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.

Morphological pattern of intrinsic nerve plexus distributed on the rabbit heart and interatrial septum.

Although the rabbit is routinely used as the animal model of choice to investigate cardiac electrophysiology, the neuroanatomy of the rabbit heart is not well documented. The aim of this study was to examine the topography of the intrinsic nerve plexus located on the rabbit heart surface and interatrial septum stained histochemically for acetylcholinesterase using pressure-distended whole hearts and whole-mount preparations from 33 Californian rabbits. Mediastinal cardiac nerves entered the venous part of the heart along the root of the right cranial vein (superior caval vein) and at the bifurcation of the pulmonary trunk. The accessing nerves of the venous part of the heart passed into the nerve plexus of heart hilum at the heart base. Nerves approaching the heart extended epicardially and innervated the atria, interatrial septum and ventricles by five nerve subplexuses, i.e. left and middle dorsal, dorsal right atrial, ventral right and left atrial subplexuses. Numerous nerves accessed the arterial part of the arterial part of the heart hilum between the aorta and pulmonary trunk, and distributed onto ventricles by the left and right coronary subplexuses. Clusters of intrinsic cardiac neurons were concentrated at the heart base at the roots of pulmonary veins with some positioned on the infundibulum. The mean number of intrinsic neurons in the rabbit heart is not significantly affected by aging: 2200 ± 262 (range 1517-2788; aged) vs. 2118 ± 108 (range 1513-2822; juvenile). In conclusion, despite anatomic differences in the distribution of intrinsic cardiac neurons and the presence of well-developed nerve plexus within the heart hilum, the topography of all seven subplexuses of the intrinsic nerve plexus in rabbit heart corresponds rather well to other mammalian species, including humans.

Parasympathetic and substance P-immunoreactive nerve denervation in atrial fibrillation models.

BACKGROUND: Recent studies demonstrated that atrial fibrillation (AF) induced heterogeneous sympathetic hyperinnervation and baroreflex impartation, but the changes of vagal and afferent nerve are not clear. METHODS: Six dogs underwent atrial pacing at 600 beats/min (AF group). All paced dogs developed sustained AF by 5 weeks of pacing. Tissues from six healthy dogs were used as controls. Immunohistochemistry staining of cardiac nerves was performed using anti-growth-associated protein 43 (anti-GAP43), anti-tyrosine hydroxylase, antiacetylcholine (anti-ACh), and anti-substance P (anti-SP) antibodies. RESULTS: In AF group, the density of GAP43-positive in the right atrium (RA), atrial septum (AS), and left atrium (LA) was 5590.24±1417.51, 8083.22±1271.39, and 10854.56±1877.56 µm(2)/mm(2), respectively, which was significantly (P<.01) higher than the control group. Most of the newly sprouting nerves are sympathetic nerve. Sympathetic nerve density in AF group was significantly higher than that of control group (P<.001). Whereas denervation of parasympathetic and SP-immunoreactive nerve occurred in AF group. In the dogs with AF, the density of ACh-positive nerve in the RA, AS, and LA was 506.04±104.44, 317.72±84.10, and 114.9±29. 62 µm(2)/mm(2), respectively, which was lower than the control group (P<.01). At the same time, the density of SP-positive nerve in the atria of AF dogs was also significantly lower than the control tissues (P<.01). CONCLUSION: AF led to significant nerve sprouting and sympathetic hyperinnervation in the canine models, but the newly sprouting nerve did not include parasympathetic and SP-immunoreactive nerve. Heterogeneous parasympathetic and SP-immunoreactive nerve denervation occurred in the AF dogs.

Does Bachmann's bundle pacing prevent atrial fibrillation in myotonic dystrophy type 1 patients? A 12 months follow-up study.

AIMS: Paroxysmal atrial arrhythmias occur in myotonic dystrophy type 1 (MD1) patients frequently. Pacemaker (PM) including detailed diagnostic functions may facilitate the diagnosis and management of frequent paroxysmal atrial tachyarrhythmias that may remain undetected during conventional clinical follow-up. Aim of our study was to evaluate the preventive effects of interatrial septum pacing in the Bachmann's Bundle region on atrial fibrillation (AF) in MD1 patients during 12 months follow up period. METHODS AND RESULTS: Thirty MD1 patients (age 50.3 +/- 7.3; 11 F) who underwent dual chamber PM implantation were randomized at implantation to receive right atrial appendage pacing (16 patients) or Bachmann's bundle pacing (14 patients). No statistically significant difference in the electrical parameters (P wave amplitude, pacing threshold and lead impedance) was found between the two groups at implantation. Patients were followed at 1 month, 3 months, and every 6 months thereafter. They underwent clinical assessment, a standard 12-lead ECG and assessment of device performance at every visit. We counted the number of episodes of atrial arrhythmia occurred during the collection period and the duration of each episode. At 12 months of follow-up, no statistically significant differences in the number of AF episodes or in AF duration were found. Lead parameters remained stable over time and there were no displacements of the electrodes after implantation. CONCLUSION: Implantation of an atrial-active fixation lead on the atrial septum is safe and feasible. However, this study showed no significant difference between septal pacing and high atrial pacing, using the endpoints of AF duration and number of AF episodes.

Substrates for intra-atrial and interatrial conduction in the atrial septum: anatomical study on 84 human hearts.

BACKGROUND: Technical developments in the management of atrial arrhythmias revived interest into the detailed knowledge of atrial anatomy. The atrial septum (AS), known for its complex structure, has been particularly difficult to study, and our knowledge of the muscular bundles providing routes for intra-atrial and interatrial conduction within the AS remains limited. OBJECTIVE: The purpose of this study was to describe myocardial arrangement within the AS and adjacent parts of atrial walls for delineation of possible substrates for interatrial and intra-atrial conduction. METHODS: Human heart specimens from 84 postmortem studies were studied using conventional morphometric assessment, blunt dissection, and light microscopy of serial histological sections of AS. RESULTS: Interatrial muscular connections are present anteriorly, posteriorly between right pulmonary veins, and inferiorly between the coronary sinus and the right inferior pulmonary vein. The inferior connections can be more prominent than the Bachmann bundle. Atrial musculature in the fossa ovalis consists of muscular bands isolated by fatty tissue from the endocardium of the right and left atrium. They are arranged along the anterior-posterior axis and have connections with left atrial myocardium. Myocardial fascicles in the posterior-inferior and superior portions of the muscular rim of fossa ovalis originate on the right atrial side and can be traced toward the atrioventricular node. CONCLUSION: The general myocardial arrangement in the AS and adjacent regions of atrial walls are important for understanding propagation of atrial activation for selection of the optimal treatment strategy.

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.

Septal atrial pacing for the prevention of atrial fibrillation.

AIMS: Atrial fibrillation (AF) produces significant morbidity and mortality. The current method of permanent pacing of the right atrium (RA) may cause delayed interatrial conduction and predispose to AF. We hypothesized that atrial septal pacing would reduce AF compared with high RA pacing. METHODS AND RESULTS: The patients were randomized into two groups. After randomization, patients received a dual-chamber rate-responsive device capable of mode-switching with advanced telemetry features. Devices were programmed in a standardized manner. To be eligible, the patients were required to have a conventional indication for a permanent pacemaker and recurrent paroxysmal AF. Group 1 was paced from high RA and Group 2 was paced from the atrial septum. Analysis of 43 patients who have completed 6 months of follow-up and 22 patients who completed 12 months of follow-up showed no significant differences in the number of mode-switching episodes or in AF burden between groups (P = NS by Mann-Whitney) although there was a trend for less AF with septal pacing. There were no differences in thresholds, sensing, or lead impedance. Lead parameters remained stable over time and there were no displacements of the electrodes after implantation. No patient experienced lead-related complications. A significant variability in AF burden was noted in this patient population. CONCLUSIONS: Implantation of an atrial-active fixation lead on the atrial septum is safe and feasible. However, this study showed no significant difference between septal pacing and high atrial pacing, using the endpoints of AF duration and number of AF episodes.