***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVES The purpose of this study was to compare the effects of N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided therapy with those of intensive clinical management and with usual care ( UC ) on clinical outcomes in chronic symptomatic heart failure . BACKGROUND Initial trial results suggest titration of therapy guided by serial plasma B-type natriuretic peptide levels improves outcomes in patients with chronic heart failure , but the concept has not received widespread acceptance . Accordingly , we conducted a longer-term study comparing the effects of NT-proBNP-guided therapy with those of intensive clinical management and with UC of patients with heart failure . METHODS Three hundred sixty-four patients admitted to a single hospital with heart failure were r and omly allocated 1:1:1 ( stratified by age ) to therapy guided by NT-proBNP levels or by intensive clinical management , or according to UC . Treatment strategies were applied for 2 years with follow-up to 3 years . RESULTS One-year mortality was less in both the hormone- ( 9.1 % ) and clinical ly-guided ( 9.1 % ) groups compared with UC ( 18.9 % ; p = 0.03 ) . Three-year mortality was selectively reduced in patients < or=75 years of age receiving hormone-guided treatment ( 15.5 % ) compared with their peers receiving either clinical ly managed treatment ( 30.9 % ; p = 0.048 ) or UC ( 31.3 % ; p = 0.021 ) . CONCLUSIONS Intensive management of chronic heart failure improves 1-year mortality compared with UC . Compared with clinical ly guided treatment and UC , hormone-guided treatment selectively improves longer-term mortality in patients < or=75 years of age . ( NT-proBNP-Assisted Treatment To Lessen Serial Cardiac Readmissions and Death [ BATTLESCARRED ] ; Australian New Zeal and Clinical Trials Registry 12605000735651 ) Background —The prognostic value of serum sodium in patients hospitalized for worsening heart failure has not been well defined . Methods and Results —The Outcomes of a Prospect i ve Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure ( OPTIME-CHF ) study r and omized 949 patients with systolic dysfunction hospitalized for worsening heart failure to receive 48 to 72 hours of intravenous milrinone or placebo in addition to st and ard therapy .  In a retrospective analysis , we investigated the relationship between admission serum sodium and the primary end point of days hospitalized for cardiovascular causes within 60 days of r and omization , as well as the secondary end points of in-hospital mortality , 60-day mortality , and 60-day mortality/rehospitalization . The number of days hospitalized for cardiovascular causes was higher in the lowest sodium quartile : 8.0 ( 4.5 , 18.5 ) versus 6 ( 4 , 13 ) versus 6 ( 4 , 11.5 ) versus 6 ( 4 , 12 ) days ( P<0.015 for comparison with the lowest quartile ) . Lower serum sodium was associated with higher in-hospital and 60-day mortality : 5.9 % versus 1 % versus 2.3 % versus 2.3 % ( P<0.015 ) and 15.9 % versus 6.4 % versus 7.8 % versus 7 % ( P=0.002 ) , respectively . There was a trend toward higher mortality/rehospitalization for patients who were in the lowest sodium quartile . Multivariable-adjusted Cox proportional hazards analysis showed that serum sodium on admission , when modeled linearly , predicted increased 60-day mortality : sodium ( per 3-mEq/L decrease ) had a hazard ratio of 1.18 with a 95 % CI of 1.03 to 1.36 ( P=0.018 ) . Conclusions —In patients hospitalized for worsening heart failure , admission serum sodium is an independent predictor of increased number of days hospitalized for cardiovascular causes and increased mortality within 60 days of discharge OBJECTIVES This study was design ed to investigate whether selected baseline variables and early response markers predict the effects of cardiac resynchronization therapy ( CRT ) on long-term mortality . BACKGROUND Cardiac resynchronization therapy reduces long-term morbidity and mortality in patients with moderate or severe heart failure and markers of cardiac dyssynchrony , but not all patients respond to a similar extent . METHODS In the CARE-HF ( Cardiac Resynchronization in Heart Failure ) study , 813 patients with heart failure and markers of cardiac dyssynchrony were r and omly assigned to receive or not receive CRT in addition  to  pharmacological treatment  and were followed for a median of 37.6 months . A model including assigned treatment , 15 pre-specified baseline variables , and 8 markers of response at 3 months was constructed to predict all-cause mortality . RESULTS On multivariable analysis , plasma concentration of amino terminal pro-brain natriuretic peptide ( univariate and multivariable model chi-square test : 105.0 and 48.4 ; both p < 0.0001 ) and severity of mitral regurgitation ( chi-square test : 44.0 and 17.9 ; both p < 0.0001 ) at 3 months , regardless of assigned treatment , were the strongest predictors of mortality . Ischemic heart disease as the cause of ventricular dysfunction ( chi-square test : 34.9 and 7.4 ; p < 0.0001 and p = 0.0066 ) , being in New York Heart Association functional class IV ( chi-square test : 18.8 and 9.6 ; p < 0.0001 and p = 0.0020 ) , or having less interventricular mechanical delay ( chi-square test : 29.8 and 8.8 ; p < 0.0001 and p = 0.0029 ) at baseline all predicted a worse outcome . However , the reduction in mortality in patients assigned to CRT was similar before ( hazard ratio : 0.602 ; 95 % confidence interval : 0.468 to 0.774 ) and after ( hazard ratio : 0.679 ; 95 % confidence interval : 0.494 to 0.914 ) adjustment for variables measured at baseline and at 3 months . CONCLUSIONS Patients who have more severe mitral regurgitation or persistently elevated amino terminal pro-brain natriuretic peptide  despite treatment for heart failure , including CRT , have a higher mortality . However , patients assigned to CRT had a lower mortality even after adjusting for variables measured before and 3 months after intervention . The effect of CRT on mortality can not be usefully predicted using such information . ( CARE-HF CArdiac Resynchronization in Heart Failure ; NCT00170300 ) Brain natriuretic peptide ( BNP ) is a cardiac ventricular hormone that may be a sensitive and specific marker of changes in ventricular function . In a prospect i ve , r and omised open trial with 16 patients followed for 6 months after first Q wave anterior myocardial infa rct ion we set out to determine : whether BNP concentrations are raised acutely , the effect on circulating BNP of angiotensin-converting enzyme ( ACE ) inhibition , how BNP and atrial natriuretic peptide ( ANP ) concentrations compared as correlates of left-ventricular ejection fraction , and whether plasma BNP concentrations could distinguish patients with low ( < 40 % ) and relatively preserved ( > 40 % ) ejection fractions . Plasma concentrations of BNP measured on days 2 , 7 , 8 , 42 , and 180 postinfa rct ion were significantly raised in patients compared with normal controls and to a proportionately greater degree than ANP concentrations . Treatment with placebo ( n = 8) or oral captopril ( n = 8) from day 8 result ed in significantly lower BNP concentrations at days 42 ( p = 0.05 ) and 180 ( p < 0.05 ) in the captopril-treated group . Compared with ANP , BNP concentrations were much more strongly correlated with radionuclide-measured left-ventricular ejection fraction at days 2 , 42 , and 180 . All 8 patients with baseline ( day 2 ) ejection fractions of 40 % or above had plasma BNP concentrations less than 10 pmol/L , whereas the 8 patients with ejection fractions less than 40 % had BNP concentrations greater than 10 pmol/L. Our findings suggest that measurements of circulating BNP may identify those patients with significant left-ventricular dysfunction who have been highlighted by the Survival and Ventricular Enlargement study as likely to benefit from long-term ACE inhibition after myocardial infa rct ion AIMS Plasma levels of individual neurohormones ( NH )  have been proposed as reliable indicators for risk stratification of patients with heart failure ( HF ) . Mainly because of small sample size , the predictive value of different NH has never been compared , while taking into account demographic , clinical and echocardiographic markers of risk in HF . METHODS AND RESULTS Plasma brain natriuretic peptide ( BNP ) , norepinephrine ( NE ) , renin activity ( PRA ) , aldosterone ( aldo ) and endothelin  were measured in 4300 patients before r and omization in Val-HeFT . Univariate and multivariate Cox proportional hazard analyses were performed to investigate the relationship between NH and two primary study outcomes , mortality and combined mortality and morbidity ( M/M ) . Higher baseline values for all NH were related to mortality and M/M , with univariate hazard ratios ranging from 1.13 [ 95 % CI 0.99 - 1.30 ] ( aldo ) to 2.47 [ 2.13 - 2.87 ] ( BNP ) for mortality , and from 1.24 [ 1.11 - 1.39 ] ( aldo ) to 2.56 [ 2.28 - 2.89 ] ( BNP ) for M/M. In multivariate analyses , BNP had the strongest association with outcome , followed by NE and PRA . Patients with more activation of renin-angiotensin-aldosterone system tended to show greater benefit from valsartan ; but the trend was not statistically significant . CONCLUSION All the NHs evaluated in 4300 patients with stable moderate to severe HF were found to be significant markers of outcome , despite therapy with ACEi , BB and r and omization to an angiotensin receptor blocker or placebo . Several of these markers have been implicated as contributors to progression of HF , but BNP , which is thought to be protective , was the most powerful indicator for poor outcome OBJECTIVES We investigated whether plasma amino-terminal pro-brain natriuretic peptide ( NT-proBNP ) , a marker of cardiac dysfunction and prognosis measured in CORONA ( Controlled Rosuvastatin Multinational Trial in Heart Failure ) , could be used to identify the severity of heart failure at which statins become ineffective . BACKGROUND Statins reduce cardiovascular morbidity and mortality in many patients with ischemic heart disease but not , overall , those with heart failure . There must be a transition point at which treatment with a statin becomes futile . METHODS In CORONA , patients with heart failure , reduced left ventricular ejection fraction , and ischemic heart disease were r and omly assigned to 10 mg/day rosuvastatin or placebo . The primary composite outcome was cardiovascular death , nonfatal myocardial infa rct ion , or stroke . RESULTS Of 5,011 patients enrolled , NT-proBNP was measured in 3,664 ( 73 % ) . The midtertile included values between 103 pmol/l ( 868 pg/ml ) and 277 pmol/l ( 2,348 pg/ml ) . Log NT-proBNP was the strongest predictor ( per log unit ) of every outcome assessed but was strongest for death from worsening heart failure ( hazard ratio [ HR ] : 1.99 ; 95 % confidence interval [ CI ] : 1.71 to 2.30 ) , was weaker for sudden death ( HR : 1.69 ; 95 % CI : 1.52 to 1.88 ) , and was weakest for atherothrombotic events ( HR : 1.24 ; 95 % CI : 1.10 to 1.40 ) . Patients in the lowest tertile of NT-proBNP had the best prognosis and , if assigned to rosuvastatin rather than placebo , had a greater reduction in the primary end point ( HR : 0.65 ; 95 % CI : 0.47 to 0.88 ) than patients in the other tertiles ( heterogeneity test , p = 0.0192 ) . This reflected fewer atherothrombotic events and sudden deaths with rosuvastatin . CONCLUSIONS Patients with heart failure due to ischemic heart disease who have NT-proBNP values < 103 pmol/l ( 868 pg/ml ) may benefit from rosuvastatin OBJECTIVES The aim of this multicenter study was to evaluate the prognostic impact of a therapeutic strategy using plasma brain natriuretic peptide ( BNP 
    Output:
    
Natriuretic peptides , including B-type natriuretic peptide ( BNP ) and N-terminal-proBNP ( NT-proBNP ) , have emerged as powerful markers of cardiovascular risk in patients with heart failure.1  Circulating natriuretic peptide ( NP ) levels add incremental prognostic value to st and ard clinical risk stratification algorithms for both ambulatory and hospitalized heart failure patients , with a steady increase in the risk of mortality and recurrent heart failure hospitalization as NT-proBNP levels rise above 1000 pg/mL.2–5 A systematic review of 19 studies of patients with heart failure demonstrated that for every 100-pg/mL rise in BNP concentration , there was a corresponding 35 % increase in the relative risk of death.6 Response by Januzzi and Troughton on p 516 Beyond the prognostic value of a single NP measurement , changes in NP concentrations over time may help to further stratify risk.2,7 Reductions in NP levels , whether achieved spontaneously or through application of appropriate medical therapy , appear to be associated with improvement in clinical outcomes .8,9 In the Valsartan Heart Failure Trial , subjects with the largest proportional reductions in BNP levels at 4 months after r and omization experienced the best outcomes , whereas those with the greatest increase in BNP levels experienced the highest event rates.7 Among patients hospitalized with decompensated heart failure , both predischarge NP levels and the relative change in NP levels during hospital treatment are strong predictors of the risk for death or hospital readmission at 6 months.8,10,11 In addition to their association with risk for adverse cardiovascular outcomes , circulating levels of NP appear to vary in relationship to the biology of heart failure progression .
NP levels tend to rise during acute heart failure decompensation and to fall with successful treatment in a pattern that mirrors reductions in filling pressure , improvements in left ventricular structure and function ,