How often we need to measure brain natriuretic peptide (BNP) blood levels in patients admitted to the hospital for acute severe heart failure? Role of serial measurements to improve short-term prognostic stratification.

BACKGROUND: Brain natriuretic peptide (BNP) is increasingly used in the management of patients with heart failure (HF). It is still unclear how to use serial BNP measurement in HF. AIM: To evaluate the usefulness of three consecutive measurements of BNP in patients (pts) hospitalized for acute HF. METHODS: Clinical evaluation, BNP levels and echocardiography were assessed in 150 pts (67% males, age: 69+/-12 years; left ventricular ejection fraction: 34+/-14%) admitted for severe HF (NYHA class III-IV: 146/150). BNP measurements were obtained: at admission (basal, T0), at discharge (T1) and at first ambulatory control (T2), after optimization of medical therapy in those with discharge BNP level >250 pg/mL. End-points were death and hospital readmission during 6-month follow-up. RESULTS: According to BNP levels 3 groups of patients were identified: Group 1 (62 pts, 41%), in whom discharge (T1) BNP was high and persisted elevated at T2 despite aggressive medical therapy; at 6-month follow-up 72% died or were hospitalized for HF. Group 2 (36 pts, 24%), in whom discharge (T1) BNP was high but decreased after medical therapy (T2); death and HF-readmission were observed in 8 pts (26%). Group 3 (52 pts, 35%), in whom discharge (T1) BNP levels were <250 pg/mL and persisted below this value at T2; death and HF-hospital readmission were observed in 6 pts (12%). Event rate differences among groups were statistically significant (p<0.001). At Cox-analysis discharge BNP cutoff of 250 pg/mL was the only parameter predictive of a worse outcome. CONCLUSION: These data suggest that 3 BNP measurements, at admission, at discharge and few weeks later can allow to identify HF pts whom, despite a further potentiation of medical therapy, will present a worsening or even will die during short-term follow-up.

Plasma brain natriuretic peptide predicts short-term clinical outcome in heart failure patients with restrictive filling pattern.

OBJECTIVE: Plasma brain natriuretic peptide (BNP) is an important parameter of severity in congestive heart failure (CHF). We analyzed if BNP might stratify 6-month clinical outcome in outpatients with CHF with restrictive mitral filling pattern. METHODS: All subjects with New York Heart Association (NYHA) class II to IV and restrictive filling pattern were enrolled at hospital discharge after an acute decompensation. NYHA class, BNP, and echocardiogram for the evaluation of left ventricular ejection fraction (LVEF) and diastolic function were analyzed. Death and hospital readmission for CHF were the clinical events observed. RESULTS: A total of 250 patients (66% were male, mean age 73 years) were enrolled. The mean NYHA class was 2.5 +/- 0.6, LVEF was 38% +/- 15%, and mean deceleration time was 120 +/- 16 ms. The mean BNP was 643 +/- 566 pg/mL. During the 6-month follow-up, 35 patients (14%) died and 106 patients (42.4%) were readmitted for CHF (event group); in 109 patients (43.6%) no events were observed (no-event group). Higher NYHA class (2.7 +/- 0.6 vs 2.4 +/- 0.6, P = .001) and reduced LVEF (34% +/- 13% vs 42% +/- 17%, P = .01) but similar deceleration time (119 +/- 16 ms vs 122 +/- 17 ms, P = not significant) were observed in the event group. A higher level of mean BNP (833 +/- 604 pg/mL vs 397 +/- 396 pg/mL, P = .01) was recorded in the event group. The multivariate Cox analysis confirmed that LVEF (P = .04), NYHA class (P = .02), and plasma BNP (P = .0001) were associated with adverse short-term clinical outcome. CONCLUSION: Patients with CHF with a restrictive diastolic pattern had poor short-term clinical outcome. NYHA class and LVEF at discharge might predict cardiovascular events, but plasma BNP proved to be the strongest predictor.

B-type natriuretic Peptide-guided treatment for predicting outcome in patients hospitalized in sub-intensive care unit with acute heart failure.

BACKGROUND: Studies with natriuretic peptides have suggested that physicians do not treat heart acute failure (AHF) aggressively enough, and predischarge B-type natriuretic peptide (BNP) levels may be a useful reminder that more treatment is required. The purpose of this study was to demonstrate that variations in BNP levels during hormone-guided treatment and measured body hydration status enable the timing of the patient's discharge to be optimized. METHODS AND RESULTS: We retrospectively evaluated 186 patients admitted for AHF. All subjects underwent serial bioelectrical impedance analysis and BNP measurement. Therapy was titrated according to BNP value to reach a BNP value of <250 pg/mL, whenever is possible. A BNP value on discharge of <250 pg/mL (obtained in 54% of the patients) predicted a 16% event rate within 6 months, whereas a value >250 pg/mL was associated with a far higher percentage (78%) of adverse events. Among the former, no significant differences in event rate were seen in relation to the time necessary to obtain a reduction in BNP values below 250 pg/mL (14 versus 18%, chi-square = 0.3, NS). Cox regression showed that a BNP cutoff value of 250 pg/mL is the most accurate predictors of events. CONCLUSIONS: Our study demonstrates the usefulness of BNP in intrahospital stratification of AHF, in the decision-making process, and as a tool for "tailored therapy." Integrating this approach into the routine assessment of HF patients would allow clinicians to more accurately identify high-risk patients, who may derive increased benefit from intensive in-hospital management strategies.

Fall in readmission rate for heart failure after implementation of B-type natriuretic peptide testing for discharge decision: a retrospective study.

BACKGROUND: B-type natriuretic peptide is the most powerful predictor of long term prognosis in patients hospitalised with heart failure. On an outsetting basis, a decrease in B-type natriuretic peptide levels is associated to a decrease in event rate for outpatients managed using the neuro-hormone levels as the target in heart failure therapy. We have retrospectively checked whether the addition of pre-discharge B-type natriuretic peptide levels to a clinical-instrumental decisional score for discharge decision in patients admitted for heart failure reduced readmission rate for heart failure and related cost. METHODS: We studied two series of consecutive patients admitted to the Heart Failure Unit due to acute heart failure as a main diagnosis. One-hundred and forty-nine patients discharged on the basis of the sole clinical acumen were compared to one hundred and sixty-six subjects discharged adding B-type natriuretic peptide levels to the decisional score. RESULTS: During a six-month follow-up period, there were 52 readmissions (35%) among the clinical group (n=149) compared with 38 (23%) readmissions in the B-type natriuretic peptide group (n=166) (chi(2)=5.5; P=0.02). Survival did not differ between groups (87%). Changes in B-type natriuretic peptide values were correlated to clinical events: a B-type natriuretic peptide value on discharge of < or =250 pg/ml or a reduction of > or =30% in B-type natriuretic peptide values predicted a 23% event rate (death, plus readmission for heart failure), whereas a far higher percentage (71%) were observed in the remaining patients (chi(2)=32.7; P=0.001). Likewise, the overall costs of care were lower (-7%) in the B-type natriuretic peptide group: 2.781+/-923 vs 2.978+/-1.057 euros per patient respectively. CONCLUSIONS: our study suggest that the addition of pre-discharge B-type natriuretic peptide levels to a clinical-instrumental decisional score for discharge decision in patients admitted for heart failure may contribute to reduce the number of readmissions and related cost.

[BNP-guided therapy optimizes the timing of discharge and the medium term risk stratification in patients admitted for congestive heart failure]. / La terapia guidata dal BNP consente l'ottimizzazione del timing di dimissione e la stratificazione del rischio a medio termine nel paziente ricoverato per scompenso cardiaco.

BACKGROUND: Congestive heart failure (HF) is one of the most important cause of hospitalizations and is associated with high cost. Despite a consistent body of data demonstrating the benefits of drug therapy in HF, persistently high rates of readmission, especially within six months of discharge, continue to be documented. Neurohormonal activation characterizes the disease; plasma brain natriuretic peptide (BNP), is correlated with the severity of left ventricular dysfunction and relates to outcome. OBJECTIVE: The aim of the study was to evaluate if plasma levels of BNP would provide an index to guide drug treatment and to predict medium-term prognosis in HF patients (pts) after hospital discharge. METHODS AND RESULTS: We evaluated 200 consecutive pts (age 77 +/- 10 (35-96) years, 49% male versus 51% female) hospitalized for HF (DRG 127). Standard echocardiography was performed and left ventricular systolic/diastolic function was assessed; plasma BNP levels were measured with a rapid point-of-care assay (Triage BNP Test, Biosite Inc, San Diego, CA) on days 1 and after initial treatment. Using a cut-off of 240 pg/ml and/or changes in plasma BNP (days 2-3 after admission), 2 groups were identified: the low BNP group-responders (n = 68, BNP < 240 pg/ml and/or > or = 30% reduction) and the high BNP group-non responders (n = 132, BNP > or = 240 pg/ml and/or < 30% reduction). The high BNP group showed a different pattern of clinical variables according to the severity of the disease New York Heart Association (NYHA) functional class, left ventricular ejection fraction, ischemic etiology and age. A sustained elevation of plasma BNP (> 240 pg/mL) indicated the presence of a clinical unstable condition requiring further intervention whereas pts with low BNP values were discharged after 24 hours. During a mean follow-up period of 3 months, there were 62 cardiac events, including 15 cardiac deaths, 22 readmissions for worsening heart failure and 25 clinical decompensation requiring diuretic treatment. The incidence of clinical events was significantly greater in pts with higher levels of BNP (admission and discharge) than in those with lower levels (42% vs. 10%) and plasma values > 500 pg/ml identified a subgroup at high risk of death. CONCLUSIONS: The influence of BNP in the clinical course and prognosis of patients hospitalized for HF has not been studied. After initial treatment pts need to be risk stratified by means of the BNP test, to guide further management and to identify subjects with poor prognosis. An aggressive therapeutic and follow-up strategy may be justified for pts with high BNP levels and/or no changes after hospital admission for worsening HF. The changes in plasma BNP level at discharge were significantly related to cardiac events.

Rapid brain natriuretic peptide test and Doppler echocardiography for early diagnosis of mild heart failure.

BACKGROUND: The early identification of patients at risk for the development of clinical heart failure (HF) is a new challenge in an effort to improve outcomes. METHODS: We prospectively evaluated whether the combination of brain natriuretic peptide (BNP) measurements (Triage BNP test, Biosite Diagnostics) and echocardiography would effectively stratify patients with new symptoms in a cost-effective HF program aimed at early diagnosis of mild HF. A total of 252 patients were referred by 100 general practitioners. RESULTS: Among the study population, the median BNP value was 78 ng/L (range, 5-1491 ng/L). BNP concentrations were lower among patients without heart disease [median 15 ng/L (range, 5-167 ng/L); n = 96] than among patients with confirmed HF [median, 165 ng/L (22-1491 ng/L); n = 157; Mann-Whitney U-test, 12.3; P <0.001]. Patients were grouped into diastolic dysfunction [BNP, 195 (223) ng/L], systolic dysfunction [BNP, 290 (394) ng/L], and both systolic and diastolic dysfunction [BNP, 776 (506) ng/L]. In this model, a cutoff value of 50 ng/L BNP increases the diagnostic accuracy in predicting mild HF, avoiding 41 echocardiograms per 100 patients studied, with a net saving of 14% of total costs. CONCLUSIONS: Blood BNP concentrations, in a cost effective targeted screening, can play an important role in diagnosing mild HF and stratifying patients into risk groups of cardiac dysfunction.

B-type natriuretic peptide predicts postdischarge prognosis in elderly patients admitted due to cardiogenic pulmonary edema.

To examine the prognostic role of predischarge B-type natriuretic peptide (BNP) levels in elderly patients admitted to the hospital due to cardiogenic pulmonary edema, 203 patients consecutively admitted to the Heart Failure Unit of the Cardiology Department were retrospectively evaluated. The primary clinical end point selected was a combination of: 1) deaths; plus 2) readmissions to the hospital for heart failure in the 6 months after discharge. Thirty-one deaths (15.3%) and 44 readmissions for heart failure (21.7%) were recorded. Cox multivariate regression analysis confirmed that BNP cutoff values (identified on receiver-operated curve analysis) are the most accurate predictor of events. Hazard ratios (HRs) increased from the lowest, for BNP < or = 200 pg/mL (HR=1), through BNP 201-499 pg/mL (HR=2.3200; p=0.0174), to the highest, for BNP > or = 500 pg/mL (HR=3.6233; p=0.0009). This study demonstrates that BNP is useful in predischarge risk stratification of elderly patients with cardiogenic pulmonary edema.

Early diagnosis of congestive heart failure: clinical utility of B-type natriuretic peptide testing associated with Doppler echocardiography.

OBJECTIVE: B-type natriuretic peptide (BNP) has emerged as an important diagnostic serum marker of congestive heart failure (CHF). The aim of this study was to evaluate whether BNP measurement associated with echocardiography could effectively stratify patients with new symptoms as part of a cost-effective heart failure programme based on cooperation between hospital cardiologists and primary care physicians. METHODS: Patients were referred to the cardiology clinic by general practitioners in case of clinical suspect of CHF. All patients underwent clinical examination, transthoracic echocardiography and plasma determination of BNP. Systolic dysfunction was defined as a left ventricular ejection fraction < 45%; diastolic dysfunction was defined as a preserved systolic function with signs of diastolic impairment. RESULTS: Three hundred and fifty-seven subjects were examined (50% males, mean age 73 years). BNP concentration was 469 +/- 505 pg/ml in the 240 patients diagnosed with CHF, compared with 43 +/- 105 pg/ml in the 117 patients without CHF (P = 0.001). CHF patients were grouped into those with diastolic dysfunction (n = 110; BNP 373 +/- 335 pg/ml), systolic dysfunction (n = 108; BNP 550 +/- 602 pg/ml), and both systolic and diastolic dysfunction (n = 22; BNP 919 +/- 604 pg/ml). At receiver operating characteristic analysis, the optimal BNP cut-off level for diagnosing CHF was 80 pg/ml (sensitivity 84%, specificity 91%). According to cost analysis, this cut-off level might provide a cost saving of 31% without affecting diagnostic accuracy. CONCLUSIONS: In patients referred by general practitioners for suspected CHF, plasma BNP levels might help to stratify subjects into different groups of cardiac dysfunction.

B-type natriuretic peptide can predict the medium-term risk in patients with acute heart failure and preserved systolic function.

BACKGROUND: Half of patients with heart failure (HF) have preserved left ventricular ejection fraction (LVEF). Neurohormonal activation characterizes the disease and measurement of plasma B-type natriuretic peptide (BNP) indicates the severity of left ventricular dysfunction. The purpose of this study was to test the hypothesis that measurement of BNP levels in ambulatory patients with HF and preserved LVEF can predict the occurrence of cardiovascular events in the next 6 months. METHODS AND RESULTS: We enrolled 233 consecutive patients admitted to the Outpatient Heart Failure Clinic (OHFC), on stabilization after an episode of acute HF, with a LVEF > 50%. Standard echocardiography was performed and left ventricular systolic/diastolic function was assessed. Plasma BNP levels were measured on admission to OHFC. Patients were followed for 6 months; the main endpoint combined cardiovascular death or readmission for HF. Among the 233 patients discharged, 48 endpoints occurred (death: n = 15; readmission: n = 33). Receiver operated curve analysis shows that BNP levels are strong predictors of subsequent events (area under the curve = 0.84; CI = 0.78-0.88). Multivariate Cox regression showed that the cutoff values identified by receiver operated curve analysis (200-500 pg/mL) of the neurohormone are the most accurate predictors of events: HR = 2.2 (P < .04) and HR = 5.8 (P < .001), respectively, for 201-499 pg/mL and > or = 500 pg/mL ranges. CONCLUSION: BNP level is a strong predictor for cardiovascular mortality and early readmission in patients with diastolic HF. The results suggest that BNP levels might be used successfully to guide the intensity of follow-up after a decompensation, because increased BNP levels were associated with a progressively bad prognosis.

Prognostic value of plasma brain natriuretic peptide, urea nitrogen, and creatinine in outpatients >70 years of age with heart failure.

This study analyzed the relevance of plasma brain natriuretic peptide (BNP) and echocardiography in predicting cardiovascular events in a large population >70 years old with heart failure (HF). Three hundred four outpatients with HF (51.6% men, mean age 78.6) underwent transthoracic echocardiography and plasma BNP testing shortly before hospital discharge. Echocardiography was intended to reveal systolic dysfunction (left ventricular [LV] ejection fraction [EF] <50%) or diastolic dysfunction (EF > or =50% and abnormalities of ventricular relaxation). During 6-month follow-up, all-cause death and readmission were assessed. One hundred seventeen patients had diastolic dysfunction with preserved systolic LV function, and 187 had systolic dysfunction. At 6-month clinical follow-up, 33 subjects (10.9%) had died, and 62 (20.4%) needed readmission for cardiac decompensation. In all patients, univariate logistic regression demonstrated significant correlations between age (r = 0.14, p = 0.01), plasma BNP (r = 0.36, p = 0.0001), the EF (r = 0.16, p = 0.003), urea nitrogen (r = 0.35, p = 0.0001), serum creatinine (r = 0.27, p = 0.0001), and New York Heart Association (NYHA) class (r = 0.35, p = 0.0001) and the occurrence of cardiovascular events. In patients with HF in NYHA class III or IV, a BNP cut-off level of 200 pg/ml identified different outcomes (BNP <200 pg/ml in 1 of 20 events vs BNP >200 pg/ml in 55 of 85 events, p = 0.0001). In patients with HF who were >70 years old, BNP, NYHA class, and renal function predicted adverse outcome. In patients with severe HF, BNP was better than NYHA class in predicting future events.

The NT-proBNP assay identifies very elderly nursing home residents suffering from pre-clinical heart failure.

BACKGROUND: Little is known about the prevalence of heart failure among very old people, although hospitalisation rates for chronic heart failure are very high. Recently, brain natriuretic peptides have emerged as important diagnostic and prognostic serum markers for congestive heart failure. AIMS: The main purpose of our study was to determine whether there is a cut-off for NT-proBNP for detecting the echocardiographic features of left ventricular systolic and/or diastolic dysfunction and clinical heart failure among old people living in nursing homes. Secondarily, we investigated the medium-term prognostic power of the neurohormone levels. METHODS: We screened 101 old people (80% females, aged 84+/-9 years) from two nursing homes. We prospectively evaluated whether we could effectively stratify patients using a combination of (1) restrictive clinical criteria, (2) NT-proBNP measurements (Elecsys System, Roche Diagnostics) and (3) echocardiography for all patients. RESULTS: Forty-two percent of the subjects had left ventricular dysfunction: 11% systolic, 23% diastolic and 8% both systolic and diastolic. The mean NT-proBNP concentration was 2806+/-7028 pg/ml in the 42 patients with left ventricular systolic and/or diastolic dysfunction, compared with 365+/-456 pg/ml in the 59 patients with normal left ventricular function (p<0.01, Z=-4.8 Mann-Whitney U test). The neurohormone proved to be a good predictor of events within 6 months [area under the receiver-operated curve (ROC)=0.79]. CONCLUSIONS: Blood NT-proBNP concentrations can play an important role in stratifying old people into left ventricular dysfunction risk groups. The neurohormone is an independent marker for death or admission for heart failure in the medium term.

[Is early discharge possible in patients with uncomplicated heart failure? Cost-efficacy analysis]. / E possibile dimettere precocemente il paziente con scompenso cardiaco non complicato? Un'analisi costo-efficacia.

BACKGROUND: Heart failure is a common indication for admission to the hospital among old adults. The hospital stay for uncomplicated heart failure is often too long. We hypothesized that a rapid optimization of care and a guideline-based approach would allow an early discharge of patients, still maintaining a greater quality and efficiency of care. METHODS: We conducted a randomized trial of the effect of a guideline-based intervention on rates of readmission within 90 days of hospital discharge and costs of care for patients who were hospitalized for heart failure and discharged after 4 days of stay. The intervention consisted of early echocardiography, aggressive diuretic therapy, comprehensive education of the patient and family, a prescribed diet, and intensive application of the guidelines' recommendations on pharmacological therapy. Fifty early-discharged patients were compared to 50 concurrent normally-discharged patients. RESULTS: Average length of stays during baseline admissions was shorter for early-discharged patients respect to controls (3.9 +/- 0.8 vs 7.0 +/- 1.9 days, p < 0.001). At discharge, when compared with control patients, early-discharged patients were similarly prescribed and/or were taking similar dosages of ACE-inhibitors (84 vs 80% and 17 vs 15 mg/die, p = NS), beta-blockers (64 vs 56% and 14 vs 16 mg/die, p = NS), spironolactone (86 vs 70% and 36 vs 32 mg/die, p = NS), digoxin (74 vs 70% and 0.18 vs 0.15 mg/die, p = NS), and losartan (8 vs 6% and 50 mg/die for both groups, p = NS). Hospital readmission rates and days of stay were similar between groups (6 vs 8% and 18 vs 26 days, respectively for study and control patients), whilst the overall costs of care were lower for early-discharged patients (289 vs 449 [symbol: see text] per patient per month), due to the shorter length of stay at baseline. Survival for 90 days was achieved in 47 patients both in the study and control groups (p = NS). CONCLUSIONS: Our study showed that patients admitted for heart failure may be safely discharged 4 days after admission. An in-hospital guideline-based management of patients allows relevant cost savings, reducing hospital readmission for heart failure.