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Heart Rhythm Feb 2013The structure and functioning of the atrioventricular (AV) node has remained mysterious owing to its high degree of complexity. In this review article, we integrate... (Review)
Review
The structure and functioning of the atrioventricular (AV) node has remained mysterious owing to its high degree of complexity. In this review article, we integrate advances in knowledge regarding connexin expression in the AV node. Complex patterning of 4 different connexin isoforms with single channel conductances ranging from ultralow to high explains the dual pathway electrophysiology of the AV node, the presence of 2 nodal extensions, longitudinal dissociation in the penetrating bundle, and, most importantly, how the AV node maintains slow conduction between the atria and the ventricles. It is shown that the complex patterning of connexins is the consequence of the embryonic development of the cardiac conduction system. Finally, it is argued that connexin dysregulation may be responsible for AV node dysfunction.
Topics: Animals; Atrioventricular Node; Cardiac Electrophysiology; Connexins; Heart Atria; Heart Conduction System; Heart Ventricles; Humans; Immunohistochemistry; Mice; Rabbits; Sensitivity and Specificity; Tachycardia, Atrioventricular Nodal Reentry
PubMed: 23085482
DOI: 10.1016/j.hrthm.2012.10.020 -
ESC Heart Failure Dec 2023Atrial fibrillation (AF) worsens the prognosis of patients with heart failure (HF). Successful treatments are still very scarce for those with permanent AF and preserved... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Atrial fibrillation (AF) worsens the prognosis of patients with heart failure (HF). Successful treatments are still very scarce for those with permanent AF and preserved (HFpEF) or mildly reduced (HFmrEF) ejection fraction. In this study, the long-term benefits and safety profile of heart rate regularization through left-bundle branch pacing (LBBP) and atrioventricular node ablation (AVNA) will be explored in comparison with pharmacological rate-control strategy.
METHODS AND RESULTS
The PACE-FIB trial is a multicentre, prospective, open-label, randomized (1:1) clinical study that will take place between March 2022 and February 2027. A total of 334 patients with HFpEF/HFmrEF and permanent AF will receive either LBBP followed by AVNA (intervention arm) or optimal pharmacological treatment for heart rate control according to European guideline recommendations (control arm). All patients will be followed up for a minimum of 36 months. The primary outcome measure will be the composite of all-cause mortality, HF hospitalization, and worsening HF at 36 months. Other secondary efficacy and safety outcome measures such as echocardiographic parameters, functional status, and treatment-related adverse events, among others, will be analysed too.
CONCLUSION
LBBP is a promising stimulation mode that may foster the clinical benefit of heart rate regularization through AV node ablation compared with pharmacological rate control. This is the first randomized trial specifically addressing the long-term efficacy and safety of this pace-and-ablate strategy in patients with HFpEF/HFmrEF and permanent AF.
Topics: Humans; Atrioventricular Node; Heart Failure; Prospective Studies; Stroke Volume; Atrial Fibrillation
PubMed: 37731197
DOI: 10.1002/ehf2.14488 -
Circulation Research Jul 2020
Topics: Atrioventricular Node; Heart Conduction System; Heart Rate; Myocytes, Cardiac; Ventricular Function
PubMed: 32614716
DOI: 10.1161/CIRCRESAHA.120.317291 -
Circulation. Arrhythmia and... Dec 2016Heart block is associated with pulmonary hypertension, and the aim of the study was to test the hypothesis that the heart block is the result of a change in the ion...
BACKGROUND
Heart block is associated with pulmonary hypertension, and the aim of the study was to test the hypothesis that the heart block is the result of a change in the ion channel transcriptome of the atrioventricular (AV) node.
METHODS AND RESULTS
The most commonly used animal model of pulmonary hypertension, the monocrotaline-injected rat, was used. The functional consequences of monocrotaline injection were determined by echocardiography, ECG recording, and electrophysiological experiments on the Langendorff-perfused heart and isolated AV node. The ion channel transcriptome was measured by quantitative PCR, and biophysically detailed computer modeling was used to explore the changes observed. After monocrotaline injection, echocardiography revealed the pattern of pulmonary artery blood flow characteristic of pulmonary hypertension and right-sided hypertrophy and failure; the Langendorff-perfused heart and isolated AV node revealed dysfunction of the AV node (eg, 50% incidence of heart block in isolated AV node); and quantitative PCR revealed a widespread downregulation of ion channel and related genes in the AV node (eg, >50% downregulation of Ca1.2/3 and HCN1/2/4 channels). Computer modeling predicted that the changes in the transcriptome if translated into protein and function would result in heart block.
CONCLUSIONS
Pulmonary hypertension results in a derangement of the ion channel transcriptome in the AV node, and this is the likely cause of AV node dysfunction in this disease.
Topics: Animals; Atrioventricular Node; Disease Models, Animal; Down-Regulation; Echocardiography; Electrocardiography; Electrophysiologic Techniques, Cardiac; Heart Block; Hypertension, Pulmonary; Ion Channels; Male; Monocrotaline; Polymerase Chain Reaction; Rats; Rats, Wistar; Transcriptome
PubMed: 27979911
DOI: 10.1161/CIRCEP.115.003432 -
JACC. Clinical Electrophysiology Sep 2020
Review
Topics: Atrioventricular Node; Humans; Tachycardia, Atrioventricular Nodal Reentry
PubMed: 32972562
DOI: 10.1016/j.jacep.2020.08.006 -
Anatolian Journal of Cardiology Nov 2017
Topics: Atrioventricular Node; Vagus Nerve
PubMed: 29145228
DOI: No ID Found -
Journal of the American Heart... Oct 2017Linear accelerator-based stereotactic radiosurgery delivered to cardiac arrhythmogenic foci could be a promising catheter-free ablation modality. We tested the...
BACKGROUND
Linear accelerator-based stereotactic radiosurgery delivered to cardiac arrhythmogenic foci could be a promising catheter-free ablation modality. We tested the feasibility of in vivo atrioventricular (AV) node ablation in swine using stereotactic radiosurgery.
METHODS AND RESULTS
Five Large White breed swine (weight 40-75 kg; 4 females) were studied. Single-chamber St Jude pacemakers were implanted in each pig. The pigs were placed under general anesthesia, and coronary/cardiac computed tomography simulation scans were performed to localize the AV node. Cone beam computed tomography was used for target positioning. Stereotactic radiosurgery doses ranging from 35 to 40 Gy were delivered by a linear accelerator to the AV node, and the pigs were followed up with weekly pacemaker interrogations to observe for potential electrocardiographic changes. Once changes were observed, the pigs were euthanized, and pathology specimens of various tissues, including the AV node and tissues surrounding the AV node, were taken to study the effects of radiation. All 5 pigs had disturbances of AV conduction with progressive transition into complete heart block. Macroscopic inspection did not reveal damage to the myocardium, and pigs had preserved systolic function on echocardiography. Immunostaining revealed fibrosis in the target region of the AV node, whereas no fibrosis was detected in the nontargeted regions.
CONCLUSIONS
Catheter-free radioablation using linear accelerator-based stereotactic radiosurgery is feasible in an intact swine model.
Topics: Ablation Techniques; Action Potentials; Animals; Arrhythmias, Cardiac; Atrioventricular Node; Cone-Beam Computed Tomography; Electrocardiography; Feasibility Studies; Female; Heart Block; Heart Rate; Humans; Male; Models, Animal; Radiosurgery; Sus scrofa; Time Factors
PubMed: 29079566
DOI: 10.1161/JAHA.117.007193 -
Journal of Interventional Cardiac... Aug 2015The sinoatrial node (SAN) and the atrioventricular node (AVN) are the anatomical and functional regions of the heart which play critical roles in the generation and... (Review)
Review
The sinoatrial node (SAN) and the atrioventricular node (AVN) are the anatomical and functional regions of the heart which play critical roles in the generation and conduction of the electrical impulse. Their functions are ensured by peculiar structural cytological properties and specific collections of ion channels. Impairment of SAN and AVN activity is generally acquired,but in some cases familial inheritance has been established and therefore a genetic cause is involved. In recent years, combined efforts of clinical practice and experimental basic science studies have identified and characterized several causative gene mutations associated with the nodal syndromes. Channelopathies, i.e., diseases associated with defective ion channels, remain the major cause of genetically determined nodal arrhythmias; however, it is becoming increasingly evident that mutations in other classes of regulatory and structural proteins also have profound pathophysiological roles. In this review, we will present some aspects of the genetic identification of the molecular mechanism underlying both SAN and AVN dysfunctions with a particular focus on mutations of the Na, pacemaker (HCN), and Ca channels. Genetic defects in regulatory proteins and calcium-handling proteins will be also considered. In conclusion, the identification of the genetic defects associated with familial nodal dysfunction is an essential step for implementing an appropriate therapeutic treatment.
Topics: Arrhythmias, Cardiac; Atrioventricular Node; Channelopathies; Genetic Predisposition to Disease; Humans; Ion Channels; Mutation; Sinoatrial Node
PubMed: 25863800
DOI: 10.1007/s10840-015-9998-z -
Circulation. Cardiovascular Genetics Apr 2015Several transcription factors regulate cardiac conduction system (CCS) development and function but the role of each in specifying distinct CCS components remains...
BACKGROUND
Several transcription factors regulate cardiac conduction system (CCS) development and function but the role of each in specifying distinct CCS components remains unclear. GATA-binding factor 6 (GATA6) is a zinc-finger transcription factor that is critical for patterning the cardiovascular system. However, the role of GATA6 in the embryonic heart and CCS has never been shown.
METHODS AND RESULTS
We report that Gata6 is expressed abundantly in the proximal CCS during midgestation in mice. Myocardial-specific deletion of the carboxyl zinc-finger of Gata6 induces loss of hyperpolarizing cyclic nucleotide-gated channel, subtype 4 staining in the compact atrioventricular node with some retention of hyperpolarizing cyclic nucleotide-gated channel, subtype 4 staining in the atrioventricular bundle, but has no significant effect on the connexin-40-positive bundle branches. Furthermore, myocardial-specific deletion of the carboxyl zinc-finger of Gata6 alters atrioventricular conduction in postnatal life as assessed by surface and invasive electrophysiological evaluation, as well as decreasing the number of ventricular myocytes and inducing compensatory myocyte hypertrophy. Myocardial-specific deletion of the carboxyl zinc-finger of Gata6 is also associated with downregulation of the transcriptional repressor ID2 and the cardiac sodium-calcium exchanger NCX1 in the proximal CCS, where GATA6 transactivates both of these factors. Finally, carboxyl zinc-finger deletion of Gata6 reduces cell-cycle exit of TBX3+ myocytes in the developing atrioventricular bundle during the period of atrioventricular node specification, which results in fewer TBX3+ cells in the proximal CCS of mature mutant mice.
CONCLUSIONS
GATA6 contributes to the development and postnatal function of the murine atrioventricular node by promoting cell-cycle exit of specified cardiomyocytes toward a conduction system lineage.
Topics: Animals; Atrioventricular Node; GATA6 Transcription Factor; Gene Expression Regulation, Developmental; Mice; Mice, Mutant Strains; Myocardium; Myocytes, Cardiac
PubMed: 25613430
DOI: 10.1161/CIRCGENETICS.113.000587 -
Texas Heart Institute Journal Dec 2016
Topics: Action Potentials; Anti-Arrhythmia Agents; Atrial Flutter; Atrioventricular Node; Catheter Ablation; Electrocardiography; Flecainide; Heart Rate; Humans; Male; Middle Aged; Predictive Value of Tests; Tachycardia, Supraventricular; Treatment Outcome
PubMed: 28100969
DOI: 10.14503/THIJ-16-6088