|Year : 2019 | Volume
| Issue : 4 | Page : 1501-1505
Galectin-3 in children with heart failure secondary to congenital heart diseases
Ahmed A Khattab1, Nagwan Y Saleh1, Mohamed S Rizk2, Shimaa T El-Taweel3
1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Pediatrics, Ministry of Health, Shebin El-Kom, Menoufia Governorate, Menoufia, Egypt
|Date of Submission||19-Dec-2018|
|Date of Decision||23-Jan-2019|
|Date of Acceptance||28-Jan-2019|
|Date of Web Publication||31-Dec-2019|
Shimaa T El-Taweel
Shebin El-Kom, Menoufia
Source of Support: None, Conflict of Interest: None
The aim was to assess serum level of galectin-3 in children with heart failure (HF) secondary to congenital heart disease (CHD) and correlate it with diagnosis and outcome.
Galectin-3 is an emerging biomarker that has been linked to tissue fibrosis, a hallmark in cardiac remodeling and HF. Galectin-3 can reliably be measured in the circulation to detect early failure.
Patients and methods
This prospective cohort study was conducted at Pediatric Intensive Care Units of Menoufia University Hospital from September 2017 to July 2018. The assessed serum galectin-3 levels in 30 children with CHD with HF were compared with 30 children who had CHD without symptoms of HF and 20 apparently healthy children, used as controls, who visited the pediatric outpatient clinic and were subjected to routine clinical examinations.
The demographic data of the studied groups showed that there was no statistically significant difference among the studied groups regarding sex, age, weight, and height, but there was a statistically significant difference among the studied groups regarding BMI, where P value was 0.03. There was a highly statistically significant difference among the studied groups regarding galectin-3 levels. There was a highly statistically significant correlation between galectin-3 levels and echo finding, i.e., ejection fraction, but there was no statistically significant correlation between galectin-3 and outcome of CHD with or without HF.
Galectin-3 has a promising diagnostic value in pediatric HF.
Keywords: congenital heart disease, galectin-3 in heart failure, galectin-3, heart failure in children, heart failure
|How to cite this article:|
Khattab AA, Saleh NY, Rizk MS, El-Taweel ST. Galectin-3 in children with heart failure secondary to congenital heart diseases. Menoufia Med J 2019;32:1501-5
|How to cite this URL:|
Khattab AA, Saleh NY, Rizk MS, El-Taweel ST. Galectin-3 in children with heart failure secondary to congenital heart diseases. Menoufia Med J [serial online] 2019 [cited 2020 Jun 6];32:1501-5. Available from: http://www.mmj.eg.net/text.asp?2019/32/4/1501/274276
| Introduction|| |
Heart failure (HF) describes a state in which a cardiac problem leads to insufficient oxygen delivery to the peripheral organs. Clinically, HF is manifested as dyspnea or fatigue owing to the functional or structural impairment of ventricular filling or ejection of blood .
Congenital heart disease (CHD) is a structural and functional heart disease, which is present at birth. It is the most common birth defect, affecting ∼1% of all live born infants .
Three putative routes have been proposed for the development of HF in CHD: rare monogenetic entities that cause both CHD and HF, severe CHD in which acquired hemodynamic effects of CHD or surgery result in HF, and a combined effect of complex genetics and acquired stressors .
Galectin-3 (gal-3) is a carbohydrate-binding protein produced by activated macrophages, generated intracellularly in both the nucleus and cytoplasm and at the cell surface . Galectin-3 is an emerging biomarker that has been linked to tissue fibrosis and is the hallmark in cardiac remodeling and HF, which can reliably be measured in the circulation, and several recent studies have shown the diagnostic value of galectin-3 in acute and chronic HF and its potential utility in the general population .
The aim of this study was to assess the value of galectin-3 measurements in pediatric HF.
| Patients and Methods|| |
The study was performed at Pediatric Intensive Care Units of Menoufia University Hospital from September 2017 to July 2018. It was approved by the local ethics committee. A written informed consent for children was obtained from their parents before inclusion. In this prospective study, 30 children who were aged more than 1 month to 5 years old and had CHD with HF confirmed with low ejection fraction (EF%) as group A were compared with both 30 children with CHD without HF (group B) and 20 healthy children (group C), used as controls, who were subjected to routine clinical examinations. The studied groups were matched for age and sex. However, children with chronic abnormalities, multiple congenital anomalies, HF secondary cardiomyopathy, and HF secondary to rheumatic heart diseases were excluded.
All patients were subjected to full history taking (age, sex, residence, consanguinity of parents, and duration of symptoms) and clinical examination, including general examination (HR, RR, T, BP, and pulse), anthropometric measurements [weight (kg), height (cm), and BMI], local examination (CVS, respiratory, and neurological), Ross scores, plain chest radiography and heart posterior anterior view, ECG, and echocardiography.
For most of the laboratory investigations, including blood picture (complete blood count), liver function tests, kidney function tests, serum electrolytes, cardiac troponin I (cTnI), and galectin-3, approximately 5 ml of venous blood samples was collected, where 2 ml was collected in EDTA tubes for complete blood count and 3 ml was stored for 2 h after collection at room temperature, and centrifugation at 3000 rpm for 10 min. Blood gas analyses were done by using a special heparinized blood syringe. Galectin-3 ELISA test kits were obtained from Sun Red Manufacturer (Shanghai China). Instructions inside the kit were followed for evaluation of galectin-3 using monoclonal antibody against human galectin-3 as the first antibody.
Values were expressed as means and SD or counts and percentages as appropriate. The primary outcome was HF (Ross class II–IV) versus no HF (Ross class I). To assess the association between galectin-3 levels and EF% in patients with clinical HF (EF <50%), a binary variable was created. Spearman's correlation coefficients were calculated. Data were collected, tabulated, and statistically analyzed using a personal computer with statistical package for social sciences (SPSS; SPSS Inc., Chicago, Illinois, USA) version 20 where the following statistics were applied. Two types of statistics were done: descriptive statistics, for example, number, percentage, mean, and SD, and analytic statistics, for example, χ2-test, Student's t-test, Kruskal–Wallis test (K), one-way analysis of variance test (F), and Mann–Whitney test (U). P value less than or equal to 0.05 was considered to be statistically significant, and P value less than or equal to 0.001 to be highly statistically significant.
| Results|| |
There were no statistically significant differences among the studied groups regarding sex, age, weight, and height, but there was a statistically significant difference among the studied groups regarding BMI, where P value was 0.03. Moreover, there were highly statistical significant differences among the three groups regarding heart rate and respiratory rate, where P value was less than or equal to 0.001, and there was a highly statistically significant difference between the two groups A and B regarding EF, where P value was less than or equal to 0.001 [Table 1].
|Table 1: Clinicodemographic data and laboratory investigations of the studied groups|
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There was a highly statistically significant difference among the studied groups regarding total leukocyte count and serum creatinine, where P value was less than or equal to 0.001 [Table 1].
The was a highly significant difference in the serum level of galectin-3 among the studied groups (mean: 20.3 ± 5.3 ng/ml in group A, 6.3 ± 4.4 in group B, and 3.08 ± 1.5 in controls), where P value was less than or equal to 0.001. Moreover, there was a highly significant difference in the troponin levels among the studied groups (mean: 0.304 ± 0.523 ng/ml in group A, 0.201 ± 0.39 in group B, and 0.017 ± 0.02 in controls), where P value was less than or equal to 0.001 [Table 2].
There was a highly statistically significant correlation between galectin-3 and total leukocyte count, where P value was 0.01, and no statistically significant correlation was found between galectin-3 and aspartate transaminase, alanine transaminase, and serum creatinine [Table 3].
There was no statistically significant correlation between galectin-3 and outcome of CHD with or without HF [Table 4].
|Table 4: Correlation between galectin-3 and outcome of congenital heart disease|
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The overall outcome percentage of CHD was 23.3% died and 76.7% improved; in group A, 20% died and 30% improved, whereas in group B 3.3% died and 46.7% improved [Figure 1].
A highly statistically significant correlation was founded between galectin-3 levels and echo finding, i.e., EF%, with P value was less than or equal to 0.001 [Figure 2].
| Discussion|| |
HF results when cardiac output is insufficient to meet the metabolic demands of the body. Over time, decreased cardiac output leads to a cascade of compensatory responses that are aimed directly or indirectly at restoring normal perfusion to the body's organs and tissues . The largest HF burden is seen in children born with congenital malformations. It has been estimated that 15–25% of children who have structural heart disease develop HF . Galectin-3 has emerged as a biomarker of inflammation and fibrosis in HF. Tissue fibrosis is a central pathway in the progression of HF. Cardiac fibrosis impairs ventricular function and contributes to both systolic and diastolic pressure dysfunctions. Studies have shown that galectin-3 plays a key role in tissue fibrosis and ventricular remodeling. Galectin-3 is expressed at higher levels in cardiac fibroblasts . Our study agrees with the study by El-Amrousy et al. . which found that there was no significant difference between HF group and control group in age, sex, or body weight. There were statistically significant differences among the studied groups regarding BMI in our study, which agrees with Mohammed et al. , and Rubia and Kher  who demonstrated that children with CHD had significant evidence of growth impairment for both weight and length for age (BMI). Schwartz et al.  found that decreased energy intake, malabsorption, and increased basal energy requirements may all lead to compromised growth and underweight in children with CHD. This study found that there were highly statistically significant differences among the three groups regarding heart rate and respiratory rate. This agrees with the studies by Masatsugu and Hiroshi  and El-Amrousy et al. . These studies found that heart rate and respiratory rate are mainly regulated by autonomic nerve activities and increased with attenuated vagal nerve activity or enhanced sympathetic nerve activity in patients with HF. Our study found a significant increase in total leukocyte count because increased concentration of leukocytes is a classical marker of acute or chronic systemic inflammation and a risk marker for cardiovascular disease. The study by Engström et al.  showed that moderately increased leukocyte concentrations are associated with incidence of hospitalizations owing to HF. There was significant increase in creatinine level in patient groups in our study. This was in line with the study by Shlipak et al. , which have determined the importance of renal function in HF and found that increased creatinine levels during hospitalization are a marker of poor cardiac output leading to diminished renal blood flow and reduced ability to tolerate inpatient HF treatment. Thus, the change in creatinine is more likely to be indicative of the severity of cardiac dysfunction rather than of acute renal damage. The outcome percentage of CHD with or without HF was in agreement with Moussa et al.  and Zomer et al. . These studies found that HF is a severe event in CHD associated with a high mortality rate (20%) and found mortality was fivefold higher in patients with HF in CHD compared with patients without HF in CHD. Moreover, HF-related hospitalization was associated with a strong increase in the risk of cardiovascular events. In this study, we found the significance of gal-3 and cTnI between studied groups, which were in line with Hanan Mahmoud et al.  Their study found gal-3 and cTnI plasma levels were statistically significantly higher in subjects with HF compared with control, with mean gal-3 of 18.40 ± 11.5 ng/ml among patients with HF and 5.75 ± 1.427 ng/ml among control group (P < 0.001). Moreover, mean cTnI was 0.429 ± 0.630 ng/ml among patients with HF and 0.019 ± 0.0544 ng/ml among control group (P = 0.004). The study by Mohammed et al.  revealed significantly elevated serum galectin-3 levels in patients with HF compared with controls, with P value less than 0.001. This can be explained by the fact that myocardial injury generates inflammatory signals that recruit activated macrophages to the myocardium and that mediators such as osteopontin stimulate these macrophages to secrete galectin-3.
In this study, there was a positively correlation between galectin-3 and leukocytic count. This agreed with the study by Tsai et al. , which compared the circulating galectin-3 level and white blood cells count, an index of inflammation, and found that these were significantly higher in patients with HF, an indirect index of a higher degree of inflammation. This was significantly more frequently seen in patients with high galectin-3 than in those with low galectin-3, so there seems to be a significant positive correlation between circulating level of galectin-3 and white blood cells count.
The study by Hamdy et al.  showed a positive correlation between level of galectin-3 and EF (P < 0.000), which was similar to the present study. Similarly, the study by Iqbal et al.  showed that there was significant evidence of cardiac remodeling and significantly worsened EF detected by echocardiography between cardiac patients and healthy children. They considered that the clinical and cardiac structural correlations with galectin-3 in their study provide indirect evidence supporting a potential role for galectin-3 in the pathogenesis of cardiac remodeling in HF.
| Conclusion|| |
Galectin-3 has emerged as a biomarker of inflammation and fibrosis in HF and is elevated in pediatric patients with suspected or known HF secondary to CHDs along with troponin I levels.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kim MS, Lee JH, Kim EJ, Park DG, Park SJ, Park JJ, et al
. Korean guidelines for diagnosis and management of chronic heart failure. Korean Circ J 2017; 47
Timothy JN, Susana CP. Stem cell therapy and congenital heart disease. J Cardiovasc Dev Dis 2016; 3
Fahed AC, Roberts AE, Mital S, Lakdawala NK. Heart failure in congenital heart disease: a confluence of acquired and congenital. Heart Failure Clinics 2014; 10
Nguyen Nguyen MN, Su Y, Vizi D, Fang L, Andris HE, et al
. Mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure. Sci Rep 2018; 8
Filipe MD, Meijers WC, Rogier van der Veld A, de Boer RA. Galectin-3 and heart failure: prognosis, prediction & clinical utility. Clin Chim Acta 2015; 443
Daniele M, Fabio V, Marta R, Rossella V, Rita G, Alessandra R, et al
. Pediatric heart failure: a practical guide to diagnosis and management. Pediatr Neonatol 2017; 58
Madriago E, Silberbach M. Heart failure in infants and children. Pediatr Rev 2010; 31
French B, Wang L, Ky B, Jeffrey B, Anupam B, Fang JC, et al
. Prognostic value of galectin-3 for adverse outcomes in chronic heart failure. J Card Fail 2016; 22
El-Amrousy D, Samir H, Hossam H. Prognostic value of homocysteine and highly sensitive cardiac troponin T in children with acute heart failure. J Saudi Heart Assoc 2018; 30
Mohammed LA, Gafar HS, Hussien NR. Galectin-3 as early detector of heart failure in children with congenital acyanotic heart disease. Clin Med Diagn 2014; 4
Rubia B, Kher A. Anthropometric assessment in children with congenital heart disease. Int J Contemp Pediatr 2018; 5
Schwartz S, Olsen M, Woo JG, Madsen N. Congenital heart disease and the prevalence of underweight and obesity from age 1 to 15 years: data on a nationwide sample of children. BMJ Pediatr 2017; 1
Masatsugu H, Hiroshi O. Heart rate as a target of treatment of chronic heart failure. J Cardiol 2012; 60
Engström G, Melander O, Hedblad B. Leukocyte count and incidence of hospitalizations due to heart failure. Circ Heart Fail 2009; 2
Shlipak MG, Chertow GC, Massie BM. Beware the rising creatinine level. J Card Fail 2003; 9
Moussa NB, Karsenty C, Pontnau F, Malekzadeh-Milani S, Boudjemline Y, Legendre A, et al
. Characteristics and outcomes of heart failure-related hospitalization in adults with congenital heart disease. Arch Cardiovasc Dis 2017; 110
Zomer AC, Vaartjes I, van der Velde ET, de Jong HM, Konings TC, Wagenaar LJ, et al
. Heart failure admissions in adults with congenital heart disease: risk factors and prognosis. Int J Cardiol 2013; 168
Hanan Mahmoud F, Mohamed Abdelrazek A, Tahia Hashim S, Marwa Abd-Elhady A. Comparative study of circulating cardiac biomarker galectin-3 and troponin I in heart failure patients. Clin Med Diagn 2013; 3
Mohammed LA, Gafar HS, Hussien NR. Galectin-3 as early detector of heart failure in children with congenital acyanotic heart disease. Clin Med Diagn 2014; 4
Tsai TH, Sung PH, Chang LT, Sun CK, Yeh KH, Chung SY, et al
. Value and level of galectin-3 in acute myocardial infarction. J Atheroscler Thromb 2012; 19
Hamdy R, Mohamed L, Abdel-Rahman T, El-Malah A, Abd-Allah M. Clinical and echocardiographic correlation of galectin-3 in well-defined heart failure patients. AAMJ 2014; 12
Iqbal N, Wentworth B, Choudhary R, Landa AD, Kipper B, Fard A, et al
. Cardiac biomarkers: new tools for heart failure management. Cardiovasc Diagn Ther 2012; 2
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]