Atrioventricular Nodal Region Research Articles

Distribution and morphology of calcitonin gene-related peptide (CGRP) innervation in flat mounts of whole rat atria and ventricles

Calcitonin gene-related peptide (CGRP) is widely used as a marker for nociceptive afferent axons. However, the distribution of CGRP-IR axons has not been fully determined in the whole rat heart. Immunohistochemically labeled flat-mounts of the right and left atria and ventricles, and the interventricular septum (IVS) in rats for CGRP were assessed with a Zeiss imager to generate complete montages of the entire atria, ventricles, and septum, and a confocal microscope was used to acquire detailed images of selected regions. We found that 1) CGRP-IR axons extensively innervated all regions of the atrial walls including the sinoatrial node region, auricles, atrioventricular node region, superior/inferior vena cava, left pre-caval vein, and pulmonary veins. 2) CGRP-IR axons formed varicose terminals around individual neurons in some cardiac ganglia but passed through other ganglia without making appositions with cardiac neurons. 3) Varicose CGRP-IR axons innervated the walls of blood vessels. 4) CGRP-IR axons extensively innervated the right/left ventricular walls and IVS. Our data shows the rather ubiquitous distribution of CGRP-IR axons in the whole rat heart at single-cell/axon/varicosity resolution for the first time. This study lays the foundation for future studies to quantify the differences in CGRP-IR axon innervation between sexes, disease models, and species.

Cartilaginous Intrusion of the Atrioventricular Node in a Quarter Horse with a High Burden of Second-Degree AV Block and Collapse: A Case Report

Second-degree atrioventricular (AV) block is the most common cardiac arrhythmia in horses, affecting 40-90% depending on breed. Usually, the AV blocks occur while the horses are resting and disappear upon exercise and are, therefore, considered to be uneventful for horses. However, if the AV blocks occur frequently, this may result in syncope and collapse. Identifying the cause of second-degree AV block is difficult and often subscribed to high vagal tone. In this report, we present an eight-year-old Quarter horse with a high burden of second-degree AV blocks and multiple collapses. The clinical examination, including neurological examination, blood analysis, 24-h ECG recording and cardiac echocardiography, did not reveal any signs of general or cardiovascular disease besides a high burden of second-degree AV blocks (~300 blocks per hour) and a hyperechoic area in the AV nodal region. An implantable loop recorder (ILR) was inserted to monitor the cardiac rhythm. The ILR detected several consecutive second-degree AV blocks and pauses above 5 s. However, unfortunately, no recordings were available during the collapses. Eventually, the horse was euthanized and the heart inspected. The aortic root was severely cartilaginous and appeared to penetrate the AV node, especially in the His bundle region, possibly explaining the hampered AV conduction. Nevertheless, it is still uncertain if the AV nodal disruption caused the collapses and more knowledge on AV nodal diseases in horses is warranted.

Functional modulation of atrio-ventricular conduction by enhanced late sodium current and calcium-dependent mechanisms in Scn5a1798insD/+ mice.

Aims SCN5A mutations are associated with arrhythmia syndromes, including Brugada syndrome, long QT syndrome type 3 (LQT3), and cardiac conduction disease. Long QT syndrome type 3 patients display atrio-ventricular (AV) conduction slowing which may contribute to arrhythmogenesis. We here investigated the as yet unknown underlying mechanisms.Methods and resultsWe assessed electrophysiological and molecular alterations underlying AV-conduction abnormalities in mice carrying the Scn5a1798insD/+ mutation. Langendorff-perfused Scn5a1798insD/+ hearts showed prolonged AV-conduction compared to wild type (WT) without changes in atrial and His-ventricular (HV) conduction. The late sodium current (INa,L) inhibitor ranolazine (RAN) normalized AV-conduction in Scn5a1798insD/+ mice, likely by preventing the mutation-induced increase in intracellular sodium ([Na+]i) and calcium ([Ca2+]i) concentrations. Indeed, further enhancement of [Na+]i and [Ca2+]i by the Na+/K+-ATPase inhibitor ouabain caused excessive increase in AV-conduction time in Scn5a1798insD/+ hearts. Scn5a1798insD/+ mice from the 129P2 strain displayed more severe AV-conduction abnormalities than FVB/N-Scn5a1798insD/+ mice, in line with their larger mutation-induced INa,L. Transverse aortic constriction (TAC) caused excessive prolongation of AV-conduction in FVB/N-Scn5a1798insD/+ mice (while HV-intervals remained unchanged), which was prevented by chronic RAN treatment. Scn5a1798insD/+-TAC hearts showed decreased mRNA levels of conduction genes in the AV-nodal region, but no structural changes in the AV-node or His bundle. In Scn5a1798insD/+-TAC mice deficient for the transcription factor Nfatc2 (effector of the calcium-calcineurin pathway), AV-conduction and conduction gene expression were restored to WT levels.ConclusionsOur findings indicate a detrimental role for enhanced INa,L and consequent calcium dysregulation on AV-conduction in Scn5a1798insD/+ mice, providing evidence for a functional mechanism underlying AV-conduction disturbances secondary to gain-of-function SCN5A mutations.

Localization of the sinoatrial and atrioventricular nodal region in neonatal and juvenile ovine hearts.

Localization of the components of the cardiac conduction system (CCS) is essential for many therapeutic procedures in cardiac surgery and interventional cardiology. While histological studies provided fundamental insights into CCS localization, this information is incomplete and difficult to translate to aid in intraprocedural localization. To advance our understanding of CCS localization, we set out to establish a framework for quantifying nodal region morphology. Using this framework, we quantitatively analyzed the sinoatrial node (SAN) and atrioventricular node (AVN) in ovine with postmenstrual age ranging from 4.4 to 58.3 months. In particular, we studied the SAN and AVN in relation to the epicardial and endocardial surfaces, respectively. Using anatomical landmarks, we excised the nodes and adjacent tissues, sectioned those at a thickness of 4 μm at 100 μm intervals, and applied Masson’s trichrome stain to the sections. These sections were then imaged, segmented to identify nodal tissue, and analyzed to quantify nodal depth and superficial tissue composition. The minimal SAN depth ranged between 20 and 926 μm. AVN minimal depth ranged between 59 and 1192 μm in the AVN extension region, 49 and 980 μm for the compact node, and 148 and 888 μm for the transition to His Bundle region. Using a logarithmic regression model, we found that minimal depth increased logarithmically with age for the AVN (R2 = 0.818, P = 0.002). Also, the myocardial overlay of the AVN was heterogeneous within different regions and decreased with increasing age. Age associated alterations of SAN minimal depth were insignificant. Our study presents examples of characteristic tissue patterns superficial to the AVN and within the SAN. We suggest that the presented framework provides quantitative information for CCS localization. Our studies indicate that procedural methods and localization approaches in regions near the AVN should account for the age of patients in cardiac surgery and interventional cardiology.

Intraoperative localization of cardiac conduction tissue regions using real-time fibre-optic confocal microscopy: first in human trial.

The aim of this study was to evaluate the feasibility and safety of fibre-optic confocal microscopy (FCM) using fluorescein sodium dye for the intraoperative location of conduction tissue regions during paediatric heart surgery. The pilot study included 6 patients undergoing elective surgery for the closure of isolated secundum atrial septal defect aged 30 days to 21 years. FCM imaging was integrated within the normal intraoperative protocol for atrial septal defect repair. Fluorescein sodium dye was applied on the arrested heart. FCM images were acquired at the atrioventricular node region, sinus node region and right ventricle (RV). Total imaging time was limited to 3 min. Any adverse events related to the study were recorded and analysed. Subjects received standard postoperative care. Trained reviewers (n = 9) classified, de-identified and randomized FCM images (n = 60) recorded from the patients as presenting striated, reticulated or indistinguishable microstructures. The reliability of reviewer agreement was assessed using Fleiss' kappa. The FCM imaging instruments were integrated effectively into the cardiac surgery operating room. All adverse events found in the study were deemed expected and not related to FCM imaging. Reticulated myocardial microstructures were found during FCM imaging at atrioventricular node and sinus node regions, while striated microstructures were observed in RV. Reliability of agreement of reviewers classifying the FCM images was high (Fleiss' kappa: 0.822). FCM using fluorescein sodium dye was found to be safe for use during paediatric heart surgery. The study demonstrates the potential for FCM to be effective in identifying conduction tissue regions during congenital heart surgery. NCT03189134.

Resident Macrophages Orchestrating Heart Rate.

The electrical conduction system of the heart is essential for maintaining normal heart rhythm and function. This is due to the presence of specialized cells that generate electrical impulses that propagate throughout the heart tissue, quickly and efficiently. This electrical impulse starts at the sinoatrial node (SAN) and propagates sequentially to atrioventricular node (AVN), subsequently being transmitted to the ventricles via specialized conduction pathways. The electrical signals are conducted from cell to cell through a cardiomyocyte permeability control system formed by proteins called connexins, and connexin-43 is the type found in the heart and is associated with the formation of so-called gap junctions. By providing the single electrical connection between the atria and the ventricles, AVN plays an essential role in the dynamics of cardiac contraction. Clinically, when the PR interval is observed in the electrocardiographic recordings, we can correlate the electrical impulse conduction time from its generation in the SAN to the delay in the AVN region, which is called decremental conduction.1 When prolongation of the PR interval or an AV block occurs, which delays excessively or even eliminates the conduction of the electrical impulse from the atria to the ventricles, will result in hemodynamic deterioration, syncope and death, in case the patient is not submitted to the brand heart.2 Over the years, several studies have described the macrophages as cells of phagocytic functions that would exclusively act in the immune system protecting the organism against pathogens. However, more recently this paradigm was mainly questioned about the origin of macrophages. Several studies have provided evidence that a subpopulation of macrophages, which originated from embryonic development and do not come from the bloodstream, reside and proliferate in virtually all body tissues and apparently act specifically on each organ. For example, resident macrophages of adipose tissue contribute to the regulation of thermogenesis,3 iron recycling in the spleen and liver,4 and participate in the process of synaptic maturation in the healthy brain.5 Such non-canonical activities emphasize the functional diversity of macrophages and their ability to perform specific tasks in the various tissues, in addition to host defence.6 In cardiac tissue, macrophages are intrinsic components of the myocardium in normal functioning, where they appear as spindle cells intercalated between cardiomyocytes, fibroblasts and endothelial cells.7 Macrophages and the heartbeat Cardiac function depends on the appropriate moment of contraction in several distinct regions, as well as the heart rate.8 Hulsmans et al.9 observed that mice that had their macrophage fauna weakened, had bradycardia and irregular beats. It is known that connexin-43 is predominant in ventricles of humans and that its reduction promotes bradycardia and AV block,8 thus, in observing specialized cells in non-muscular electrical conduction, they found that macrophages are electrically coupled to cardiomyocytes and that these resident macrophages facilitate electrical conduction through the AV node. Such conducting cells interleave with macrophages expressing connexin-43 forming additional gap junctions between cardiomyocytes (Figure 1). The investigators observed that the animals that had a reduction of resident macrophages, besides having bradycardia, had AV blockade of 2nd and 3rd degrees (Figure 2),9 whose cause in humans is still unknown.10 Another intriguing point is that cardiac macrophages have a resting membrane potential of -35 mV on average and depolarize in synchrony with cardiomyocytes. This makes the membrane potential at the rest of the cardiomyocytes more positive and according to the results obtained by computational simulation, accelerate both depolarization and repolarization phases.9 The cardioprotective role of cardiac resident macrophages can go beyond the modulation of the electrophysiological properties of the coupled cardiomyocytes. The perivascular localization of cardiac macrophages makes them uniquely positioned to interpret systemic signals in the bloodstream.10 Open in a separate window Figure 1 The normal condition of macrophage-cardiomyocyte couplings. Communications between cardiomyocytes and macrophages through connexin-43 (A) promoting normal cardiac rhythm (B).

Disruption of RHOA-ROCK Signaling Results in Atrioventricular Block and Disturbed Development of the Putative Atrioventricular Node.

The RHOA-ROCK signaling pathway is involved in numerous developmental processes, including cell proliferation, differentiation and migration. RHOA is expressed in the atrioventricular node (AVN) and altered expression of RHOA results in atrioventricular (AV) conduction disorders in mice. The current study aims to detect functional AVN disorders after disturbing RHOA-ROCK signaling in chicken embryos. RHOA-ROCK signaling was inhibited chemically by using the Rho-kinase inhibitor compound Y-27632 in avian embryos (20 experimental and 29 control embryos). Morphological examination of control embryos show a myocardial sinus venosus to atrioventricular canal continuity, contributing to the transitional zone of the AVN. ROCK inhibited embryos revealed lateralization and diminished myocardial sinus venosus to atrioventricular canal continuity and at the severe end of the phenotype hypoplasia of the AVN region. Ex ovo micro-electrode recordings showed an AV conduction delay in all treated embryos as well as cases with first, second (Wenkebach and Mobitz type) and third-degree AV block which could be explained by the spectrum of severity of the morphological phenotype. Laser capture microdissection and subsequent qPCR of tissue collected from this region revealed disturbed expression of HCN1, ISL1, and SHOX2. We conclude that RHOA-ROCK signaling is essential for normal morphological development of the myocardial continuity between the sinus venosus and AVN, contributing to the transitional zone, and possibly the compact AVN region. Disturbing the RHOA-ROCK signaling pathway results in AV conduction disturbances including AV block. The RHOA-ROCK inhibition model can be used to further study the pathophysiology and therapeutic strategies for AV block. Anat Rec, 302:83-92, 2019. © 2018 Wiley Periodicals, Inc.

Cystic tumor of the atrioventricular node: a review of the literature.

Primary cardiac tumors are uncommon clinical entities with an incidence of 0.0017% to 0.03% of all autopsies. Cystic tumor of the atrioventricular (AV) node, also known as mesothelioma of the AV node, is a benign congenital tumor that is located in the triangle of Koch in the AV nodal region of the atrial septum of the heart. It comprises of 2.7% of cardiac tumors and is the most common primary cardiac tumor causing sudden death. We herein review the etiology, presentation, differential diagnosis, diagnosis, management, surgical approaches and outcomes of this rare tumor.

Electrophysiological properties of myocytes isolated from the mouse atrioventricular node: L-type ICa, IKr, If, and Na-Ca exchange.

The atrioventricular node (AVN) is a key component of the cardiac pacemaker-conduction system. This study investigated the electrophysiology of cells isolated from the AVN region of adult mouse hearts, and compared murine ionic current magnitude with that of cells from the more extensively studied rabbit AVN. Whole-cell patch-clamp recordings of ionic currents, and perforated-patch recordings of action potentials (APs), were made at 35–37°C. Hyperpolarizing voltage commands from −40 mV elicited a Ba2+-sensitive inward rectifier current that was small at diastolic potentials. Some cells (Type 1; 33.4 ± 2.2 pF; n = 19) lacked the pacemaker current, If, whilst others (Type 2; 34.2 ± 1.5 pF; n = 21) exhibited a clear If, which was larger than in rabbit AVN cells. On depolarization from −40 mV L-type Ca2+ current, ICa,L, was elicited with a half maximal activation voltage (V0.5) of −7.6 ± 1.2 mV (n = 24). ICa,L density was smaller than in rabbit AVN cells. Rapid delayed rectifier (IKr) tail currents sensitive to E-4031 (5 μmol/L) were observed on repolarization to −40 mV, with an activation V0.5 of −10.7 ± 4.7 mV (n = 8). The IKr magnitude was similar in mouse and rabbit AVN. Under Na-Ca exchange selective conditions, mouse AVN cells exhibited 5 mmol/L Ni-sensitive exchange current that was inwardly directed negative to the holding potential (−40 mV). Spontaneous APs (5.2 ± 0.5 sec−1; n = 6) exhibited an upstroke velocity of 37.7 ± 16.2 V/s and ceased following inhibition of sarcoplasmic reticulum Ca2+ release by 1 μmol/L ryanodine, implicating intracellular Ca2+ cycling in murine AVN cell electrogenesis.

Ex vivo, microelectrode analysis of conduction through the AV node of wild-type and Nkx2-5 mutant mouse hearts as guided by a Cx40-eGFP transgenic reporter.

Mutations of the cardiac transcription factor NKX2‐5 cause hypoplastic development of the AV node and conduction block. How the anatomy of the mutant AV node relates to its function is unknown. We thus studied conduction through the AV nodal region in ex vivo preparations of wild‐type and Nkx2‐5+/− mouse hearts in which the central conduction system was highlighted by a transgenic Cx40‐eGFP reporter. Fluorescence imaging guided electrode placement and pacing of the inferior and superior approaches to the AV node. Nkx2‐5+/− hearts had a prolonged atrio‐His interval compared to the wild type, consistent with previous in vivo observations. The conduction time to the His bundle from the Cx40− AV nodal region that is superior to and immediately adjacent to the Cx40+ lower node is slightly, but not significantly greater in Nkx2‐5+/− than wild‐type hearts. A novel phenotype was also observed. Pacing the Cx40− inferior approach to the AV node with increasing stimulus strength led to progressive shortening of the stimulus‐to‐His conduction interval in wild‐type but not Nkx2‐5+/− hearts. The strength of pacing at the Cx40− superior approach had no effect on the conduction interval in either group. The prolonged AV delay in the Nkx2‐5+/− heart appears to arise before the Cx40+ lower node. Whether the pacing phenotype explains the mutant's conduction defect is uncertain, but the observation adds to a number of unique properties of the inferior approach to the AV node.

Abstract 18204: Activation of the Pro-Hypertrophic Calcineurin/Nfat-Pathway Mediates Atrio-Ventricular Conduction Disturbances in Cardiac Sodium Channelopathy

Introduction: SCN5A mutations have been associated with progressive atrio-ventricular conduction disturbances and development of cardiac structural abnormalities. In transgenic Scn5a-1798insD+/- mice, intracellular sodium and calcium concentrations are increased, setting the stage for potential activation of calcium-dependent signaling pathways. Here we investigated the impact of the pro-hypertrophic calcineurin/Nfat signaling pathway on atrio-ventricular (AV) conduction in Scn5a-1798insD+/- mice. Methods and Results: Aged (12-18 months old) Scn5a-1798insD+/- (MUT) mice developed cardiac hypertrophy (increased heart weight and Anf mRNA levels) and progressive AV-conduction abnormalities on surface ECG. Isolated Langendorff-perfused aged MUT hearts showed profound AV-delay and AV-block at high right atrial stimulation frequencies (basic cycle length 90-120 ms). To study the contribution of the calcineurin/Nfat signaling pathway to the AV-conduction phenotype, adult (age 3-5 months) wild-type (WT) and MUT mice were subjected to 2 weeks of transverse aortic constriction (TAC). WT and MUT mice showed similar hypertrophic responses to TAC. However, MUT-TAC mice displayed increased PR-interval on surface ECG and a higher incidence of sudden death. Furthermore, isolated MUT-TAC hearts showed AV-block and significantly prolonged AV-delay as compared to WT-TAC or sham hearts. Atrial and His-ventricular conduction was unaffected in MUT-TAC hearts, indicating that conduction delay occurred within the AV-nodal region. Since Nfatc2 is a well-described downstream effector of the calcineurin pathway, adult MUT mice were crossed with mice lacking Nfatc2 (Nfatc2-KO). In MUT/Nfatc2-KO hearts, AV-delay after TAC was attenuated as compared to MUT-TAC, indicating rescue of the AV-conduction disturbances by Nfatc2 deficiency. Conclusions: Scn5a-1798insD+/- mice develop profound atrio-ventricular conduction disturbances with increased age and after activation of the calcium-dependent pro-hypertrophic calcineurin/Nfat-pathway. These findings indicate that cardiac hypertrophy may modulate disease severity in cardiac sodium channelopathy.

Cystic Atrioventricular Node Tumor Excision by Minimally Invasive Surgery

Cystic tumor in the atrioventricular (AV) node region is a rare cardiac primary tumor that can lead to sudden death. Our patient was a 43-year-old woman who presented with dyspnea and a first-degree AV block seen on electrocardiography. Echocardiography revealed a cystic mass attached to the inferior portion of the interatrial septum. After surgical excision of the mass, placement of a permanent pacemaker was required for complete heart blockage. Histopathologic examination revealed the mass to be a cystic tumor of the AV node region. To our knowledge, this is the first report of this condition diagnosed ante mortem and treated successfully with minimally invasive surgery.

Neuroanatomy of the murine cardiac conduction system

The mouse heart is a popular model to study the function and autonomic control of the specialized cardiac conduction system (CCS). However, the precise identity and anatomical distribution of the intrinsic cardiac nerves that modulate the function of the mouse CCS have not been adequately studied. We aimed at determining the organization and distribution of the intrinsic cardiac nerves that supply the CCS of the mouse. In whole mouse heart preparations, intrinsic neural structures were revealed by histochemical staining for acetylcholinesterase (AChE). Adrenergic, cholinergic and peptidergic neural components were identified, respectively, by immunohistochemical labeling for tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), calcitonin gene related peptide (CGRP), substance P (SP), and protein gene product 9.5 (PGP 9.5). Myocytes of the CCS were identified by immunolabeling of hyperpolarization activated cyclic nucleotide-gated potassium channel 4 (HCN4). In addition, the presence of CCS myocytes in atypical locations was verified using fluorescent immunohistochemistry performed on routine paraffin sections. The results demonstrate that four microscopic epicardial nerves orientated toward the sinuatrial nodal (SAN) region derive from both the dorsal right atrial and right ventral nerve subplexuses. The atrioventricular nodal (AVN) region is typically supplied by a single intrinsic nerve derived from the left dorsal nerve subplexus at the posterior interatrial groove. SAN myocytes positive for HCN4 were widely distributed both on the medial, anterior, lateral and even posterior sides of the root of the right cranial (superior caval) vein. The distribution of HCN4-positive myocytes in the AVN region was also wider than previously considered. HCN4-positive cells and thin slivers of the AVN extended to the roots of the ascending aorta, posteriorly to the orifice of the coronary sinus, and even along both atrioventricular rings. Notwithstanding the fact that cholinergic nerve fibers and axons clearly predominate in the mouse CCS, adrenergic nerve fibers and axons are abundant therein as well. Altogether, these results provide new insight into the anatomical basis of the neural control of the mouse CCS.

RGS proteins in heart: brakes on the vagus

It has been nearly a century since Otto Loewi discovered that acetylcholine (ACh) release from the vagus produces bradycardia and reduced cardiac contractility. It is now known that parasympathetic control of the heart is mediated by ACh stimulation of Gi/o-coupled muscarinic M2 receptors, which directly activate G protein-coupled inwardly rectifying potassium (GIRK) channels via Gβγ resulting in membrane hyperpolarization and inhibition of action potential (AP) firing. However, expression of M2R–GIRK signaling components in heterologous systems failed to recapitulate native channel gating kinetics. The missing link was identified with the discovery of regulator of G protein signaling (RGS) proteins, which act as GTPase-activating proteins to accelerate the intrinsic GTPase activity of Gα resulting in termination of Gα- and Gβγ-mediated signaling to downstream effectors. Studies in mice expressing an RGS-insensitive Gαi2 mutant (G184S) implicated endogenous RGS proteins as key regulators of parasympathetic signaling in heart. Recently, two RGS proteins have been identified as critical regulators of M2R signaling in heart. RGS6 exhibits a uniquely robust expression in heart, especially in sinoatrial (SAN) and atrioventricular nodal regions. Mice lacking RGS6 exhibit increased bradycardia and inhibition of SAN AP firing in response to CCh as well as a loss of rapid activation and deactivation kinetics and current desensitization for ACh-induced GIRK current (IKACh). Similar findings were observed in mice lacking RGS4. Thus, dysregulation in RGS protein expression or function may contribute to pathologies involving aberrant electrical activity in cardiac pacemaker cells. Moreover, RGS6 expression was found to be up-regulated in heart under certain pathological conditions, including doxorubicin treatment, which is known to cause life-threatening cardiotoxicity and atrial fibrillation in cancer patients. On the other hand, increased vagal tone may be cardioprotective in heart failure where acetylcholinesterase inhibitors and vagal stimulation have been proposed as potential therapeutics. Together, these studies identify RGS proteins, especially RGS6, as new therapeutic targets for diseases such as sick sinus syndrome or other maladies involving abnormal autonomic control of the heart.

Aberrant penetrating posterior descending artery from proximal right coronary artery

We report a rare variant of the posterior descending artery (PDA) in a 51-year-old African-American male discovered in coronary CT angiography. Arising from the proximal right coronary artery near its ostium, the anomalous PDA penetrated posteriorly toward the atrioventricular junction septum, exited through the inferior pyramidal space into the posterior interventricular groove and continued in the groove as a short PDA. Along its course it gave rise to small branches to the medial wall of the right atrium, the atrioventricular node region, and the inferoseptal wall of the right ventricle.

Anatomical Perspective on Radiofrequency Ablation of AV Nodal Reentry Tachycardia after Mustard Correction for Transposition of the Great Arteries

A case of radiofrequency catheter ablation of atrioventricular (AV) nodal reentry tachycardia, in a patient with transposition of the great arteries after venous rerouting according to Mustard, is described. An electroanatomical map of the His and AV nodal region was created from inside the systemic venous atrium. Retrograde mapping of the pulmonary venous atrium was performed and the arterial catheter retracted to a position in close proximity to the venous catheter inside the intraatrial baffle. This position was chosen to deliver radiofrequency current.

Apparent short PR interval during atrial tachycardia: what is the mechanism?

A 69-year-old woman with an incessant narrow QRS tachycardia underwent catheter ablation 5 days after failed ablation attempt at another center. Figure 1a shows 12-lead ECG of the tachycardia with a PR interval = 80 ms and cycle length of 450 ms. Ventricular overdrive pacing showed ventriculoatrial dissociation. Figure 1b shows atrial overdrive pacing with the cycle length of 420 ms, with PR interval of 160 ms, which excludes very long PR interval manifesting as apparent short PR interval. In addition incremental atrial pacing showed a Wenckebach point of 350 ms and no preexcitation. Pacing during sinus rhythm with the same cycle length (420 ms) generated a PR interval of 160 ms. Figure 2 shows activation mapping of atrial tachycardia in right atrium with the earliest activation recorded in fast pathway region near His (Fig. 2b). Activation mapping also showed slow conduction from this point (Fig. 2a, b) to the rest of atria (Fig. 2c), which was responsible for the apparent short PR interval. Radiofrequency ablation (Navistar 4 mm, Biosense Webster Inc, Diamond Bar, California, USA) at the earliest activation point (30 W, 50 C) slowed down and then terminated the atrial tachycardia with transient first degree atrioventricular (AV) block. The P wave morphology was not compatible with a septal atrial tachycardia; however, we postulated that delayed and changed atrial activation pattern due to earlier linear ablation lesions as shown in activation mapping may have resulted the observed apparent short PR interval and unusual changed P wave morphology (Fig. 2) [1, 2]. In conclusion, the slow conduction from the earliest activation point to the rest of the right and left atria despite normal conduction to and through the AV node resulted in the delayed atrial depolarization which in turn caused the apparent short PR interval during atrial tachycardia in the absence of an accessory pathway. During catheter ablation the patient transiently developed first degree AV Block. We used a low power setting to avoid high-degree AV block; however, using cryoablation with EnSite NavX Navigation system (St. Jude Medical, Inc. St. Paul, MN) could have been a safe alternative for catheter ablation in this area. Junctional tachycardia should be considered in the differential diagnosis. However, in this case the earliest activation would be at the AV node region. As shown in Fig. 2, the earliest activation during tachycardia was superior and posterior to the fast pathway/AV node region. In addition, the polarity of the P wave and its relation to QRS complex (short PR) argues against junctional tachycardia. Finally, the total atrial activation time was 160 ms which excludes macro-reentry as the underlying mechanism of the tachycardia. True focal atrial tachycardia due to abnormal automaticity or microreentry remains the possible mechanism of this tachycardia.

RGS6, a Modulator of Parasympathetic Activation in Heart

Parasympathetic regulation of heart rate is mediated by acetylcholine binding to G protein-coupled muscarinic M2 receptors, which activate heterotrimeric G(i/o) proteins to promote G protein-coupled inwardly rectifying K(+) (GIRK) channel activation. Regulator of G protein signaling (RGS) proteins, which function to inactivate G proteins, are indispensable for normal parasympathetic control of the heart. However, it is unclear which of the more than 20 known RGS proteins function to negatively regulate and thereby ensure normal parasympathetic control of the heart. To examine the specific contribution of RGS6 as an essential regulator of parasympathetic signaling in heart. We developed RGS6 knockout mice to determine the functional impact of loss of RGS6 on parasympathetic regulation of cardiac automaticity. RGS6 exhibited a uniquely robust expression in the heart, particularly in sinoatrial and atrioventricular nodal regions. Loss of RGS6 provoked dramatically exaggerated bradycardia in response to carbachol in mice and isolated perfused hearts and significantly enhanced the effect of carbachol on inhibition of spontaneous action potential firing in sinoatrial node cells. Consistent with a role of RGS6 in G protein inactivation, RGS6-deficient atrial myocytes exhibited a significant reduction in the time course of acetylcholine-activated potassium current (I(K)(ACh)) activation and deactivation, as well as the extent of I(K)(ACh) desensitization. RGS6 is a previously unrecognized, but essential, regulator of parasympathetic activation in heart, functioning to prevent parasympathetic override and severe bradycardia. These effects likely result from actions of RGS6 as a negative regulator of G protein activation of GIRK channels.

Tachycardia and the AV Nodal Region

Tachycardias that are successfully ablated in the vicinity of the atrioventricular (AV) node are common, and although frequently successfully treated, are among the most difficult arrhythmias to understand in cardiac electrophysiology. Even AV node reentrant tachycardia (AVNRT), despite near universal cure, is complex with the anatomic constructs for typical, atypical forms, left-sided AVNRT, upper common pathway block, and lower common pathway block, not readily apparent.1 Even less understood arrhythmias in this group are junctional tachycardias and peri–AV nodal “atrial” tachycardias that may or may not be reentrant and may or may not involve AV node–like tissue.2,3⇓ Article see p 54 One unique member of this group of peri–AV nodal tachycardias is verapamil and adenosine-sensitive “atrial” tachycardia described to arise from the apex of the triangle of Koch’s and considered reentrant mechanism involving the AV node or AV node–like transitional tissue.4–6⇓⇓ In this issue of the Circulation: Arrhythmia and Electrophysiology , Yamabe et al7 provide novel insights into the mechanism of this arrhythmia. They analyzed characteristics by placing late-coupled atrial extrastimuli at 9 predetermined locations in the region of the triangle of Koch’s and the coronary sinus ostium and concluded that the AV node, His bundle, and atrial tissue within the triangle of Koch’s are not involved in the tachycardia circuit. The importance of their study far exceeds the frequency with which we encounter this uncommon arrhythmia. Their findings highlight the incredible complexity of the electroanatomy and electrophysiology of the peri–AV nodal region, brings to focus the difficulties in defining mechanism of arrhythmia, and perhaps, most importantly, forces us to ask the question, “What is AVNRT?” It is perhaps easier to gain appreciation of these broader concepts by first acknowledging the difficulties in answering seemingly simpler questions. ### Entrainment and Reset Reentry as a mechanism of tachycardia is …

Cystic tumour of the atrioventricular node: three cases of sudden death

Cystic tumour of the atrioventricular nodal region is a rare primary cardiac tumour that can cause sudden death. Antemortem diagnosis and successful excision of this type of tumour are extremely rare. Three cases of sudden death are reported: A 25- and 40-year-old with a history of heart block and a 60-year-old with no medical history. There have been more than 120 cases of sudden death attributed to primary cardiac tumours in the literature. Although over 100 of these lesions were histologically benign, their intracardiac locations precipitated conductive and haemodynamic abnormalities that resulted in sudden death. The most common intracardiac lesion causing sudden death, cystic tumour of the atrioventricular node, however, may not be discovered unless the atrioventricular node is microscopically examined.