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Nature Nov 2020Atrial fibrillation, the most common cardiac arrhythmia, is an important contributor to mortality and morbidity, and particularly to the risk of stroke in humans....
Atrial fibrillation, the most common cardiac arrhythmia, is an important contributor to mortality and morbidity, and particularly to the risk of stroke in humans. Atrial-tissue fibrosis is a central pathophysiological feature of atrial fibrillation that also hampers its treatment; the underlying molecular mechanisms are poorly understood and warrant investigation given the inadequacy of present therapies. Here we show that calcitonin, a hormone product of the thyroid gland involved in bone metabolism, is also produced by atrial cardiomyocytes in substantial quantities and acts as a paracrine signal that affects neighbouring collagen-producing fibroblasts to control their proliferation and secretion of extracellular matrix proteins. Global disruption of calcitonin receptor signalling in mice causes atrial fibrosis and increases susceptibility to atrial fibrillation. In mice in which liver kinase B1 is knocked down specifically in the atria, atrial-specific knockdown of calcitonin promotes atrial fibrosis and increases and prolongs spontaneous episodes of atrial fibrillation, whereas atrial-specific overexpression of calcitonin prevents both atrial fibrosis and fibrillation. Human patients with persistent atrial fibrillation show sixfold lower levels of myocardial calcitonin compared to control individuals with normal heart rhythm, with loss of calcitonin receptors in the fibroblast membrane. Although transcriptome analysis of human atrial fibroblasts reveals little change after exposure to calcitonin, proteomic analysis shows extensive alterations in extracellular matrix proteins and pathways related to fibrogenesis, infection and immune responses, and transcriptional regulation. Strategies to restore disrupted myocardial calcitonin signalling thus may offer therapeutic avenues for patients with atrial fibrillation.
Topics: Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Calcitonin; Collagen Type I; Female; Fibrinogen; Fibroblasts; Fibrosis; Heart Atria; Humans; Male; Mice; Myocardium; Myocytes, Cardiac; Paracrine Communication; Receptors, Calcitonin
PubMed: 33149301
DOI: 10.1038/s41586-020-2890-8 -
The New England Journal of Medicine Nov 2023Two siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in , the gene encoding atrial...
Two siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in , the gene encoding atrial natriuretic peptide (ANP)-converting enzyme. A plasma sample obtained from one of the siblings had no detectable levels of corin or N-terminal pro-ANP but had elevated levels of B-type natriuretic peptide (BNP) and one of the two protein markers of fibrosis that we tested. These and other findings support the hypothesis that BNP cannot fully compensate for a lack of activation of the ANP pathway and that corin is critical to normal ANP activity, left atrial function, and cardiovascular homeostasis.
Topics: Humans; Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Natriuretic Factor; Cardiomyopathies; Fibrosis; Heart Atria; Hypertension; Natriuretic Peptide, Brain; Serine Endopeptidases; Siblings
PubMed: 37913506
DOI: 10.1056/NEJMoa2301908 -
Circulation Journal : Official Journal... Apr 2021
Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Cardiac Pacing, Artificial; Heart Atria; Humans
PubMed: 33716258
DOI: 10.1253/circj.CJ-21-0061 -
Physiological Reports Feb 2016
Topics: Arrhythmias, Cardiac; Fibroblasts; Heart Atria; Humans
PubMed: 26869687
DOI: 10.14814/phy2.12711 -
Heart Rhythm Oct 2005The Fontan circulation has been a major success in the management of patients with functionally single-ventricle cardiac lesions, although arrhythmia remains one of the... (Review)
Review
The Fontan circulation has been a major success in the management of patients with functionally single-ventricle cardiac lesions, although arrhythmia remains one of the major complications in the long term and historically has been difficult to treat. The electrophysiologic substrate within the right atrium is complex, with areas of scarring and/or anatomic structures acting as central barriers to conduction in reentrant circuits, which may be mechanistically and anatomically different from typical atrial flutter. Developments in three-dimensional mapping have improved our understanding of different arrhythmia mechanisms, which is fundamental to developing a better strategy for arrhythmia ablation using percutaneous techniques.
Topics: Arrhythmias, Cardiac; Catheter Ablation; Electrophysiologic Techniques, Cardiac; Fontan Procedure; Heart Atria; Heart Conduction System; Humans
PubMed: 16188597
DOI: 10.1016/j.hrthm.2005.07.009 -
Europace : European Pacing,... Dec 2016: Atrial arrhythmias involving a fibrotic substrate are an important cause of morbidity and mortality. In many cases, effective treatment of such rhythm disorders is... (Review)
Review
: Atrial arrhythmias involving a fibrotic substrate are an important cause of morbidity and mortality. In many cases, effective treatment of such rhythm disorders is severely hindered by a lack of mechanistic understanding relating features of fibrotic remodelling to dynamics of re-entrant arrhythmia. With the advent of clinical imaging modalities capable of resolving the unique fibrosis spatial pattern present in the atria of each individual patient, a promising new research trajectory has emerged in which personalized computational models are used to analyse mechanistic underpinnings of arrhythmia dynamics based on the distribution of fibrotic tissue. In this review, we first present findings that have yielded a robust and detailed biophysical representation of fibrotic substrate electrophysiological properties. Then, we summarize the results of several recent investigations seeking to use organ-scale models of the fibrotic human atria to derive new insights on mechanisms of arrhythmia perpetuation and to develop novel strategies for model-assisted individualized planning of catheter ablation procedures for atrial arrhythmias.
Topics: Action Potentials; Atrial Fibrillation; Atrial Flutter; Atrial Function; Atrial Remodeling; Cardiac Imaging Techniques; Catheter Ablation; Electrophysiologic Techniques, Cardiac; Fibrosis; Heart Atria; Heart Rate; Humans; Imaging, Three-Dimensional; Models, Cardiovascular; Patient-Specific Modeling; Predictive Value of Tests
PubMed: 28011841
DOI: 10.1093/europace/euw358 -
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 -
Cardiovascular Research May 2014Atrial fibrillation (AF) is the most frequent cardiac arrhythmia in clinical practice. AF is often associated with profound functional and structural alterations of the... (Review)
Review
Atrial fibrillation (AF) is the most frequent cardiac arrhythmia in clinical practice. AF is often associated with profound functional and structural alterations of the atrial myocardium that compose its substrate. Recently, a relationship between the thickness of epicardial adipose tissue (EAT) and the incidence and severity of AF has been reported. Adipose tissue is a biologically active organ regulating the metabolism of neighbouring organs. It is also a major source of cytokines. In the heart, EAT is contiguous with the myocardium without fascia boundaries resulting in paracrine effects through the release of adipokines. Indeed, Activin A, which is produced in abundance by EAT during heart failure or diabetes, shows a marked fibrotic effect on the atrial myocardium. The infiltration of adipocytes into the atrial myocardium could also disorganize the depolarization wave front favouring micro re-entry circuits and local conduction block. Finally, EAT contains progenitor cells in abundance and therefore could be a source of myofibroblasts producing extracellular matrix. The study on the role played by adipose tissue in the pathogenesis of AF is just starting and is highly likely to uncover new biomarkers and therapeutic targets for AF.
Topics: Adipose Tissue; Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Biomarkers; Brugada Syndrome; Cardiac Conduction System Disease; Heart Atria; Heart Conduction System; Humans; Myocardium
PubMed: 24648445
DOI: 10.1093/cvr/cvu045 -
Current Cardiology Reviews 2015Atrial tachycardias are common after open heart surgery. Most commonly these are macro-reentrant including cavotricuspid isthmus dependent atrial flutter, incisional... (Review)
Review
Atrial tachycardias are common after open heart surgery. Most commonly these are macro-reentrant including cavotricuspid isthmus dependent atrial flutter, incisional right atrial flutter and left atrial flutter. Focal atrial tachycardias occur less frequently. The specific type of atrial tachycardia highly depends on the type of surgical incision. Catheter ablation can be very effective, however requires a thorough understanding of anatomy and surgical technique.
Topics: Arrhythmias, Cardiac; Atrial Flutter; Cardiac Surgical Procedures; Catheter Ablation; Heart Atria; Humans; Postoperative Complications
PubMed: 25308810
DOI: 10.2174/1573403x10666141013122021 -
The American Journal of Emergency... Mar 1995Cardiac dysfunction is often manifested as arrhythmia, with disruption of the normal periodicity and regularity of electromechanical activity. Cardiac arrhythmias, or... (Review)
Review
Cardiac dysfunction is often manifested as arrhythmia, with disruption of the normal periodicity and regularity of electromechanical activity. Cardiac arrhythmias, or abnormalities of cardiac rhythm, are associated with a diverse group of conditions, including congenital, metabolic, structural, physiological, and immunological, and infectious abnormalities. Dysarrhythmia may also be classified as primary because of endogenous electrical abnormalities, or secondary, because of exogenous influences such as ischemia or adrenergic stimuli. Clinical arrhythmia syndromes begin with a single asymptomatic abnormal complex that is benign, progressing to grouped, sustained complexes associated with worsened symptoms and outcome. Proper diagnosis of arrhythmia reflecting symptomology and outcome is essential in acute cardiac care.
Topics: Arrhythmias, Cardiac; Electrocardiography; Heart Atria; Heart Conduction System; Heart Ventricles; Humans
PubMed: 7893310
DOI: 10.1016/0735-6757(95)90095-0