalization. RESULTS The prevalence of COPD was 39.2% (73/186). No difference was detected between the COPD and non-COPD groups in the rate of bB use (86.3% vs 87.6%, P = .97) and withdrawal (11.1% and 8.1%, P = .71). Mean follow-up was 14.2 +/- 8.8 months. The primary end point occurred in 71 (38.2%) patients--32 in the COPD group and 39 in the remaining (43.8% and 34.5%, respectively; hazard ratio 1.40, 95% CI 0.88-2.24). Severe COPD (GOLD stages III and IV) was associated with an adverse outcome (hazard ratio 2.10, 95% CI 1.05-4.22). CONCLUSIONS We observed a high COPD prevalence in stable patients with HF. Severe COPD predicted worse prognosis. Rates of bB use were high and rates of bB withdrawal were low; both were independent of COPD.

Prognostic information provided by serial measurements of brain natriuretic peptide in heart failure

BACKGROUND Brain natriuretic peptide (BNP) levels predict prognosis in heart failure patients. We aimed to evaluate if serial measurements of BNP can give additional prognostic information. METHODS Eighty-four patients with systolic dysfunction had two measurements of BNP with an interval of 8 to 12 months and were followed in order to register the occurrence of death. The study was observational and prospectively designed. During follow-up, patients were treated according to state of the art. Physicians were kept blind to BNP levels. RESULTS The median follow-up was 1190 days. The median initial BNP level was 260.4 pg/ml and decreased to 123 pg/ml in the second measurement (P=0.001). The decrease in BNP was significantly associated with ACE-i dosage and with the use of a beta-blocker. All-cause mortality was 20.2%. Patients whose initial BNP level was above the median had a significantly higher hazard of dying (HR 2.96, 95% CI 1.06-8.26). The same was observed for those whose BNP increased between the first and the second measurement (HR 2.64, 95% CI 1.00-7.00). In multivariable analysis, baseline BNP above the median and increasing BNP were associated with shorter survival. CONCLUSIONS Higher baseline BNP and the increasing levels during follow-up were independently associated with mortality. The decrease in BNP levels was proportional to ACE-i dosage and larger among patients on beta-blockers. These results confirm the prognostic information provided by BNP determination and suggest that serial measurements give additional prognostic information.

The effect of dietary sodium restriction on neurohumoral activity and renal dopaminergic response in patients with heart failure

This work evaluates the effect of a low‐sodium diet on clinical and neurohumoral parameters and on renal dopaminergic system activity in heart failure (HF) patients.

NT-proBNP and BNP: biomarkers for heart failure management.

Guidelines for the pharmacological treatment of heart failure (HF) are based on results from large clinical trials demonstrating benefit. State of the art pharmacological management of HF assumes that target doses should be the same as those used in trials. Thus equal doses are recommended for all in practical guidelines, but this strategy might not fit individual needs. NT‐proBNP and BNP emerged as potential biomarkers of clinical interest in HF management. NT‐proBNP and BNP are related to HF severity and to clinical status. NT‐proBNP and BNP are strongly associated with prognosis across the whole spectrum of HF patients. A pilot study has shown that NT‐proBNP‐guided therapy is associated with improved outcome in HF. Although at present there are still few data to make firm recommendations on the use of NT‐proBNP or BNP levels as biomarkers for HF management, future studies will provide further insight on this issue.

Evaluation of Brain Natriuretic Peptide in the Diagnosis of Heart Failure

A diagnosis of heart failure (HF) can be difficult, especially in patients with mild symptomatology. The purpose of this study was to evaluate the significance of brain natriuretic peptide (BNP) in the diagnosis of HF with systolic or isolated diastolic ventricular dysfunction. One hundred patients and 9 controls were included in the study. Eighty-five patients were diagnosed with HF, based on clinical and echocardiographic findings. BNP levels were accurate for the diagnosis of HF, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.92. In addition, BNP levels showed an excellent accuracy for the diagnosis of isolated diastolic HF (AUC = 0.89). These data suggest that the measurement of BNP levels may be helpful in the diagnosis of HF and in selecting patients for further evaluation. Furthermore, BNP measurement can play an important role in the diagnosis of isolated diastolic HF.

Neutrophil Gelatinase-Associated Lipocalin in the Diagnosis of Type 1 Cardio-Renal Syndrome in the General Ward

BACKGROUND AND OBJECTIVES The early identification of acute heart failure (HF) patients with type 1 cardio-renal syndrome should be the first step for developing prevention and treatment strategies for these patients. This study aimed to assess the performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C in the early detection of type 1 cardio-renal syndrome in patients with acute HF. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS One-hundred nineteen patients admitted with acute HF were studied. NGAL and creatinine were measured in the first hospitalization morning; creatinine was also measured at least after 48 to 72 hours. Physicians were blinded to NGAL and cystatin C levels. Type 1 cardio-renal syndrome was defined as an increase in the creatinine level of at least 0.3 mg/dl or 50% of basal creatinine. RESULTS Type 1 cardio-renal syndrome developed within 48 to 72 hours in 14 patients (11.8%). Admission NGAL levels were higher in these patients: 212 versus 83 ng/dl. At a cutoff value of 170 ng/L, NGAL determined type 1 cardio-renal syndrome with a sensitivity of 100% and a specificity of 86.7%. The area under the receiver-operating characteristic curve of NGAL was 0.93 and that of cystatin C was 0.68. CONCLUSIONS Above a cutoff value of 170 ng/L, NGAL predicts 48- to 72-hour development of type 1 cardio-renal syndrome with a negative predictive value of 100% and a positive predictive value of 50%. NGAL independently associates with type 1 cardio-renal syndrome and might be a useful biomarker in the early recognition of these patients.

Prognostic value of neutrophil gelatinase-associated lipocalin in acute heart failure

BACKGROUND The identification of patients at risk for worse outcome is still a challenge. We hypothesized that cystatin C, a marker of renal function, and neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute renal injury, would have a role in the prognostic stratification of these patients. METHODS We prospectively evaluated 121 patients admitted for acute HF. Serum NGAL and cystatin C levels were measured on the first morning after admission. The outcome measures used were the occurrence of death from all causes, and the combined endpoint defined as the first occurrence of either death or hospital admission. Patients were followed for up to 3 months. RESULTS The variables associated with a higher occurrence of death in a univariate approach were older age and higher levels of BNP, cystatin C and NGAL, and those associated with the occurrence of the combined endpoint were older age, Diabetes mellitus, lower GFR, type 1 cardio-renal syndrome, BNP, cystatin C and NGAL. BNP and NGAL remained independent predictors of the occurrence of both all-cause death and the combined endpoint. NGAL levels in the 75th percentile (>167.5 ng/mL) were associated with a 2.7-fold increase in the risk of death and a 2.9-fold increase in the risk of the first occurrence of either death or hospitalization. CONCLUSIONS Serum NGAL, a marker of acute renal injury, is an independent predictor of worse short term prognosis in patients with acute HF. This suggests a role of renal damage, apart from renal function, in the prognosis of these patients.