risk stratification in patients suffering from heart failure ( hf ) is based on a variety of clinical and laboratory variables . indeed , several prognostic parameters have been identified , including age , new york heart association ( nyha ) class , renal function , comorbidity such as atrial fibrillation , diabetes mellitus , and ischemic heart disease . in acute decompensated heart failure ( adhf ) episodes , the degree of renal dysfunction and arterial hypotension easily stratified patients with worst clinical outcome . a single determination of brain natriuretic peptide ( bnp ) plasma level represents a reliable risk stratification procedure and its increase is considered a sensitive diagnostic marker of left ventricular dysfunction having a clear prognostic relevance in predicting cardiovascular events in hf patients . in discharged hf patients the combination of galectin-3 and nt - probnp seemed to be the best predictor for short - term ( 60-day ) mortality in the pride study . furthermore , in the substudy of coach galectin-3 demonstrated to be a robust independent marker of cardiovascular mid - term ( 18-month ) outcome in hf patients with much stronger relevance in patients with preserved left ventricular ejection fraction ( lvef ) in comparison with reduced lvef . finally , shah et al documented as a single determination of galectin-3 during an adhf hospitalization predicted mortality ( in 63% being above the median value ) in a longer follow - up ( 4-year ) independently of echocardiographic parameters of hf severity . advanced hf patients constitute a challenge for cardiologists according to their high mortality and rehospitalization rate . therefore , a strategy for stratify planning tailored clinical follow - up in those patients seems to be mandatory . the objective of this study was to analyze the value of a single , predischarged determination of plasma galectin-3 alone and in correlation with plasma bnp in predicting mid - term clinical outcome in worst clinical outcome [ frequent - flyers ( ff )  +  death ] chronic hf patients discharged after an adhf episode . all chronic hf subjects discharged after an acute episode of cardiac decompensation were enrolled in an out - patient clinic follow - up . patients were classified as having chf according to the criteria commonly accepted in literature , namely the presence of 2 major criteria or 1 major criterion + 2 minor criteria according to the framingham score and an nyha functional class ii , iii , or iv , due to an exacerbation of symptoms with at least 1 class deterioration . the presence of inadequate echo images or no adherence to the therapy and disagreement with the periodical follow - up were considered exclusion criteria . all patients underwent a clinical examination , a 12-lead electrocardiogram , plasma determination of bnp , water composition ( on admission and at discharge ) , 6-minute walk test , noninvasive cardiac output , and a transthoracic echocardiogram within 48  hours upon hospital discharge . the criteria for discharging hf patients were the following : subjective improvement on the basis of nyha class , with no orthopnea ; 90  <  sbp  <  120  mm  hg ; heart rate  <  100  bpm ; pulse oxymetry in ambient air  >  90% ; and diuresis  > serum creatinine was checked on clinical stability . according to the study protocol , hf out - patients were checked at 3 and 6 months after discharge . in case of worsening of the clinical status ( worsening dyspnea , body weight increase or edema , and cardiac arrhythmias ) , the therapy prescribed in those patients included angiotensin - converting enzyme inhibitors ( enalapril , ramipril ) , angiotensin receptor blockade ( valsartan ) in case of enalapril / ramipril intolerance , beta - blockers ( bisoprolol ) , digoxin , loop diuretic , and spironolactone at low dose . for beta - blockers , angiotensin - converting enzyme inhibitors , and angiotensin receptor blockade , the patients echocardiograms were performed with a vivid 7 computed sonography system ( ge medical systems , waukesha , wi ) according to the recommendations of the american society of echocardiography . two - dimensional apical 2- and 4-chamber views were used for volume measurements ; left ventricle ejection fraction ( lvef ) was calculated with a modified simpson method using biplane apical ( 2- and 4-chamber ) views . the left ventricle ( lv ) end - diastolic volume and all the echo examinations were performed by expert operators blinded to the results of bnp assay ; the intraobserver variability in the evaluation of lvef was found to be<5% . echocardiographic measurements , including lv end - diastolic diameter and the diastolic thickness of the ventricular septum and the posterior lv wall , were determined according to the american society echocardiography recommendations . the definition of restrictive filling pattern ( grade 3 ) was a predefined modification of classifications used in prior studies : e / a    2 , dt    150  msec , s / d ratio  <  1 , and ar  >  35  cm / sec . the other diastolic filling patterns were classified as : grade 1 ( abnormal relaxation ) when e / a  <  1 with a dt  >  240  ms ; grade 2 ( pseudonormal ) when e / a between 0.75 and 1.5 , dt between 160 and 240  ms and finally e / ea  >  15 . the doppler sample was set 1 to 2  mm under the free edges of the mitral valve using the apical 4-chamber projection ; an average of 5 beats was considered . in patients suffering from atrial fibrillation at the time of the echocardiogram , the diastolic function was classified as : restrictive pattern ( dt    150  msec ) or indeterminate ( dt  >  150  msec ) . the presence of this diastolic pattern with an lvef  >  50% was defined as an isolated diastolic dysfunction . the tricuspid annular plane systolic excursion was measured in a 4-chamber view by placing the 2d cursor at the tricuspid lateral annulus and measuring the distance of systolic annular rv excursion along a longitudinal line defining the end of systole as the end of the t wave in the electrocardiogram . systolic right ventricular ( or pulmonary artery ) pressure was calculated using the modified bernoulli equation : pap = 4    ( tricuspid systolic jet )  +  10  mm  hg ( estimated right atrial pressure ) . whole blood was obtained from subjects via standard venipuncture just before discharging , when patients were considered stabilized after an acute hf admission . serum was isolated within 60  minutes of sampling , shipped overnight refrigerated and stored at 70 colder until the time of testing . this assay has a lower limit of detection of 1.13  g / l and demonstrated no cross - reactivity with other galectins or collagens . the bedside triage b type natriuretic fluorescence immunoassay ( alere diagnostics , ca ) was also used in all population studied . the triage meter is used to measure bnp concentration by detecting a fluorescent emission that reproduces the amount of bnp in the blood . a total of 250  l of whole blood was added to the disposable device , then the cells were filtered and separated from the plasma with bnp , which entered a reaction chamber , containing fluorescent bnp antibodies . after 2-minute incubation , the bnp  antibody mixture migrated to an area containing immobilized antibodies and remained fixed . performance characteristics of the test : assay range 5 to 5000  pg / ml ; total cv 9.2% to 11.4% . death by any cause , cardiac transplantation , and worsening hf requiring readmission to the hospital were considered cardiovascular events . data regarding the occurrence of cardiovascular events were collected from multiple sources in all patients ( follow - up consultations or phone calls ) . the study protocol conforms to the ethical guidelines of the 1975 declaration of helsinki ; an informed consent was required for every patients and our local ethic committee approved this study . categorical data were presented as numbers ( percent ) , continuous data as mean    standard deviation ( sd ) for normally distributed variables . wilk test was used to evaluate whether or not the distribution of the variables was normal . the mean values of any 2 groups were compared using the student t test and the means of more 2 groups were assessed using analysis of variance followed by the bonferroni multiple - comparison test . the pearson  test and the fischer exact test were used for comparing categorical variables ( nyha class , cardiovascular events ) . the spearman rank - order correlation coefficient ( rho ) was used to measure the strength and direction of association between galectin-3 and glomerular filtrate and between galectin-3 and bnp . event - free survival was estimated by kaplan  meier method , and curves were compared with the log - rank test . all statistical calculations were performed on stata software ( version 11.0 stata corporation , college station , tx ) . categorical data were presented as numbers ( percent ) , continuous data as mean    standard deviation ( sd ) for normally distributed variables . wilk test was used to evaluate whether or not the distribution of the variables was normal . the mean values of any 2 groups were compared using the student t test and the means of more 2 groups were assessed using analysis of variance followed by the bonferroni multiple - comparison test . the pearson  test and the fischer exact test were used for comparing categorical variables ( nyha class , cardiovascular events ) . the spearman rank - order correlation coefficient ( rho ) was used to measure the strength and direction of association between galectin-3 and glomerular filtrate and between galectin-3 and bnp . all statistical calculations were performed on stata software ( version 11.0 stata corporation , college station , tx ) . eighty - three patients ( 67 males , age 73.2    8.6 years old ) were discharged after a new diagnosis of chf or for acute decompensation in chronic chf and were requested to enter the study , signing an informed consent and were enrolled ( mean follow - up 11.6    5.2 months ; range 422 months ) . the etiology of hf was interpreted as : 35 ischemic ( 42.1% ) , 23 cardiomyopathy ( 28% ) , 22 hypertensive ( 26.5% ) , and finally 3 others ( 3.6% ) . during the follow - up 48 events ( 57.8% ) twenty - eight hf patients were hospitalized 2  times / year ( range 24  times / year ) and were defined ff ( 8 patients out of 28 died because of a cardiac death ) . therefore , the group with a worst clinical prognosis ( ff  +  cardiac death ) was formed by 33 patients ( 39.8% ) . although the events group population seemed to be not older or hyponatremic , the predischarge value of galectin-3 and plasma bnp were significantly higher ( p = 0.027 and 0.005 , respectively ) . in hf patients with worst clinical outcome a more severe impairment in lv systolic function ( p = 0.0037 ) emerged , without a significant lv enlargement or a right ventricular involvement . however , the diastolic filling pattern evaluated with echocardiography seemed to be not different in the 2 groups . at univariate analysis , a negative spearman coefficient ( rho ) of 0.38 indicates a moderate decreasing monotonic trend between galectin-3 and glomerular filtrate ( p = 0.0055 ) , while a positive correlation ( rho = 0.44 , p = 0.002 ) between galectin-3 and bnp was detected . at multivariate analysis , only galectin-3 showed a significant correlation with worst clinical prognosis ( p = 0.047 ; odds ratio 1.05 , confidence interval 1.0011.10 ) , independently to age and renal function , being for each galectin-3 increment of 1  ng / ml determined an increase of 5% in probability of cardiovascular events . choosing adequate cut - off points , the kaplan  meier curves depicted the powerful stratification using a galectin-3 level of 17.6  pg / ml ( fig . 1 ) added to plasma bnp level of 500  pg / ml ( log rank 5.65 ; p = 0.017 ) . differences between main parameters in event group ( ff  +  death ) versus control group . the kaplan  meier event - free curve ( with the log - rank ) according to the selected cut - off values for galectin-3 ( 17.6  ng / ml ) and brain natriuretic peptide ( bnp ) ( 500  pg / ml ) . elderly patients with chronic hf represent most of subjects ( 70% ) admitted to hospitals for acute cardiac decompensation ; the length of hospitalization lasts usually > 2 weeks in geriatric wards and readmissions are frequent . recently , the optimize - hf study included more than 30,000 hf patients discharged from 215 hospitals , described a short length of hospitalization ( 4 days ) but a 21.3% of rate of readmission within 30-day . this study evidenced as an early ( 1-week ) outpatient clinical follow - up after discharged helped hf patients to undergo to a lower probability to be readmitted within 30-day . in the in - hf outcome , an italian nationwide registry , the 30-day mortality after discharging for an acute episode of hf proved to be 2.8% and hospital readmission 6.2% . older age , longer in - hospital stay , the necessity of inotrope use , and worsening nyha class identified hf patients discharged home who are at highest risk of death or readmission . multiple interventions such as patients education , discharge planning , complete adherence to a correct and tailored medical therapy , scheduling follow - up after discharge , attention to caregivers , and follow - up telephone calls might be useful in reducing the 30-day risk of readmission and , generally , more comprehensive interventions reported greater success . according to the huge number of hf patients discharged from our hospitals , easy and practical prognostic parameters able to predict adverse outcome are mandatory in order to allocate correctly our resources and established tailoring specific follow - up . the analysis of this single - center hf clinic experience demonstrates as in older systolic hf patients discharged after an adhf episode , the single determination of galectin-3 and bnp permitted to predict worst clinical outcome ( death or multiple hospital admissions ) at mid - term ( 11 months ) follow - up . galectin-3 is a lectin secreted in plasma usually at low levels but increased substantially the secretion under conditions like injury or stress , having a biological role in cell adhesion , inflammation , and above all , tissue fibrosis . a single value of galectin-3 in patients admitted for an episode of adhf clearly demonstrated a powerful prognostic power in predicting mortality and rehospitalization at short- or long - term follow - up . on the contrary , a low plasma level of galectin-3 ( < 11.8  ng / ml ) proved to be an independent predictor ( odds ratio 20.9 ; p = 0.003 ) for the absence of mortality and rehospitalization at a short - term follow - up ( 6 months ) suggesting that a reclassification of the alive hf patients at discharge might help in planning an adequate clinical follow - up however , nt - probnp did not add an incremental value in order to predict low - risk events outcome postulating as natriuretic peptide , exploring hemodynamic loading conditions , might be less specific in detecting hf patients with favorable outcome . moreover , the pooled analysis of 3 clinical trials including 902 hf patients demonstrated as hf patients with galectin-3 > 17.8  pg / ml had more risk ( 2.63 times ) to be readmitted for adhf from 30 to 120 days after discharge . in our experience , none of other demonstrated parameters ( renal function , length of hospital stay [ los ] , and hemoglobin ) seemed to correlate with an unfavorable outcome . in particular , the los was not different in the 2 groups , being prolonged ( > 10 days ) according to the older age and the presence of comorbidity in a real - world population . in fact , while in optimize - hf the los was documented very short , in in - hf outcome , based on data coming from cardiology department , a prolonged los ( 10 days ) emerged and significantly correlated with the risk of 30-day readmission . data coming from the everest trial suggested as a longer los was associated with cardiovascular and all cause hospital admissions , but indicated a lower risk of hf readmissions for hf within 30 days after discharging . in our experience , the limited series and the prolonged los did not permit to observe an influence by los in clinical outcome . finally , in a paramount of interesting predicting parameters in hf , clinicians should concentrate their attention on the most specific and cheapest at the moment of discharging your patients . therefore , chronic hf patients discharged alive after an adhf with an elevated predischarge value of galectin-3 ( 17.6  ng / ml ) together with bnp ( 500  pg / ml ) might be inserted into a rigid clinical follow - up , performed by the general practitioner or the hf out - clinic ambulatory , providing a strict control of body weight , hydration status , pharmacological adherence , and clinical status in order to prevent multiple readmissions . the main limitation of this study was the small sample size observed that might reduce the power of some consolidated prognostic parameters ( as renal function ) . moreover , the sample size did not permit a correct distinction between hfref and hfpef . finally , the risk of multiple rehospitalization for hf has normally correlated to the severity of cardiac condition as well as other nontested patient - related factors ( social status , cognitive performance , and presence / absence of caregiver ) that might significantly influence the rate of readmissions . in fact , it has been documented in the dig trial , as about 58% of the nation variations in hospital readmission were correlated with socioeconomic factors .