Randomized Clinical and Biochemical Study Comparing the Effect of L-arginine and Sildenafil in Beta Thalassemia Major Children With High Tricuspid Regurgitant Jet Velocity.

BACKGROUND: Pulmonary hypertension (PHT) is common in ß-thalassemia patients due to hemolysis, iron overload and diminished nitric oxide (NO) levels. Biochemical markers can help to understand the pathophysiology and to introduce new therapies for this condition. AIM: This study aimed to evaluate the effectiveness of L-arginine and sildenafil in thalassemia children with PHT at both clinical and biochemical levels. METHODS AND RESULTS: In a randomized controlled study, 60 ß-thalassemia major children with PHT were divided into 3 equal groups; Control group (Conventional thalassemia and PHT management), L-arginine group (Conventional + Oral L-arginine 0.1 mg.kg-1 daily), and sildenafil group (Conventional + Oral sildenafil 0.25 mg.kg-1 two times a day) for 60 days. Tricuspid Regurgitant Jet Velocity (TRJV) with Doppler echocardiography along with serum levels of NO, asymmetric dimethylarginine (ADMA), interleukin 1-beta (IL-1ß), E-selectin, and visfatin were followed-up at baseline, 30, and 60 days after treatment. Both drugs reduced the TRJV significantly. NO was significantly higher in both L-arginine and sildenafil groups after 60 days compared to baseline, while visfatin levels were lower. Only L-arginine reduced ADMA levels compared to baseline, while sildenafil did not. E-selectin and IL-1ß levels did not change remarkably by both drugs. NO and TRJV showed significant negative correlations in both treatment groups. CONCLUSION: L-arginine and sildenafil could clinically ameliorate chronic PHT whereas, L-arginine showed superiority to sildenafil on some biochemical markers.

Cardiac changes in infants of diabetic mothers.

Diabetes mellitus (DM) is a systemic chronic metabolic disorder characterized by increased insulin resistance and/or ß- cell defects. It affects all ages from the foetal life, neonates, childhood to late adulthood. Gestational diabetes is a critical risk factor for congenital heart diseases (CHDs). Moreover, the risk increases with low maternal education, high body mass index at conception, undiagnosed pre-gestational diabetes, inadequate antenatal care, improper diabetes control, and maternal smoking during pregnancy. Maternal DM significantly affects the foetal heart and foetal-placental circulation in both structure and function. Cardiac defects, myocardial hypertrophy are three times more prevalent in infants of diabetic mothers (IDMs). Antenatal evaluation of the cardiac function and structures can be performed with foetal electrocardiography and echocardiography. Postnatal cardiac evaluation can be performed with natal and postnatal electrocardiography and echocardiography, detection of early atherosclerotic changes by measuring aortic intima-media thickness, and retinal vascular changes by retinal photography. Ameliorating the effects of diabetes during pregnancy on the offspring depends mainly on pregestational and gestational diabetes prevention. However, other measures to reduce the risk, such as using medications, nutritional supplements, or probiotics, still need more research. This review discusses the mechanism of foetal sequels and the risk factors that increase the prevalence of CHDs in gestational DM, the various cardiac outcomes of gestational DM on the foetus and offspring, cardiac evaluation of foetuses and IDMs, and how to alleviate the consequences of gestational DM on the offspring.

Comparative study of the efficacy of captopril, simvastatin, and L-carnitine as cardioprotective drugs in children with type 1 diabetes mellitus: a randomised controlled trial.

OBJECTIVES: To assess the efficacy and safety of captopril, simvastatin, and L-carnitine as cardioprotective drugs in children with type 1 diabetes mellitus on different echocardiographic parameters, electrocardiographic parameter, lipid profile, and carotid intima-media thickness. METHODS: This randomised controlled trial was conducted on 100 children with type 1 diabetes mellitus for more than 3 years during the period from September 2018 to June 2020. Fifty healthy children of matched age and sex served as a control group. The patients were randomly assigned into four groups (25 children each): no-treatment group who received no cardioprotective drug, simvastatin group who received simvastatin (10-20 mg/day), captopril group who received captopril (0.2 mg/kg/day), and L-carnitine group who received L-carnitine (50 mg/kg/day) for 4 months. Lipid profile, serum troponin I, carotid intima-media thickness, and echocardiographic examinations were performed on all included children before and after the treatment. RESULTS: Total cholesterol and low-density lipoprotein were significantly decreased in children who received simvastatin or L-carnitine. Triglycerides significantly decreased only in children who received simvastatin. High-density lipoprotein significantly increased in simvastatin and L-carnitine groups only. Serum troponin I decreased significantly in all the three treatment groups. Carotid intima-media thickness showed no significant change in all treatment groups. Echocardiographic parameters significantly improved in simvastatin, L-carnitine, and captopril groups. CONCLUSION: Captopril, simvastatin, and L-carnitine have a significant beneficial effect on cardiac functions in children with type 1 diabetes mellitus. However, only simvastatin and L-carnitine have a beneficial effect on the lipid profile. The drugs were safe and well tolerated.Clinical trial registration: The clinical trial was registered at www.clinicaltrial.gov (NCT03660293).

Three-dimensional speckle tracking echocardiography for early detection of left ventricular dysfunction in children with non-alcoholic fatty liver diseases.

OBJECTIVES: To detect early left ventricular dysfunction in children with non-alcoholic fatty liver disease using three-dimensional speckle tracking echocardiography. METHODS: Forty obese children with non-alcoholic fatty liver disease were included as group I. Another 40 obese children without non-alcoholic fatty liver disease of matched age, sex, and weight were included as group II. Forty healthy controls of matched age and sex served as a control group. Anthropometric measurements, laboratory investigations, and echocardiographic examinations including three-dimensional speckle tracking echocardiography were measured for all included children. RESULTS: Abnormal lipid profile was detected in children with non-alcoholic fatty liver disease. Troponin I levels were significantly higher in children with non-alcoholic fatty liver disease compared to obese children without non-alcoholic fatty liver disease and to healthy controls. Three-dimensional speckle tracking echocardiography examination revealed a significant reduction of left ventricular global longitudinal strain, circumferential strain, radial strain, and area strain in children with non-alcoholic fatty liver disease inspite of normal left ventricular fraction shortening measured by conventional echocardiography. All strains were negatively correlated with the grade of non-alcoholic fatty liver disease. CONCLUSION: Non-alcoholic fatty liver disease is associated with subclinical left ventricular dysfunction. Three-dimensional speckle tracking echocardiography can be helpful in identifying early left ventricular dysfunction in children with non-alcoholic fatty liver disease even in the presence of normal left ventricular ejection fraction.

Left Ventricular Layer-Specific Myocardial Strains in Children with Recovered Primary Dilated Cardiomyopathy: What Lies Beneath the Iceberg?

We aimed to detect residual cardiac dysfunction-if any-in children with recovered primary dilated cardiomyopathy (DCM) by using the left ventricular (LV) layer-specific myocardial strains. Fifty children with recovered primary DCM both clinically and echocardiographically were included as the patient group. Fifty healthy children of matched age and sex served as the control group. Echocardiographic evaluation was performed for all included children in the form of conventional echocardiography, tissue Doppler imaging (TDI), two-dimensional speckle tracking echocardiography (2D-STE), and LV layer-specific myocardial strain. Both LV systolic and diastolic functions measured by conventional echocardiography were similar in children with recovered DCM and the control group. There was a significant reduction in LV systolic and diastolic functions measured by TDI in the patient group. Moreover, there was a significant reduction of LV global longitudinal systolic strain (GLSS) by 2D-STE in children with recovered DCM. Interestingly, there was a significant reduction of LV layer-specific myocardial strain from endocardium to epicardium in children with recovered DCM compared to the healthy control. There was a significant positive correlation between different layer-specific myocardial strains and LV GLSS, LV ejection fraction, and LV peak systolic velocity. Left ventricular layer-specific myocardial strain can be a promising tool for early identifications of LV dysfunction in children with DCM. Subtle cardiac dysfunction is present in patients with recovered DCM, so long-term follow-up is recommended in these patients.

Left Ventricular Regional Function in Children with Beta Thalassemia with No Cardiac Manifestations (Four-Dimensional Echocardiographic Study).

Early detection of myocardial dysfunction is essential for the management of patients with thalassemia. Four-dimensional echocardiography imaging technique may be useful for detecting subclinical cardiovascular disease. To evaluate the 4-dimensional echocardiographic strain in children with beta thalassemia major with no cardiac manifestation and correlate it with other echocardiographic parameters. This is a prospective cross-sectional cohort Study included 200 children, 1-18 years-old. They were divided into: One hundred children with p-Thalassemia major with no clinical cardiac manifestations and 100 healthy children as a control group. They were subjected to the following investigations: Complete blood count, serum ferritin and Four-dimensional echocardiographic strains (Longitudinal, Circumferential, Radial and Area strains). There was no significant difference between the two groups as regard mitral annulus systolic velocity (S wave), E/A ratio and iso-volumic acceleration, but there was a significant difference as regard to ejection fraction, left ventricle mass, sphericity index and myocardial performance index. The mean values of Left Ventricular Strains (Longitudinal, Circumferential, Radial and Area strains) were significantly lower in patients with thalassemia (- 14.86 ± 12.13, - 8.01 ± 3.829, 33.13 ± 10.61, - 19.45 ± 6.866) than controls (- 19.13 ± 1.502, - 16.32 ± 1.34, 37.28 ± 4.209, - 22.94 ± 3.06) than controls respectively with a positive correlation with 2-Dimensional strain. Strain parameters of the left ventricle obtained by four-dimensional.

Three-dimensional speckle tracking echocardiography: Is it the magic wand in the diagnosis of subclinical myocardial dysfunction in children with type 1 diabetes mellitus?

OBJECTIVES: To revaluate the role of three-dimensional speckle tracking echocardiography (3D-STE) in the evaluation of subclinical myocardial dysfunction in asymptomatic children with type 1 diabetes mellitus (DM). PATIENTS AND METHODS: Fifty asymptomatic children with type 1 DM were included as a patient group. Fifty healthy children of matched age, sex, and weight served as a control group. Laboratory investigations in the form of complete blood count (CBC), liver function test, renal function test, complete blood lipid profile, glycosylated hemoglobin (HbA1c), fasting and 2 hours postprandial (PP) glucose levels, and cardiac troponin I (cTnT I) were drawn. Complete echocardiographic evaluation of the left ventricular (LV) function was performed in the form of conventional echo, 2D strain, tissue Doppler imaging (TDI), and 3D- STE. RESULTS: cTnT I levels were significantly higher in the patient group than the control group, and this increase was significantly correlated with Hb A1c. Conventional echocardiography showed normal systolic and diastolic function of the LV. Diastolic (by TDI) as well as systolic functions of LV (by 4D LV quantification tool) were found to be significantly lower in patient group than control group. 3D-STE examination showed that there was a significant decrease in all component of strain in patient group than control group and that decrease correlated well with 4D LV EF but did not correlate with the duration of DM. There was a significant negative correlation between longitudinal strain and the control of DM. CONCLUSION: 3D-STE is a good tool for prediction of early cardiac dysfunction in asymptomatic children with type 1 DM.

Cardiac changes in moderately malnourished children and their correlations with anthropometric and electrolyte changes.

OBJECTIVE: To evaluate electrocardiographic and echocardiographic changes in moderately malnourished children and to correlate them with both anthropometric and electrolyte changes. PATIENTS AND METHOD: Sixty moderately malnourished children were taken as patient group, and 60 healthy children of matched age and sex were taken as control group. Weight, height, body mass index (BMI), serum albumin, and electrolytes were measured for all children. Electrocardiographic evaluation for calculated QT (QTc) and QT dispersion (QTd) was performed. Left ventricular (LV) function was also evaluated using conventional echocardiography, tissue Doppler, and strain methods. Left ventricular mass index (LVMI) was also calculated. RESULTS: Weight, BMI, serum levels of albumin, total calcium, and ionized calcium were significantly lower, while QTc and QTd were significantly prolonged in malnourished children (P = .001 for all). There was significant reduction in LV fraction shortening (FS), LV E'/A', LV strain (S), LV myocardial performance index (MPI), LV global systolic strain (GLSS), and LVMI (P = .001 for all) in malnourished children. There was significant correlation between BMI and all cardiac variables. Moreover, there was significant positive correlation between serum albumin level and LV E'/A' (P = .02), LV GLSS (P = .03), and LVMI (P = .03).Total and ionized calcium level were significantly correlated with QTc, QTd, and LVMI (P < .05 for all). BMI was the most powerful predictor of these electrocardiographic and echocardiographic changes. CONCLUSION: Cardiac changes were present in moderately malnourished children as documented by electrocardiographic and echocardiographic changes, and these changes are in strong association with BMI and for a lesser extent with electrolyte changes especially serum calcium.