Current Concepts of Anatomy, Electrophysiology, and Therapeutic Implications of the Interatrial Septum.

The interatrial septum (IAS), a fibromuscular structure separating the right (RA) and left (LA) atrium, plays an important role in both intra- and interatrial conduction. Electropathological changes in the IAS such as discordant activation of the right and left septal layer and conduction disorders may facilitate intraseptal re-entry and promote development of atrial tachyarrhythmias such as atrial fibrillation (AF). Various experimental studies have emphasized the importance of the IAS in AF initiation and perpetuation. Moreover, a thicker IAS has been associated with atrial tachyarrhythmias and a lower success rate of catheter ablation. Therefore, it is assumed that the septal interatrial connections, which may be more pronounced in patients with a thicker IAS, may furnish an anatomic pathway for re-entry and may explain failure of catheter ablation therapy. However, the exact role of the IAS in the treatment of AF still remains an enigma. More profound understanding of the role of the IAS in the pathophysiology of AF and other atrial tachyarrhythmias is necessary to improve success of current therapeutic options and develop new treatment modalities. This review outlines the current knowledge on the relationship between anatomic and electrophysiological properties of the IAS and discusses its involvement in atrial tachyarrhythmias.

Interatrial septal pacing to suppress atrial fibrillation in patients with dual chamber pacemakers: A meta-analysis of randomized, controlled trials.

BACKGROUND: Atrial fibrillation (AF) is of frequent occurrence in a population with bradycardia indicated for permanent dual chamber pacing. Whether selective site pacing at interatrial septum (IAS) could better prevent AF as compared with standard atrial pacing (AP) from right atrial appendage or high right atrium in these conditions remains in question. Its safety profile has yet to be elucidated. METHODS: Major web databases were searched up to February 2015 for controlled, randomized clinical trials on IAS versus conventional pacing. The primary end point was freedom from persistent/permanent AF. Secondary outcomes included device-recorded AF burden and frequency of AF episodes, lead-related complications, and major adverse events (MAEs). RESULTS: We identified 10 eligible studies incorporating a total of 1245 patients. Compared to conventional AP, IAS pacing conferred no additional benefit on the persistent/permanent AF free survival (hazard ratio 0.76, 95% confidence interval [CI] 0.48 to 1.22); it was associated with notably reduced device-detected AF burden (standard mean difference [SMD] -0.32, 95% CI -0.55 to -0.09) and AF frequency (SMD -0.54, 95% CI -0.83 to -0.24). The odds of lead-related complications (odds ratio [OR] 1.64, 95% CI 0.87 to 3.08) and combined rate of MAEs (OR 1.05, 95% CI 0.60 to 1.82) were similar between two groups. CONCLUSIONS: IAS pacing has no influence on the persistent/permanent AF progression and MAEs, although it appears to lower device-detected AF burden and AF frequency, and may carry similar risks of lead-related complications as compared to standard AP.

Tissue properties of the fossa ovalis as they relate to transseptal punctures: a translational approach.

OBJECTIVES: This study focused on how catheter size affects transseptal puncture, what transseptal indication means, and whether the swine model is predictive for humans. BACKGROUND: Transseptal puncture is a common procedure that gains access to the left atrium, allowing percutaneous mitral valve repair, left atrial appendage closure, and left-sided ablations. The basic approach has not changed in many years; however, the frequency of transseptal punctures and the size of devices are increasing with emerging treatments. METHODS: A broad range of devices (4 F to 18 F) were advanced through atrial septa of swine hearts; some devices were inserted in both swine and human hearts using 10 F catheters. RESULTS: Greater forces were required to puncture through the septa of human hearts compared to those of swine. Larger catheters used in swine hearts required greater force to advance them through the septa, causing greater dilation of tissue and sometimes tearing the floor of the fossa ovalis; analyses indicated an exponential increase in the size of the iatrogenic atrial septal defect. Specific tissue property testing of the septum primum showed that this tissue sheared at a lower exerted force in a superior to inferior direction. CONCLUSIONS: Results may provide physicians with important knowledge about what to expect when treating a possible iatrogenic atrial septal defect or help them understand the consequences of transseptal punctures. Comparative data between swine and human atrial septal tissue properties provide critical insights between the species and offer clinicians and device designers important information relative to differences in tissue behaviors.

Interatrial septum motion but not Doppler assessment predicts elevated pulmonary capillary wedge pressure in patients undergoing cardiac surgery.

BACKGROUND: Left atrial pressure and its surrogate, pulmonary capillary wedge pressure (PCWP), are important for determining diastolic function. The role of transthoracic echocardiography (TTE) in assessing diastolic function is well established in awake subjects. The objective was to assess the accuracy of predicting PCWP by TTE and transesophageal echocardiography (TEE) during coronary artery surgery. METHODS: In 27 adult patients undergoing on-pump coronary artery surgery, simultaneous echocardiographic and hemodynamic measurements were obtained immediately before anesthesia (TTE), after anesthesia and mechanical ventilation (TTE and TEE), during conduit harvest (TEE), and after separation from cardiopulmonary bypass (TEE). RESULTS: Twenty patients had an ejection fraction (EF) of 0.5 or greater. With the exception of E/e' and S/D ratios, echocardiographic values changed over the echocardiographic studies. In patients with low EF, E velocity, deceleration time, pulmonary vein D, S/D, and E/e' ratios correlated well with PCWP before anesthesia. After induction of anesthesia using TTE or TEE, correlations were poor. In normal EF patients, correlations were poor for both TEE and TTE at all five stages. The sensitivity and specificity of echocardiographic values were not high enough to predict raised PCWP except for a fixed curve pattern of interatrial septum (area under the curve 0.89 for PCWP ≥ 17, and 0.98 for ≥ 18 mmHg) and S/D less than 1 (area under the curve 0.74 for PCWP ≥ 17, and 0.78 for ≥ 18 mmHg). CONCLUSION: Doppler assessment of PCWP was neither sensitive nor specific enough to be clinically useful in anesthetized patients with mechanical ventilation. The fixed curve pattern of the interatrial septum was the best predictor of raised PCWP.

Expression of the BMP receptor Alk3 in the second heart field is essential for development of the dorsal mesenchymal protrusion and atrioventricular septation.

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 (AV) septal defect. 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 AV septal defects. 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/transforming growth factor ß signaling were 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.

An image-based model of atrial muscular architecture: effects of structural anisotropy on electrical activation.

BACKGROUND: Computer models that capture key features of the heterogeneous myofiber architecture of right and left atria and interatrial septum provide a means of investigating the mechanisms responsible for atrial arrhythmia. The data necessary to implement such models have not previously been available. The aims of this study were to characterize surface geometry and myofiber architecture throughout the atrial chambers and to investigate the effects of this structure on atrial activation. METHODS AND RESULTS: Atrial surface geometry and myofiber orientations were reconstructed in 3D at 50×50×50-µm(3) resolution from serial images acquired throughout the sheep atrial chambers. Myofiber orientations were determined by Eigen-analysis of the structure tensor. These data have been incorporated into an anatomic model that provides the first quantitative representation of myofiber architecture throughout the atrial chambers. By simulating activation on this 3D structure, we have confirmed the roles of specialized myofiber tracts such as the crista terminalis, pectinate muscles, and the Bachman bundle on the spread of activation from the sinus node. We also demonstrate how the complex myocyte arrangement in the posterior left atrium contributes to activation time dispersion adjacent to the pulmonary veins and increased vulnerability to rhythm disturbance generated by ectopic stimuli originating in the pulmonary vein sleeves. CONCLUSIONS: We have developed a structurally detailed, image-based model of atrial anatomy that provides deeper understanding of the role that myocyte architecture plays in normal and abnormal atrial electric function.

The use of balloon atrial septostomy to facilitate difficult transseptal access in patients undergoing catheter ablation for atrial fibrillation.

INTRODUCTION: With the increasing number of patients undergoing repeat catheter ablation procedures for atrial fibrillation, it is not uncommon to encounter a fibrotic interatrial septum that resists the conventional manual advancement of the transseptal sheath. Forceful advancement of the transseptal apparatus can reduce fine control and potentially lead to a higher rate of perforation. CASE: We report a case where adjunctive balloon atrial septostomy was used to facilitate transseptal access in a patient with fibrotic interatrial septum. Using a small-caliber angioplasty balloon and under direct fluoroscopic and transesophageal echocardiogram visualization, balloon septostomy was performed with hand inflation until a "waist" was seen. This technique provides a safe way to control the size of the transseptal access created, and allows the passage of a relatively soft-tipped transseptal sheath across a resistive septum. To our knowledge this is the first published use of balloon atrial septostomy during transseptal puncture for left atrium access in a catheter ablation procedure. CONCLUSION: Balloon atrial septostomy should be considered as an alternative technique for safe transseptal cannulation in select patients in the electrophysiology laboratory or other interventional procedures requiring left atrial access or delivery of large-caliber catheters or sheaths.

The initial zones of the atrioventricular node: really neglected anatomical features of potential clinical significance?

The constant evolution of medical knowledge and accompanying development of diagnostic and treatment possibilities for arrhythmias and conduction disturbances has reawakened interest in the structure and function of the conduction system of the human heart, especially in the region of the atrioventricular (AV) junction and within the junction itself. Of the large number of studies dealing with the AV junction few focus on the initial zones of the AV node. These were described for the first time by Tawara in 1906. Similarly, Anderson et al. distinguished two origins of the AV node, the left one running towards the basis of the mitral valve and the right one leading towards the tricuspid valve. The differences in length and scale could be the result of the adoption of different reference points. The study was carried out on the material of 50 human hearts, of both sexes and ranging in age from 22 to 93, which were fixed in 10% formalin and 98% ethanol solution. The tissue obtained was fixed in the 10% formalin solution and, after being sunk in the paraffin, was cut into layers of about 10 mum thick. According to the age of the hearts, every 10(th) or 6(th) section was stained by the Masson-Goldner method. The preparations were examined under a LEICA 2000 and BIOLAR 2 microscope at magnifications of 2x to 400x. Each of the 50 examined hearts contained the atrioventricular node and its initial parts. We observed that the initial zone of the AV node is created by an assembly of cells typical for a conduction system that can create three groups that are initially independent of each other and are always arranged around the AV nodal artery. In all the hearts examined we found at least two initial parts of the node: the superior and inferior. These two groups were present in 45 hearts (90%). In the last 5 cases (10%) there was also a middle group. No cases were found either with a single initial group or without any initial groups. In the sections examined the superior group appeared to be first in 27 hearts (54%), while in 23 cases (46%) the inferior group was first. The length of each group was measured from its first appearance to its first direct contact with the second part. The length of the superior part varied from 0.15 to 2.91 mm (mean 0.90 +/- 0.6 mm), the inferior from 0.11 to 2.41 mm (mean 0.88 +/- 0.6 mm) and the middle from 0.67 to 2.21 mm (mean 1.04 +/- 0.7 mm). As mentioned above, in all 50 hearts there was a direct connection between the atrial muscle and the upper origin of AV node. Furthermore, in all sections (100%) the same part of the interatrial septal muscle was connected to the compact part of the node. Additionally, in 3 cases (6%) we were able to observe direct connections between the muscle fibres running from the fasciculus limbicus inferior to the initial zone of the AV node: in 2 cases (4%) with the superior group and in 1 case (2%) with the inferior group. In 8% of the material the atrial muscle of the supra-orificial zone made direct contact with the superior initial group and the compact zone of the node and in 10% there was contact between the suborificial muscle and the inferior group and the compact part of the node. This configuration was not observed in relation to the middle and inferior groups.

The structure and components of the atrial chambers.

We discuss the implications of accurate knowledge of the human atrial chambers for those seeking to model atrial structure, and correlate the muscular activity with electrical signals. We stress first the importance of describing atrial components in attitudinally appropriate fashion, a feature sadly ignored by generations of morphologists. When considered relative to the body, the right atrium is positioned anteriorly relative to its alleged left-sided counterpart. We then described how each atrium possesses a venous component, an appendage, a vestibule, these parts being supported by the body of the atrium, and how the two chambers are separated by the septum. We extend this information by describing the detailed structure of each atrium, and then emphasise that it is only the floor of the oval fossa, and its antero-inferior rim, that are true septal structures. The so-called 'septum secundum' is the superior interatrial fold. Emphasis is then given to the muscular connections between the atriums, these unions obviously underscoring the potential for interatrial conduction. We then continue by discussing the structure of the atrial walls, which vary markedly in their thickness. It is the alignment of the myocytes within these walls that determines the velocity of conduction through them. In this setting, we also discuss the morphological features that distinguish between working myocytes and the myocytes of the conduction system, stressing the importance of rules established almost 100 years ago.