Atrioventricular Junction Research Articles

SAT0435 A1G T-Type Calcium Channel is Expressed in Human Fetal Hearts and Has an Extracellular Epitope Bound by Autoantibodies from Congenital Heart Block Maternal Sera

BackgroundBackground: Congenital heart block (CHB) is a transplacentally acquired autoimmune disease associated with anti-Ro/La maternal autoantibodies and is characterized primarily by atrioventricular (AV) block of the fetal heart. Since the...

How Best Can We Define Double Outlet Right Ventricle When Describing Congenitally Malformed Hearts?

How Best Can We Define Double Outlet Right Ventricle When Describing Congenitally Malformed Hearts?

263 AGEING IS ASSOCIATED WITH CHANGES IN STRUCTURE AND ION CHANNEL EXPRESSION WITHIN THE ATRIOVENTRICULAR CONDUCTION AXIS

<h3>Introduction</h3> The inferior nodal extension (INE), compact atrioventricular (AV) node and penetrating/His bundle (PB) form the AV conduction axis and are responsible for delay and propagation of the action potential from the atria to the ventricles. With ageing, dysfunction in these tissues results in prolongation of the PR interval and first, second and third degree AV block. The only treatment is implantation of permanent pacemakers, which are known to be associated with various complications. Previous studies have described age-related structural and functional changes in the AV conduction axis, but detailed examination of morphological changes (such as fibrosis and hypertrophy) as well as changes in ion channel expression with ageing have not been investigated. <h3>Methods</h3> We have compared the regions of the AV conduction axis (INE, compact AV node, CN, proximal PB, PPB and distal PB, His bundle) from 3 (n=9) and 24 (n=8) months old male rats (humanely killed in accordance with UK Animals Scientific Procedures Act 1986). From the survival curve, 3 months old rats correspond to 20 years old humans, whereas 24 months old rats correspond to ∼70 years old humans. Morphological characteristics of these tissues were studied using serial cryosections and Masson’s trichrome (MT) and picrosirius red (PR) histological stains and light and polarised microscopy. The expression of the ion channel HCN4 (responsible for pacemaking) and the gap junction channels Cx43 and Cx40 (responsible for electrical coupling between cardiac cells) was studied using immunofluorescence and confocal microscopy on sister sections to those used for histology. Qualitative signal intensity of these channels was measured using Volocity software. Statistical analysis was performed with SPSS version 20.1. <h3>Results</h3> At the structural level, we observed significant changes with ageing. MT staining showed that the cells of INE, CN, PPB and His bundle are more loosely packed and irregularly arranged in older animals. Age-dependent cellular hypertrophy was confirmed by a statistically significant increase in cell size across all regions of the AV junction. With ageing, total collagen content estimation showed a statistically significant increase in thin (but not in thick) collagen fibres in the CN, PPB and His bundle. Immunohistochemistry revealed a decrease in Cx43 expression in the INE (P=0.003), PPB (P=0.005), His bundle (P=0.02), but an increase in Cx40 expression in the INE (P=0.01) and CN (P=0.005) with ageing. There was also trend to downregulation of HCN4 expression especially in the His bundle (P=0.051). <h3>Conclusion</h3> Ageing is associated with structural changes of the AV junction tissues, which include fibrosis, hypertrophy and changes in Cx43 and Cx40 and possibly HCN4 expression. Our current findings may explain the prolongation of the PR interval with ageing observed in our previous study.

Experimental Model of Focal Atrial Tachycardia: Clinical Correlates

The mechanisms underlying focal atrial tachycardia (AT) are unclear. In 14 pentobarbital anesthetized dogs, a right thoracotomy allowed electrical stimulation (ES) of the anterior right ganglionated plexi (ARGP). After ES was applied to the ARGP at baseline, atropine, 1 mg/cc, was injected into the ARGP and repeat stimulation applied. After a left thoracotomy (n = 8), a similar procedure was followed by atropine injected into the superior left (SL) GP. ES (0.6-3.2 V) applied to the ARGP and SLGP caused an average reduction in sinus rate from 151 ± 14/min to 60 ± 11/min. At ≥4.5 V atrial fibrillation (AF) was induced (duration 48 ± 14 seconds). After injection of atropine into the ARGP or SLGP, ES applied to these GP induced no slowing of the sinus rate. Runs of AT were induced at an average voltage of 10 ± 2 V in 14 experiments (duration ≥4 minutes). AT was localized by ice mapping or by 3D noncontact mapping to the crista terminalis (n = 6), AV junction (n = 2) or a focal site at the left superior pulmonary vein (6). In AT lasting <4 minutes (n = 2), epinephrine injected into the GP significantly increased the AT duration. In 4/4 experiments, sustained AT could be terminated by intravenous esmolol. Atropine injected into the ARGP or SLGP promotes ES-induced AT whose duration is increased by adrenergic agonists and terminated by beta blockade. Presumably cholinergic blockade and accentuated release of adrenergic neurotransmitters provide the AT mechanism. The induced AT was found to be localized at sites similar to those reported clinically.

Invited Commentary

Dr Gillinov discloses financial relationships with Edwards, AtriCure, Intuitive, and Medtronic. Dr Gillinov discloses financial relationships with Edwards, AtriCure, Intuitive, and Medtronic. Dr Fukuhara and colleagues describe a small series of patients with left atrial dissection, a rare but relevant complication of mitral valve operations [1Fukuhara S. Dimitrova K.R. Geller C.M. Hoffman D.M. Ko W. Tranbaugh R.F. Left atrial dissection: etiology and treatment.Ann Thorac Surg. 2013; 95: 1557-1562Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar]. The incidence of diagnosis of left atrial dissection increases along with the skill of the transesophageal echocardiography operators in operating rooms. In our experience, not every left atrial dissection diagnosed intraoperatively requires revision and left atrial reconstruction. Often left atrial dissection presents as a discrete thickening of the left atrial wall with no hemodynamic influence on mitral valve function. In such cases, dissection can be successfully treated by heparin reversal. Left atrial dissections can also present as an overture to the life-threatening disruption of the atrioventricular junction, requiring immediate intraoperative repair. It is important to differentiate between these two entities because they are associated with substantially different prognoses. Perforation of the coronary sinus can lead to the formation of epicardial hematoma or, in rare cases, as described in this article, to left atrial dissection. The reason for the complication is likely related not to simple perforation of the low-pressured coronary sinus but rather to the pressurized infusion of cardioplegia through a displaced retrograde cardioplegia catheter. Early recognition of a misplaced retrograde cardioplegia catheter prevents this rare complication. Left Atrial Dissection: Etiology and TreatmentThe Annals of Thoracic SurgeryVol. 95Issue 5PreviewLeft atrial dissection (LatD) is a rare entity most commonly associated with mitral valve surgery. We have reviewed our experience with 4 patients to better define the etiology and the treatment of LatD. Full-Text PDF

Role of Atrio-Ventricular Junction Ablation in Symptomatic Atrial Fibrillation for Optimization of Cardiac Resynchronization Therapy.

Cardiac resynchronization (CRT) therapy is indicated in patients with at least mildly symptomatic heart failure, left ventricular ejection fraction ≤35% and wide QRS, and has been associated with decreased morbidity and mortality. Unfortunately, approximately 30% of the patients appropriately selected for therapy do not respond to CRT. Among the reasons for non-response, atrial fibrillation (AF) plays a prominent role. AF limits the degree of biventricular pacing during CRT, not only when the ventricular rate is fast and highly irregular, but also during periods of of relatively constant rate, by causing fusion and pseudo-fusion complexes. Importantly, achievement of nearly 100% biventricular pacing is necessary to derive benefit from CRT. A simple, albeit irreversible, method to maximize biventricular pacing in patients with AF who are otherwise eligible for CRT is atrioventricular junction (AVJ) ablation. In this review, we discuss the role of AVJ ablation in CRT optimization in patients with AF. The available evidence from observational non-randomized studies suggests that AVJ ablation in patients with AF qualifying for CRT may offer improvement in heart failure symptoms, better survival, and better cardiac function. In light of the inherent limitations of non-randomized studies, further randomized studies are needed to support this treatment option.

Quantifying Function in the Early Embryonic Heart

Congenital heart defects arise during the early stages of development, and studies have linked abnormal blood flow and irregular cardiac function to improper cardiac morphogenesis. The embryonic zebrafish offers superb optical access for live imaging of heart development. Here, we build upon previously used techniques to develop a methodology for quantifying cardiac function in the embryonic zebrafish model. Imaging was performed using bright field microscopy at 1500 frames/s at 0.76 μm/pixel. Heart function was manipulated in a wild-type zebrafish at ∼55 h post fertilization (hpf). Blood velocity and luminal diameter were measured at the atrial inlet and atrioventricular junction (AVJ) by analyzing spatiotemporal plots. Control volume analysis was used to estimate the flow rate waveform, retrograde fractions, stroke volume, and cardiac output. The diameter and flow waveforms at the inlet and AVJ are highly repeatable between heart beats. We have developed a methodology for quantifying overall heart function, which can be applied to early stages of zebrafish development.

Can a swallowed foreign body cause severe mitral valve regurgitation ?

Very rarely a foreign body in the esophagus may penetrate anteriorly to heart or aorta. Such foreign bodies may cause pericardial effusion and cardiac tamponade. To report that an accidentally swallowed foreign body in the esophagus may penetrate the heart and even cause severe mitral regurgitation. A 20 month old girl previously healthy presented to the emergency department with 3 days history of fever, respiratory distress, vomiting and poor feeding. The mother reported that her child had some choking event almost a week before, when the child was admitted to another hospital where diagnosis was made of myocarditis. Anti-failure medications prescribed. On examination she had palpable peripheral pulses, a pansystolic murmur on the cardiac apex, and hepatomegaly. EKG showed sinus tachycardia with left ventricular hypertrophy. Chest X-ray revealed normal cardiac size with lungs congestion and suspicion of possible foreign body. Echocardiography showed dilatation of the left atrium and of the pulmonary veins, severe mitral regurgitation with an echogenic structure in next to the posterior mitral valve leaflet with consensual moving. Chest CT scan revealed a high-density metallic foreign body inside the heart in correspondence of the left atrio-ventricular junction. The foreign body was removed surgically and proved to be a thin shiny metal bar, 2 cm in length. The mitral valve was completely damaged and was replaced by mechanical valve (Carbomedics 18 mm). The postoperative course was uneventful and patient was discharged home with anti-failure medications (frusemide, captopril) and warfarin. She remained asymptomatic one year after surgery. The process of diagnosing a foreign body in an infant or a toddler, eroding from the esophagus to the heart was very tricky. The diagnosis was suspected by the history of chocking. The x-ray of the chest showed an abnormal structure on the heart shadow, which was further underlined by the echocardiogram suggesting abnormal structure in the heart. Finally CT angio of heart confirmed a metallic foreign body in the left atrium. Happily, MRI was not done; it may have proved disastrous in such a case. The strategy regarding foreign body management either conservative or by its removal either by cardiac catheterization or surgery, depends on location, size of foreign body as well as on whether the patient is symptomatic and in danger to develop further complications. In our case, as the foreign body was in the left atrium and the patient was very critically ill, we opted to remove it by surgery. Moreover, it was thought that patient might need mitral valve repair but unfortunately the valve was so damaged that we opted for mitral valve replacement.

Letter by Gasparini and Boriani Regarding Article, “Cardiac Resynchronization Therapy in Patients With Permanent Atrial Fibrillation: Results From the Resynchronization for Ambulatory Heart Failure Trial (RAFT)”

To the Editor: We read with great interest the article by Healey et al1 presenting data of patients with permanent atrial fibrillation (AF) enrolled in the Resynchronization for Ambulatory Heart Failure Trial (RAFT). Being a field in which no randomized trial has been specifically performed, these data might have an important impact on managing this large portion of the heart failure population. The recent guidelines of the European Society of Cardiology2 consider patients with permanent AF as a class IIa level B only if atrioventricular junction (AVJ) ablation is performed, permitting to reach almost 100% biventricular (BIV) pacing. Starting from our experience published in 2008,3 it was almost …

Left Atrial Dissection: Etiology and Treatment

Left atrial dissection (LatD) is a rare entity most commonly associated with mitral valve surgery. We have reviewed our experience with 4 patients to better define the etiology and the treatment of LatD. From 1991 to 2012, 4 patients experienced LatD after surgery (1 of 6,302, or 0.02%, of isolated coronary artery bypass grafting patients and 3 of 1,895, or 0.16%, of mitral valve patients). Patient and perioperative data and management were reviewed. Two patients were women, and ages ranged from 49 to 80 years. Three patients underwent mitral procedures (two replacements with coronary artery bypass grafting and one repair) for mitral regurgitation. One patient underwent emergent isolated coronary artery bypass grafting after cardiopulmonary resuscitation for a left main dissection during percutaneous coronary intervention. Three LatDs were found during surgery, and one LatD was found 12 days after mitral repair and was successfully treated nonoperatively. The LatD was located along the posterior atrial wall originating from the atrioventricular junction in all cases and obstructed mitral valve inflow. Operative repair focused on the evacuation of hematoma, obliteration of the false lumen, and repair of the entry injury. No mortality occurred. Left atrial dissection is a rare complication of cardiac surgery, probably related to a contained atrioventricular separation allowing pressurized blood to separate the layers of the posterior left atrium. Prompt intraoperative diagnosis, obliterating the false cavity, and addressing the entry point are essential. In contrast, a nonoperative approach in a stable patient with a delayed LatD suggests healing of the dissection, and atrial remodeling occurs.

A simple model of the right atrium of the human heart with the sinoatrial and atrioventricular nodes included.

Existing atrial models with detailed anatomical structure and multi-variable cardiac transmembrane current models are too complex to allow to combine an investigation of long time dycal properties of the heart rhythm with the ability to effectively simulate cardiac electrical activity during arrhythmia. Other ways of modeling need to be investigated. Moreover, many state-of-the-art models of the right atrium do not include an atrioventricular node (AVN) and only rarely—the sinoatrial node (SAN). A model of the heart tissue within the right atrium including the SAN and AVN nodes was developed. Looking for a minimal model, currently we are testing our approach on chosen well-known arrhythmias, which were until now obtained only using much more complicated models, or were only observed in a clinical setting. Ultimately, the goal is to obtain a model able to generate sequences of RR intervals specific for the arrhythmias involving the AV junction as well as for other phenomena occurring within the atrium. The model should be fast enough to allow the study of heart rate variability and arrhythmias at a time scale of thousands of heart beats in real-time. In the model of the right atrium proposed here, different kinds of cardiac tissues are described by sets of different equations, with most of them belonging to the class of Liénard nonlinear dynamical systems. We have developed a series of models of the right atrium with differing anatomical simplifications, in the form of a 2D mapping of the atrium or of an idealized cylindrical geometry, including only those anatomical details required to reproduce a given physiological phenomenon. The simulations allowed to reconstruct the phase relations between the sinus rhythm and the location and properties of a parasystolic source together with the effect of this source on the resultant heart rhythm. We model the action potential conduction time alternans through the atrioventricular AVN junction observed in cardiac tissue in electrophysiological studies during the ventricular-triggered atrial tachycardia. A simulation of the atrio-ventricular nodal reentry tachycardia was performed together with an entrainment procedure in which the arrhythmia circuit was located by measuring the post-pacing interval (PPI) at simulated mapping catheters. The generation and interpretation of RR times series is the ultimate goal of our research. However, to reach that goal we need first to (1) somehow verify the validity of the model of the atrium with the nodes included and (2) include in the model the effect of the sympathetic and vagal ANS. The current paper serves as a partial solution of the 1). In particular we show, that measuring the PPI–TCL entrainment response in proximal (possibly-the slow-conducting pathway), the distal and at a mid-distance from CS could help in rapid distinction of AVNRT from other atrial tachycardias. Our simulations support the hypothesis that the alternans of the conduction time between the atria and the ventricles in the AV orthodromic reciprocating tachycardia can occur within a single pathway. In the atrial parasystole simulation, we found a mathematical condition which allows for a rough estimation of the location of the parasystolic source within the atrium, both for simplified (planar) and the cylindrical geometry of the atrium. The planar and the cylindrical geometry yielded practically the same results of simulations.

The Transitional Cardiac Pumping Mechanics in the Embryonic Heart.

Several studies have linked abnormal blood flow dynamics to the formation of congenital heart defects during the early stages of development. The objective of this study is to document the transition of pumping mechanics from the early tube stage to the late looping stage of the embryonic heart. The optically transparent zebrafish embryonic heart was utilized as the in vivo model and was studied using standard bright field microscopy at three relevant stages within the transitional period: (1) tube stage at 30hours post-fertilization (hpf); (2) early cardiac looping stage at 36hpf; and (3) late cardiac looping stage at 48hpf. High-speed videos were collected at 1000fps at a spatial resolution of 1.1μm/pixel at each of these stages and were post-processed to yield blood velocity patterns as well as wall kinematics. Results show that several relevant trends exist. Morphological trends from tube through late looping include: (a) ballooning of the chambers, (b) increasing constriction at the atrioventricular junction (AVJ), and (c) repositioning of the ventricle toward the side of the atrium. Blood flow trends include: (a) higher blood velocities, (b) increased AVJ regurgitation, and (c) larger percentages of blood from the upper atrium expelled backward toward the atrial inlet. Pumping mechanics trends include: (a) increasing contraction wave delay at the AVJ, (b) the AVJ begins acting as a rudimentary valve, (c) decreasing chamber constriction during maximum contraction, and (d) a transition in ventricular kinematics from a pronounced propagating wave to an independent, full-chamber contraction. The above results provide new insight into the transitional pumping mechanics from peristalsis-like pumping to a displacement pumping mechanism.

A case of pericardial tuberculoma presenting as a left anterior chest wall mass

IntroductionTuberculosis (TB) can present both in its pulmonary or extra-pulmonary forms. Cardiac tuberculoma previously described only after autopsy is continuously seen with the advent of more advanced imaging modalities.Case reportA 23-year-old male with a four month history of a progressively increasing left anterior thoracic wall mass of 5 cm in diameter was referred from oncology for clinical re-evaluation and for echocardiography. Systemic examination was essentially normal. Transthoracic and trans-oesophageal echocardiography showed the presence of a pericardial mass around the right atrioventricular junction. Thoracic CT scan showed an anterior mass in left chest wall extending to the pericardium and also the presence of mediastinal lymphadenopathy. Mantoux test was positive and histological examination of tissue biopsy confirmed the presence of TB. However, blood tests and culture of aspirated purulent fluid were unyielding. A diagnosis of pericardial tuberculoma with mediastinal and parietal extension was made and patient was successfully treated with standard anti-TB chemotherapy.DiscussionThe possible differential diagnoses for chest wall tumors are varied and a high degree of suspicion is needed to diagnose cardiac tuberculoma especially in endemic regions. Imaging though helpful in morphological description cannot make precise diagnosis. The diagnosis depends on histological and culture studies. There is usually a good evolution with anti-TB treatment.ConclusionIn an era of an increasing number of acquired immune-compromised patients, and with increasing number of diagnoses of tuberculosis, a diagnosis of cardiac tuberculoma should be considered in patients presenting with a thoracic wall mass.

Cardiac MRI correlates of diastolic left ventricular function assessment by echocardiography

Background Transthoracic echocardiography (TTE) provides noninvasive measures of diastolic left ventricular (LV) function by assessing mitral inflow and mitral annular motion. Given the excellent spatial and temporal resolution of CMR, we developed a novel method to calculate several correlative measures of diastolic and systolic LV function. The maximum velocity of the atrioventricular junction (AVJ) during early diastole represents a correlate of the maximum velocity of the mitral annulus (e’). To determine the correlation between CMR and TTE indices of diastolic function, we performed a retrospective analysis.

The saddle shape of the mitral valve: More than just a shape

The knowledge about mitral valve (MV) has tremendously increased from the days when Andreas Vesalius suggested the picturesque term “mitral” to describe the left atrioventricular valve owing to its resemblance to a plan view of the bishop’s mitre. In its open state, the MV leaflets extend like a funnel from its base at the atrioventricular junction to the free margins. Tendinous chords attach the MV leaflets to two closely arranged anterolateral and posteromedial papillary muscle. The MV leaflets, the annulus, the atrial and ventricular wall surrounding the annulus, the tendinous chords, the papillary muscles, and the myocardium surrounding the papillary muscle attachment constitute the MV complex/apparatus. For the prevention of the back flow during systole, precisely timed interaction of all the anatomical components of the MV complex is essential. Alterations in the structure and function of any of these elements can lead to MV dysfunction. [1] The MV annulus is a concept and not an anatomically well-defined structure. The anterior one-third of the MV annulus that houses the anterior mitral leaflet (AML) is fibrous and well defined. Fibroelastic tissue extends posteriorly from the extremes of the anterior fibrous partial ring and forms the posterior two-thirds of the MV annulus; this part of the annulus tends to be “weak” and lacks a well-formed fibrous cord. The posterior mitral leaflet (PML) is attached to this part of the MV annulus. This is the area affected in “annular dilatation” and is often involved in calcification of the annulus.The MV is non-planar and obliquely located in the heart, and the annulus is saddle shaped. It is not known how the MV annulus acquires non-planar and saddle shape. Also, it is not known how this saddle shape is maintained. The finite element analyses consistently Access this article online

Unbalanced Atrioventricular Septal Defect: Defining the Limits of Biventricular Repair

Unbalanced atrioventricular septal defect (uAVSD) is a challenging lesion with suboptimal outcomes in the current era. Severe forms of uAVSD mandate univentricular repair with well-documented outcomes. Determining the feasibility of biventricular repair (BVR) in patients with moderate forms of uAVSD is difficult. Ventricular hypoplasia has traditionally formed the cornerstone of defining uAVSD. However, malalignment of the atrioventricular junction and related derangements of the anatomy and physiology of the atrioventricular inflow play a central role in establishing and sustaining a biventricular end state. Atrioventricular valve index, left ventricular inflow index, and right ventricle/left ventricle inflow angle are important recently described measures of inflow physiology. Additional patient anatomic and physiologic factors that impact BVR feasibility undoubtedly exist. A recently launched Congenital Heart Surgeons Society prospective inception cohort study will address these and other issues that impair our ability to predict BVR feasibility in uAVSD.

Atrioventricular Septal Defect with Common Atrioventricular Junction Guarded by a Common Valve Consisting of Left Atrioventricular Trifoliate Valve

Introduction:Atrioventricular septal defect with common atrioventricular junction is a rare adult congenital cardiac syndrome. This occurrence with prolonged survival is exceptionally rare.Case report:We present the case of a patient who presented with this defect with common atrioventricular junction who survived to the age of 32. We describe a 32-year-old man with atrioventricular septal defect with common atrioventricular junction guarded by a common valve. His history, clinical course, and anatomic findings are discussed along with the factors which may have contributed to his longevity, which is unique in the medical literature. His management reflected the state of medical knowledge at the time when he presented, and although alternate approaches may have been utilized if the patient presented today. We discuss the findings, frequency, classifi cation, and management of congenital defects. Development of embryonic structure is altered by interaction between genetics and environmental factors toward a rare associated of congenital cardiac defects-complex congenital heart disease.Conclusion:This case demonstrates that patients with very complex congenital cardiac disease may survive to adulthood, presenting challenges in both medical and surgical treatment.

Narrow Irregular QRS Tachycardia with AV Dissociation: What Is the Mechanism?

A 39-year-old woman with no structural heart disease and frequent episodes of sudden onset palpitations was referred for the electrophysiological study. During the study, a slightly irregular narrow QRS tachycardia with AV dissociation was repeatedly induced and spontaneously terminated. Apparently, irregular cycles and termination of the tachycardia were related to the dissociated sinus rhythm: atrial depolarizations timed when the AV junction was refractory were able to reset the tachycardia, while early atrial depolarizations caused its termination. This observation was enough to diagnose the tachycardia mechanism in our case.

Spatiotemporal regulation of an Hcn4 enhancer defines a role for Mef2c and HDACs in cardiac electrical patterning

Regional differences in cardiomyocyte automaticity permit the sinoatrial node (SAN) to function as the leading cardiac pacemaker and the atrioventricular (AV) junction as a subsidiary pacemaker. The regulatory mechanisms controlling the distribution of automaticity within the heart are not understood. To understand regional variation in cardiac automaticity, we carried out an in vivo analysis of cis-regulatory elements that control expression of the hyperpolarization-activated cyclic-nucleotide gated ion channel 4 (Hcn4). Using transgenic mice, we found that spatial and temporal patterning of Hcn4 expression in the AV conduction system required cis-regulatory elements with multiple conserved fragments. One highly conserved region, which contained a myocyte enhancer factor 2C (Mef2C) binding site previously described in vitro, induced reporter expression specifically in the embryonic non-chamber myocardium and the postnatal AV bundle in a Mef2c-dependent manner in vivo. Inhibition of histone deacetylase (HDAC) activity in cultured transgenic embryos showed expansion of reporter activity to working myocardium. In adult animals, hypertrophy induced by transverse aortic constriction, which causes translocation of HDACs out of the nucleus, resulted in ectopic activation of the Hcn4 enhancer in working myocardium, recapitulating pathological electrical remodeling. These findings reveal mechanisms that control the distribution of automaticity among cardiomyocytes during development and in response to stress.

Current Role of Atrioventricular Junction (AVJ) Ablation

Atrioventricular junction ablation with permanent pacemaker insertion is a highly effective treatment approach in patients with atrial fibrillation that is resistant to other treatment modalities, especially in the elderly or those with severe comorbidities. This effect likely reflects reversal of rapid ventricular rates and regularizing ventricular rates. There is increasing evidence that cardiac resynchronization therapy devices may be beneficial in selected populations after atrioventricular node ablation. The limitations of this approach include continued need for anticoagulation and lifelong pacemaker therapy.