Evidence for concealed fasciculo-ventricular connections as revealed by His bundle pacing.

BACKGROUND: It is almost 100 years ago since Mahaim described the so-called paraspecific connections between the ventricular conduction axis and the crest of the muscular ventricular septum, believing such pathways to be ubiquitous. These pathways, however, have yet to be considered as potential pathways for septal activation during His bundle pacing. MATERIALS: So as to explore the hypothesis that specialised septal pathways might provide the substrate for septal activation during His bundle pacing, we compared the findings from 22 serially sectioned histological datasets and 34 different individuals undergoing His bundle pacing. RESULTS: We found histologically specialised pathways connecting the branching component of the atrioventricular conduction axis with the crest of the muscular ventricular septum in almost four-fifths of the histological datasets. In 32 of 34 patients undergoing His bundle pacing, the QRS complex closely resembled published images of known conduction through fasciculo-ventricular pathways. In only two patients was a delta wave not seen at any pacing voltages. Capture of these connections varied according to pacing voltage, a finding which correlated with the distance of the pathways from the site of penetration of the ventricular conduction axis. Ventricular activation times remained normal in the presence of the delta wave at higher pacing voltage but were prolonged at lower voltages. CONCLUSIONS: Our histologic findings confirm fasciculo-ventricular connections, initially described by Mahaim as being paraspecific, are likely ubiquitous. Analysis of 12-lead electrocardiograms leads us to conclude that fasciculo-ventricular pathways, concealed during sinus rhythm, become manifest with His bundle pacing.

Vulnerability of the ventricular conduction axis during transcatheter aortic valvar implantation: A translational pathologic study.

The ventricular components of the conduction axis remain vulnerable following transcatheter aortic valvar replacement. We aimed to describe features which may be used accurately by interventionalists to predict the precise location of the conduction axis, hoping better to avoid conduction disturbances. We scanned eight normal adult heart specimens by 3T magnetic resonance, using the images to simulate histological sections in order accurately to place the conduction axis back within the heart. We then used histology, tested in two pediatric hearts, to prepare sections, validated by the magnetic resonance images, to reveal the key relationships between the conduction axis and the aortic root. The axis was shown to have a close relationship to the nadir of the right coronary leaflet, in particular when the aortic root was rotated in counterclockwise fashion. The axis was more vulnerable in the setting of a narrow inferoseptal recess, when the inferior margin of the membranous septum was above the plane of the virtual basal ring, and when minimal myocardium was supporting the right coronary sinus. The features identified in our study are in keeping with the original description provided by Tawara, but at variance with more recent accounts. They suggest that the vulnerability of the axis during transcatheter valvar replacement can potentially be inferred on the basis of knowledge of the position of the aortic root within the ventricular base. If validated by clinical studies, our findings may better permit avoidance of new-onset left bundle branch block following transcatheter aortic valvar replacement.

Miniseries 1-Part IV: How frequent are fasciculo-ventricular connections in the normal heart?

AIMS: Seeking to account for accessory atrioventricular conduction potentially leading to ventricular pre-excitation, Mahaim in the mid-20th century had described pathways between the atrioventricular conduction axis and the muscular ventricular septum. We aimed to look for such 'paraspecific' connections in adult human hearts. METHODS AND RESULTS: We serially sectioned 21 hearts, covering the triangle of Koch and the aortic root, and assessing the atrioventricular node, the penetration of the conduction axis, and the bundle branches in our search for fasciculo-ventricular connections. We also calculated the length of the non-branching bundle, and if present the origin of the fasciculo-ventricular connections. The non-branching bundle was 3.6 ± 1.7 mmin length, varying from 1.7 mm to 7.2 mm. Fasciculo-ventricular connections were found in more than half of the hearts, making direct contact with the muscular septum at an average of 3.5 ± 1.7 mm from the origin of the left bundle branch, with the site of origin varying from 1.1 mm to 5.5 mm from the first fascicle of the left bundle branch. In three hearts, additional fasciculo-fascicular connections were observed in the left bundle branch. Two loops were small, but one loop extended over 9.5 mm. CONCLUSION: We endorse the finding of Mahaim that fasciculo-ventricular pathways exist in most human hearts. We presume the identified connections had the capability of producing ventricular pre-excitation. More studies are needed to determine the potential clinical manifestations.

Miniseries 1-Part II: the comparative anatomy of the atrioventricular conduction axis.

AIMS: The arrangement of the conduction axis is markedly different in various mammalian species. Knowledge of such variation may serve to question the validity of using animals as prospective models for design of systems for clinical use. METHODS AND RESULTS: We compared the arrangement of the atrioventricular conduction axis in human, murine, canine, porcine, and bovine hearts, examining serially sectioned datasets from 20 human, 16 murine, 3 porcine, 5 canine, and 1 bovine hearts. We also analysed computed tomographic datasets obtained from bovines and one human heart. Unlike the situation in the human heart, there is no formation of an atrioventricular fibrous membranous septum in the murine, canine, porcine, nor bovine hearts. Canine, porcine, and bovine hearts also lack an infero-septal recess, when defined as a fibrous plate supporting the buttress of the atrial septum. In these species, half of the non-coronary leaflet is directly opposed to the ventricular septal surface. CONCLUSION: There is a long right-sided non-branching component of the axis, which skirts the attachment of the non-coronary sinus of the aortic root. In the bovine heart, moreover, the left bundle branch usually extends intramyocardially as a solitary tape before surfacing and ramifying on the left ventricular septal surface. The difference in the atrioventricular conduction axis between species may influence the anatomical substrates for atrioventricular re-entry tachycardia, as well as providing inferences for assessing the risks of transcatheter implantation of the aortic valve. Further studies are now needed to assess these possibilities.

Miniseries 1-Part I: the Development of the atrioventricular conduction axis.

Despite years of research, many details of the formation of the atrioventricular conduction axis remain uncertain. In this study, we aimed to clarify the situation. We studied three-dimensional reconstructions of serial histological sections and episcopic datasets of human embryos, supplementing these findings with assessment of material housed at the Human Developmental Biological Resource. We also examined serially sectioned human foetal hearts between 10 and 30 weeks of gestation. The conduction axis originates from the primary interventricular ring, which is initially at right angles to the plane of the atrioventricular canal, with which it co-localizes in the lesser curvature of the heart loop. With rightward expansion of the atrioventricular canal, the primary ring bends rightward, encircling the newly forming right atrioventricular junction. Subsequent to remodelling of the outflow tract, part of the primary ring remains localized on the crest of the muscular ventricular septum. By 7 weeks, its atrioventricular part has extended perpendicular to the septal parts. The atrioventricular node is formed at the inferior transition between the ventricular and atrial parts, with the transition itself marking the site of the penetrating atrioventricular bundle. Only subsequent to muscularization of the true second atrial septum does it become possible to recognize the definitive node. The conversion of the developmental arrangement into the definitive situation as seen postnatally requires additional remodelling in the first month of foetal development, concomitant with formation of the inferior pyramidal space and the infero-septal recess of the subaortic outflow tract.

The atrioventricular conduction axis and the aortic root-Inferences for transcatheter replacement of the aortic valve.

Conduction problems still occur following transcatheter aortic valvar replacement. With this in mind, we have assessed the relationship of the conduction axis to the aortic root. We used serial histological sections, made perpendicular to the base of the triangle of Koch in nine hearts, and perpendicular to the aortic root in 11 hearts. We first defined the extent of the fibrous tissues forming the boundaries of an infero-septal recess of the subaortic outflow tract, found in all datasets but one. When the recess was present, the axis penetrated through its rightward wall, giving rise to the left bundle branch prior to entering the outflow tract. The axis itself was usually on the crest of the ventricular septum, but could be deviated leftward or rightward. Its proximity to the virtual basal plane reflected the angulation of the muscular septum. On average, the superior edge of the left bundle was within 3.3 mm of the hinge of the right coronary leaflet, with a range from 0.4 to 10.2 mm. The arrangement was markedly different in the case lacking an infero-septal recess. Our findings necessitated a redefinition of the right fibrous trigone and the central fibrous body. The atrioventricular conduction axis, having entered the aortic root, is usually closest at the hinge of the right coronary leaflet. Knowledge of the depth of the infero-septal recess, and the angulation of the muscular ventricular septal, may help to avoid conduction problems following transcatheter implantation of the aortic valve.

Trunk Range of Motion Is Related to Axial Rigidity, Functional Mobility and Quality of Life in Parkinson's Disease: An Exploratory Study.

BACKGROUND: People with Parkinson's disease (PD) present deficits of the active range of motion (ROM), prominently in their trunk. However, if these deficits are associated with axial rigidity, the functional mobility or health related quality of life (HRQoL), remains unknown. The aim of this paper is to study the relationship between axial ROM and axial rigidity, the functional mobility and HRQoL in patients with mild to moderate PD. METHODS: An exploratory study was conducted. Non-probabilistic sampling of consecutive cases was used. Active trunk ROM was assessed by a universal goniometer. A Biodex System isokinetic dynamometer was used to measure the rigidity of the trunk. Functional mobility was determined by the Get Up and Go (GUG) test, and HRQoL was assessed with the PDQ-39 and EuroQol-5D questionnaires. RESULTS: Thirty-six mild to moderate patients with PD were evaluated. Significant correlations were observed between trunk extensors rigidity and trunk flexion and extension ROM. Significant correlations were observed between trunk flexion, extension and rotation ROM and GUG. Moreover, significant correlations were observed between trunk ROM for flexion, extension and rotations (both sides) and PDQ-39 total score. However, these correlations were considered poor. CONCLUSIONS: Trunk ROM for flexion and extension movements, measured by a universal goniometer, were correlated with axial extensors rigidity, evaluated by a technological device at 30°/s and 45°/s, and functional mobility. Moreover, trunk ROM for trunk flexion, extension and rotations were correlated with HRQoL in patients with mild to moderate PD.

Relationship between the aortic root and the atrioventricular conduction axis.

Damage to the atrioventricular conduction axis continues to be a problem subsequent to transcatheter implantation of aortic valvar prostheses. Accurate knowledge of the precise relationships of the conduction axis relative to the aortic root could greatly reduce the risk of such problems. Current diagrams highlighting these relationships rightly focus on the membranous septum. The current depictions, however, overlook a potentially important relationship between the superior fascicle of the left bundle branch and the nadir of the semilunar hinge of the right coronary leaflet of the aortic valve. Recent histological investigations demonstrate, in many instances, a very close relationship between the left bundle branch and the right coronary aortic leaflet. The findings also highlight two additional variable features, which can be revealed by clinical imaging. The first of these is the extent of an inferoseptal recess of the left ventricular outflow tract. The second is the extent of rotation of the aortic root within the base of the left ventricle. Much more of the conduction axis is within the confines of the circumference of the outflow tract when the root is rotated in counterclockwise fashion as assessed from the perspective of the imager, with this finding itself associated with a much narrower inferoseptal recess. A clear understanding of the marked variability within the aortic root is key to avoiding future problems with atrioventricular conduction.

The Atrioventricular Conduction Axis Revisited for the 21st Century.

Although first described in the final decade of the 19th century, the axis responsible for atrioventricular conduction has long been the source of multiple controversies. Some of these continue to reverberate. When first described by His, for example, many doubted the existence of the bundle we now name in his honour, while Kent suggested that multiple pathways crossed the atrioventricular junctions in the normal heart. It was Tawara who clarified the situation, although many of his key definitions have not universally been accepted. In key studies in the third decade of the 20th century, Mahaim then suggested the presence of ubiquitous connections that provided "paraspecific" pathways for atrioventricular conduction. In this review, we show the validity of these original investigations, based on our own experience with a large number of datasets from human hearts prepared by serial histological sectioning. Using our own reconstructions, we show how the atrioventricular conduction axis can be placed back within the heart. We emphasise that newly emerging techniques will be key in providing the resolution to map cellular detail to the gross evidence provided by the serial sections.

Clinical Implications of Buccinator Fiber Attachment on Interventions Aiming at Enhancing the Peri-Implant Keratinized Mucosa: An Ex-Vivo Study.

A clinical observation usually encountered after vestibuloplasty or interventions aiming at deepening the vestibule with or without simultaneous free epithelialized grafts in the posterior ridges is that they are subjected to major dimensional changes attributed to the buccinator fibers attachment. Hence, this study aimed at assessing the attachment of the buccinator muscles in relation to other anatomical landmarks. An ex-vivo study was performed in cadaver heads to explore the association of fibers attachment in relation to the distance from the crestal aspect of edentulous alveolar process (CAP) and the vestibular depth (VD), crestal band of keratinized mucosa (KM), and ridge height (RH). Interestingly, VD and KM were found to be strongly correlated. Likewise, VD/KM and CAP-BUC were further noted being correlated. CAP-BUC was negatively correlated with RH. Accordingly, the more atrophic the alveolar ridge (being more noticeable in the mandible) is, the shallower the vestibule, the lesser the crestal band of KM and the more crestal attachment of the buccinator muscular fibers. That might be the reason why whenever performing free epithelized graft in the posterior ridges to enhance the peri-implant soft tissue phenotype and deepening the vestibule, the graft is subjected to major dimensional changes.

Molecular monitoring of patient response to painkiller drugs.

INTRODUCTION: Non-steroidal anti-inflammatory drugs and opioids are widely prescribed for the treatment of mild to severe pain. Wide interindividual variability regarding the analgesic efficacy and adverse reactions to these drugs (ADRs) exist although the mechanisms responsible for these ADRs are not well understood. AREAS COVERED: We provide an overview of the clinical impact of variants in genes related to the pharmacokinetics and pharmacodynamics of painkillers, as well as those associated with the susceptibility to ADRs. In addition, we discuss the current pharmacogenetic-guided treatment recommendations for the therapeutic use of non-steroidal anti-inflammatory drugs and opioids. EXPERT OPINION: In the light of the data analyzed, common variants in genes involved in pharmacokinetic and pharmacodynamic processes may partially explain the lack of response to painkiller treatment and the occurrence of adverse drug reactions. The implementation of high-throughput sequencing technologies may help to unveil the role of rare variants as considerable contributors to explaining the interindividual variability in drug response. Furthermore, a consensus between the diverse pharmacogenetic guidelines is necessary to extend the implementation of pharmacogenetic-guided prescription in daily clinical practice. Additionally, the physiologically based pharmacokinetic and pharmacodynamic modeling techniques may contribute to the improvement of these guidelines and facilitate clinician drug dose adjustment.

Anatomy of the left atrial appendage for the interventional cardiologist.

Exact knowledge of the anatomy of the left atrial appendage (LAA) is crucial for LAA isolation by catheter ablation and for interventional LAA occlusion in patients with atrial fibrillation. This review outlines the current anatomical understanding of LAA morphology from ostium to distal lobes, myocardial fiber orientation and wall structure, and adjacent structures such as the left upper pulmonary vein with the Coumadin ridge, the circumflex artery with its side branches, the aortic root, pulmonary artery, and the pericardial space. Insight into these details will facilitate these interventions and reduce the risk of complications.

Anatomical knowledge for the ablation of left and right atrial flutter.

The different forms of atrial flutter (AFL) and atrial macroreentrant tachycardias are strongly related to the atrial anatomy in structurally normal atria, and even more so in patients with dilated chambers or with previous interventions. Atrial anatomy, macro- and microscopic tissue disposition including myocardial fibers, conduction system and connective tissue is complex. This review summarizes knowledge of atrial anatomy for the interventional electrophysiologist to better understand the pathophysiology of and ablation options for these complex arrhythmias, as well as to perform catheter ablation procedures safely and effectively.

Electrophysiological and histological characterization of atrial scarring in a model of isolated atrial myocardial infarction.

Background: Characterization of atrial myocardial infarction is hampered by the frequent concurrence of ventricular infarction. Theoretically, atrial infarct scarring could be recognized by multifrequency tissue impedance, like in ventricular infarction, but this remains to be proven. Objective: This study aimed at developing a model of atrial infarction to assess the potential of multifrequency impedance to recognize areas of atrial infarct scar. Methods: Seven anesthetized pigs were submitted to transcatheter occlusion of atrial coronary branches arising from the left coronary circumflex artery. Six weeks later the animals were anesthetized and underwent atrial voltage mapping and multifrequency impedance recordings. The hearts were thereafter extracted for anatomopathological study. Two additional pigs not submitted to atrial branch occlusion were used as controls. Results: Selective occlusion of the atrial branches induced areas of healed infarction in the left atrium in 6 of the 7 cases. Endocardial mapping of the left atrium showed reduced multi-frequency impedance (Phase angle at 307 kHz: from -17.1° ± 5.0° to -8.9° ± 2.6°, p < .01) and low-voltage of bipolar electrograms (.2 ± 0.1 mV vs. 1.9 ± 1.5 mV vs., p < .01) in areas affected by the infarction. Data variability of the impedance phase angle was lower than that of bipolar voltage (coefficient of variability of phase angle at307 kHz vs. bipolar voltage: .30 vs. .77). Histological analysis excluded the presence of ventricular infarction. Conclusion: Selective occlusion of atrial coronary branches permits to set up a model of selective atrial infarction. Atrial multifrequency impedance mapping allowed recognition of atrial infarct scarring with lesser data variability than local bipolar voltage mapping. Our model may have potential applicability on the study of atrial arrhythmia mechanisms.

Axial rigidity and quality of life in patients with Parkinson's disease: a preliminary study.

PURPOSE: Rigidity is a cardinal symptom of Parkinson's disease (PD) and is often clinically assessed by passively flexing and extending a patient's limb. Objective measurements had been employed to examine rigidity in PD subjects, including wrist, elbow, knee and trunk. This study aimed to investigate the relationship between an objective measurement of trunk rigidity and health-related quality of life (HRQoL) and functional status in patients with mild to moderate PD. METHODS: An isokinetic dynamometer Biodex System 3 was employed to assess trunk rigidity in 36 PD patients. HRQoL was assessed with the EuroQol-5D and Parkinson's Disease Questionnaire-39 items (PDQ-39). Functional status was measured with the Schwab and England scale. RESULTS: Trunk rigidity was correlated with the HRQoL assessed with the mobility, cognition and stigma PDQ-39 domains and the total PDQ-39 scores. No correlations were found among trunk muscle tone assessed with the isokinetic dynamometer and the EuroQoL-5D. Functional status was correlated with the trunk extensors rigidity at all angular velocities. CONCLUSION: The results from this study suggest that the axial motor impairments impact on QoL and functional status in patients with PD. Further studies are needed with quantitative devices for axial rigidity assessment to determine the relationship between trunk rigidity in PD patients with higher disease severity and HRQoL scales.

Diagnostic Accuracy of Cone Beam Computed Tomography in Identifying Peri-implantitis-Like Bone Defects Ex Vivo.

This pilot study aimed to assess the diagnostic accuracy of CBCT in identifying peri-implantitis-like bone defects in cadavers. Three cadaver dental arches treated with the Thiel embalming method were used. Three different types of peri-implant bone defects (buccal dehiscence, two- to three-wall defects, and circumferential defects) were prepared on 15 implants. Defect depths and lengths were identified clinically using a periodontal probe, radiologically by means of CBCT images, and histologically with a micrometer using an optic microscope. Peri-implant bone defect morphology evaluated using CBCT images matched the clinical defect configuration (100% accuracy). CBCT assessment demonstrated lower values in defect depth and defect length when compared with the clinical evaluation. A statistically significant difference in defect depth (0.35 ± 0.45 mm; P = .037) was recorded between the clinical and CBCT data. Regarding defect length, a statistically significant mean difference of 0.81 ± 0.83 mm (P = .003) was noted between the clinical and CBCT data. Similarly, a mean difference of 1.09 ± 1.52 mm was recorded between the defect length assessed histologically and the CBCT data (P = .031). No statistically significant differences were observed between the other evaluated variables. CBCT is a reliable tool for peri-implantitis diagnosis and treatment planning, though the underestimation of defect severity may affect the prognosis and clinical decision-making. Clinicians need to be flexible in establishing prognoses and treatment based on CBCT assessment.

First-year health degree students in the dissection room: Analysis of adaptation to practical classes.

Human anatomy is a core subject that students of all health degrees are required to pass. Practical classes with human cadavers are a widely used educational resource in medicine, but are less frequent in other health degrees. Determining how first-year podiatry, nursing, and physiotherapy students cope with human anatomy practical classes and identifying the presence of physical reactions and possible causes of distress they experience in the dissection room are essential steps in designing a guidance plan to address students' needs. A questionnaire was distributed to 172 first-year students in non-medical health degrees immediately after their first visit to the dissection room. The questionnaire comprised 29 Yes/No questions to determine students' physical reactions, causes of distress and coping methods. The most frequent physical reactions were disgust, uneasiness and nausea. The main causes of distress were the smell of the cadavers, the smell of the dissection room and the sight of the cadavers. The coping methods used were being with friends, eating before the practical class and practicing beforehand with anatomical atlases and CDs. No significant differences were found between gender and the three variables analyzed (number of physical reactions, number of causes of distress and number of coping methods) (p-value >0.216), although differences were found between the type of health degree and the number of physical reactions and causes of distress (p-values = 0.028 and 0.001, respectively).

The Atrioventricular Conduction Axis and its Implications for Permanent Pacing.

Extensive knowledge of the anatomy of the atrioventricular conduction axis, and its branches, is key to the success of permanent physiological pacing, either by capturing the His bundle, the left bundle branch or the adjacent septal regions. The inter-individual variability of the axis plays an important role in underscoring the technical difficulties known to exist in achieving a stable position of the stimulating leads. In this review, the key anatomical features of the location of the axis relative to the triangle of Koch, the aortic root, the inferior pyramidal space and the inferoseptal recess are summarised. In keeping with the increasing number of implants aimed at targeting the environs of the left bundle branch, an extensive review of the known variability in the pattern of ramification of the left bundle branch from the axis is included. This permits the authors to summarise in a pragmatic fashion the most relevant aspects to be taken into account when seeking to successfully deploy a permanent pacing lead.

Similarities and differences in the arrangement of the atrioventricular conduction axis in the canine compared to the human heart.

BACKGROUND: Subtle differences exist between dog and human, despite use of the dog as a model for cardiac surgical and electrophysiological research. OBJECTIVE: The purpose of this study was to investigate the differences in the atrioventricular conduction axis and adjacent structures between dogs and humans. METHODS: We prepared 33 human and 5 canine hearts for serial histologic sections of the atrioventricular conduction axis, making correlations with gross anatomic findings. We additionally examined and photographed 15 intact normal human hearts obtained from infants undergoing autopsy. Furthermore, we interrogated a computed tomographic dataset from a human adolescent and from 2 autopsied canine hearts, both with normal cardiac anatomy. RESULTS: All canine hearts lacked an inferoseptal recess, with the noncoronary leaflet of the aortic valve and the right fibrous trigone having direct attachments to the septal surface of the left ventricular outflow tract. This correlated with an extensive nonbranching component of the ventricular conduction axis, which skirted half of the noncoronary aortic sinus. This anatomic arrangement was observed in 2 of 15 of autopsied infant hearts. In the human hearts with an inferoseptal recess, the relatively shorter nonbranching bundle is embedded within the fibrous tissue forming its right wall. CONCLUSION: We found a major difference between canine and the majority of human hearts, namely, the presence or absence of an inferoseptal recess. When this recess is absent, as in the canine heart and in some human hearts, a greater proportion of the atrioventricular conduction axis is found within the circumference of the subaortic outflow tract.

Inferior Extensions of the Atrioventricular Node.

The pathways for excitation of the atrioventricular node enter either superiorly, as the so-called 'fast' pathway, or inferiorly as the 'slow' pathway. However, knowledge of the specific anatomical details of these pathways is limited. Most of the experimental studies that established the existence of these pathways were conducted in mammalian hearts, which have subtle differences to human hearts. In this review, the authors summarise their recent experiences investigating human cardiac development, correlating these results with the arrangement of the connections between the atrial myocardium and the compact atrioventricular node as revealed by serial sectioning of adult human hearts. They discuss the contributions made from the atrioventricular canal myocardium, as opposed to the primary ring. Both these rings are incorporated into the atrial vestibules, albeit with the primary ring contributing only to the tricuspid vestibule. The atrial septal cardiomyocytes are relatively late contributors to the nodal inputs. Finally, they relate our findings of human cardiac development to the postnatal arrangement.