Partitioning of the four-chambered heart requires the proper formation, interaction and fusion of several mesenchymal tissues derived from different precursor populations that together form the atrioventricular mesenchymal complex. This includes the major endocardial cushions and the mesenchymal cap of the septum primum, which are of endocardial origin, and the dorsal mesenchymal protrusion (DMP), which is derived from the Second Heart Field. Failure of these structures to develop and/or fully mature results in atrial septal defects (ASDs) and atrioventricular septal defects (AVSD). AVSDs are congenital malformations in which the atria are permitted to communicate due to defective septation between the inferior margin of the septum primum and the atrial surface of the common atrioventricular valve. The clinical presentation of AVSDs is variable and depends on both the size and/or type of defect; less severe defects may be asymptomatic while the most severe defect, if untreated, results in infantile heart failure. For many years, maldevelopment of the endocardial cushions was thought to be the sole etiology of AVSDs. More recent work, however, has demonstrated that perturbation of DMP development also results in AVSD. Here, we discuss in detail the formation of the DMP, its contribution to cardiac septation and describe the morphological features as well as potential etiologies of ASDs and AVSDs.

Rationale The Dorsal Mesenchymal Protrusion (DMP) is a prong of mesenchyme derived from the Second Heart Field (SHF) located at the venous pole of the developing heart. Recent studies have shown that perturbation of its development is associated with the pathogenesis of atrioventricular septal defect (AVSD). Although the importance of the DMP to AV septation is now established, the molecular and cellular mechanisms underlying its development are far from fully understood. Prior studies have demonstrated that bone morphogenetic protein (BMP) signaling is essential for proper formation of the AV endocardial cushions and the cardiac outflow tract. A role for BMP signaling in regulation of DMP development remained to be elucidated. Objective To determine the role of BMP signaling in DMP development. Methods and Results Conditional deletion of the BMP receptor Alk3 from venous pole SHF cells leads to impaired formation of the DMP and a completely penetrant phenotype of ostium primum defect, a hallmark feature of AVSDs. Analysis of mutants revealed decreased proliferative index of SHF cells and, consequently, reduced number of SHF cells at the cardiac venous pole. In contrast, volume and expression of markers associated with proliferation and active BMP/TGFβ signaling was not significantly altered in the AV cushions of SHF-Alk3 mutants. Conclusions BMP signaling is required for expansion of the SHF-derived DMP progenitor population at the cardiac venous pole. Perturbation of Alk3-mediated BMP signaling from the SHF results in impaired development of the DMP and ostium primum defects.

AimTo investigate atrial flow patterns in the normal adult heart, to explore whether caval vein arrangement and patency of the foramen ovale (PFO) may be associated with flow pattern.Materials and MethodsTime-resolved, three-dimensional velocity encoded magnetic resonance imaging (4D flow) was employed to assess atrial flow patterns in thirteen healthy subjects (6 male, 40 years, range 25–50) and thirteen subjects (6 male, 40 years, range 21–50) with cryptogenic stroke and patent foramen ovale (CS-PFO). Right atrial flow was defined as vortical, helico-vortical, helical and multiple vortices. Time-averaged and peak systolic and diastolic flows in the caval and pulmonary veins and their anatomical arrangement were compared.ResultsA spectrum of right atrial flow was observed across the four defined categories. The right atrial flow patterns were strongly associated with the relative position of the caval veins. Right atrial flow patterns other than vortical were more common (p = 0.015) and the separation between the superior and inferior vena cava greater (10±5mm versus 3±3mm, p = 0.002) in the CS-PFO group. In the left atrium all subjects except one had counter-clockwise vortical flow. Vortex size varied and was associated with left lower pulmonary vein flow (systolic r = 0.61, p = 0.001, diastolic r = 0.63 p = 0.002). A diastolic vortex was less common and time-averaged left atrial velocity was greater in the CS-PFO group (17±2cm/sec versus 15±1, p = 0.048). One CS-PFO subject demonstrated vortical retrograde flow in the descending aortic arch; all other subjects had laminar descending aortic flow.ConclusionRight atrial flow patterns in the normal heart are heterogeneous and are associated with the relative position of the caval veins. Patterns, other than ‘typical’ vortical flow, are more prevalent in the right atrium of those with cryptogenic stroke in the context of PFO. Left atrial flow patterns are more homogenous in normal hearts and show a relationship with flow arising from the left pulmonary veins.

Background: Atrial flutter is the most common arrhythmia post cardiac transplantation. Observational studies in the non-transplant population have shown prognostic benefit with catheter ablation; however, there are no data in the heart transplant population.

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Introduction Platydeoxia orthopnoea is a rare syndrome characterised by desaturation and dyspnoea on movement from standing to supine in the presence of an intra-cardiac shunt. The pathophysiology is poorly understood. Methods We report a case with patent foramen ovale (PFO). Cardiac catheterisation and 4D-flow magnetic resonance (MR) were performed (Philips Achieva 3T, 6-channel array, retrospective ECG and respiratory gated TFE, spat res: 3 mm3, temp res: 50–55 ms, 20 phases). Pathline analysis was performed with GTflow (v2.0, Gyrotools). Results A 65 year-old man presented with desaturation during anaesthetic induction for anterior vitrectomy. He was asymptomatic. He had Type 2 diabetes mellitus, hypertension, hypercholesterolemia and centripetal obesity (BMI 38). Pulse oximetry showed saturations of 92% (standing) and 80% (supine). Supine pO2 was 5.9KPa. Spirometry was normal and CT excluded arterio-venous malformation. TOE demonstrated a tunnel-type PFO with spontaneous right to left shunt. At catheterisation (Table 1), right and left atrial pressures were normal (6 and 8 KPa). There was no pulmonary hypertension. On PFO balloon occlusion, pulse oximetry showed saturations of 97%. 4D-flow MR demonstrated reversal of the usual right atrial vortex. Inferior vena cava flow intersected with superior vena cava flow in a perpendicular fashion and was directed towards the PFO (Figure 1). The usual anticlockwise left atrial vortex was absent with a small clockwise vortex seen in the region of the right upper pulmonary vein, entraining the PFO flow. Amplatzer PFO device closure normalised saturations in both upright and supine positions. Abstract 120 Figure 1 Right atrial flow (anterior aspect) in a) control showing usual forward turning right atrial vortex and in b) subject showing perpendicular arrival of IVC flow. Reversal of vortex and laree shunt across PFO Abstract 120 Table 1 Saturations at cardiac Discussion This case is one of a handful reported and the first to begin to define the pathophysiology of this condition. Despite suboptimal 4D-flow MR due to body habitus and breathing pattern, we demonstrate disturbance of the usual flow patterns that facilitate substantial shunting across the PFO. Whilst the positional component needs further investigation, we hypothesise that the relationship between the inferior vena cava and right atrium may contribute.

Catheter ablation versus escalation of antiarrhythmic medications for management of ventricular tachycardia in patients with ischaemic heart disease (Protocol).

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