Staged Percutaneous Management of Pulmonary Atresia and Intact Interventricular Septum: Stretching the Limits.

Aims: Pulmonary atresia with intact ventricular septum (PA/IVS) can be treated by catheter-based interventions and complemented by various surgical procedures. We aim to determine a long-term treatment strategy to enable patients to be surgery free, depending solely on percutaneous interventions. Methods and Results: We selected five patients from among a cohort of patients with PA/IVS treated at birth with radiofrequency perforation and dilatation of the pulmonary valve. Patients had reached a pulmonary valve annulus of 20 mm or larger on their biannual echocardiographic follow-up, with right ventricular dilatation. The findings, together with the right ventricular outflow tract and pulmonary arterial tree, were confirmed by multislice computerised tomography. Based on the angiographic size of the pulmonary valve annulus, all patients were successfully implanted with either Melody® or Edwards® pulmonary valves percutaneously, regardless of their small weights and ages. No complications were encountered. Conclusion: We managed to stretch the age and weight limitations for performing percutaneous pulmonary valve implantation (PPVI): interventions were attempted whenever a pulmonary annulus size of >20 mm was reached, which was rationalised by the prevention of progressive right ventricular outflow tract dilatation and accommodating valves between 24 and 26 mm, which is enough to sustain a normal pulmonary flow in adulthood.

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.

Rheology of right ventricular outflow tract obstruction: sub-pulmonary membrane developing months after primary intervention to treat pulmonary atresia with intact interventricular septum.

Isolated sub-pulmonary membrane is a rare condition, the origin of which has been debatable. Transcatheter treatment of pulmonary valve atresia with intact interventricular septum by radiofrequency perforation and balloon dilatation to restore biventricular circulation is gaining more popularity, with improving results over time. We report in our experience of 79 cases in 10 years the development of a sub-pulmonary membrane in 4 cases: causing significant obstruction requiring surgical excision in one case that revealed a fibrous membrane on pathology; causing mild right ventricular outflow tract obstruction in another and not yet causing obstruction in 2. On cardiac MRI, the right ventricular outflow tract and the right ventricular outflow tract/pulmonary atresia angle showed no morphological abnormalities.

Molecular analysis of dilated and left ventricular noncompaction cardiomyopathies in Egyptian children.

BACKGROUND: Paediatric cardiomyopathy is a progressive, often lethal disorder and the most common cause of heart failure in children. Despite its severe outcomes, the genetic aetiology is still poorly characterised. High-throughput sequencing offers a great opportunity for a better understanding of the genetic causes of cardiomyopathy. AIM: The current study aimed to elucidate the genetic background of cardiomyopathy in Egyptian children. METHODS: This hospital-based study involved 68 patients; 58 idiopathic primary dilated cardiomyopathy and 10 left ventricular noncompaction cardiomyopathy. Cardiomyopathy-associated genes were investigated using targeted next-generation sequencing. RESULTS: Consanguinity was positive in 53 and 70% of dilated cardiomyopathy and left ventricular noncompaction cardiomyopathy patients, respectively. Positive family history of cardiomyopathy was present in 28% of dilated cardiomyopathy and 10% of the left ventricular noncompaction cardiomyopathy patients. In 25 patients, 29 rare variants were detected; 2 likely pathogenic variants in TNNI3 and TTN and 27 variants of uncertain significance explaining 2.9% of patients. CONCLUSIONS: The low genetic detection rate suggests that novel genes or variants might underlie paediatric cardiomyopathy in Egypt, especially with the high burden of consanguinity. Being the first national and regional report, our study could be a reference for future genetic testing in Egyptian cardiomyopathy children. Genome-wide tests (whole exome/genome sequencing) might be more suitable than the targeted sequencing to investigate the primary cardiomyopathy patients. Molecular characterisation of cardiomyopathies in different ethnicities will allow for global comparative studies that could result in understanding the pathophysiology and heterogeneity of cardiomyopathies.

Genetic study of pediatric hypertrophic cardiomyopathy in Egypt.

Paediatric cardiomyopathy is a progressive and often lethal disorder and the most common cause of heart failure in children. Despite their severe outcomes, their genetic etiology is still poorly characterised. The current study aimed at uncovering the genetic background of idiopathic primary hypertrophic cardiomyopathy in a cohort of Egyptian children using targeted next-generation sequencing. The study included 24 patients (15 males and 9 females) presented to the cardiomyopathy clinic of Cairo University Children's Hospital with a median age of 2.75 (0.5-14) years. Consanguinity was positive in 62.5% of patients. A family history of hypertrophic cardiomyopathy was present in 20.8% of patients. Ten rare variants were detected in eight patients; two pathogenic variants (8.3%) in MBPC3 and MYH7, and eight variants of uncertain significance in MYBPC3, TTN, VCL, MYL2, CSRP3, and RBM20.Here, we report on the first national study in Egypt that analysed sarcomeric and non-sarcomeric variants in a cohort of idiopathic paediatric hypertrophic cardiomyopathy patients using next-generation sequencing. The current pilot study suggests that paediatric hypertrophic cardiomyopathy in Egypt might have a particular genetic background, especially with the high burden of consanguinity. Including the genetic testing in the routine diagnostic service is important for a better understanding of the pathophysiology of the disease, proper patient management, and at-risk detection. Genome-wide tests (whole exome/genome sequencing) might be better than the targeted sequencing approach to test primary hypertrophic cardiomyopathy patients in addition to its ability for the identification of novel genetic causes.

Left ventricular diastolic dysfunction without left ventricular hypertrophy in obese children and adolescents: a Tissue Doppler Imaging and Cardiac Troponin I Study.

BACKGROUND: Obesity increases the risk for various cardiovascular problems. Increase in body mass index is often an independent risk factor for the development of elevated blood pressure and clustering of various cardiovascular risk factors. OBJECTIVE: To determine early markers of left ventricular affection in obese patients before the appearance of left ventricular hypertrophy. METHODS: In this cross-sectional study, we evaluated 42 obese patients and 30 healthy controls. Their ages ranged from 6 to 19 years. Studied children were subjected to anthropometric, lipid profile, and serum Troponin I level measurements. Echocardiographic evaluation performed to assess the left ventricle included left ventricular dimension measurement using motion-mode echocardiography, based on which patients with left ventricular hypertrophy (10 patients) were eliminated, as well as conventional and tissue Doppler imaging. RESULTS: Tissue Doppler findings in the study groups showed that the ratio of transmitral early diastolic filling velocity to septal peak early diastolic myocardial velocity (E/e') was significantly higher in cases compared with controls [6.9±1.4 versus 9.0±1.6, p (Pearson's coefficient)=0.001, respectively]. The level of cardiac troponin I was significantly higher in cases compared with controls [0.14±0.39 ng/ml versus 0.01±0.01 ng/ml, p (Pearson's coefficient)=0.047, respectively] and there was a significant correlation between troponin I and transmitral early diastolic filling velocity to septal peak early diastolic myocardial velocity ratio (E/e') [R (correlation coefficient)=0.6]. CONCLUSION: Tissue Doppler Imaging and Troponin I evaluation proved useful tools to detect early affection of the left ventricle in obese patients even in the absence of left ventricular hypertrophy.

Incomplete RV Remodeling After Transcatheter ASD Closure in Pediatric Age.

Published data showing the intermediate effect of transcatheter device closure of atrial septal defect (ASD) in the pediatric age-group are scarce. The objective of the study was to assess the effects of transcatheter ASD closure on right and left ventricular functions by tissue Doppler imaging (TDI). The study included 37 consecutive patients diagnosed as ASD secundum by transthoracic echocardiography and TEE and referred for transcatheter closure at Cairo University Specialized Pediatric Hospital, Egypt, from October 2010 to July 2013. Thirty-seven age- and sex-matched controls were selected. TDI was obtained using the pulsed Doppler mode, interrogating the right cardiac border (the tricuspid annulus) and lateral mitral annulus, and myocardial performance index (MPI) was calculated at 1-, 3-, 6- and 12-month post-device closure. Transcatheter closure of ASD and echocardiographic examinations were successfully performed in all patients. There were no significant differences between two groups as regards the age, gender, weight or BSA. TDI showed that patients with ASD had significantly prolonged isovolumetric contraction, relaxation time and MPI compared with control group. Decreased tissue Doppler velocities of RV and LV began at one-month post-closure compared with the controls. Improvement in RVMPI and LVMPI began at 1-month post-closure, but they are still prolonged till 1 year. Reverse remodeling of right and left ventricles began 1 month after transcatheter ASD closure, but did not completely normalize even after 1 year of follow-up by tissue Doppler imaging.

Hypertrophic cardiomyopathy: prognostic factors and survival analysis in 128 Egyptian patients.

BACKGROUND: Hypertrophic cardiomyopathy is an important cause of disability and death in patients of all ages. Egyptian children may differ from Western and Asian patients in the pattern of hypertrophy distribution, clinical manifestations, and risk factors. OBJECTIVES: The aim of our study was to report the clinical characteristics and outcomes of Egyptian children with hypertrophic cardiomyopathy studied over a 7-year duration and to determine whether the reported adult risk factors for sudden cardiac death are predictive of the outcome in these affected children. STUDY DESIGN AND METHODS: This retrospective study included 128 hypertrophic cardiomyopathy children. The data included personal history, family history, physical examination, baseline laboratory measurements, electrocardiogram, and Holter and echocardiographic results. Logistic regression analysis was used for the detection of risk factors of death. RESULTS: Fifty-one out of 128 patients died during the period of the study. Of the 51 deaths, 36 (70.5%) occurred in patients presenting before 1 year of age. Only eight patients had surgical intervention. Extreme left ventricular hypertrophy, that is, interventricular septal wall thickness or posterior wall thickness Z-score >6, sinus tachycardia, and supraventricular tachycardia were found to be independent risk factors for prediction of death in patients with hypertrophic cardiomyopathy. CONCLUSIONS: At our Egyptian tertiary care centre, hypertrophic cardiomyopathy has a relatively worse prognosis when compared with reports from Western and Asian series. Infants have a worse outcome than children presenting after the age of 1 year. A poorer prognosis in childhood hypertrophic cardiomyopathy is predicted by an extreme left ventricular hypertrophy, the presence of sinus tachycardia, and supraventricular tachycardia.

New Strategies in the Treatment of Advanced Heart Failure in Children and the Current Consensus of Cairo University Children Hospital Heart Failure Working Group.

The long-term treatment of congestive heart failure (CHF) in children includes digoxin, diuretics and afterload reduction with angiotensin-converting enzyme (ACE) inhibitors. In spite of the wide use of these drugs being the standard, yet, pediatric heart failure (PHF) continued to be an important cause of morbidity and mortality in childhood. Introduction of new drugs has elevated the level of tolerance of these patients and played a role in delaying their urgent need to have heart transplant or Mechanical circulatory support (MCS). Together with a patient by patient tailored combination of different diuretics. We aim to present and discuss these new drugs and the combinations of regular drugs to reach the best outcome, as well as the consensus of our pediatric heart failure working group in Egypt.

Outcome Predictors in Catheter Interventions for Severe Right Ventricular Outflow Tract Obstructions.

Introduction & aim of work: Transcatheter treatment for critical pulmonary stenosis and membranous pulmonary atresia has become the gold standard of care in many centers. We aimed at evaluating the predictors of outcome in interventions for treatment of duct-dependent right ventricular outflow tract obstruction with intact interventricular septum. Subjects & methods: 68 cases with pulmonary atresia with intact interventricular septum (PA/IVS) and 50 cases with critical pulmonary stenosis (CPS), all younger than 3 months of age, were operated during the period of 10 years; excluding patients with tricuspid valve annulus Z-score smaller than -4, evidence of right ventricular-dependent coronary circulation or additional malformations. Results: Age, weight, body surface area as well as tricuspid & pulmonary valve Z-scores were significantly less in PA/IVS; right ventricular pressure was similar in both groups however procedural success and survival to hospital discharge was higher in the CPS group. Lower age, weight and body surface area were associated with procedural failure. Weight was the only predictor of procedural success; while weight and lower post-procedural right ventricular pressure were independent predictors for survival to hospital discharge. Post-procedural right ventricular pressure and length of stay were less in the CPS group. tricuspid and pulmonary valve annulus Z-scores were the only independent predictors of the post-procedural milrinone duration in PA/IVS. Conclusion: We advocate for the use of larger balloon/pulmonary annulus ratio, to achieve a lower right ventricular pressure not fearing excessive pulmonary regurgitation that might be beneficial for right ventricular growth; and for the combination with ductal stenting in borderline or bipartite right ventricles.

miR-454-3p and miR-194-5p targeting cardiac sarcolemma ion exchange transcripts are potential noninvasive diagnostic biomarkers for childhood dilated cardiomyopathy in Egyptian patients.

BACKGROUND: Childhood dilated cardiomyopathy (CDCM) is the most common cardiomyopathy in children and it is risk factor to heart failure and sudden death. Most of the different etiologic factors which have been postulated to DCM are idiopathic, and its pathogenesis remains uncertain. So it was worth investigating the potential DCM pathogenicity models to establish early noninvasive diagnosis parameters especially in CDCM patients. Beside that miRNAs in the circulatory blood are genetically considered the best option for noninvasive diagnosis; also, implementation of miRNAs as early diagnostic markers for children with DCM is urgent because those children have high risk to sudden heart death. We aimed to identify discriminator diagnostic circulatory miRNA expression levels in CDCM patients. RESULTS: The expression levels of miR-454-3p and miR-194-5p were found significant upregulated (p value = 0.001 and 0.018; CI 95%, respectively), while miR-875-3p was found significant downregulated (p value = 0.040; CI 95%). A receiver operating characteristic (ROC) curve analysis showed significant AUC = 1.000 and 0.798 for miR-454-3p and miR-194-5p, respectively, and the optimal discriminated diagnostic cut-points were computed by index of union (IU) method. Enrichment analysis for the potential targeted mature mRNAs by miR-454-3p and miR-194-5p pointed that Ca, Na and K ions homeostasis in cardiac sarcolemma consider potential CDCM pathogenicity model. CONCLUSIONS: miR-454-3p and miR-194-5p are highly influencing noninvasive biomarkers for CDCM, and further circulatory miRNAs-implicated studies are highly recommended.

Correlating SFTPC gene variants to interstitial lung disease in Egyptian children.

BACKGROUND: Interstitial lung disease (ILD) is a broad heterogeneous group of lung disorders that is characterized by inflammation of the lungs. Surfactant dysfunction disorders are a rare form of ILD diseases that result from mutations in surfactant protein C gene (SFTPC) with prevalence of approximately 1/1.7 million births. SFTPC patients are presented with clinical manifestations of ILD ranging from fatal respiratory failure of newborn to chronic respiratory problems in children. In the current study, we aimed to investigate the spectrum of SFTPC genetic variants as well as the correlation of the SFTPC gene mutations with ILD disease in twenty unrelated Egyptian children with diffuse lung disease and suspected surfactant dysfunction using Sanger sequencing. RESULTS: Sequencing of SFTPC gene revealed five variants: c.42+35G>A (IVS1+35G>A) (rs8192340) and c.43-21T>C (IVS1-21T>C) (rs13248346) in intron 1, c.436-8C>G (IVS4-8C>G) (rs2070687) in intron 4, c.413C>A p.T138N (rs4715) in exon 4, and c.557G>Ap.S186N (rs1124) in exon 5. CONCLUSION: The present study confirms the association of detecting variants of SFTPC with surfactant dysfunction disorders.

Novel biomarkers for subtle myocardial involvement in type I diabetes mellitus.

BACKGROUND: Evaluation of certain biomarkers could be used to predict left ventricular (LV) and right ventricular (RV) function impairment in children with type 1 diabetes mellitus. The aim of this study was to determine the best cardiac biomarker for prediction of diabetic cardiomyopathy. METHODOLOGY: This study was designed as case-control study. A total of 55 children with type 1 diabetes mellitus (group/G1) and 55 healthy controls (G2) were subjected to echocardiography including 3D-Speckle Tracking Echocardiography and tissue Doppler imaging for assessment of RV and LV systolic and diastolic functions. As well as HbA1c, troponin I, brain natriuretic peptide (BNP), plasma cardiotrophin (CT-1), activin-A, transforming growth factor-ß, and human insulin-like growth factor binding protein-7 (IGFBP-7) measurements. RESULTS: Diabetic patients showed RV and LV systo-diastolic dysfunction compared to controls, the best predictor of LV systolic dysfunction was CT-1 (sensitivity: 69%, while IGFBP-7 was found to be the best predictor of RV systolic dysfunction (sensitivity: 63%). BNP was found to the best predictor of diastolic RV and LV dysfunction (sensitivity: 82% for both). CONCLUSION: CT-1 has proven to be a diagnostic superiority in LV systolic dysfunction whilst BNP continues to prove every day through our study and through many others that it is the chief marker of diastolic dysfunction and HFpEF. This potential accuracy and the increasing availability of BNP in the outpatient setting make it clear that it should be used as a screening test for diabetic patients.

Parameters affecting outcome of paediatric cardiomyopathies in the intensive care unit: experience of an Egyptian tertiary centre over 7 years.

Introduction: Paediatric cardiomyopathies are rare but serious and often life-threatening conditions. In the absence of cardiac transplant and ventricular assist device as treatment options in our region, it is very important to identify patients at higher risk. The aim of this study was to determine the outcome of patients diagnosed with cardiomyopathies and their prognostic indicators. Patients and methods: This study included 92 cases representing all patients diagnosed with cardiomyopathy who were admitted into the pediatric cardiac intensive care unit during the period from January 2012 to September 2018. The patients were classified into two groups according to the outcome: the first group comprised 69 patients who survived, and the second group comprised 23 patients who died. All medical records were reviewed, and data were recorded and analysed. Results: Patients with cardiomyopathies represented 8.6% (92/1071) of all patients with cardiac diseases who were admitted in the study period and in the target age group (0.5-12 years). Dilated cardiomyopathy (DCM) was the most frequent type of cardiomyopathy among the admitted patients (80 patients), while 6 patients were diagnosed with hypertrophic cardiomyopathy (HCM), 4 were diagnosed with restrictive cardiomyopathy (RCM), and only 2 were diagnosed with mixed DCM-RCM. Seventy patients required inotropic support (76.1%). Assisted mechanical ventilation was used on 15 patients (16.3%). Twenty-three patients (25.0%) died during the 7-year study period. Conclusions Conclusions The occurrence of hypotension, abnormally high liver enzymes, the need for mechanical ventilation and the need for multiple inotropic drugs were found to be statistically significant predictors of mortality, while age, sex, fractional shortening, ejection fraction, presence of mitral regurgitation, mural thrombus, electrolyte disturbance and arrhythmias did not predict or affect patients' outcomes.

ASD device closure in pediatrics: 3-Dimensional transthoracic echocardiography perspective.

OBJECTIVE: Real-time three-dimensional echocardiography, using both reconstruction methods and RT3D, has been used as an extra helping tool in several forms of congenital heart diseases. Our aim was to understand the relation of the ASD device to all surrounding structures by 3-dimensional echocardiography (3D). METHODS: This prospective study included 37 patients diagnosed as ASD secundum by transthoracic (TTE) and transesophageal echocardiography (TEE) referred for transcatheter closure from October 2013 to July 2016. Follow-up for 1 year using 2D and 3D-echocardiography was performed to assess the relations of the device to the surrounding structures. RESULTS: Transcatheter ASD closure and echocardiographic examinations were successfully performed for all patients. By 3D echocardiography, 16 patients (43.24%) had their ASD device close to the aortico-mitral continuity plane without apparent regurgitation, while the rest of our patients (56.75%) the devices were away from this plane. The following variables were significantly different between the two groups; body surface area, atrioventricular rim (AV), device size, left disc size and ratio of left disc to interatrial septum. A cut-off AV rim length not less than 8 mm was found optimal to avoid device encroachment on the sensitive surrounding structures. New Formula was constructed to aid in device choice. CONCLUSION: Use of 3D before and after ASD closure is of value to determine the device relation to the surrounding structures. AV rim by TEE is an important rim to avoid eventual encroachment on the mitral valve and aorta.

Cost-effectiveness analysis of different devices used for the closure of small-to-medium-sized patent ductus arteriosus in pediatric patients.

AIMS: In this study, we examined the differences in cost and effectiveness of various devices used for the closure of small to medium sized patent ductus arteriosus (PDA). SETTING AND DESIGN: We retrospectively studied 116 patients who underwent closure of small PDAs between January 2010 and January 2015. SUBJECTS AND METHODS: Three types of devices were used: the Amplatzer duct occluder (ADO) II, the cook detachable coil and the Nit Occlud coil (NOC). Immediate and late complications were recorded and patients were followed up for 3 months after the procedure. STATISTICAL METHODS: All statistical calculations were performed using Statistical Package for the Social Science software. P <0.05 were considered significant. RESULTS: We successfully deployed ADO II devices in 33 out of 35 cases, cook detachable coils in 36 out of 40 cases and NOCs in 38 out of 41 cases. In the remaining nine cases, the first device was unsuitable or embolized and required retrieval and replacement with another device. Eleven patients (9.5%) developed vascular complications and required anticoagulation therapy. Patients who had hemolysis or vascular complications remained longer in the intensive care unit, with consequently higher total cost (P = 0.016). Also, the need for a second device increased the cost per patient. CONCLUSIONS: The cook detachable coil is the most cost-effective device for closure of small-to medium-sized PDAs. Calculations of the incremental cost-effectiveness. (ICE) revealed that the Cook detachable coil had less ICE than the ADO II and NOC. The NOC was more effective with fewer complications.

New Pediatric Version of Balloon-Assisted Technique for Atrial Septal Defect Closure Using Self-Centering Devices: Relation to Interatrial Septal Thickness.

AIM: Some difficult atrial septal defect (ASD) cases with deficient rims or large defects may require specific maneuvers to facilitate transcatheter occlusion of these defects with self-centering devices. In our center, we developed a modification of balloon-assisted technique (BAT) for difficult ASDs to assist proper positioning of the device. Our aim was to demonstrate the efficiency of ASD closure with self-centering devices in children and to present the results of the new pediatric version of BAT (PBAT) in young children and its relation to the interatrial septal thickness. METHODS AND RESULTS: Over 2 years, a total of 65 patients with ASD secundum were referred for closure, from which 50 cases were deemed suitable for transcatheter closure by transthoracic echocardiography during precatheter evaluation. Ten difficult defects required assisted techniques; 6 of these were successfully closed using the PBAT with a small-sized valvuloplasty balloon. The cut-off levels for needing an assistance technique in pediatric patients were age >5 years, ASD >16 mm, and weight >22 kg. The interatrial septal thickness was thinner in young ASD patients. CONCLUSION: The PBAT was needed to optimize device closure in difficult cases, especially in large defects without rim deficiency. This technique is easy to learn and results in quick and simple device closure.