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Biochimica Et Biophysica Acta Jul 2016Atrial cardiomyocytes are essential for fluid homeostasis, ventricular filling, and survival, yet their cell biology and physiology are incompletely understood. It has... (Review)
Review
Atrial cardiomyocytes are essential for fluid homeostasis, ventricular filling, and survival, yet their cell biology and physiology are incompletely understood. It has become clear that the cell fate of atrial cardiomyocytes depends significantly on transcription programs that might control thousands of differentially expressed genes. Atrial muscle membranes propagate action potentials and activate myofilament force generation, producing overall faster contractions than ventricular muscles. While atria-specific excitation and contractility depend critically on intracellular Ca(2+) signalling, voltage-dependent L-type Ca(2+) channels and ryanodine receptor Ca(2+) release channels are each expressed at high levels similar to ventricles. However, intracellular Ca(2+) transients in atrial cardiomyocytes are markedly heterogeneous and fundamentally different from ventricular cardiomyocytes. In addition, differential atria-specific K(+) channel expression and trafficking confer unique electrophysiological and metabolic properties. Because diseased atria have the propensity to perpetuate fast arrhythmias, we discuss our understanding about the cell-specific mechanisms that lead to metabolic and/or mitochondrial dysfunction in atrial fibrillation. Interestingly, recent work identified potential atria-specific mechanisms that lead to early contractile dysfunction and metabolic remodelling, suggesting highly interdependent metabolic, electrical, and contractile pathomechanisms. Hence, the objective of this review is to provide an integrated model of atrial cardiomyocytes, from tissue-specific cell properties, intracellular metabolism, and excitation-contraction (EC) coupling to early pathological changes, in particular metabolic dysfunction and tissue remodelling due to atrial fibrillation and aging. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.
Topics: Action Potentials; Animals; Atrial Fibrillation; Atrial Function; Atrial Remodeling; Calcium Signaling; Cell Differentiation; Cell Lineage; Heart Atria; Humans; Myocardial Contraction; Myocytes, Cardiac; Phenotype
PubMed: 26620800
DOI: 10.1016/j.bbamcr.2015.11.025 -
Annals of Biomedical Engineering Jan 2021Atrial anisotropy affects electrical propagation patterns, anchor locations of atrial reentrant drivers, and atrial mechanics. However, patient-specific atrial fibre...
Atrial anisotropy affects electrical propagation patterns, anchor locations of atrial reentrant drivers, and atrial mechanics. However, patient-specific atrial fibre fields and anisotropy measurements are not currently available, and consequently assigning fibre fields to atrial models is challenging. We aimed to construct an atrial fibre atlas from a high-resolution DTMRI dataset that optimally reproduces electrophysiology simulation predictions corresponding to patient-specific fibre fields, and to develop a methodology for automatically assigning fibres to patient-specific anatomies. We extended an atrial coordinate system to map the pulmonary veins, vena cava and appendages to standardised positions in the coordinate system corresponding to the average location across the anatomies. We then expressed each fibre field in this atrial coordinate system and calculated an average fibre field. To assess the effects of fibre field on patient-specific modelling predictions, we calculated paced activation time maps and electrical driver locations during AF. In total, 756 activation time maps were calculated (7 anatomies with 9 fibre maps and 2 pacing locations, for the endocardial, epicardial and bilayer surface models of the LA and RA). Patient-specific fibre fields had a relatively small effect on average paced activation maps (range of mean local activation time difference for LA fields: 2.67-3.60 ms, and for RA fields: 2.29-3.44 ms), but had a larger effect on maximum LAT differences (range for LA 12.7-16.6%; range for RA 11.9-15.0%). A total of 126 phase singularity density maps were calculated (7 anatomies with 9 fibre maps for the LA and RA bilayer models). The fibre field corresponding to anatomy 1 had the highest median PS density map correlation coefficient for LA bilayer simulations (0.44 compared to the other correlations, ranging from 0.14 to 0.39), while the average fibre field had the highest correlation for the RA bilayer simulations (0.61 compared to the other correlations, ranging from 0.37 to 0.56). For sinus rhythm simulations, average activation time is robust to fibre field direction; however, maximum differences can still be significant. Patient specific fibres are more important for arrhythmia simulations, particularly in the left atrium. We propose using the fibre field corresponding to DTMRI dataset 1 for LA simulations, and the average fibre field for RA simulations as these optimally predicted arrhythmia properties.
Topics: Anisotropy; Arrhythmias, Cardiac; Atlases as Topic; Atrial Function; Diffusion Magnetic Resonance Imaging; Heart Atria; Humans; Patient-Specific Modeling
PubMed: 32458222
DOI: 10.1007/s10439-020-02525-w -
American Family Physician Jan 2011Atrial fibrillation is the most common cardiac arrhythmia. It impairs cardiac function and increases the risk of stroke. The incidence of atrial fibrillation increases... (Review)
Review
Atrial fibrillation is the most common cardiac arrhythmia. It impairs cardiac function and increases the risk of stroke. The incidence of atrial fibrillation increases with age. Key treatment issues include deciding when to restore normal sinus rhythm, when to control rate only, and how to prevent thromboembolism. Rate control is the preferred management option in most patients. Rhythm control is an option for patients in whom rate control cannot be achieved or who have persistent symptoms despite rate control. The current recommendation for strict rate control is a resting heart rate of less than 80 beats per minute. However, one study has shown that more lenient rate control of less than 110 beats per minute while at rest was not inferior to strict rate control in preventing cardiac death, heart failure, stroke, and life-threatening arrhythmias. Anticoagulation therapy is needed with rate control and rhythm control to prevent stroke. Warfarin is superior to aspirin and clopidogrel in preventing stroke despite its narrow therapeutic range and increased risk of bleeding. Tools that predict the risk of stroke (e.g., CHADS2) and the risk of bleeding (e.g., Outpatient Bleeding Risk Index) are helpful in making decisions about anticoagulation therapy. Surgical options for atrial fibrillation include disruption of abnormal conduction pathways in the atria, and obliteration of the left atrial appendage. Catheter ablation is an option for restoring normal sinus rhythm in patients with paroxysmal atrial fibrillation and normal left atrial size. Referral to a cardiologist is warranted in patients who have complex cardiac disease; who are symptomatic on or unable to tolerate pharmacologic rate control; or who may be candidates for ablation or surgical interventions.
Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Blood Cell Count; Cardiac Surgical Procedures; Catheter Ablation; Echocardiography; Electrocardiography; Heart Atria; Humans; Physical Examination; Radiography, Thoracic; Referral and Consultation; Stroke; Thyrotropin
PubMed: 21888129
DOI: No ID Found -
Experimental Biology and Medicine... Jun 2023Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1) has a well-established role in myocardial infarction, yet its involvement in atrial fibrosis and...
Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1) has a well-established role in myocardial infarction, yet its involvement in atrial fibrosis and atrial fibrillation (AF) has not been elucidated. As cardiac arrhythmias caused by AF are a major global health concern, we investigated whether SHP-1 modulates AF development. The degree of atrial fibrosis was examined using Masson's trichrome staining, and SHP-1 expression in the human atrium was assessed using quantitative polymerase chain reaction (qPCR), immunohistochemistry (IHC), and western blotting (WB). We also examined SHP-1 expression in cardiac tissue from an AF mouse model, as well as in angiotensin II (Ang II)-treated mouse atrial myocytes and fibroblasts. We found that SHP-1 expression was reduced with the aggravation of atrial fibrosis in clinical samples of patients with AF. SHP-1 was also downregulated in the heart tissue of AF mice and Ang II-treated myocytes and fibroblasts, compared with that in the control groups. Next, we demonstrated that SHP-1 overexpression alleviated AF severity in mice by injecting a lentiviral vector into the pericardial space. In Ang II-treated myocytes and fibroblasts, we observed excessive extracellular matrix (ECM) deposition, reactive oxygen species (ROS) generation, and transforming growth factor beta 1 (TGF-β1)/mothers against decapentaplegic homolog 2 (SMAD2) pathway activation, all of which were counteracted by the overexpression of SHP-1. Our WB data showed that STAT3 activation was inversely correlated with SHP-1 expression in samples from patients with AF, AF mice, and Ang II-treated cells. Furthermore, administration of colivelin, a STAT3 agonist, in SHP-1-overexpressing, Ang II-treated myocytes and fibroblasts resulted in higher levels of ECM deposition, ROS generation, and TGF-β1/SMAD2 activation. These findings indicate that SHP-1 regulates AF fibrosis progression by modulating STAT3 activation and is thus a potential treatment target for atrial fibrosis and AF.
Topics: Humans; Mice; Animals; Atrial Fibrillation; Transforming Growth Factor beta1; Reactive Oxygen Species; Heart Atria; Fibrosis; Angiotensin II; STAT3 Transcription Factor
PubMed: 37226737
DOI: 10.1177/15353702231165717 -
British Heart Journal Mar 1970Two cases of atrial parasystole showing the various manifestations of the arrhythmia are presented. Analysis of the underlying mechanisms shows that atrial parasystolic...
Two cases of atrial parasystole showing the various manifestations of the arrhythmia are presented. Analysis of the underlying mechanisms shows that atrial parasystolic bigeminy with ;reversed' coupling is a form of escape-capture begeminy, sinus escapes being followed by an ectopic capture of the atria. Reasons are given for the rarity of atrial fusion beats. The similarities and differences between atrial and ventricular parasystole are explored. It is suggested that an atrial parasystolic pacemaker may lie within a major atrial preferential conducting pathway, and may consist of a congenitally ectopic fragment of sinus nodal tissue. The clinical significance of the arrhythmia is discussed; the associated diseases apparently represent a cross-section of medical ward experience.
Topics: Aged; Arrhythmias, Cardiac; Electrocardiography; Heart Atria; Humans; Male
PubMed: 5440513
DOI: 10.1136/hrt.32.2.172 -
Pharmacological Research Feb 2023Atrial fibrillation (AF) is the most frequent arrhythmia and is associated with substantial morbidity and mortality. Pathophysiological aspects consist in the activation... (Review)
Review
Atrial fibrillation (AF) is the most frequent arrhythmia and is associated with substantial morbidity and mortality. Pathophysiological aspects consist in the activation of pro-fibrotic signaling and Ca handling abnormalities at atrial level. Structural and electrical remodeling creates a substrate for AF by triggering conduction abnormalities and cardiac arrhythmias. The care of AF patients focuses predominantly on anticoagulation, symptoms control and the management of risk factors and comorbidities. The goal of AF therapy points to restore sinus rhythm, re-establish atrioventricular synchrony and improve atrial contribution to the stroke volume. New layer of information to better comprehend AF pathophysiology, and identify targets for novel pharmacological interventions consists of the epigenetic phenomena including, among others, DNA methylation, histone modifications and noncoding RNAs. Moreover, the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in diabetic and non-diabetic patients at cardiovascular risk as well as emerging evidence on the ability of SGLT2i to modify epigenetic signature in cardiovascular diseases provide a solid background to investigate a possible role of this drug class in the onset and progression of AF. In this review, following a summary of pathophysiology and management, epigenetic mechanisms in AF and the potential of sodium-glucose SGLT2i in AF patients are discussed.
Topics: Humans; Atrial Fibrillation; Heart Atria; Risk Factors; Glucose; Sodium
PubMed: 36502999
DOI: 10.1016/j.phrs.2022.106591 -
Cardiovascular Research Mar 2015Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is associated with significant morbidity, mostly secondary to heart failure and stroke, and... (Review)
Review
Atrial fibrillation (AF) is the most common sustained clinical arrhythmia and is associated with significant morbidity, mostly secondary to heart failure and stroke, and an estimated two-fold increase in premature death. Efforts to increase our understanding of AF and its complications have focused on unravelling the mechanisms of electrical and structural remodelling of the atrial myocardium. Yet, it is increasingly recognized that AF is more than an atrial disease, being associated with systemic inflammation, endothelial dysfunction, and adverse effects on the structure and function of the left ventricular myocardium that may be prognostically important. Here, we review the molecular and in vivo evidence that underpins current knowledge regarding the effects of human or experimental AF on the ventricular myocardium. Potential mechanisms are explored including diffuse ventricular fibrosis, focal myocardial scarring, and impaired myocardial perfusion and perfusion reserve. The complex relationship between AF, systemic inflammation, as well as endothelial/microvascular dysfunction and the effects of AF on ventricular calcium handling and oxidative stress are also addressed. Finally, consideration is given to the clinical implications of these observations and concepts, with particular reference to rate vs. rhythm control.
Topics: Animals; Atrial Fibrillation; Atrial Function; Calcium Signaling; Coronary Circulation; Heart Atria; Heart Rate; Heart Ventricles; Humans; Inflammation Mediators; Oxidative Stress; Ventricular Function, Left; Ventricular Remodeling
PubMed: 25587048
DOI: 10.1093/cvr/cvv001 -
Circulation Research Apr 2014Atrial fibrillation (AF) is a complex disease with multiple inter-relating causes culminating in rapid, seemingly disorganized atrial activation. Therapy targeting AF is... (Review)
Review
Atrial fibrillation (AF) is a complex disease with multiple inter-relating causes culminating in rapid, seemingly disorganized atrial activation. Therapy targeting AF is rapidly changing and improving. The purpose of this review is to summarize current state-of-the-art diagnostic and therapeutic modalities for treatment of AF. The review focuses on reviewing treatment as it relates to the pathophysiological basis of disease and reviews preclinical and clinical evidence for potential new diagnostic and therapeutic modalities, including imaging, biomarkers, pharmacological therapy, and ablative strategies for AF. Current ablation and drug therapy approaches to treating AF are largely based on treating the arrhythmia once the substrate occurs and is more effective in paroxysmal AF rather than persistent or permanent AF. However, there is much research aimed at prevention strategies, targeting AF substrate, so-called upstream therapy. Improved diagnostics, using imaging, genetics, and biomarkers, are needed to better identify subtypes of AF based on underlying substrate/mechanism to allow more directed therapeutic approaches. In addition, novel antiarrhythmics with more atrial specific effects may reduce limiting proarrhythmic side effects. Advances in ablation therapy are aimed at improving technology to reduce procedure time and in mechanism-targeted approaches.
Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Catheter Ablation; Diffusion of Innovation; Forecasting; Heart Atria; Heart Conduction System; Humans; Treatment Outcome
PubMed: 24763469
DOI: 10.1161/CIRCRESAHA.114.302362 -
Discovery Medicine Sep 2010Atrial fibrillation (AF) is the most common heart rhythm problem and a leading cause of morbidity and mortality. Serious complications associated with this disorder... (Review)
Review
Atrial fibrillation (AF) is the most common heart rhythm problem and a leading cause of morbidity and mortality. Serious complications associated with this disorder include cardioembolic stroke, heart failure, and death. The worldwide prevalence of AF is rapidly increasing owing to aging of the population. Abnormal impulse formation in the pulmonary veins is known to trigger paroxysmal AF and radiofrequency isolation of these veins is recommended in drug-refractory AF. Active pharmacological research is directed towards selectively targeting the culprit venous cells. Persistent AF is more likely to be an atrial disease. Intrinsic and extrinsic stressors are believed to cause electrostructural alterations in the atrial tissue leading to profibrillatory state. Further research will elucidate the role of stressors and help develop biomarkers to guide early management of AF. An ideal therapy for AF aims at prevention of onset and progression of AF and reduction of AF-related symptoms, hospitalization, stroke, and mortality.
Topics: Animals; Anti-Arrhythmia Agents; Atrial Fibrillation; Catheter Ablation; Heart Atria; Humans; Pulmonary Veins
PubMed: 20875341
DOI: No ID Found -
Journal of the Chinese Medical... Feb 2009Atrial flutter (AFL) is a common arrhythmia in clinical practice. Several experimental models, such as tricuspid regurgitation model, tricuspid ring model, sterile... (Review)
Review
Atrial flutter (AFL) is a common arrhythmia in clinical practice. Several experimental models, such as tricuspid regurgitation model, tricuspid ring model, sterile pericarditis model and atrial crush injury model, have provided important information about reentrant circuit and can test the effects of antiarrhythmic drugs. Human AFL has typical and atypical forms. Typical AFL rotates around the tricuspid annulus and uses the crista terminalis and sometimes sinus venosa as the boundary. The tricuspid isthmus is a slow conduction zone and the target of radiofrequency ablation. Atypical AFL may arise from the right or left atrium. Right AFL includes upper loop reentry, free wall reentry and figure-of-8 reentry. Left AFL includes mitral annular AFL, pulmonary vein-related AFL and left septal AFL. Radiofrequency ablation of the isthmus between the boundaries can eliminate these arrhythmias.
Topics: Animals; Atrial Flutter; Disease Models, Animal; Heart Atria; Heart Conduction System; Humans; Pericarditis; Tricuspid Valve Insufficiency
PubMed: 19251532
DOI: 10.1016/S1726-4901(09)70024-3