Safety of Occlutech Septal Occluder ACCELL Flex II for Transcatheter Closure of Secundum Atrial Septal Defects in Children: A Long-Term Follow-Up.

OBJECTIVES: To assess the long-term safety and efficacy of the Occlutech® ACCELL® Flex II device used for atrial septal defect (ASD) closure. This device differs from the regular device by having two very thin patches that are made of polyethylene terephthalate (PET). These patches enhance faster sealing of the defect. BACKGROUND: Transcatheter closure has become the method of choice to manage most patients with secundum ASDs. There are different types of devices. The regular Occlutech device used to close an ASD is called the Occlutech Figulla Flex II. A newer modification of this device (Occlutech® ACCELL® Flex II) has been designed to eliminate/reduce thrombus formation and to enhance faster sealing. METHODS: Thirty patients were followed up after occlusion of secundum ASD using the Occlutech® ACCELL® Flex II Device. The follow-up period ranged from 5.2-5.5 years with median of 5.3 years. Detailed history and full clinical examination, twelve-lead electrocardiogram (ECG), plain chest radiograph, and full 2D transthoracic echocardiography (TTE) were performed at discharge, at one month, six months, and yearly thereafter. RESULTS: The mean age of the study group at the last follow-up was 10.4 ± 4.6 years, with 63.3% (nineteen patients) females. There were no residual shunts or complications encountered immediately after the procedure and at the latest follow-up. CONCLUSION: This study confirmed the transcatheter closure (TCC) of secundum ASDs using the Occlutech® ACCELL® Flex II device to be safe and effective with no complications detected in children and adolescents.

Experience with balloon pulmonary valvuloplasty and predictors of outcome: a ten-year study.

BACKGROUND: Balloon pulmonary valvuloplasty is the treatment of choice for patients with moderate to severe pulmonary valve stenosis. METHODS: An observational retrospective cross-sectional study including neonates, small infants, and children who underwent balloon pulmonary valvuloplasty in the period from 2007 to 2016 in the cardiac catheterisation unit of the paediatric cardiology department in Cairo University. Multivariable models were built to report the predictors of the outcome of balloon pulmonary valvuloplasty and its complications. RESULTS: A total of 1200 patients were included in the study and divided according to age into 3 groups: neonates and early infants (n = 282), infants (n = 362), and children (n = 556). Procedural success, defined as a drop pressure gradient across the pulmonary valve to less than or equal to 50% of the baseline measurements, was achieved in 82.7% of the patients. Multivariate analysis revealed that only infundibular pulmonary stenosis (p value 0.032), supravalvular in association with valvular pulmonary stenosis (p value <0.001), and pulmonary valve diameter by angiogram (p value <0.001) were significant predictors of success. The presence of supravalvular in association with valvular pulmonary stenosis (p value <0.001) was associated with a lower weight (p value 0.007) and higher right ventricular pressure before the intervention (p value <0.001), and a minor immediate drop in the pressure gradient post-intervention (p value <0.001) was found to be the most significant predictor of the occurrence of complications. CONCLUSION: The absence of infundibular and supravalvular stenosis and a large pulmonary valve diameter were the most significant predictors of success.

Clinical and biochemical spectrum of metabolic cardiomyopathy in Egyptian children.

Background: Inborn errors of metabolism (IEMs) commonly present with pediatric cardiomyopathy. Identification of the underlying cause is necessary as it may lead to improved outcomes. Objectives: We aimed to investigate the diagnostic rate, the clinical, and biochemical spectra of IEMs among Egyptian pediatric patients presenting with cardiomyopathy, and their outcome measures. Methods: We retrospectively analyzed the clinical, biochemical, and radiological data of 1512 children diagnosed with cardiomyopathy at Cairo University Children's Hospital over a 5-year duration. Results: Two hundred twenty-nine children were clinically suspected as IEMs and underwent metabolic workup. Nineteen different IEMs were confirmed in 57 (24.4%) of the suspected children. Their median age at presentation was 2.6 years and the majority had extra-cardiac manifestations. Hypertrophic cardiomyopathy represented 43/57 (75.4%) of confirmed cases, while dilated cardiomyopathy represented 13/57 (22.8%), and one patient presented with a mixed phenotype. Twenty- six patients (45.6%) survived, while 31 patients (54%) either died or were lost to follow up and assumed deceased. Conclusions: We developed for the first time a database and a diagnostic scheme for metabolic cardiomyopathies in Egyptian children. With the recent introduction of enzyme replacement therapy, many metabolic disorders became treatable, thus establishing an early and accurate diagnosis is extremely important.

Erythropoietin protects against doxorubicin-induced heart failure.

The hormone erythropoietin (EPO) has been demonstrated to have cardioprotective properties. The present study investigates the role of EPO to prevent heart failure following cancer treatment with doxorubicin [adriamycin (AD)]. Male Wistar rats (150 ± 10 g) were treated with saline (vehicle control group); with EPO, subcutaneously at 1,000 IU/kg body wt, three times per week for 4 wk (EPO group); with adriamycin, intraperitoneally at 2.5 mg/kg body wt, three times per week for 2 wk (AD group); and with adriamycin and EPO (EPO-AD group). Echocardiographic measurements showed that EPO-AD treatment prevented the AD-induced decline in cardiac function. Each of the hearts was then exposed to ischemia and reperfusion during Langendorff perfusion. The percentage of recovery after ischemia-reperfusion was significantly greater in EPO-AD than the AD-treated group for left ventricular developed pressure, maximal increase in pressure, and rate pressure product. The level of oxidative stress was significantly higher in AD (5 µM for 24 h)-exposed isolated cardiomyocytes; EPO (5 U/ml for 48 h) treatment prevented this. EPO treatment also decreased AD-induced cardiomyocyte apoptosis, which was associated with the decrease in the Bax-to-Bcl2 ratio and caspase-3 activation. Immunostaining of myocardial tissue for CD31 showed a significant decrease in the number of capillaries in AD-treated animals. EPO-AD treatment restored the number of capillaries. In conclusion, EPO treatment effectively prevented AD-induced heart failure. The protective effect of EPO was associated with a decreased level of oxidative stress and apoptosis in cardiomyocytes as well as improved myocardial angiogenesis.

Incidental diagnosis of 17 alpha-hydroxylase deficiency: a case report.

A 17 alpha-hydroxylase deficiency (17OHD) is a rare form of congenital adrenal hyperplasia (CAH). In this article we discuss a case of 8-year-old girl presented with upper respiratory infection symptoms and a history of hospital admission of fatigue and dehydration. She was incidentally found to have hypertension and hypokalemia. After an endocrine workup her biochemical tests showed: metabolic alkalosis, low levels of cortisol, high levels of adrenocorticotropic hormone (ACTH) and follicle-stimulating hormone (FSH) with normal female phenotype and (46,XY) karyotype. These findings led to the diagnosis of 17OHD confirmed by regression of hypertension and hypokalemia with hydrocortisone prescription. This case shows the importance of vital signs measurement, medical history and commitment to a systematic approach.

Diagnostic dilemma of cardiac syncope in pediatric patients.

AIMS: Syncope is defined as temporary loss of consciousness and postural tone resulting from an abrupt transient decrease in cerebral blood flow. The present work aimed at determining how diagnostic tests are used in the evaluation of pediatric syncope at a tertiary pediatric referral center and to report on the utility and the yield of these tests. SETTINGS AND DESIGN: Retrospective study conducted at a tertiary referral arrhythmolology service METHODS AND MATERIAL: The clinical charts of 234 pediatric patients presenting with a primary complaint of syncope with an average age of 7.48 +/- 3.82(3.5-16) years were reviewed by the investigators. STATISTICAL ANALYSIS USED: Statistical Package of social science (SPSS) version 9,0 was used for analysis of data. RESULTS: The commonest trigger for syncope in the study population was early following exercise (n=65) and the commonest prodrome was palpitation, noted in 25 patients. A murmur was present in 19 of our patients (8.3%) while 10.7% (n=25) had abnormal ECGs. Of the 106 echocardiograms done, 14 (13.2%) were abnormal. Only two of them were missed by ECG. All patients were offered ambulatory 24 hour ECG. One patient with sick sinus syndrome was diagnosed only with Holter. CONCLUSIONS: Clues to the presence of cardiac syncope may include acute onset of syncope, frequent episodes, low difference between blood pressure readings in supine and erect positions (after standing for 2 minutes) and most importantly an abnormal 12 lead ECG. Transthoracic echo and Holter monitoring have low yield in pediatric syncope.

Comparison of adipose tissue- and bone marrow- derived mesenchymal stem cells for alleviating doxorubicin-induced cardiac dysfunction in diabetic rats.

INTRODUCTION: Doxorubicin (DOX) is a well-known anticancer drug. However its clinical use has been limited due to cardiotoxic effects. One of the major concerns with DOX therapy is its toxicity in patients who are frail, particularly diabetics. Several studies suggest that mesenchymal stem cells (MSCs) have the potential to restore cardiac function after DOX-induced injury. However, limited data are available on the effects of MSC therapy on DOX-induced cardiac dysfunction in diabetics. Our objective was to test the efficacy of bone marrow-derived (BM-MSCs) and adipose-derived MSCs (AT-MSCs) from age-matched humans in a non-immune compromised rat model. METHODS: Diabetes mellitus was induced in rats by streptozotocin injection (STZ, 65 mg/kg b.w, i.p.). Diabetic rats were treated with DOX (doxorubicin hydrochloride, 2.5 mg/kg b.w, i.p) 3 times/wk for 2 weeks (DOX group); or with DOX+ GFP labelled BM-MSCs (2x106cells, i.v.) or with DOX + GFP labelled AT-MSCs (2x106cells, i.v.). Echocardiography and Langendorff perfusion analyses were carried out to determine the heart function. Immunostaining and western blot analysis of the heart tissue was carried out for CD31 and to assess inflammation and fibrosis. Statistical analysis was carried out using SPSS and data are expressed as mean ± SD. RESULTS: Glucose levels in the STZ treated groups were significantly greater than control group. After 4 weeks of intravenous injection, the presence of injected MSCs in the heart was confirmed through fluorescent microscopy and real time PCR for ALU transcripts. Both BM-MSCs and AT-MSCs injection prevented DOX-induced deterioration of %FS, LVDP, dp/dt max and rate pressure product. Staining for CD31 showed a significant increase in the number of capillaries in BM-MSCs and AT-MSCs treated animals in comparison to DOX treated group. Assessment of the inflammation and fibrosis revealed a marked reduction in the DOX-induced increase in immune cell infiltration, collagen deposition and αSMA in the BM-MSCs and AT-MSCs groups. CONCLUSIONS: In conclusion BM-MSCs and AT-MSCs were equally effective in mitigating DOX-induced cardiac damage by promoting angiogenesis, decreasing the infiltration of immune cells and collagen deposition.

MEFV gene mutations and cardiac phenotype in children with familial Mediterranean fever: a cohort study.

BACKGROUND: Familial Mediterranean fever (FMF) is the most common autoinflammatory disorder in the world. It is characterized by recurrent febrile inflammatory attacks of serosal and synovial membranes. MEFV gene mutations are responsible for the disease and its protein product, pyrin or marenostrin, plays an essential role in the regulation of the inflammatory reactions. Although the disease may carry a potential for cardiovascular disorders because of sustained inflammation during its course, the spectrum of cardiac involvement in children with FMF has not been well studied. We aimed at defining the frequency and spectrum of cardiac affection in children with FMF. The correlation between these affections and MEFV gene mutations was searched for to establish the relationship between cardiac phenotype and the patient's genotype in FMF. METHODS: The present work is a cohort study including 55 patients with the clinical diagnosis of FMF based on the Tel-Hashomere criteria, confirmed by genetic analysis showing homozygous or compound heterozygous mutation of MEFV genes. Fifty age- and sex-matched normal children were included as controls. The entire study group underwent detailed cardiac examination, 12-lead ECG and echocardiography. All data was statistically analysed using SPSS version-15. RESULTS: Patients had an average age of 8.5+/-4.2 years; with an average disease duration of 2.1+/-2.2 years; 28 were males. All controls showed no MEVF gene mutations. The most frequent gene mutation of the studied cases was E148Q mutation seen in 34% of cases and the most frequent compound mutation was E148Q/V726A seen in 16.6% of cases. Echocardiographic examination revealed pericardial effusion in nine patients. Twelve had aortic regurgitation; nine had mitral regurgitation and six had pulmonary regurgitation. The most common mutation associated with pericardial effusion was E148Q/V726A in 5/9 of cases. Valvular involvement were significantly more common in FMF patients with gene mutations. Also cardiac involvement was more common in patients with positive consanguinity. However, these cardiac manifestations showed no correlation to age, family history of FMF, or response to therapy or laboratory data. CONCLUSIONS: In our cohort of children with FMF, cardiac involvement appears to be common. Pericardial effusions are significantly related to presence of mutation types E48Q, P 369S, V726A. These associations may warrant genetic screening of children with FMF to detect cardiac risk.

Transcatheter closure of secundum ASD using Occlutech Figulla-N device in symptomatic children younger than 2 years of age.

INTRODUCTION: Atrial septal defect (ASD) transcatheter occlusion techniques have become alternatives to surgical procedures. We evaluated the efficiency and safety of the Occlutech Figulla-N device in percutaneous closure of secundum ASDs in symptomatic children younger than 2 years of age. METHODS: The study included 17 patients (9 girls, 8 boys; mean age, 10.3 ± 2.1 months). Mean weight was 7.4 ± 1.3 kg, with secundum ASDs measuring more than 8 mm with a hemodynamically significant shunt, resulting in failure to thrive, right ventricular dilatation, and pulmonary hypertension. Two girls had fenestrated ASD secundum. Defect size and total interatrial septal length were estimated by transthoracic (TTE) and transesophageal (TEE) echocardiography in 3 views. Procedures were performed under fluoroscopic and TEE guidance. Patients were followed-up at 1, 3, 6, and 12 months with TTE. RESULTS: The mean defect size was 15.4 ± 2.7 mm on TTE and 17.1 ± 1.9 mm on TEE. The mean device size was 17.8 ± 3.6 mm (range, 10 to 24 mm). The mean pulmonary artery pressure was 54 ± 18 mm Hg. The device was placed successfully in all patients including fenestrated ASDs that were closed with a single device placement. No residual flow was seen after device placement in patients. Complications were seen in 2/17 patients (11.8%) in the form of sinus tachycardia in 1 patient and femoral vein hematoma in 1 patient. At 6 and 12 months, all the patients were asymptomatic. No cardiac perforation, device erosion, embolization, thrombus formation, or malposition of the device was observed. Three patients developed mild insignificant mitral regurgitation. CONCLUSIONS: ASD closure in severely symptomatic children younger than 2 years of age using the Occlutech Figulla-N occluder is safe and efficient. Meticulous care to patient selection, adequate defect sizing, and device size selection are keys to lower incidence of complications.

Balloon angioplasty for native aortic coarctation in children and infants younger than 12 months: immediate and medium-term follow-up.

BACKGROUND: Despite more than 20 years of experience, balloon angioplasty as treatment for native coarctation of the aorta (CoA) during childhood remains controversial. METHODS AND RESULTS: Fifty-three pediatric patients with discrete native coarctation for whom balloon angioplasty (BA) was performed were included in this study. Patients were divided into 3 groups: group A patients, ≤3 months of age (n = 20); group B patients, between 4-12 months of age (n = 15); and group C patients, between 1 and 12 years (n = 18). Mean age at BA was 0.9 months for group A, 6.5 months for group B, and 7.8 years for group C. The mean body weight was 4.2 kg for group A, 8.6 kg for group B, and 15.3 kg for group C. Successful BA was achieved in 48 of 53 patients (90.6%). Follow-up revealed re-coarctation in 13/53 patients (24.5%); 6 patients with restenosis were referred for surgery, and 7 underwent a second BA procedure. At the end of the study period, BA was effective in 88.7% of patients. The incidence of peripheral vascular complications following BA was higher in group A (17%). Aneurysms were detected in 3/20 (15%) in group A and 2/15 (13.3%) in group B. CONCLUSIONS: BA is a safe and effective treatment for native aortic coarctation. Due to the risk of aneurysm formation in children, cautious selection of patients, the use of low-profile balloons, and state-of-the-art postoperative care are imperative to improve patient outcomes and decrease the risk of complications.

Percutaneous closure of medium and large PDAs using amplatzer duct occluder (ADO) I and II in infants: safety and efficacy.

BACKGROUND: The use of the Amplatzer duct occluder (ADO; AGA Medical Corporation) is well established and reported in children and adults, but there are only occasional reports on use in symptomatic infants. METHODS AND RESULTS: Between March 2009 and January 2011, a group of 47 infants less than 2 years of age with symptomatic patent ductus arteriosus (PDA) was treated using ADO I and II devices. Patients were divided into infants less than 1 year old (group A; n = 28/47; 59.6%) and children between 1 and 2 years old (group B; n = 19/47; 40.4%). Physical examinations and echocardiograms were performed before the procedure and at follow-up (3, 6, and 12 months). Mean age was 5.3 ± 2.3 months for group A and 12.6 ± 1.7 months for group B. Mean weight at closure was 4.8 ± 1.9 kg for group A and 7.3 ± 2.1 kg for group B. ADO I was deployed in 19/28 of group A (67.9%) and 16/19 of group B (84.2%). ADO II was used in 9/28 of group A (32.1%) and 3/19 of group B (15.8%). No residual shunt at the end of the procedure was detected by angiography in any of the cases closed with ADO I and only 3/12 (25%) closed with ADO II showed a minimal residual flow. No mortality or major complications occurred. Six months after closure, weight gain, control of respiratory infections, and regression of left ventricular dilatation with improved systolic function were observed. CONCLUSIONS: Percutaneous closure of moderate to large PDAs using ADO I and II devices in infants and children younger than 2 years of age is safe and effective.

Association of tumor necrosis factor-alpha polymorphisms with susceptibility and clinical outcomes of rheumatic heart disease.

OBJECTIVE: To examine the association of tumor necrosis factor-alpha (TNF-alpha) gene polymorphisms with rheumatic heart disease (RHD) and valve damage, and their influence on TNF-alpha production and disease outcome. METHODS: We performed this cross-sectional study at Kasr El-Aini Hospital, Cairo University, Cairo, Egypt, from December 2008 to October 2009. Eighty children with chronic RHD and valve affection, and 50 controls were included. Patients with any other diseases or complications were excluded. Blood samples (5 ml) were collected. Genotyping for TNF-alpha polymorphisms was performed by the polymerase chain reaction-restriction fragment length polymorphism method. Serum TNF-alpha was measured by enzyme-linked immunosorbent assay. RESULTS: Serum TNF-alpha was significantly increased in RHD compared with controls (p=0.00003). The TNF-alpha -238 adenine (AA) (p=0.036) and -308AA (p=0.003) genotypes were more frequent in RHD patients than in controls, and were associated with increased production of TNF-alpha (p=0.00001 for 238AA) and (p=0.001 for 308AA). Both polymorphisms contributed to increased susceptibility for RHD (-308AA and adenine guanine (AG), odds ratio [OR]=4.72 [95% confidence interval [CI] 2.03-11.05], p=0.0001); (-238 AA and AG, OR=2.33 [CI: 1.05-5.19], p=0.035). The presence of -308AA was associated with mitral (p=0.001) and multivalvular (p=0.003) lesions and was more prevalent in moderate (p=0.001), and severe (p<0.001) cases than in controls. The -238AA variant was associated with mitral lesions (p=0.04) and severe cases (p=0.05) as compared with controls. CONCLUSION: The TNF-alpha-238G/A and -308G/A polymorphisms were associated with susceptibility to RHD and increased production of TNF-alpha. Both polymorphisms were related to valve damage, and a more severe outcome of RHD.