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heart failure ( hf ) remains one of the most prevalent and challenging medical conditions . despite adoption of guideline  based therapy ,
hf is associated with high morbidity and mortality rates ; such a way that 80% of men and 70% of women aged 65 years or above die within 8 years after the initial diagnosis .
hf is also one of the most costly medical conditions ( 1 , 2 ) .
this deleterious condition is associated with progressive ventricular dysfunction and cardiac remodeling ( 3 , 4 ) .
changes in cardiac structure and function often occur before the symptoms appear , resulting in difficulty in prediction of clinical outcomes .
thus , many patients require specialized imaging techniques , such as cardiac magnetic resonance imaging , which are not always available ( 5 , 6 ) . risk factors , such as age , diabetes , and smoking , and severity of symptom are indicative of at risk patients , but are not enough to risk stratify patients ( 7 ) .
the disease may even progress in the patients who are under treatment ; therefore , it is necessary to monitor these patients during the course of treatment .
hf biomarkers have growing importance in daily clinical practice as well as in clinical trials .
biomarkers can help in monitoring of response to therapy , prediction of patients outcome in clinical practice , and appropriate patient stratification ( 8) .
galectin-3 ( also known as mac-2 , cbp-35 , l29 , lbp or ebp ) belongs to the family of -galactoside binding proteins with an extended n terminal region composed of tandem repeats of short amino acid segments and c terminal domain which is responsible for lectin activity ( 8 , 9 ) .
galectin-3 is a product of active macrophages and plays a pivotal role in pathogenesis of remodeling , including inflammation and fibrosis , in hf patients ( 10 , 11 ) .
galectin-3 is not only prognosticate , but it also plays a direct role in hf progression making it a potential target for acute or chronic intervention ( 7 ) .
in this study , serum galectin-3 concentration was measured in compensated hf patients . besides , distribution of the patients in different new york heart association ( nyha ) functional classes i , ii , iii and iv and ejection fraction ( ef ) groups ( 44  35% , 34  25% , < 25% ) was determined by quartile of galectin-3 levels . then , the associations between galectin-3 levels and ef and functional capacity ( fc ) were assessed in these patients .
in this study , 76 patients ( age range of 45 to 75 years ) diagnosed with chronic hf class i  iv ( according to nyha classification ) and left ventricular ejection fraction ( lvef ) < 45% were selected from the patients who regularly visited the heart failure clinic in shahid beheshti hospital , kashan , iran .
baseline demographic data , functional status , cardiovascular risk factors , and medications were recorded , as well .
the exclusion criteria of the study were suffering from renal failure and chronic inflammation disease .
then , male patients with cr > 1.3 and female ones with cr > 1.2 and positive c - reactive protein ( cpr ) were excluded from the study .
it should be mentioned that written informed consents were obtained from all the patients . at baseline ,
galectin-3 was measured by an enzyme - linked immunosorbent assay kit ( shanghai crystal day biotech c ) .
the intra - assay and inter - assay variances for galectin-3 were < 10% and < 12% , respectively .
moreover , echocardiography was used to evaluate lvef with reference to braunwalds classification of systolic hf ( 12 ) .
furthermore , fc was determined based on the patients ability to perform a set of activities .
it should be noted that galectin-3 levels ( pg / ml ) were divided in quartiles as follows : first quartile : < 441 , second quartile : 441 - 501 , third quartile : 501  560 , and fourth quartile > 560 . after all ,
the data were entered in to the spss statistical software ( v. 16 ) and analyzed using t - test , kruskal - wallis , one  way anova , and chi - square test .
the characteristics of the study groups according to the galectin-3 levels have been presented in table 1 .
as the table depicts , the patients age ranged from 45 to 75 years , with the mean age of 63.85  9 years .
the mean age of male and female patients was 63.77  8.5 and 63.98  9.5 years , respectively ( p = 0.950 ) .
besides , 35.5% , 44.7% , and 19.7% of the patients were in the nyha functional class i , ii , and iii , respectively .
it should be noted that due to the small number of subjects with class iv , classes iii and iv were combined .
co - morbidities included diabetes mellitus in 25% and myocardial infarction in 35.5% of the patients .
abbreviations : nyha , new york heart association ; lvef , left ventricular ejection fraction ; bmi , body mass index ; ace , angiotensin converting enzyme ; arb , angiotensin receptor blockers ; lvef 1 : 44 - 35% , lvef 2 : 34 - 25% , lvef 3 : < 25% after removal of the outliers ( the variables values greater than 3 iqr are assumed as outliers ) from the data , galectin-3 showed normal distribution and the mean galectin-3 level was 490  95 pg / ml ( figure 1 ) .
the study results revealed no significant correlation between galectin-3 levels and age ( r = 0.108 , p = 0.358 ) , body mass index ( bmi ) ( r = -0.029 , p = 0.807 ) , and estimated glomerular filtration rate ( egfr ) ( r = -0.070 , p = 0.550 ) .
moreover , the mean of galectin-3 was 666  467 pg / ml in males and 499  199 pg / ml in females and the difference was statistically significant ( p = 0.039 ) .
however , no significant correlation was found between galectin-3 levels and lvef ( p = 0.166 ) and fc ( p = 0.420 ) in the hf patients .
the study results revealed no significant relationship between galectin-3 and ef and fc in any of the quartiles .
galectin-3 is a novel biomarker that has been shown to mediate fibrosis in a variety of organs , including the heart .
the role of galectin-3 ( a -galactoside - binding lectin macrophage product ) in hf was initially described in rat models , in which galectin-3 expression was found to be up - regulated in endomyocardial biopsies of the rats with cardiac hypertrophy that subsequently progressed to hf .
mechanistically , galectin-3 is a product of active macrophages with binding sites on cardiac - resident fibroblasts , leading to an increase in myocardial collagen expression and interstitial fibrosis , transformation of growth factor- activation , and subsequently lv dysfunction .
hence , galectin-3 may play a pivotal role in the response to injury and inflammation during hf , including being an important part of ventricular remodeling ( 6 ) .
galectin-3 was found to be significantly up - regulated in hypertrophied hearts of the patients with aortic stenosis ( 10 ) . after initiated systolic hf , several compensatory mechanisms are activated , including enlargement of the heart , increased thickness of the heart muscle fibers , and increased heart rate , that cause symptoms partial recovery . yet , drug therapy can be effective in improvement of cardiac symptoms .
nonetheless , even though some cases present no symptoms , the disease may still progress . based on our findings , serum levels of galectin-3 could not predict ef and fc in the treated patients .
therefore , serum levels of galectin-3 can not be a sign of disease progression or severity in these patients .  
n - acetyl - seryl - aspartyl - lysyl - proline ( ac - sdkp ) , a monocyte - derived anti - inflammatory and antifibrotic peptide that is reduced by angotansin converting enzyme ( ace ) , inhibits galectin-3 expression in the left ventricle and reduces galectin-3induced macrophage activation and migration ( 13 , 14 ) . in a rat model ,
intrapericardial infusion of ac - sdkp mitigated many of the adverse effects of galectin-3 , leading to reduced myocardial macrophage and mast cell density , decreased left ventricular collagen burden , and improved diastolic and systolic function .
these findings suggested that the adverse consequences associated with galectin-3 might be modifiable ( 13 ) . in the present study ,
the patients were under treatment with ace inhibitors , which perhaps could explain low galectin-3 levels in these patients .
the patients with coronary disease demonstrated a weak negative correlation between galectin-3 and ef ( r = -0.31 , p = 0.0002 ) ( 13 ) .
similarly , the results of a research conducted by chen on the patients diagnosed with chronic heart failure ( chf ) and coronary heart disease with stable angina showed that plasma galectin-3 level was inversely correlated to lvef ( r = 0.683 , p < 0.01 ) ( 15 ) .
this difference might be due to the fact that unlike our study , the patients in the two above - mentioned studies had not received any treatments .
the difference might have also resulted from the difference in the etiologies of the disease in these studies .
it seems that after long - term treatment , galectin-3 level returns to its initial value .
consequently , it can be used for monitoring the patients during the course of treatment .
these results were not in agreement with those of other studies , which might be because of participation of younger subjects in this study compared to other studies ( 4 , 10 ) or the effect of drugs .
although numerous studies have shown that galectin-3 level is increased substantially in acute or decompensated chronic heart failure , it can not be a suitable marker for detection of hf .
the findings of the study lok et al . conducted on 232 patients with chronic heart failure indicated that galectin-3 levels were elevated in only half of the patients with advanced but stable hf .
however , 90% of the patients with hf showed abnormal levels of brain natriuretic peptide ( bnp ) , indicating its poor diagnostic property unlike its high prognostic value as a biomarker for detection of galectin-3 ( 4 , 16 ) .
moreover , van kimmenade and colleagues studied 209 patients with hf and showed that galectin-3 had lower specificity and sensitivity in identification of hf compared to amino terminal pro - brain natriuretic peptide ( nt - probnp ) ( 17 ) , but serum galectin-3 levels were elevated and showed a better predictive value of prognosis compare to nt - probnp and apelin ( 17 ) .
several studies conducted on the correlation between galectin-3 and hf have given rise to more questions instead of answering the existing questions .
therefore , further studies are necessary to investigate the use of galectin-3 in clinics to determine whether it can be used as a biomarker for detection of hf or only as a tool for monitoring the progression of the disease .
first , this study was cross - sectional and was conducted on a relatively small number of patients .
thus , further follow - up studies are required to demonstrate the prognostic value of galectin-3 .
in addition , our study was a correlational study and was not sufficient to make mechanistic conclusions . furthermore , an interval was there between performance of echocardiography and taking blood samples in some patients .
since galectin-3 half - life was not identified in our patients , this time interval might have affected the results .
however the process of myocardial fibrosis and remodeling ( putatively reflected by galectin-3 concentrations ) is not evanescent , and is likely to have been reflected in the associations between galectin-3 values on admission and echocardiographic findings .
the findings of the present study showed no significant association between serum galectin-3 concentration and ef and fc in the patients with compensated systolic hf .
therefore , our findings suggested that galectin-3 could not be used as a marker of disease progression in the treated patients , which might be the result of medication use in these patients .
background : galectin-3 is a soluble  - galactoside  binding lectin released by activated cardiac macrophages . 
 galectin-3 has been proposed for diagnosis and prognosis of hf patients.objectives:the present study aimed to investigate the relationship between galectin-3 as a biomarker and ejection fraction and functional capacity in the patients with compensated systolic heart failure.patients and methods : in this study , serum levels of galectin-3 were measured in 76 patients with compensated heart failure with new york heart association class i  iv and left ventricular ejection fraction < 45% . 
 galectin-3 was measured by an elisa kit . besides 
 , echocardiography was used to evaluate left ventricular ejection fraction . 
 additionally , functional capacity was determined based on the patients ability to perform a set of activities . 
 after all , the data were analyzed used t - test , kruskal - wallis , one  way anova , and chi - square test . 
 p < 0.05 was considered as statistically significant.results:the patients age ranged from 45 to 75 years , with the mean age of 63.85  9 years . in addition 57.9% of the patients 
 were male . 
 the results revealed no significant correlation between galectin-3 and age , body mass index , and estimated glomerular filtration rate . 
 also , no significant correlation was observed between galectin-3 levels and left ventricular ejection fraction ( p = 0.166 ) and functional capacity ( p = 0.420 ) . yet , a significant difference was found between males and females regarding the mean of galectin-3 ( p = 0.039).conclusions : the study results suggested that galectin-3 could not be used as a marker of disease progression in the patients under treatment , which could probably be the result of medication use in these patients .