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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 -
JACC. Clinical Electrophysiology Sep 2020
Review
Topics: Atrioventricular Node; Humans; Tachycardia, Atrioventricular Nodal Reentry
PubMed: 32972562
DOI: 10.1016/j.jacep.2020.08.006 -
PloS One 2020Localization of the components of the cardiac conduction system (CCS) is essential for many therapeutic procedures in cardiac surgery and interventional cardiology....
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.
Topics: Animals; Atrioventricular Node; Sheep; Sinoatrial Node
PubMed: 32379798
DOI: 10.1371/journal.pone.0232618 -
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 -
Anatolian Journal of Cardiology Nov 2017
Topics: Atrioventricular Node; Vagus Nerve
PubMed: 29145228
DOI: No ID Found -
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 -
Journal of the American Heart... Dec 2021Background Left atrial (LA) and right ventricular (RV) performance play an integral role in the pathophysiology and prognosis of heart failure. We hypothesized that...
Background Left atrial (LA) and right ventricular (RV) performance play an integral role in the pathophysiology and prognosis of heart failure. We hypothesized that subclinical left ventricular dysfunction adversely affects LA/RV geometry and function even in a preclinical setting. This study aimed to investigate the atrioventricular and ventricular functional interdependence in a community-based cohort without overt cardiovascular disease. Methods and Results Left ventricular global longitudinal strain (LVGLS), RV free-wall longitudinal strain and LA phasic strain were assessed by speckle-tracking echocardiography in 1080 participants (600 men; 62±12 years) between 2014 and 2018. One hundred and forty-three participants (13.2%) had an abnormal LVGLS (>-18.6%). LA reservoir strain, conduit strain, and RV free-wall longitudinal strain were significantly decreased in abnormal LVGLS group compared with normal LVGLS group (all <0.001). LA and RV dysfunction (LA reservoir strain<31.4% and RVLS>-19.2%) were present in 18.9% and 19.6% of participants with abnormal LVGLS. Decreased LVGLS was associated with worse LA reservoir strain, conduit strain and RV free-wall longitudinal strain (standardized β=-0.20, -0.19 and 0.11 respectively, all <0.01) independent of cardiovascular risk factors. LA and/or RV dysfunction concomitant with abnormal LVGLS carried significantly increased risk of elevated B-type natriuretic peptide levels (>28.6 pg/mL for men and >44.4 pg/mL for women) compared with normal LVGLS (odds ratio, 2.01; =0.030). Conclusions LA/RV dysfunction was present in 20% individuals with abnormal LVGLS and multi-chamber impairment was associated with elevated B-type natriuretic peptide level, which may provide valuable insights for a better understanding of atrioventricular and ventricular interdependence and possibly heart failure preventive strategies.
Topics: Aged; Atrioventricular Node; Heart Diseases; Humans; Middle Aged; Ventricular Function
PubMed: 34775816
DOI: 10.1161/JAHA.121.021624 -
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