Clinical presentation and genetic characterization of early-onset atrial fibrillation in patients affected by long QT syndrome: A single-center experience.

INTRODUCTION: Early-onset atrial fibrillation (AF) has already been observed in approximately 2% of patients with genetically proven long QT syndrome (LQTS). This frequency is higher than population-based estimates of early-onset AF. However, the concomitant expression of AF in LQTS is likely underestimated. The purpose of this study was to examine the clinical presentation, genetic background, and outcomes of a cohort of patients with LQTS and early-onset AF referred to a single tertiary center. METHODS: Twenty-seven patients diagnosed with congenital LQTS were included in the study based on the documentation of early-onset (age ≤50 years) clinical or subclinical AF episodes in all available medical records, including standard electrocardiograms, wearable monitor or cardiac implantable electronic devices. RESULTS: Seventeen patients experienced clinical AF during the follow-up period. Subclinical AF was detected in 10 patients through insertable or wearable cardiac monitors. In our series, the mean heart rate during AF episodes was found to be relatively low despite the patients' young age and the low or minimal effective doses of beta-blockers used for QTc interval control. All patients exhibiting LQTS and early-onset AF were genotype positive, carrying mutations in the KCNQ1 (66%), KCNH2, KCNE1, and SCN5A genes. Notably, most of these patients carried the same p.(R231C) mutation in the KCNQ1 gene (59%) and were from the same families, suggesting concurrent expression of familial AF and LQTS. CONCLUSION: LQTS patients are prone to developing clinical and subclinical AF, even at a younger age. The occurrence of early-onset AF in the LQTS population could be more frequent than previously assumed. AF should be considered as a potential dysrhythmia related to LQTS. Our study emphasizes the importance of carefully researching clinical and/or subclinical episodes of AF through strict heart rhythm monitoring in the LQTS population.

The clinical anatomy of the atrioventricular conduction axis.

It is axiomatic that the chances of achieving accurate capture of the conduction axis and its fascicles will be optimized by equally accurate knowledge of the relationship of the components to the recognizable cardiac landmarks, and we find it surprising that acknowledged experts should continue to use drawings that fall short in terms of anatomical accuracy. The accuracy achieved by Sunao Tawara (1906) in showing the location of the atrioventricular conduction axis is little short of astounding. Our purpose in bringing this to current attention is to question the need of the experts to have produced such inaccurate representations, since the findings of Tawara have been extensively endorsed in very recent years. The recent studies do no more than point to the amazing accuracy of the initial account of Tawara. At the same time, we draw attention to the findings described in the middle of the 20th century by Ivan Mahaim (1947). These observations have tended to be ignored in recent accounts. They are, perhaps, of equal significance to those seeking specifically to pace the left fascicles of the branching atrioventricular bundle.

Effect of Maternal Ursodeoxycholic Acid Treatment on Fetal Atrioventricular Conduction in Patients with Intrahepatic Cholestasis of Pregnancy.

INTRODUCTION: The aim of this study was, first, to investigate the difference in fetal atrioventricular conduction in patients with and without intrahepatic cholestasis of pregnancy (ICP) by measuring the fetal PR interval; second, to evaluate the altering effect of ursodeoxycholic acid (UDCA) treatment on the fetal PR interval in ICP patients. METHODS: The study consisted of 42 ICP patients and 48 healthy pregnant women. Fetal echocardiography was performed to measure the mechanical PR interval. The fetal PR interval and the clinical characteristics were compared between the two groups. The effect of UDCA treatment on the fetal PR interval in ICP patients was evaluated. RESULTS: In ICP patients, significantly longer fetal PR intervals were observed than in the control group (123.21 ± 8.54 vs. 115.13 ± 5.95 ms, p < 0.001). In the ICP group, there was a positive correlation between the fetal PR interval and maternal fasting total bile acid (TBA) levels (r = 0.514, p = 0.001). After 1 week of treatment with UDCA in patients with ICP, the PR interval was shorter than before, although the reduction was not statistically significant (120.98 ± 6.70 vs. 123.21 ± 8.54 ms, p = 0.095). In patients with severe ICP (TBA >40 mmol/L, n = 10), a significant reduction in the fetal PR interval was observed after treatment with UDCA (127.5 ms [IQR, 118.0-134.75] before vs. 122 ms [IQR, 109.5-126.5] after, p = 0.037). CONCLUSION: Fetal PR interval increased in ICP patients in correlation with maternal serum TBA concentration. Treatment with UDCA may have limited positive effects on the fetal AV conduction system. The beneficial effects of UDCA on the fetal PR interval may be more pronounced in patients with higher bile acid levels.

Efficient generation of TBX3+ atrioventricular conduction-like cardiomyocytes from human pluripotent stem cells.

Atrioventricular conduction cardiomyocytes (AVCCs) regulate the rate and rhythm of heart contractions. Dysfunction due to aging or disease can cause atrioventricular (AV) block, interrupting electrical impulses from the atria to the ventricles. Generation of functional atrioventricular conduction like cardiomyocytes (AVCLCs) from human pluripotent stem cells (hPSCs) provides a promising approach to repair damaged atrioventricular conduction tissue by cell transplantation. In this study, we put forward the generation of AVCLCs from hPSCs by stage-specific manipulation of the retinoic acid (RA), WNT, and bone morphogenetic protein (BMP) signaling pathways. These cells express AVCC-specific markers, including the transcription factors TBX3, MSX2 and NKX2.5, display functional electrophysiological characteristics and present low conduction velocity (0.07 ± 0.02 m/s). Our findings provide new insights into the understanding of the development of the atrioventricular conduction system and propose a strategy for the treatment of severe atrioventricular conduction block by cell transplantation in future.

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.

T-box transcription factor 3 governs a transcriptional program for the function of the mouse atrioventricular conduction system.

Genome-wide association studies have identified noncoding variants near TBX3 that are associated with PR interval and QRS duration, suggesting that subtle changes in TBX3 expression affect atrioventricular conduction system function. To explore whether and to what extent the atrioventricular conduction system is affected by Tbx3 dose reduction, we first characterized electrophysiological properties and morphology of heterozygous Tbx3 mutant (Tbx3+/-) mouse hearts. We found PR interval shortening and prolonged QRS duration, as well as atrioventricular bundle hypoplasia after birth in heterozygous mice. The atrioventricular node size was unaffected. Transcriptomic analysis of atrioventricular nodes isolated by laser capture microdissection revealed hundreds of deregulated genes in Tbx3+/- mutants. Notably, Tbx3+/- atrioventricular nodes showed increased expression of working myocardial gene programs (mitochondrial and metabolic processes, muscle contractility) and reduced expression of pacemaker gene programs (neuronal, Wnt signaling, calcium/ion channel activity). By integrating chromatin accessibility profiles (ATAC sequencing) of atrioventricular tissue and other epigenetic data, we identified Tbx3-dependent atrioventricular regulatory DNA elements (REs) on a genome-wide scale. We used transgenic reporter assays to determine the functionality of candidate REs near Ryr2, an up-regulated chamber-enriched gene, and in Cacna1g, a down-regulated conduction system-specific gene. Using genome editing to delete candidate REs, we showed that a strong intronic bipartite RE selectively governs Cacna1g expression in the conduction system in vivo. Our data provide insights into the multifactorial Tbx3-dependent transcriptional network that regulates the structure and function of the cardiac conduction system, which may underlie the differences in PR duration and QRS interval between individuals carrying variants in the TBX3 locus.

Prediction of atrioventricular conduction disturbance after ablation of persistent atrial fibrillation.

The prevalence of atrioventricular conduction disturbance (AVCD) in patients with persistent atrial fibrillation (AF) has not yet been fully investigated. We sought to identify the predictors of AVCD in patients with AF by analyzing the relationship between pre-ablation heart rate during AF and the PR interval in sinus rhythm after ablation. We analyzed pre-ablation 24-h Holter electrocardiogram (ECG) and 12 lead ECG 12 months after ablation of 121 consecutive patients with persistent AF who underwent their first ablation procedure and maintained sinus rhythm at 12 months. AVCD was defined as a first-degree atrioventricular block (AVB), second-degree AVB, high-degree AVB, or third-degree AVB observed on ECG at 12 months after ablation. Seventeen out of 121 patients (14.0%) had AVCD at 12 months. In the group with AVCD, total heartbeat (THB) and maximum heart rate (Max HR) were significantly lower, and the prevalence of concomitant Cavo-tricuspid isthmus-dependent atrial flutter before ablation and the appearance of macro reentrant atrial tachycardia (AT) during the procedure were significantly higher than those in the group without AVCD. Multiple regression analysis revealed that maximum HR and macro reentrant AT were significant predictors of AVCD. Receiver operating characteristic curve analysis revealed that Max HR of <165.0 bpm predicts AVCD with a sensitivity of 76.47% and a specificity of 74.00%. In patients with persistent AF, low Max HR and the presence of macro reentrant AT during the ablation procedure were predictors of AVCD.

Electrocardiographic changes in hospitalised children with COVID-19.

OBJECTIVES: Cardiac manifestations of the coronavirus disease 2019 (COVID-19) have mainly been reported in adults. Therefore, we aimed to determine the electrocardiographic abnormalities in hospitalised paediatric patients with COVID-19 and multisystemic inflammatory syndrome in children. METHODS: We retrospectively evaluated hospitalised paediatric patients <18 years of age with a diagnosis of COVID-19 (n = 168) and multisystem inflammatory syndrome in children (n = 48) between March 2021 and December 2021. A daily electrocardiography was performed for the patients who had electrocardiographic abnormalities on admission or developed electrocardiographic abnormality on the follow-up. The characteristics of these patients, underlying predisposing conditions, and clinical course were also examined. RESULTS: Two-hundred sixteen paediatric patients (55% were male) with a mean age of 10.7 ± 4.69 years were evaluated. There was an underlying disease in 84 (38.8%) patients and 51 (23.6%) required paediatric ICU admission. Electrocardiography abnormality was detected in 12 (5.5%) which were as follows: 7 (3.2%) had sinus bradycardia, 3 (1.4%) patients had transient ST elevation and concomitant T negativity, and 2 (0.9%) developed first-degree Atrioventricular (AV) block. The median time from the onset of disease symptoms to detecting electrocardiographic abnormality was 9 days. Electrocardiographic abnormalities returned to normal uneventfully 3 days later. CONCLUSIONS: The prevalence of arrhythmia in paediatric patients with COVID-19 was detected in 5.5% of the patients. While two-thirds of the electrocardiography abnormalities were sinus bradycardia, ST elevation was remarkable (1.4%). Clinicians should be aware of electrocardiographic abnormalities and consider electrocardiographic monitoring in paediatric patients with COVID-19 and multisystemic inflammatory syndrome in children.

Atrioventricular conduction recovery immediately after the re-operation in a repaired CHD patient.

This is a case of a 2.7-year-old girl with trisomy 21 and double outlet right ventricle who underwent epicardial pacemaker system placement for a surgical atrioventricular block and achieved atrioventricular conduction recovery immediately after residual ventricular septal defect closure. Although ventricular pacing ratio was 100% before re-operation, it declined to approximately 25% on the 6th post-operative day and was <1% 3 years after re-operation.

Miniseries 2-Septal and paraseptal accessory pathways-Part I: The anatomic basis for the understanding of para-Hisian accessory atrioventricular pathways.

AIMS: Although the anatomy of the atrioventricular conduction axis was well described over a century ago, the precise arrangement in the regions surrounding its transition from the atrioventricular node to the so-called bundle of His remain uncertain. We aimed to clarify these relationships. METHODS AND RESULTS: We have used our various datasets to examine the development and anatomical arrangement of the atrioventricular conduction axis, paying particular attention to the regions surrounding the point of penetration of the bundle of His. It is the areas directly adjacent to the transition of the atrioventricular conduction axis from the atrioventricular node to the non-branching atrioventricular bundle that constitute the para-Hisian areas. The atrioventricular conduction axis itself traverses the membranous part of the ventricular septum as it extends from the node to become the bundle, but the para-Hisian areas themselves are paraseptal. This is because they incorporate the fibrofatty tissues of the inferior pyramidal space and the superior atrioventricular groove. In this initial overarching review, we summarize the developmental and anatomical features of these areas along with the location and landmarks of the atrioventricular conduction axis. We emphasize the relationships between the inferior pyramidal space and the infero-septal recess of the subaortic outflow tract. The details are then explored in greater detail in the additional reviews provided within our miniseries. CONCLUSION: Our anatomical findings, described here, provide the basis for our concomitant clinical review of the so-called para-Hisian arrhythmias. The findings also provide the basis for understanding the other variants of ventricular pre-excitation.

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 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.

AV timing in pacemaker patients with first-degree AV block: which is preferable, intrinsic AV conduction or pacing?

Some patients with pacemakers present with first-degree atrioventricular (AV) block. To avoid right ventricular (RV) pacing, preserving intrinsic AV conduction as much as possible is recommended. However, there is no clear cutoff AV interval to determine whether intrinsic AV conduction should be preserved or RV pacing should be delivered. This study aimed to compare a pacing mode-preserving, intrinsic AV conduction with the DDD mode delivering RV pacing in terms of echocardiographic parameters in patients with first-degree AV block and to investigate whether RV pacing induces heart failure (HF). Stroke volume (SV) was measured to determine the optimal AV delay with the intrinsic AV conduction rhythm and the DDD pacing delivering RV pacing. Echocardiographic evaluation was performed for 6-month follow-up period. Seventeen patients were studied. At baseline, mean intrinsic PQ interval was 250 ± 40 ms. SV was greater with RV pacing with optimal AV delay of 160 ms than with intrinsic AV conduction rhythm in all patients. Therefore, pacemakers were set to the DDD to deliver RV pacing. During follow-up, seven patients developed HF. Mean baseline E/E' ratio in patients who developed HF (HF group) during RV pacing was higher than in patients without HF (non = HF group; 17.9 ± 8 versus 11.5 ± 2, P = 0.018) Even within HF group patients without a high baseline E/E' ratio, it increased with RV pacing (22.2 ± 6 versus 11.6 ± 2; P < 0.001). In patients with pacemaker and first-degree AV block, RV pacing with the optimal AV delay of 160 ms increased SV. However, the risk of HF may be increased with RV pacing if the E/E' ratio is > 15 during intrinsic AV conduction or RV pacing. RV pacing should be avoided in patients with high E/E' ratio under intrinsic AV conduction or RV pacing.

Characteristics of patients with atrial flutter and spontaneous 1:1 atrioventricular conduction with and without anti-arrhythmic drug treatment.

Atrial flutter (AFL) is a large reentrant circuit located in the right atrium. Anti-arrhythmic drugs (AADs) can provoke AFL with 1:1 atrioventricular conduction (AVC) to cause hemodynamic collapse. We elucidated the characteristics of patients with AFL exhibiting spontaneous 1:1 AVC. Fifteen patients (1:1 AFL group; 11 males, 52.4 ± 13.7 years old) who documented AFL with 1:1 AVC were enrolled and compared to 153 patients without 1:1 AVC (Control group; 137 males, 68.9 ± 11.2 years old). AFL cycle length during maximum AVC was significantly longer in the 1:1 AFL group than in the control group (274.7 ± 37.0 vs. 216.2 ± 25.6 ms, p < 0.001). Among 1:1 AVC group, 9 patients had AADs, and AFL cycle length was significantly longer during 1:1 AVC as compared with 2:1 AVC documented the other day (284.4 ± 41.3 vs. 233.3 ± 26.0 ms, p < 0.001), suggesting enhancement effect of the AADs during 1:1 AVC. Remaining 6 patients who did not take AADs, 2 patients showed enlargement of the tricuspid annulus and 3 patients developed 1:1 AVC during exercise. Multivariate analysis revealed that younger age and the use of AADs was independent risk factors for the development of 1:1 AFL group. Prolonged AFL cycle length associated with the class Ia/Ic AAD use, slower heart rate during sinus rhythm and younger age were important risk factors for the development of 1:1 AVC during AFL.

Rapid wide QRS tachycardia with an unknown cause.

One-to-one atrioventricular conduction during atrial flutter is one of the most severe life-threatening arrhythmias and is hemodynamically perilous. Rapid wide QRS tachycardia often not only occurs in patients with ventricular tachycardia but is also found in supraventricular tachycardia/atrial flutter with preexistent QRS prolongation, supraventricular tachycardia/atrial flutter with QRS prolongation caused by an IC antiarrhythmic drug, and supraventricular tachycardia/atrial flutter with preexcitation. Furthermore, atrial flutter with 1:1 AVC via an accessory pathway is an uncommon presentation of Wolff-Parkinson-White syndrome. We present a case of atrial flutter with 1:1 rapid AVC in the presence of Wolff-Parkinson-White syndrome. Physicians should be familiar with the rapid wide QRS complex ECG pattern associated with AFL with 1:1 AVC via an accessory pathway. Establishing the definitive diagnosis is essential for selecting an appropriate treatment strategy for improving outcomes.

Mapping the Conduction System in Patients Undergoing Transcatheter Device Closure of Perimembranous Ventricular Septal Defect: A Proof-of-Concept Study.

Earlier studies that investigated the relation of atrioventricular (AV) conduction system to perimembranous ventricular septal defect (pmVSD) were based on cardiopathological specimens. To study the relationship of conduction system to pmVSD using 3-dimensional electroanatomic mapping system (EAMS) in patients undergoing device closure. Fifteen consecutive cases of pmVSD from January 2014 to July 2017 (age > 2 years and weight > 8 kg) were included in the study. The course of conduction system and its relationship with the pmVSD was mapped before and after device closure, with the use of EAMS. Median age and weight of the cohort was 10 years (range 4-21 years) and 25 kg (range 13-55) respectively. Device implantation was successful in all patients except 1. The course and relation of the conduction system were posteroinferior to the pmVSD in all cases (100%), and away from the defect in 67% (10/15). In patient with baseline RBBB, the right-sided conduction system was in close proximity to the pmVSD. Two patients had part of left-sided conduction system in close proximity to pmVSD or device edges. Two patients developed RBBB following device deployment, which reverted to normal on follow up. No patient developed high grade AV block during the median follow-up of 34 months (range 24-62). This experimental study has shown the feasibility of 3D EAM of conduction system during device closure of pmVSD. This novel concept can be utilized to understand the anatomy of conduction system in other congenital heart diseases.

Catheter ablation of premature ventricular contractions originating from periprosthetic aortic valve regions.

BACKGROUND: Little is known about the ablation outcomes of premature ventricular contractions (PVCs) that originate from the periprosthetic aortic valve (PPAV) regions of patients with aortic valve replacement (AVR). METHODS AND RESULTS: Our study had 11 patients who underwent catheter ablation for PVCs arising from the PPAV regions (bioprosthetic aortic valve, n = 5; mechanical aortic valve, n = 6). The PVC characteristics, procedure characteristics, and efficacy of ablation were compared with the control group (n = 33). At baseline, the PPAV group had a lower left ventricular ejection fraction (mean [SD], 41% [12%] vs. 51% [8%]; p = .002). The rate of acute ablation success was 90.9% in the PPAV group. Ablation sites were identified above the left coronary cusp (LCC) and right coronary cusp commissure (LRCC) in one PVC, below the prosthetic valve in eight PVCs (four below LCC and four below LRCC), and within the distal coronary sinus in two PVCs. The mean procedure time, fluoroscopy time, and radiation in the PPAV group were all significantly greater than those in the control group (all p < .05). However, the number of radiofrequency ablation energy deliveries was not different. The PPAV group had a long-term success rate compared with the control group (72.7% vs. 87.9%, p = .48) and an increase of left ventricular ejection fraction from 43% to 49% after successful PVC ablation at follow-up (p < .001). Echocardiography showed no significant change in valve regurgitation after ablation. No new atrioventricular block occurred. CONCLUSION: PVCs arising from PPAV regions can be successfully ablated in patients with prior AVR, without damaging the prosthetic aortic valve and atrioventricular conduction.

Three-dimensional visualization of the bovine cardiac conduction system and surrounding structures compared to the arrangements in the human heart.

In the human heart, the atrioventricular node is located toward the apex of the triangle of Koch, which is also at the apex of the inferior pyramidal space. It is adjacent to the atrioventricular portion of the membranous septum, through which it penetrates to become the atrioventricular bundle. Subsequent to its penetration, the conduction axis is located on the crest of the ventricular septum, sandwiched between the muscular septum and ventricular component of the membranous septum, where it gives rise to the ramifications of the left bundle branch. In contrast, the bovine conduction axis has a long non-branching component, which penetrates into a thick muscular atrioventricular septum having skirted the main cardiac bone and the rightward half of the non-coronary sinus of the aortic root. It commonly gives rise to both right and left bundle branches within the muscular ventricular septum. Unlike the situation in man, the left bundle branch is long and thin before it branches into its fascicles. These differences from the human heart, however, have yet to be shown in three-dimensions relative to the surrounding structures. We have now achieved this goal by injecting contrast material into the insulating sheaths that surround the conduction network, evaluating the results by subsequent computed tomography. The fibrous atrioventricular membranous septum of the human heart is replaced in the ox by the main cardiac bone and the muscular atrioventricular septum. The apex of the inferior pyramidal space, which in the bovine, as in the human, is related to the atrioventricular node, is placed inferiorly relative to the left ventricular outflow tract. The bovine atrioventricular conduction axis, therefore, originates from a node itself located inferiorly compared to the human arrangement. The axis must then skirt the non-coronary sinus of the aortic root prior to penetrating the thicker muscular ventricular septum, thus accounting for its long non-branching course. We envisage that our findings will further enhance comparative anatomical research.

Anatomy of the cardiac conduction system.

The specialized cardiomyocytes that constitute the conduction system in the human heart, initiate the electric impulse and result in rhythmic and synchronized contraction of the atria and ventricles. Although the atrioventricular (AV) conduction axis was described more than a century ago by Sunao Tawara, the anatomic pathway for propagation of impulse from atria to the ventricles has been a topic of debate for years. Over the past 2 decades, there has been a resurgence of conduction system pacing (CSP) by implanting pacing leads in the His bundle region in lieu of chronic right ventricular pacing that is associated with worse clinical outcomes. The inherent limitations of implanting the leads in the His bundle region has led to the emergence of left bundle branch area pacing in the past 3 years as an alternative strategy for CSP. The clinical experience from performing CSP has helped electrophysiologists gain deeper insight into the anatomy and physiology of cardiac conduction system. This review details the anatomy of the cardiac conduction system, and highlights some of the recently published articles that aid in better understanding of the AV conduction axis and its variations, the knowledge of which is critical for CSP. The remarkable evolution in technology has led to visualization of the cardiac conduction system using noninvasive, nondestructive high-resolution contrast-enhanced micro-computed tomography imaging that may aid in future CSP. We also discuss from anatomical perspective, the differences seen clinically with His bundle pacing and left bundle branch area pacing.

Complete atrio-ventricular heart block, a not to be forgotten complication in transcatheter closure of perimembranous ventricular septal defect - a case report and review of literature.

Device occlusion of perimembranous ventricular septal defect is gaining popularity with the emergence of newer, softer occluders and improved technical know-how. We report a 26-year-old lady with a moderate size perimembranous ventricular septal defect who had a new onset of bundle branch block shortly after device closure. The patient subsequently developed a complete atrio-ventricular heart block.