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.

Evolution and Development of the Atrial Septum.

The complete division of the atrial cavity by a septum, resulting in a left and right atrium, is found in many amphibians and all amniotes (reptiles, birds, and mammals). Surprisingly, it is only in eutherian, or placental, mammals that full atrial septation necessitates addition from a second septum. The high incidence of incomplete closure of the atrial septum in human, so-called probe patency, suggests this manner of closure is inefficient. We review the evolution and development of the atrial septum to understand the peculiar means of forming the atrial septum in eutherian mammals. The most primitive atrial septum is found in lungfishes and comprises a myocardial component with a mesenchymal cap on its leading edge, reminiscent to the primary atrial septum of embryonic mammals before closure of the primary foramen. In reptiles, birds, and mammals, the primary foramen is closed by the mesenchymal tissues of the atrioventricular cushions, the dorsal mesenchymal protrusion, and the mesenchymal cap. These tissues are also found in lungfishes. The closure of the primary foramen is preceded by the development of secondary perforations in the septal myocardium. In all amniotes, with the exception of eutherian mammals, the secondary perforations do not coalesce to a secondary foramen. Instead, the secondary perforations persist and are sealed by myocardial and endocardial growth after birth or hatching. We suggest that the error-prone secondary foramen allows large volumes of oxygen-rich blood to reach the cardiac left side, needed to sustain the growth of the extraordinary large offspring that characterizes eutherian mammals. Anat Rec, 302:32-48, 2019. © 2018 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

Morphological variations of the interatrial septum in ovine heart.

Smooth septum interatrial septum, patent foramen ovale (PFO) channel and atrial septal pouches (SPs) are commonly described variants in humans. Recent discoveries on the clinical significance of left-sided SP may encourage the creation of new strategies and devices for the management of SPs. However, these strategies may first be tested in the ovine model before implementation in humans. Unfortunately, little is known about the presence of SPs in ovine. In this study a total of 60 ovine (Ovis aries) hearts were examined. The interatrial septum morphology was assessed and the PFO channel and SPs were measured. The most commonly occurring variant were PFO channels (25.0%) with channel lengths of 5.4±2.3 mm. Smooth septums were observed in 18.3% of hearts. In the remaining cases, septums had a left septal ridge (15.0%), left SP (11.7%), left septal bridge (10.0%), right SP (10.0%), or had both a right SP and left septal ridge (10.0%). No double SPs were observed. The mean right SP depth was 3.4 ± 1.2 mm, and its mean ostium width and height were 7.9±1.8 mm and 2.8±1.0, respectively. For the left SP, the mean depth was 6.0±1.7mm, the ostium width was 7.9±2.4mm, and the ostium height was 4.1±1.6mm (range: 2.3-6.4mm). In conclusion the interatrial septum of ovine hearts exhibit morphologies that are more similar to humans than they are to swine, which should be taken into account during experimental studies. The presence of a left SP in sheep hearts make ovine models a promising alternative to the human heart for developing left-sided SP management devices and techniques.

Demonstration of living anatomy clarifies the morphology of interatrial communications.

Inferences made regarding the postnatal anatomy of the atrial septum still tend to be based on developmental evidence. Although atrial septation is a well-defined process, it is remarkably complex and remains poorly understood. It is now established, however, that the process involves the conjugation of several myocardial structures and mesenchymal tissues of both intracardiac and extracardiac origin. The resultant postnatal morphology is equally complex, evidenced by the fact that, in the normal heart, only the floor of the oval fossa, along with its anteroinferior muscular buttress, are true anatomical septums. In this regard, septums can be defined as partitions that can be removed without creating communications with the extracavitary space. The true septal components are surrounded by grooves, which themselves largely represent infolding of the atrial walls. These anatomical features can now accurately be revealed using virtual dissection of CT data sets. These images, when carefully reconstructed, demonstrated the anatomy with as much accuracy as when hearts are dissected in the autopsy room. Such virtual dissection, furthermore, shows the components as they are seen within the chest, thus facilitating understanding for those intending to undertake interventional therapeutic procedures. By preparing such images, we show the complexity of the normal atrial septum and its surrounds. We show that it is only defects within the oval fossa, or the much rarer vestibular defects, which can appropriately be illustrated in the context of a normally constructed heart.

Porcine heart interatrial septum anatomy.

BACKGROUND: The left-sided atrial septal pouch (SP), a recently re-discovered anatomical structure within the human interatrial septum, has emerged as a possible source of thrombi formation and a trigger for atrial fibrillation, thereby potentially increasing the risk for ischemic stroke. In many studies, the swine interatrial septum has been used as model of the human heart. Also, possible new strategies and devices for management of the SPs may first be tested in this pig model. Therefore, in this study, we aimed to evaluate swine interatrial septum morphology and to compare it with the human analog, especially in the light of SP occurrence. METHODS: A total of 75 swine (Sus scrofa f. domestica) hearts were examined. The interatrial septum morphology was assessed, and SPs were measured. RESULTS: The most common variant of the interatrial septum was smooth septum (26.6%) followed by the patent foramen ovale channel and right SP (both 22.7%). No left or double SPs were observed. In 28.0% of all cases the fold of tissue (left septal ridge) was observed on the left side of the interatrial septum in the location where the left-sided SP should be expected. The mean length of the patent foramen ovale channel was 7.1±1.5mm. The mean right SP depth was 6.3±2.2mm, and its ostium width and height were 5.8±1.2 and 5.3±1.6mm, respectively. CONCLUSIONS: There are significant differences between human and porcine interatrial septum morphology that should be taken into account during experimental studies. The absence of the left SP in swine results in the inability to use porcine heart as an experimental model for left-sided SP management.

Geometry of Koch's triangle.

AIMS: The first aim of this study was to determine the size of the Koch's triangle. The second one was to investigate relation between its dimensions and other individual-specific and heart-specific parameters as well as to create universal formula to estimate triangle dimensions based on these parameters. METHODS AND RESULTS: This study is a prospective one, presenting 120 randomly selected autopsied hearts dissected from adult humans (Caucasian) of both sexes (31.7% females), with mean age of 49.3 ± 17.4 years. The length of triangle sides and angles were measured and the triangle area was calculated as well. Sixteen additional heart parameters were measured in order to analyse potential relationship between the dimensions of Koch's triangle and other dimensions of the heart, using linear regression analysis. The mean (±SD) length of the anterior edge was approximated to 18.0 ± 3.8 mm, the posterior edge to 20.3 ± 4.3 mm, and the basal edge to 18.5 ± 4.0 mm. The average values of the apex angle, the Eustachian angle, and the septal leaflet angle were 58.0 ± 14.4°, 53.8 ± 10.6°, and 67.6 ± 14.4°, respectively. The mean value of the Koch's triangle area was 151.5 ± 55.8 mm2. The 95th percentile of triangle's height (the distance from the apex to the coronary sinus) was 21.8 mm. CONCLUSION: Mean values and proportions of triangle's sides and angles were presented. Koch's triangle showed considerable individual variations in size. The dimensions of the triangle were strongly independent from individual-specific and heart-specific morphometric parameters; however, the maximum triangle's height can be estimated as 22 mm.

The first descriptions of various anatomical structures and embryological remnants of the heart: A systematic overview.

In the present study a brief overview of the history regarding the development of the knowledge of the macroscopic and microscopic anatomical elements of the heart along with some embryological remnants of the heart has been conducted. The evolution of the awareness as regards the various anatomical and embryonic structures of the heart began from Greek medico-philosophers, such as Hippocrates, Herophilus, Erasistratus and Galen, however, such knowledge was enpowered from the meticulous study of philosophers and physicians until the era of modern anatomy. In specific, the following anatomical and embryological structures are displayed: aortic and pulmonary valve, auricles, bundle of Kent, cardiac nerves, conduction system of the heart, ductus arteriosus, intervenous tubercle of Lower, left atrial oblique vein and ligament of Marshall, limbus of fossa ovalis, mitral and tricuspid valve, nodes or nodules of Arantius, ovale foramen, septomarginal trabecula, sinus of Valsava, small cardiac veins or vessels of Thebesius, tendinous chordae and papillary muscles, tendon of the valve of the inferior vena cava and triangle of Koch, valve of the coronary sinus, valve of the inferior vena cava.

Convergent evolutionary reduction of atrial septation in lungless salamanders.

Nearly two thirds of the approximately 700 species of living salamanders are lungless. These species respire entirely through the skin and buccopharyngeal mucosa. Lung loss dramatically impacts the configuration of the circulatory system but the effects of evolutionary lung loss on cardiac morphology have long been controversial. For example, there is presumably little need for an atrial septum in lungless salamanders due to the absence of pulmonary veins and the presence of a single source of mixed blood flowing into the heart, but whether lungless salamanders possess an atrial septum and whether the sinoatrial aperture is located in the left or right atrium are unresolved; authors have stated opposing claims since the late 1800s. Here, we use micro-computed tomography (µ-CT) imaging, gross dissection and histological reconstruction to compare cardiac morphology among lungless plethodontid salamanders (Plethodontidae), salamanders with lungs, and the convergently lungless species Onychodactylus japonicus (Hynobiidae). Plethodontid salamanders have partial atrial septa and incomplete separation of the atrium into left and right halves. Partial septation is also seen in O. japonicus. Hence, lungless salamanders from two lineages convergently evolved similar morphology of the atrial septum. The partial septum in lungless salamanders can make it appear that the sinoatrial aperture is in the left atrium, but this interpretation is incorrect. Outgroup comparisons demonstrate that the aperture is located in a posterodorsal extension of the right atrium into the left side of the heart. Independent evolutionary losses of the atrial septum may have a similar developmental basis. In mammals, the lungs induce formation of the atrial septum by secreting morphogens to neighboring mesenchyme. We hypothesize that the lungs induce atrial septum development in amphibians in a similar fashion to mammals, and that atrial septum reduction in lungless salamanders is a direct result of lunglessness.

Atrial septal pouch - Morphological features and clinical considerations.

BACKGROUND: The atrial septal pouch (SP) is a new anatomical entity within the interatrial septum. The left-sided SP may be the source of thrombus and contribute to ischemic stroke. The aim of this study was to provide a detailed morphometric description of the SP. METHODS: Two hundred autopsied hearts (23% deriving from females) with a mean age of 46.7±19.1years were investigated. We assessed the morphology of the interatrial septum. We obtained measurements and casts of the SPs, and we conducted histological staining of the left-sided SPs. RESULTS: Patent foramen ovale was observed in 25% of hearts. We found a left SP in 41.5%, right in 5.5% and a double SP in 5.5% of hearts. We found the patent foramen ovale (PFO) more often in younger hearts, and the SP and smooth septum were more prevalently found in older hearts (p=.0023). The mean volume of the left-sided SP was 0.31±0.11ml, which represented 13.6±9.4% (range: 3.1-44.9%) of the left atrial appendage volume. The SP shape resembled a cone or a cylinder with some smaller diverticula originating from the main body. The SP free wall was composed of two layers of endocardium, transverse muscle fibers and connective tissue. CONCLUSIONS: A left-sided SP was present in 47% of individuals. The SP arises as a result of PFO channel closure. The anatomy of left-sided SP may promote blood stasis and thrombus formation. The universal formula for SP volume was calculated.

Morphological study of fossa ovalis and its clinical relevance.

AIMS: Patent foramen ovale (PFO) has been implicated in the etiology of a number of different pathologies, including cryptogenic stroke, decompression sickness in divers, etc. It can act as a channel for paradoxical embolism. PFO is not an uncommon condition, with a probe-patency in 15-35% population. The fossa ovalis (FOv) varies in size and shape from heart to heart; the prominence of annulus FOv also varies. The entire FOv may be redundant and aneurysmal. The anatomico-functional characterization of interatrial septum seems to be of paramount importance for both atrial septal defect (ASD) and PFO, not only for the device selection, but also for the evaluation of the outcome of this procedure. METHOD: This study was conducted in 50 apparently normal hearts available in Department of Anatomy. After opening the right atrium, the shape of FOv was observed. The size was measured with the digital vernier caliper; the prominence and extent of limbus, and the redundancy or otherwise of FOv were noted; probe patency was confirmed. RESULTS: In the majority, FOv was oval (82%); average transverse diameter was 14.53mm and vertical 12.60mm. In 90%, the rim of the annulus was raised; in 20%, a recess was found deep to the margin of the annulus; and 18% showed probe patency. CONCLUSION: As no study of this nature has been carried out in the Indian population, this provides pertinent information on the morphology of FOv, which may be useful for device selection in treating ASD and PFO.

Anatomy of the true interatrial septum for transseptal access to the left atrium.

UNLABELLED: Clinical anatomy of the interatrial septum is treacherous, difficult and its unfamiliarity can cause many serious complications. This work aims to create an anatomical map of the true interatrial septum. An appreciation of the anatomical situation is essential for safe and efficacious transseptal access from the right atrium to the left heart chambers. Examination of 135 autopsied human hearts (Caucasian) of both sexes (28% females) aged from 19 to 94 years old (47.0±18.2) with BMI=27.1±6.0kg/m(2) was conducted. Focus was specifically targeted on the assessment of the fossa ovalis, patent foramen ovale (PFO), and right-sided septal pouch (RSP) morphology. Mean values of cranio-caudal and antero-posterior fossa ovalis diameters were 12.1±3.6 and 14.1±3.6mm, respectively. The fossa ovalis was situated an average of 10.1±4.4mm above the inferior vena cava ostium, 20.7±5.2mm from the right atrioventricular ring, and 12.6±5.2mm under the right atrium roof. Four types of fossa ovalis anatomy have been observed (smooth-56.3%, PFO-24.4%, RSP-11.9%, net-like formation-7.4%). The PFO mean channel length was 10.5±5.2mm. The tunnel-like PFO (channel length ≥12mm) was observed in 8.9% of specimens. The RSP was observed in 11.9% of specimens (with mean depth=6.3±3.8mm) and was directed apex upward in all observed specimens (may imitate the PFO channel). The fossa ovalis/interatrial septum surface area ratio was 18.3±9.0%. IN CONCLUSION: (1) An anatomical map of the interatrial septum from the right atrial side was presented. (2) The RSP may imitate the PFO channel. (3) The "true" interatrial septum represents only about 20% of the whole interatrial septum area. (4) There is wide variation in the location and geometry of the fossa ovalis. (5) We could distinguish four different types of the fossa ovalis area.

Tratamiento de la hipertensión arterial pulmonar / Treatment of pulmonary arterial hypertension

El tratamiento de la hipertensión arterial pulmonar ha presentado importantes avances en los últimos 20 años. En la actualidad, existen 3 grupos de fármacos que han demostrado su utilidad en el tratamiento de esta enfermedad: los bloqueantes de los receptores de endotelina, los inhibidores de la fosfodiesterasa y la prostaciclina y sus análogos. Se recomienda iniciar el tratamiento de los pacientes con uno de estos fármacos, la elección del cual dependerá de la gravedad inicial del paciente y de las preferencias del médico que trata. Cuando el paciente no presenta una respuesta satisfactoria, se suelen añadir nuevos fármacos que actúan por vías distintas a la del fármaco inicial. En este momento el médico que trata al paciente debe plantearse la necesidad del trasplante pulmonar como alternativa. Ante esta enfermedad rara se recomienda agrupar la máxima experiencia en lo que se conoce como centros expertos. El tratamiento ha mejorado la supervivencia de estos pacientes, pero aún queda un largo camino por recorrer hasta la curación de esta terrible enfermedad (AU)

Treatment of pulmonary arterial hypertension has achieved significant progress over the past 20 years. Currently, 3 groups of drugs have proven useful for the treatment of this disease: endothelin receptor antagonist, phosphodiesterase inhibitors and prostacyclin and its analogues. It is recommended to initiate treatment with one of these drugs, the choice depending on the initial severity of patient disease and the preferences of the treating physician. When the patient does not have a satisfactory response, new drugs acting at a different pathway are most commonly added. At this time, considering referral for lung transplantation could be an alternative. Most experts recommend grouping maximum experience in what is known as expert centers. Treatment has led to better survival in these patients, but there is still a long way to cure this life-threatening disease (AU)

Extreme variation in the atrial septation of caecilians (Amphibia: Gymnophiona).

Caecilians (order Gymnophiona) are elongate, limbless, snake-like amphibians that are the sister-group (closest relatives) of all other recent amphibians (frogs and salamanders). Little is known of their cardiovascular anatomy and physiology, but one nearly century old study suggests that Hypogeophis (family Indotyphlidae), commonly relied upon as a representative caecilian species, has atrial septation in the frontal plane and more than one septum. In contrast, in other vertebrates there generally is one atrial septum in the sagittal plane. We studied the adult heart of Idiocranium (also Indotyphlidae) using immunohistochemistry and confirm that the interatrial septum is close to the frontal plane. Additionally, a parallel right atrial septum divides three-fourths of the right atrial cavity of this species. Idiocranium embryos in the Hill collection reveal that atrial septation initiates in the sagittal plane as in other tetrapods. Late developmental stages, however, see a left-ward shift of visceral organs and a concordant rotation of the atria that reorients the atrial septa towards the frontal plane. The gross anatomies of species from six other caecilian families reveal that (i) the right atrial septum developed early in caecilian evolution (only absent in Rhinatrematidae) and that (ii) rotation of the atria evolved later and its degree varies between families. In most vertebrates a prominent atrial trabeculation associates with the sinuatrial valve, the so-called septum spurium, and the right atrial septum seems homologous to this trabeculation but much more developed. The right atrial septum does not appear to be a consequence of body elongation because it is absent in some caecilians and in snakes. The interatrial septum of caecilians shares multiple characters with the atrial septum of lungfishes, salamanders and the embryonic septum primum of amniotes. In conclusion, atrial septation in caecilians is based on evolutionarily conserved structures but possibly exhibits greater variation than in any other vertebrate order.

PARTIAL ANOMALOUS PULMONARY VENOUS CONNECTION WITH INTACT ATRIAL SEPTUM: A CASE REPORT.

Partial anomalous pulmonary venous connection (PAPVC) is a type of left to right shunt, when one or more lung veins drain to right atrium directly or indirectly via systemic veins. PAPVC is a rare condition, discovered by 0.4 to 0.7% of cases in autopsy series. It is often associated with atrial septal defect, but can be found with other congenital anomalies such as ventricular septal defect. Our report is about 42-year old woman who has right sided PAPVC draining into right brachiocephalic vein, which was incidental finding during pulmonary CT angiography. Patient had no symptoms associated with PAPVC and had no accompanied congenital anomaly, which is more rare condition. After consultations by surgeons, decision of conservative follow up was made, because of the fact that patient was asymptomatic. After performed multidetector computed tomography and image analysis in coronal, sagital and 3D reconstructions gave us superior quality images for data analysis. Once more, it confirms the role of modern high quality computed tomography in the diagnostic abilities of PAPVC.

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.

Intervenous tubercle of Lower: true tubercle or normal interatrial fold?

Richard Lower, in 1669, first described the tubercle that now bears his name, calling it the intervenous tubercle located between the fossa ovalis and the superior vena cava. The aim of the study was to confirm the existence of the tubercle as described initially by Lower, adding details of its location, dimensions, and prevalence. We examined 100 formalin-fixed human hearts. In no heart did we find any discrete tubercle or elevation of the right atrial wall superior to the superior limbus (rim) of the fossa ovalis. In addition, we could find no morphometric differences in the thickness of the area superior to the superior limbus of the fossa. Dissections revealed that very little of the extensive musculature can be removed without opening the right atrial wall and arriving outside the heart. This is the essential criterion in distinguishing folds from "true" septal structures. When viewed in this light, it is only the flap valve of the fossa ovalis, and its immediate muscular infero-anterior rim, the so-called lower limbus, that can be removed so as to create communications between the cavities of the atrial chambers, and not exiting at the same time from the cavities of the heart. This is because the larger part of the muscular borders of the fossa ovalis is no more than an infolding of the atrial walls, which incorporates extracardiac adipose tissue within the fold. Although this process of folding unequivocally produces an intracardiac buttress, namely, the limbuses (rims) of the fossa, the buttress, being an infolding, does not constitute, according to our definition, a true septum. On this basis, we suggest that it is the superior limbus of the fossa ovalis, or the superior interatrial fold, that previously has been considered to represent the intervenous tubercle of Lower.