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.

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.

Outcomes of Primary Bidirectional Glenn in Children with Single Ventricle Physiology and Increased Pulmonary Blood Flow.

BACKGROUND: We reported our experience in managing patients with single ventricle (SV) physiology and increased pulmonary blood flow (PBF), aiming to assess if it is feasible to proceed with primary Bidirectional Glenn (BDG) without a prior operation to limit PBF. MATERIALS AND METHODS: This is a retrospective study with 51 consecutive patients who underwent BDG operation as a primary operation or a second stage prior to the definitive Fontan operation at King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia between 2010 and 2018. Patients were categorized into two groups based on their PBF prior to the operation: Patients who had SV physiology and increased PBF (seven patients) vs. patients with SV physiology and restricted PBF (44 patients). RESULTS: The median age for the increased PBF group was 9.9 months [interquartile range (IQR): 2-16.9 months], and the median age for the restricted PBF group was 15.3 months (IQR: 6.7-42.6 months). Although the length of hospital stay was longer in patients with increased PBF (P = 0.039), we couldn't find a statistically significant difference in early mortality, duration of mechanical ventilation, length of pleural drainage, and length of intensive care unit (ICU) stay between the groups. CONCLUSION: In our experience, we found that primary BDG could be done safely for patients having SV physiology and increased PBF with acceptable short-term outcomes. It might further reduce the morbidity and mortality for those patients by avoiding the risk of initial pulmonary artery banding or aortopulmonary shunts.

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.

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.

Echocardiographic changes and growth retardation in a group of Egyptian children with rheumatic heart disease.

BACKGROUND: Advances in echocardiographic studies have identified a massive burden of rheumatic heart disease (RHD) which continues to be a major health hazard in most developing countries. The aim of this study was to investigate the correlation between cardiac affection as regards the presence of single or multiple valvular lesions, and their severity and the growth parameters in a group of Egyptian children with RHD. METHODS: This study is a cross-sectional study, that was conducted on 200 children with RHD and 400 age-matched healthy. All subjects were subjected to anthropometric measurement and echocardiographic evaluation of the different cardiac parameters. RESULTS: Isolated mitral incompetence (MI) was the most frequent type of valvular lesion in RHD (54.0%), followed by mixed MI and aortic incompetence (AI) (26.5%). Patients with RHD were more liable to be underweight and stunted compared to controls (P<0.05). Growth retardation was significantly noticed in patients with RHD in general (P<0.05), and particularly in patients mixed MI and AI in particular (P<0.05). Also a significant association was detected between growth retardation and the severity of the valvular lesion in the group of rheumatic heart patients (P<0.05). CONCLUSIONS: Associations between growth retardation and RHD with its various patterns of valvular affection and severity were detected in the present study.

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.

Nicorandil enhances the efficacy of mesenchymal stem cell therapy in isoproterenol-induced heart failure in rats.

Stem cell transplantation has emerged as a promising technique for regenerative medicine in cardiovascular therapeutics. However, the results have been less than optimal. The aim of the present study was to investigate whether nicorandil could offer an additional benefit over bone marrow-derived mesenchymal stem cell therapy in isoproterenol-induced myocardial damage and its progression to heart failure in rats. Isoproterenol was injected subcutaneously for 2 consecutive days at doses of 85 and 170 mg/kg/day, respectively. Nicorandil (3 mg/kg/day) was then given orally with or without a single intravenous bone marrow-derived mesenchymal stem cell administration. Electrocardiography and echocardiography were recorded 2 weeks after the beginning of treatment. Rats were then sacrificed and the ventricle was isolated for estimation of tumor necrosis factor-alpha, vascular endothelial growth factor and transforming growth factor-beta. Moreover, protein expressions of caspase-3, connexin-43 as well as endothelial and inducible nitric oxide synthases were evaluated. Finally, histological studies of myocardial fibrosis and blood vessel density were performed and cryosections were done for estimation cell homing. Combined nicorandil/bone marrow-derived mesenchymal stem cell therapy provided an additional improvement compared to cell therapy alone toward reducing isoproterenol-induced cardiac hypertrophy, fibrosis and inflammation. Notably, combined therapy induced significant increase in angiogenesis and cell homing and prevented isoproterenol-induced changes in contractility and apoptotic markers. In conclusion, combined nicorandil/bone marrow-derived mesenchymal stem cell therapy was superior to cell therapy alone toward preventing isoproterenol-induced heart failure in rats through creation of a supportive environment for mesenchymal stem cells.

The influence of physiological matrix conditions on permanent culture of induced pluripotent stem cell-derived cardiomyocytes.

Cardiomyocytes (CMs) from induced pluripotent stem (iPS) cells mark an important achievement in the development of in vitro pharmacological, toxicological and developmental assays and in the establishment of protocols for cardiac cell replacement therapy. Using CMs generated from murine embryonic stem cells and iPS cells we found increased cell-matrix interaction and more matured embryoid body (EB) structures in iPS cell-derived EBs. However, neither suspension-culture in form of purified cardiac clusters nor adherence-culture on traditional cell culture plastic allowed for extended culture of CMs. CMs grown for five weeks on polystyrene exhibit signs of massive mechanical stress as indicated by α-smooth muscle actin expression and loss of sarcomere integrity. Hydrogels from polyacrylamide allow adapting of the matrix stiffness to that of cardiac tissue. We were able to eliminate the bottleneck of low cell adhesion using 2,5-Dioxopyrrolidin-1-yl-6-acrylamidohexanoate as a crosslinker to immobilize matrix proteins on the gels surface. Finally we present an easy method to generate polyacrylamide gels with a physiological Young's modulus of 55 kPa and defined surface ligand, facilitating the culture of murine and human iPS-CMs, removing excess mechanical stresses and reducing the risk of tissue culture artifacts exerted by stiff substrates.

Evidence for self-maintaining pluripotent murine stem cells in embryoid bodies.

Pluripotent stem cells have great potential for regenerative medicine; however, their clinical use is associated with a risk of tumor formation. We utilized pluripotent cells expressing green fluorescent protein and puromycin resistance under control of the Oct4 promoter to study the persistence of potential pluripotent cells under embryoid body (EB) culture conditions, which are commonly used to obtain organotypic cells. We found that i.) OCT4-expressing cells dramatically decrease during the first week of differentiation, ii.) the number of OCT4-expressing cells recovers from day 7 on, iii.) the OCT4-expressing cells are similar to embryonic stem cells grown in the presence of leukemia inhibitory factor LIF but express several markers associated with germ cell formation, such as DAZL and STRA-8 and iv.) the persistence of potentially pluripotent cells is independent of supportive cells in EBs. Finally, OCT4-expressing cells, isolated from EBs after 2-month of culture, were further maintained under feeder-free conditions in absence of LIF and continued to express OCT4 in 95 % of the population for at least 36 days. These findings point to an alternative state of stable OCT4 expression. In the frame of the landscape model of differentiation two attractors of pluripotency might be defined based on their different characteristics.