Multiscale modelling of Potts shunt as a potential palliative treatment for suprasystemic idiopathic pulmonary artery hypertension: a paediatric case study.

Potts shunt (PS) was suggested as palliation for patients with suprasystemic pulmonary arterial hypertension (PAH) and right ventricular (RV) failure. PS, however, can result in poorly understood mortality. Here, a patient-specific geometrical multiscale model of PAH physiology and PS is developed for a paediatric PAH patient with stent-based PS.

Cardiovascular anatomy in children with bidirectional Glenn anastomosis, regarding the transcatheter Fontan completion.

Background: Transcatheter stent-secured completion of total cavopulmonary connection (TCPC) after surgical preparations during the Glenn anastomosis procedure has been reported, but complications from this approach have precluded its clinical acceptance.

Aims: To analyse cardiovascular morphology and dimensions in children with bidirectional Glenn anastomosis, regarding the optimal device design for transcatheter Fontan completion without special surgical "preconditionings".

Methods: We retrospectively analysed 60 thoracic computed tomography and magnetic resonance angiograms performed in patients with a median age of 4.

Safety and Feasibility of the Transcatheter Approach to Create a Reverse Potts Shunt in Children With Idiopathic Pulmonary Arterial Hypertension.

Background: The reversed Potts shunt improves right ventricular (RV) function in patients with suprasystemic pulmonary arterial hypertension (PAH). The proximity of the left pulmonary artery (LPA) to the descending aorta (DAo) permits the creation of a transcatheter connection. We sought to assess the safety, feasibility, and hemodynamic efficacy of the transcatheter Potts shunt (TPS) in children.

Valve Interventions in Utero: Understanding the Timing, Indications, and Approaches.

Efficient use of fetal echocardiography has enabled early detection of congenital heart disease and of its often irreversible complications, such as ventricular hypoplasia in case of severe stenosis of the semilunar valves. Experience of the past 25 years has proved that balloon dilatation of the severely stenotic or atretic valve in fetuses as early as the 23rd week of gestation is technically feasible with a learning curve. Reported results regarding the ultimate biventricular circulation outcome after fetal valve intervention are at best controversial, with the desired improvements in the quality of life and cost-benefits of the postnatal treatment being as yet unconfirmed.

Vascular anatomy in children with univentricular hearts regarding transcatheter bidirectional Glenn anastomosis.

Background: Transcatheter stent-secured Glenn anastomosis, aiming to reduce the invasiveness of palliation in patients with univentricular heart defects, has been reported in large experimental animals. The advent of biodegradable stents and tissue-engineered vascular grafts will make this procedure a reality in human patients. However, the relationship between the superior vena cava (SVC) and the right pulmonary artery (RPA) is different in humans.

Vascular anatomy in children with pulmonary hypertension regarding the transcatheter Potts shunt.

Objective: To morphometrically characterise the region of adjacent descending aorta (DAo) and left pulmonary artery (LPA) regarding the transcatheter creation of the reverse Potts shunt.

Methods And Results: Retrospective review of the invasive haemodynamic data and measurements of the vessel diameters, distances and angles based on the thoracic CT of children with idiopathic pulmonary arterial hypertension (PAH) with pulmonary-to-systemic systolic pressure ratio ≥0.5.

Novel materials and devices in the transcatheter management of congenital heart diseases-the future comes slowly (part 3).

Correction of malformations affecting the right ventricular outflow tract often results in residual abnormalities that require valve implantation at a later stage to prevent right ventricular deterioration. In the paediatric population, the pathology of congenital valve stenosis or insufficiency is often complex, options for surgical repair are limited, and valve replacement remains the only-albeit unattractive-alternative. Prosthetic heart valve implantation can be performed either surgically or, nowadays, percutaneously.

Novel materials and devices in the transcatheter creation of vascular anastomosis--the future comes slowly (part 2).

Completion of the total cavopulmonary connection and creation of the majority of vascular anastomoses are currently usually performed surgically. The major disadvantage of the surgical approach, however, is its invasiveness, as patients undergoing cardiac surgery generally need sternotomy and cardiopulmonary bypass - often with cardiac arrest - commonly resulting in a prolonged and complicated postoperative intensive care period. Transcatheter procedures, in contrast, have a lower risk of complications, shorter intensive care and total hospital stays, and do not need a cardiopulmonary bypass or sternotomy.

Novel materials and devices in the transcatheter management of congenital heart diseases--the future comes slowly (part 1).

Management of congenital defects of the heart and great vessels constitutes the largest part of paediatric cardiology practice. Most of these defects require interventions, either corrective or palliative, to guarantee patient survival, symptom relief and/or better quality of life. Interventions can be performed either surgically or transcatheter percutaneously.

Building foundations for transcatheter intervascular anastomoses: 3D anatomy of the great vessels in large experimental animals.

Objectives: To provide comprehensive illustrations of anatomy of the relevant vessels in large experimental animals in an interactive format as preparation for developing an effective and safe transcatheter technique of aortopulmonary and bidirectional cavopulmonary intervascular anastomoses.

Methods: Computed tomographic angiographic studies in two calves and two sheep were used to prepare 3D reconstructions of the aorta, pulmonary arteries, and caval and pulmonary veins. Based on these reconstructions, computer simulations of the creation of stent-enhanced aortopulmonary and bidirectional cavopulmonary anastomoses were made.

Development of the human aortic arch system captured in an interactive three-dimensional reference model.

Variations and mutations in the human genome, such as 22q11.2 microdeletion, can increase the risk for congenital defects, including aortic arch malformations. Animal models are increasingly expanding our molecular and genetic insights into aortic arch development.

Three-dimensional and molecular analysis of the arterial pole of the developing human heart.

Labeling experiments in chicken and mouse embryos have revealed important roles for different cell lineages in the development of the cardiac arterial pole. These data can only fully be exploited when integrated into the continuously changing morphological context and compared with the patterns of gene expression. As yet, studies on the formation of separate ventricular outlets and arterial trunks in the human heart are exclusively based on histologically stained sections.

A frameshift mutation in LRSAM1 is responsible for a dominant hereditary polyneuropathy.

Despite the high number of genes identified in hereditary polyneuropathies/Charcot-Marie-Tooth (CMT) disease, the genetic defect in many families is still unknown. Here we report the identification of a new gene for autosomal dominant axonal neuropathy in a large three-generation family. Linkage analysis identified a 5 Mb region on 9q33-34 with a LOD score of 5.

Molecular analysis of patterning of conduction tissues in the developing human heart.

Background: Recent studies in experimental animals have revealed some molecular mechanisms underlying the differentiation of the myocardium making up the conduction system. To date, lack of gene expression data for the developing human conduction system has precluded valid extrapolations from experimental studies to the human situation.

Methods And Results: We performed immunohistochemical analyses of the expression of key transcription factors, such as ISL1, TBX3, TBX18, and NKX2-5, ion channel HCN4, and connexins in the human embryonic heart.

Impairment of the tRNA-splicing endonuclease subunit 54 (tsen54) gene causes neurological abnormalities and larval death in zebrafish models of pontocerebellar hypoplasia.

Pontocerebellar hypoplasia (PCH) represents a group (PCH1-6) of neurodegenerative autosomal recessive disorders characterized by hypoplasia and/or atrophy of the cerebellum, hypoplasia of the ventral pons, progressive microcephaly and variable neocortical atrophy. The majority of PCH2 and PCH4 cases are caused by mutations in the TSEN54 gene; one of the four subunits comprising the tRNA-splicing endonuclease (TSEN) complex. We hypothesized that TSEN54 mutations act through a loss of function mechanism.

Three-dimensional and molecular analysis of the venous pole of the developing human heart.

Background: Various congenital malformations and many abnormal rhythms originate from the venous pole of the heart. Because of rapid changes during morphogenesis, lack of molecular and lineage data, and difficulties in presenting complex morphogenetic changes in the developing heart in a clear fashion, the development of this region in human has been difficult to grasp.

Methods And Results: To gain insight into the development of the different types of myocardium forming the venous pole of the human heart, we performed an immunohistochemical and 3-dimensional analysis of serial sections of human embryos ranging from 22 through 40 days of development.

Lack of Gata3 results in conotruncal heart anomalies in mouse.

The transcription factor Gata3 is an important regulator of the development of thymus, the nervous system, ear, kidney, and adrenal glands. This study analyzes the role of Gata3 in the developing heart using a mouse strain containing an nlsLacZ reporter gene fused in frame to the Gata3 gene by homologous recombination. Using in situ hybridization, RT-PCR and Gata3-LacZ histochemistry, Gata3 expression was shown in various cardiac structures up to newborn stage.