Effects of metoprolol therapy on cardiac gap junction remodelling and conduction in human chronic atrial fibrillation

Dhein, Stefan; Rothe, S; Busch, A; Gomez, D Rojas; Boldt, Andreas; Reutemann, A; Seidel, Thomas; Salameh, Aida; Pfannmüller, Bettina; Rastan, A; Kostelka, Martin; Mohr, FW

doi:10.1111/j.1476-5381.2011.01460.x

Cited by 35 publications

(36 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…163 Reduced connexin-40 expression has been reported in some studies, 88,164 whereas others reported increased expression at the transverse cell membrane, promoting heterogeneous conduction, which was reduced by β-adrenoceptor blockade. 165 Fibrosis is common in patients with AF, 166 and connexin-43 remodeling correlates with atrial fibrosis in patients, 167 suggesting an interaction between these re-entry-promoting factors. High-density electroanatomic mapping in patients identified conduction abnormalities that correlated with AF progression.…”

Section: Conduction Abnormalities and Structural Remodelingmentioning

confidence: 99%

Cellular and Molecular Electrophysiology of Atrial Fibrillation Initiation, Maintenance, and Progression

Heijman

Voigt

Nattel

et al. 2014

Circulation Research

569

603

View full text Add to dashboard Cite

Atrial fibrillation (AF) is the most common clinically relevant arrhythmia and is associated with increased morbidity and mortality. The incidence of AF is expected to continue to rise with the aging of the population. AF is generally considered to be a progressive condition, occurring first in a paroxysmal form, then in persistent, and then long-standing persistent (chronic or permanent) forms. However, not all patients go through every phase, and the time spent in each can vary widely. Research over the past decades has identified a multitude of pathophysiological processes contributing to the initiation, maintenance, and progression of AF. However, many aspects of AF pathophysiology remain incompletely understood. In this review, we discuss the cellular and molecular electrophysiology of AF initiation, maintenance, and progression, predominantly based on recent data obtained in human tissue and animal models. The central role of Ca 2+ -handling abnormalities in both focal ectopic activity and AF substrate progression is discussed, along with the underlying molecular basis. We also deal with the ionic determinants that govern AF initiation and maintenance, as well as the structural remodeling that stabilizes AF-maintaining re-entrant mechanisms and finally makes the arrhythmia refractory to therapy. In addition, we highlight important gaps in our current understanding, particularly with respect to the translation of these concepts to the clinical setting. Ultimately, a comprehensive understanding of AF pathophysiology is expected to foster the development of improved pharmacological and nonpharmacological therapeutic approaches and to greatly improve clinical management.

show abstract

Section: Conduction Abnormalities and Structural Remodelingmentioning

confidence: 99%

Cellular and Molecular Electrophysiology of Atrial Fibrillation Initiation, Maintenance, and Progression

Heijman

Voigt

Nattel

et al. 2014

Circulation Research

569

603

View full text Add to dashboard Cite

show abstract

“…A study investigating atrial tissue from patients suffering from chronic atrial fibrillation found connexin lateralization accompanied by enhanced transverse conduction velocity. Moreover, in the same study metoprolol treatment led to a lower degree of lateralization and lower transverse conduction velocity (Dhein et al, 2011). This provides evidence that at least parts of these connexins form functional lateral gap junctions, although electrode spacing of 1 mm did not allow to precisely link an activation propagation to a certain cell shape.…”

Section: Effects Of Gap Junctions-lateralization and Remodelingmentioning

confidence: 70%

“…Alterations of Cx43 and Cx40 have been described in atrial fibrillation (Dupont et al, 2001;Polontchouk et al, 2001;Boldt et al, 2003). Since in atrial fibrillation both increased and decreased Cx43 levels have been found, it was suggested that the absolute level may depend not only on the type of arrhythmia but also on the concomitant cardiac pathology (Dhein et al, 2011). In many cardiac pathologies, e.g., chronic atrial fibrillation, cardiac hypertrophy, heart failure and after myocardial infarction, connexins were no longer restricted to cell poles but also expressed at the lateral cell membrane (Polontchouk et al, 2001;Kostin et al, 2002;Cabo et al, 2006).…”

Section: Anisotropy and Non-uniformity (Inhomogeneity)mentioning

confidence: 99%

“…It remained unclear for years whether these lateral gap junctions are functional. In the case of atrial fibrillation, electrophysiological mapping together with immunohistology showed that the lateralization was accompanied by enhanced transverse conduction velocity θ T (Dhein et al, 2011), suggesting that at least a fraction of these lateral gap junctions is functional.…”

Section: Anisotropy and Non-uniformity (Inhomogeneity)mentioning

confidence: 99%

See 1 more Smart Citation

Remodeling of cardiac passive electrical properties and susceptibility to ventricular and atrial arrhythmias

2015

Frontiers Research Topics

View full text Add to dashboard Cite

“…While increased expression of Cx40 and its lateralization is observed in AF, data regarding Cx43 expression and localization are not conclusive, probably due to different patient populations studied [179][180]. Interestingly, in a recent human study, the application of the beta-adrenergic blocker metoprolol has been found to antagonize the detrimental changes in Cx43 localization and subsequent conduction changes in patients with AF [181]. The detailed discussion of this topic is beyond the scope of this paper and readers are referred to a comprehensive review on this topic published in this issue [182].…”

Section: Remodeling Of Conduction In Af and Hfmentioning

confidence: 99%

Future Perspectives in the Pharmacological Treatment of Atrial Fibrillation and Ventricular Arrhythmias in Heart Failure

Baczkó

Leprán

Kiss

et al. 2014

CPD

View full text Add to dashboard Cite

Heart failure (HF) is a clinical syndrome characterized by significant impairment of cardiac ventricular function. Atrial fibrillation (AF) is the most commonly observed sustained arrhythmia in clinical practice. Both HF and AF are associated with increased morbidity and mortality and their prevalence increases with age. Approximately 50% of patients with moderate HF die due to ventricular fibrillation that leads to sudden cardiac death. Patients with AF exhibit increased mortality due to HF and stroke. HF and AF often co-exist, and the development of the other condition further deteriorates prognosis. Both chronic HF and AF lead to structural and electrophysiological changes in the heart called remodeling, modifying therapeutic targets including those for antiarrhythmic intervention. Current pharmacological treatment of arrhythmias has major limitations due to low efficacy and serious adverse effects. In this review, the main aspects of electrical remodeling in HF and AF are discussed along with possible novel targets identified for future pharmacological antiarrhythmic therapy.Keywords: Heart failure, atrial fibrillation, cardiac arrhythmias, electrical remodeling, potassium channel expression, multi-channel blocking drugs. I. OVERVIEW AND CURRENT STATUS Epidemiology of Heart Failure, Atrial Fibrillation and their CombinationHeart failure (HF) is a clinical syndrome resulting from a wide range of cardiovascular disorders, featuring significant impairment of cardiac function that leads to reduced ventricular filling or ejection of blood. HF markedly reduces health-related quality of life [1], causes significant morbidity and high mortality and represents an enormous economic burden for the health care system [2]. The incidence of HF is increasing with age, with 20 per 1000 persons 65-69 years old and more than 80 per 1000 persons older than 85 [3] and its prevalence is increasing in a continuously aging population [2]. In spite of the significant advances in the treatment of HF, mortality rates remain poor at approximately 50% of patients dying within 5 years of diagnosis [4]. Serious ventricular arrhythmias are common in HF [5] and approximately 50% of HF patients die due to ventricular fibrillation leading to sudden cardiac death (SCD), the rate of which is several times higher in HF patients compared to the general population [6]. In addition to severe ventricular arrhythmias, atrial arrhythmias often develop in heart failure. Bradycardia can develop due to sinoatrial function impairment [7] that can exacerbate cardiac dysfunction [8], can lead to syncope and haemodynamic collapse and can be resolved by application of implantable devices [9].Atrial fibrillation (AF) is the most common sustained arrhythmia and it is associated with significant morbidity and mortality, especially due to the increased risk of heart failure and stroke [10][11][12]. The prevalence of AF increases with age, with 0.5% of patients affected in the 50 year old range, ~10% over the age of 80 [13] and the prediction is that it...

show abstract

Effects of metoprolol therapy on cardiac gap junction remodelling and conduction in human chronic atrial fibrillation

Cited by 35 publications

References 40 publications

Cellular and Molecular Electrophysiology of Atrial Fibrillation Initiation, Maintenance, and Progression

Cellular and Molecular Electrophysiology of Atrial Fibrillation Initiation, Maintenance, and Progression

Remodeling of cardiac passive electrical properties and susceptibility to ventricular and atrial arrhythmias

Future Perspectives in the Pharmacological Treatment of Atrial Fibrillation and Ventricular Arrhythmias in Heart Failure

Contact Info

Product

Resources

About