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Abstract Summary eart failure is a large medical and epidemiological problem. Studies in chronic heart failure indicate that it is still associated with a high morbidity and mortality (McMurray et al., 2012). Prognosis of HF is poor and definitive treatment is challenging (Ho et al., 2012). Heart failure with normal ejection fraction (HFNEF) accounts for more than 50% of all heart failure patients and as the prevalence of HFNEF in the heart failure population rises by-1% a year (Owan et al., 2006). Galectin-3 is a soluble β-galactoside-binding lectin. In response to myocardial insult, Galectin-3 is released by activated cardiac macrophages and induces fibroblasts proliferation and deposition of type I collagen in the myocardium and stimulating matrix production (Kramer, 2013). There is growing evidence that galectin-3 is directly involved in the pathophysiology of cardiac injury and progression to HF, making it a potential diagnostic, prognostic and therapeutic target (Hrynchyshyn et al., 2013). Recently, galectin 3 was approved by the US Food and Drug Administration as a new biomarker for HF risk stratification and has received a Class IIb recommendation for additive risk stratification in AHA/ACC guidelines (Yancy et al., 2013). H Summary 161 The aim of this work was to study galectin 3 in children with chronic heart failure and if raised correlate its level to the severity of chronic heart failure. This study was performed at the pediatric cardiology clinic and echocardiography unit, children’s hospital, Ain Shams University from April 2014 to March 2015 on 45 patients with chronic heart failure and included two groups. i. Group І: included 45 patients with chronic heart failure 23 (51.1%) males and 22 (48.9%) females their ages ranged from 0.2-15 years with a mean age of 7.46±5.73 years. This group was subdivided into: Group Іa: Included 22 (48.9%) patients with heart failure with normal Ejection Fraction with their EF > 50 % (Masutani et al., 2013) 12 (54.5%) males and 10 (45.5%) females with a mean age of 8.6±5.2 years. Group Іb: Included 23 (51.1%) patients with heart failure with Reduced Ejection Fraction with their EF ≤ 50 % (Masutani et al., 2013) 11 (47.8%) males and 12(52.2%) females with a mean age of 5.6±5.6 years. ii. Group П: Included 45 ages and sex matched healthy children 23 (51.1%) males and 22 (48.9%) females with a mean age of 7.47±5.67 years as a control group. Summary 162 All patients were subjected to the following: Full history taking laying stress on symptoms of heart failure. Classification of chronic heart failure according to the symptom based Modified Ross classification of heart failure (Ross, 2012). Thorough clinical examination laying stress on signs of heart failure. Laboratory investigations including CBC and serum Na, K and creatinine. Calculation of eGFR using Schwartz equation (Schwartz et al., 2009). Assessment of serum galectin 3 level using ELISA technique. Routine 2D echocardiography to delineate cardiac chamber dimensions and congenital heart defects. M mode echocardiography to assess the left ventricle dimension and systolic function. LV mass was calculated as recommended by the American Society of Echocardiography’s Guidelines (Lang et al., 2005) from the following formula: 0.8 {1.04[(LVEDD + LV posterior wall thickness + LV septal wall thickness)3 - LVEDD3]} + 0.6 gm (Devereux et al., 1986). Also continuous, pulsed, color Doppler echocardiography and tissue Doppler imaging to evaluate diastolic function using a commercially available cardiac ultrasound unite, by using device Summary 163 model (vivid E9 GE vingmed ultrasound A/S N-3191 Horten Norway). No significant difference was found between patients and control as regards age and sex. But patients group had a statistically significant decrease in weight, height, BMI and BSA. No significant difference was found between patients with HFREF and patients with HFNEF as regards age, sex, weight, height, BMI and BSA The patients group was divided according to type of HF into 22 patients (48.89%) with HFNEF (there EF% ≥50) and 23 patients (51.11%) with HFREF also divided according to etiology of HF into 15 patients (33.33%) with DCM, 15 patients (33.33%) with CHD and 15 patients (33.33%) with RHD. Patients group was classified according to Ross classification of heart failure in children into 4 classes and included 12 patients (26.67%) in Class I heart failure, 8 patients (17.78%) in class II heart failure, 14 patients (31.11%) in class III heart failure and 11 patients (24.44%) in class IV heart failure. As regards clinical data, the patients group included 4 patients (8.88%) with hypotension, 7 patients (15.55%) with tachycardia, 9 patients (20%) with tachypnea, 1 patient (2.22%) with lower limb edema and 23 patients (31.11%) with tender hepatomegaly. Blood pressure was statistically significant lower in patients group than controls while heart rate and respiratory rate was statistically significant higher in patients group than controls. No significant difference was found between patients with HFREF and patients with HFNEF as regards clinical data. Summary 164 As regards laboratory data, patients had higher serum creatinine than control and lower eGFR, serum Na, blood hemoglobin level and TLC than controls while no difference was found as regard PLT count and serum K. No significant difference was found between patients with HFREF and patients with HFNEF as regards serum creatinine, eGFR, TLC, hemoglobin level, platelets count, serum Na and serum K. The mean value of serum galectin 3 level among the controls was (1.52 ± 0.66) ng/ml ranging between (0.6 - 3.5) ng/dl while the mean value of serum galectin 3 level among the patients was (9.46 ± 5.43) ng/dl ranging between (3.5 - 30) ng/dl so there was a highly significant difference between patients and controls. As regards echocardiographic data, patients show statistically significant increase in LVEDD, LVESD, EDV, RVESP, LVM and LVMI of patients compared to controls and statistically significant decrease in EF% and FS% of patients compared to controls. A statistically significant increase in LVEDD, LVESD, EDV and SV was found in patients with HFREF compared to patients with HFNEF. No significant difference was found between patients with HFREF and patients with HFNEF as regards IVSD, LVPWD, LAD, RVESP, LVM and LVMI. Patients showed statistically significant increase in E wave, A wave, E/A ratio E/Em ratio and Em/Am ratio was found in patients compared to controls while a highly significant decrease in Em, Am and Sm was found in patients compared to controls. A statistically significant increase in A wave and E/A ratio was found in patients with HFNEF compared to patients with HFREF. Summary 165 A statistically significant decrease in E wave was found in patients with HFNEF compared to patients with HFREF. A highly significant increase was found in Em of patients with HFREF compared to patients with HFNEF. A highly significant decrease was found in Sm of patients with HFREF compared to patients with HFNEF. A statistically significant increase in Am, Em/Am and E/Em ratio was found in patients with HFNEF compared to patients with HFREF. Patients with HFNEF had higher serum galectin 3 levels but did not reach statistical significance. Patients with DCM had mean value 10.3 ng/ml followed by patients with CHD with a mean value 9.5 ng/ml followed by patients with RHD with a mean value 8.57 ng/ml but this did not reach statistical significance. A statistically significant increase was found in serum galectin 3 levels of patients not receiving spironolactone compared to patients receiving spironolactone. A highly significant difference was found between 4 classes of heart failure as regards mean values of the serum galectin 3 level. A highly significant increase was found in mean value of the serum galectin 3 level of patients in class ІІІ versus patients in class І, patients in class ІV versus patients in class І, patient in class ІV versus patients in class ІІІ and patient in class ІV versus patients in class ІІІ. No significant difference was found in mean values of the serum galectin 3 levels between patients in class І versus patients in class ІІ and patients in class ІІ versus patients in class ІІІ. Also, a highly significant positive correlation was found between serum galectin 3 levels and classes of heart failure according to Ross classification among patients Summary 166 A significant positive correlation was found between serum galectin 3 levels and age of patients. While no significant correlation was found between serum galectin 3 levels and body weight, height, BMI and BSA of patients. No significant correlation was found between serum galectin3 and duration of illness, number of hospital admissions, duration of hospital admissions, number of ICU admissions, duration of ICU admission, number of drugs and duration of drug intake in patients. Also, no significant correlation was found between serum galectin 3 levels and systolic blood pressure, diastolic blood pressure, respiratory rate and heart rate in patients. No significant correlation was found between serum galectin 3 levels and serum creatinine, eGFR, TLC, blood hemoglobin level, platelets count, serum Na and serum K in patients. Galectin 3 showed a significant positive correlation with LVEDD, LVESD, EDV ESV, RVESP and LVMI of patients and a significant negative correlation with EF and FS of patients while no significant correlation was found with, IVSD, LVPWD and LAD. As regards diastolic function data, a significant positive correlation was found between serum galectin 3 levels and E wave, A wave, E/A ratio, Em, Am, Em/Am and E/Em in patients. Significant negative correlation was found between serum galectin 3 levels and Sm in patients. Conclusion 167 Conclusion Serum galectin-3 level was significantly increased in patients than controls and a cut off value of 3.5 ng/mL can be used for diagnosis of heart failure. Its level was related to HF severity, including Ross classification and echocardiographic findings. Thus it can be used as a marker for heart failure staging in infants where symptoms are few and vague. Patients with HFNEF do not show manifestation of systolic dysfunction, yet the ongoing diastolic dysfunction was associated by a raised galectin 3 level indicating an ongoing process of remodeling. Serum galectin-3 level was increased in patients with HFNEF than patients with HFREF but this did not reach statistical significance. This effect might be due to the administration of spironolactone that blocked the galectin 3 mediated aldosterone induced fibrosis thus the addition of spironolactone to patients with elevated galectin 3 might decrease cardiac remodeling. |