|Year : 2019 | Volume
| Issue : 4 | Page : 1506-1511
Soluble suppression of tumorigenisity 2 as an indicator of severity of heart failure in children with congenital acyanotic heart diseases
Rania S Elzayat1, Ahmed A Khattab1, Mohammed S Rizk2, Rabab M Shaban3
1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt
2 Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt
3 Department of Pediatric, Pediatrics at Ministry of Health, Shebin El Kom, Egypt
|Date of Submission||10-Apr-2019|
|Date of Decision||19-May-2019|
|Date of Acceptance||20-May-2019|
|Date of Web Publication||31-Dec-2019|
Rabab M Shaban
Source of Support: None, Conflict of Interest: None
We aimed to evaluate the role of soluble suppression of tumorigenisity 2 (sST2) as an indicator of severity of heart failure (HF) in children with congenital acyanotic heart diseases.
HF in congenital heart diseases (CHD) is a serious problem encountered in early infancy or later. It is a significant cause of morbidity and mortality in children with CHD. SST2 is currently gaining interest as a biomarker in cardiac disease.
Patients and methods
A prospective comparative study was conducted on 60 children having CHD with left-to-right shunt from the Pediatric Department of Menoufia University Hospitals between August 2017 and August 2018 and were divided into two groups: group 1: 30 children with manifestation of HF. Group 2: 30 children without manifestation of HF. In addition, 25 age-matched and sex-matched healthy children were set as a control group. All children were subjected to a full clinical history and examination. Serum level of sST2 were determined.
Level of sST2 was 82.2 ± 22.3 and 25.63 ± 19.33 ng/ml in patients with and without HF, respectively. SST2 was significantly higher in patients who developed HF than in those without HF (P < 0.001). SST2 was significantly elevated with increased severity of HF (P < 0.001), wherein it was 25.63 ± 19.3, 55.5 ± 2.6, 86.1 ± 7.7, and 109.9 ± 6.4 ng/ml in patients with ROSS class I, II, III, and IV, respectively.
SST2 is a promising novel cardiac biomarker that could reflect the severity of HF.
Keywords: congenital heart diseases, heart failure, soluble suppression of tumorgenisity 2
|How to cite this article:|
Elzayat RS, Khattab AA, Rizk MS, Shaban RM. Soluble suppression of tumorigenisity 2 as an indicator of severity of heart failure in children with congenital acyanotic heart diseases. Menoufia Med J 2019;32:1506-11
|How to cite this URL:|
Elzayat RS, Khattab AA, Rizk MS, Shaban RM. Soluble suppression of tumorigenisity 2 as an indicator of severity of heart failure in children with congenital acyanotic heart diseases. Menoufia Med J [serial online] 2019 [cited 2020 Feb 16];32:1506-11. Available from: http://www.mmj.eg.net/text.asp?2019/32/4/1506/274219
| Introduction|| |
Cardiovascular diseases remain the leading cause of death worldwide, making it essential to realize the causes, the pathogenesis of these diseases, and to improve their diagnostic and treatment capabilities and prophylactic programs . Heart failure (HF) is a complex clinical syndrome characterized by ventricular dysfunction, neuroendocrine activation and abnormal peripheral blood flow distribution . HF in congenital heart diseases (CHD) with left-to-right shunts is a serious problem encountered in early infancy or later; depending on the size of the shunt. It is a significant cause of morbidity and mortality in children with CHD . The diagnosis of HF commonly relies on comprehensive analyses of medical history and symptoms, and the results of echocardiography and biochemical tests . Circulating biomarkers that directly reflect disease progression, hemodynamics, and ventricular remodeling at a molecular level are critical for risk stratification in HF, affording unique insights into pathophysiology not fully captured by traditional risk markers, reduce the cost effectiveness and improve the treatment outcomes of HF patients . Soluble suppression of tumorigenisity (sST2) is currently gaining mounting interest as candidate biomarkers in cardiac disease . ST2 is an interleukin (IL)-1 receptor family member with transmembrane (ST2L) and soluble isoforms . SST2 is believed to function as a 'decoy' receptor for IL-33, inhibiting the effects of IL-33/ST2L signaling . Blood concentrations of sST2 are significantly increased, for example, in inflammatory/infectious diseases, in cancer and in cardiac disease . SST2 have been included in the 2013 ACCF/AHA guideline for the purpose of additive risk stratification of patients with acute and chronic HF .
The aim of the study was to evaluate the role of sST2 as an indicator of severity of HF in children with congenital acyanotic heart diseases.
| Patients and Methods|| |
A prospective comparative study was conducted on 60 children having CHD with left-to-right shunt. They were selected from the Pediatric Department of Menoufia University Hospital between August 2017 and August 2018. Thirty of them had a manifestation of HF, and 30 were without HF; their ages ranged from 3 to 30 months. In addition, 25 age-matched and sex-matched healthy children were selected as a control group. All subjects were informed of the purpose of the study, and parent consent was obtained. We excluded from the study children with cyanotic heart diseases, valvular lesion, cardiomyopathy, patients who had undergone previous surgical correction, neonates, and patients aged more than 18 years. All children were subjected to a full clinical history and examination. The relevant clinical history includes the demographic data, presenting symptoms, any previous surgery, and current medication. Assessment of growth by anthropometric measurement was represented by weight, length/height and BMI, which were plotted on Egyptian growth charts. Measurement of sST2 level was carried out by using the enzyme-linked immunosorbent assay technique. The diagnosis of HF is based on clinical evaluation and modified ROSS score. The modified ROSS classification incorporates diaphorasis, tachypnea, type of breathing, respiratory rate (RR), heart rate (HR) and liver edge below costal margin into a numeric score. Total score: 0–2 ([no congestive heart failure (CHF)], 3–6 (mild CHF), 7–9 (moderate CHF), 10–12 (severe CHF) (). The ROSS classification was developed to provide a global assessment of HF severity in infants, and has subsequently been modified to apply to all pediatric ages.
The study is in accordance with the ethical standards of El Menoufia Faculty of Medicine Research Committee and with the 1964 Helsinki Declaration and its later amendments. Informed consent was signed by parents or (caregivers) of all included children.
About 2 ml of venous blood for each case was collected into a serum separator tube. After coagulation at room temperature for 30 min, centrifugation for 20 min at the speed of 2000–3000 rpm was carried out; thereafter, the serum was aliquoted and stored at − 80°C. Serum sST2 level was determined by using a double-antibody sandwich enzyme-linked immunosorbent assay technique. The kit was supplied by Shanghai Sunredbio Technology Co. Ltd (Shanghai, China).
All data were collected, tabulated and statistically analyzed using SPSS 19.0 for Windows (SPSS Inc., Chicago, Illinois, USA) and Med Calc 13 for Windows (Med Calc Software BVBA, Ostend, Belgium). Continuous data were expressed in the form of mean ± SD. Categorical data were expressed in the form of number and percentage. Normal distribution of the data was evaluated by Shapiro–Wilk test. Independent t-test was used for comparing the mean of continuous variables between the studied groups. For comparison of nonparametric variables between study groups, the χ2-test or Mann–Whitney U-test was used. Difference between more than two parameters was carried out using one-way analysis of variance test.
| Results|| |
Our study showed that there was no significant difference (P = 0.94) between the studied groups as regards sex, age, and diagnoses. In contrast, there was a highly significant difference (P < 0.001) between patients with HF and patients without HF, as regards the number of medications, number of times of hospital admission, and number of times and duration of PICU admission [Table 1]. Weight and height/length show highly significant decrease (P < 0.001) in children with HF compared with the control group. In contrast, there was no significant difference (P = 0.58) between children with HF and those without HF, as regards the weight and height/length. As regards BMI, there was a highly significant difference between patients with HF and others without HF (P < 0.001) and also between patients with HF and the control group (P < 0.001). However, there was no significant difference between patients without HF and the control group (P = 0.10; [Table 2]). HR and RR showed a highly significant increase, while systolic blood pressure and diastolic blood pressure showed a highly significant decrease (P < 0.001) in patients with HF compared with those without HF and the control group. There was a highly significant increase (P < 0.001) between patients without HF and the control group, as regards HR and RR. There was no significant difference (P = 0.18) between patients without HF and the control group, as regards systolic blood pressure [Table 3]. The level of sST2 was significantly higher in patients with HF compared with that of non-HF and control groups (82.2 ± 22.3, 25.63 ± 19.33, and 2.04 ± 1.09 ng/ml), respectively (P < 0.001), as demonstrated in [Table 4]. SST2 was significantly elevated with increased severity of HF (P < 0.001), wherein it was 25.63 ± 19.3 ng/ml in patients with ROSS class I, 55.5 ± 2.6 ng/ml in patients with ROSS class II, 86.1 ± 7.7 ng/ml in patients with ROSS class III and 109.9 ± 6.4 ng/ml in patients with ROSS class IV, as demonstrated in [Table 5].
|Table 4: Soluble suppression of tumorigenisity 2 level of the studied groups|
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|Table 5: Soluble suppression of tumorigenisity 2 level in different ROSS classes|
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| Discussion|| |
The development of HF is often a clinically silent process, with progressive cardiac remodeling that eventually leads to symptomatic presentation late in the course of disease progression . Using cardiac biomarkers may be one avenue in which patients may be routinely evaluated for the presence and severity of HF . SST2 is currently gaining mounting interest as a candidate biomarker in cardiac disease . Blood concentrations of sST2 are significantly increased in inflammatory/infectious diseases, in cancer and in cardiac disease . The aim of the study was to evaluate the role of sST2 as an indicator of severity of HF in children with congenital acyanotic heart diseases. Our results show that serum sST2 level was significantly high in children with HF compared with those without HF and the control group. This is in agreement with Abdel Raheem and Sedik  who showed that sST2 serum levels were significantly elevated in children (mean age of 20.3 ± 11.2 months) who were patients with HF when compared with controls. Moreover, this is in agreement with Hugo et al.  who showed that sST2 was elevated in children with left ventricular dysfunction compared with controls (25.7 vs. 21 ng/ml). This is in agreement with other studies that investigated sST2 in adults with HF: Januzzi et al.  found that Concentrations of sST2 were higher among patients with acute HF compared with those without HF in patients with dyspnea and Mueller et al.  found that serum sST2 was higher in patients with HF compared with those without HF (40 vs. 29 ng/ml). Our results show that serum sST2 was significantly elevated with increased severity of HF. This is in agreement with Abdel Raheem and Sedik  who revealed that HF patients with ROSS class IV classification had significantly higher serum levels of serum sST2 than those with ROSS III and ROSS II (also compared between III and II). These results point to the role of sST2 in predicting or evaluating severity of HF. Our results show that patients with HF show significant increase in HR and RR compared with controls. This is in agreement with Abdel Raheem and Sedik . Our results show that patients with HF show significant decrease in BMI compared with controls. This is not in agreement with Abdel Raheem and Sedik  who showed that the BMI was lower in the CHD group than in controls, but the difference was not significant.
| Conclusion|| |
SST2 is a good indicator of severity of HF in children with congenital acyanotic heart diseases.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Salazar J, Martinez J, Chávez M. C-reactive protein: clinical and epidemiological perspectives. Cardiol Res Pract 2014; 2014
Elkiran O, Sandikkaya A, Kocak G, Karakurt C, Taskapan C, Yologlu S. Evaluation by N
terminal prohormone of brain natriuretic peptide concentrations and ROSS scoring of the efficacy of digoxin in the treatment of heart failure secondary to congenital heart disease with left-to-right shunts. Pediatr Cardiol 2013; 34
Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, et al
. ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation2013; 128
Shah RV, Januzzi JL. Soluble ST2 and galectin-3 in heart failure. Clin Lab Med 2014; 34
Mueller T, Dieplinger B. Soluble ST2 and galectin-3: what we know and don't know analytically. EJIFCC 2016; 27
Mueller T, Jaffe AS. Soluble ST2 – analytical considerations. Am J Cardiol 2015; 115
Lloyd-Jones D, Adams RJ, Brown TM. Heart disease and stroke statistics – 2010 update: a report from the American Heart Association. Circulation 2010; 121
Felker GM, Fiuzat M, Shaw LK, Clare R, Whellan DJ, Bettari L, et al
. Galectin-3 in ambulatory patients with heart failure: results from the HF-ACTION study. Circ Heart Fail 2012; 5
Abdel Raheem MM, Sedik WF. Prognostic value of soluble ST2 (sST2) serum level in congenital heart disease children with heart failure. Int J Pediatr 2019; 7
Hugo RM, Casson P, Ollberding N, Ryan T, Wilmot I, Jefferies J. Assessment of soluble ST2 and BNP in pediatric with left ventricular dysfunction. J Card Fail 2018; 24
Januzzi JL, Peacock WF, Maisel AS. Measurement of the interleukin family member ST2 in patients with acute dyspnea: results from the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) Study. J Am Coll Cardiol 2007; 50
Muller T, Gegenhuber A, Leitner I, Poelz W, Haltmayer M, Dieplinger B. Diagnostic and prognostic accuracy of galectin-3 and soluble ST2 for acute heart failure. Clinica Chimica Acta 2016; 463
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]