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Background: Aging is associated with an increased incidence of atrioventricular nodal (AVN) dysfunction.Objective: The aim of this study was to investigate the structural and functional remodeling in the atrioventricular junction (AVJ) with aging.Methods: Electrophysiology, histology, and immunohistochemistry experiments on male Wistar Hannover rats aged 3 months (n = 24) and 2 years (n = 15) were performed. Atrio-His (AH) interval, Wenkebach cycle length (WBCL), and AVN effective refractory period (AVNERP) were measured. Cesium (2 mM) was used to block hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, while ryanodine (2 μM) was used to block ryanodine 2 (RyR2) channels. Protein expression from different regions of the AVJ was studied using immunofluorescence. The expression of connexins (connexin 43 and connexin 40), ion channels (Hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), voltage sensitive sodium channel (Nav1.5), and L-Type calcium channel (Cav1.3)), and calcium handling proteins (RyR2 and sarco/endoplasmic reticulum calcium ATPaset type 2a (SERCA2a)) were measured. Morphological characteristics were studied with histology.Results: Without drugs to block HCN and RyR2 channels, there was prolongation of the AH interval, WBCL, and AVNERP (P < .05) with aging. In young rats only, cesium prolonged the AH interval, WBCL, and AVNERP (P < .01). Ryanodine prolonged the AH interval and WBCL (P < .01) in both young and old rats. Immunofluorescence revealed that with aging, connexin 43, HCN4, Nav1.5, and RyR2 downregulate in the regions of the AVJ and connexin 40, SERCA2a, and Cav1.3 upregulate (P < .05). Aging results in cellular hypertrophy, loosely packed cells, a decrease in the number of nuclei, and an increase in collagen content.Conclusion: Heterogeneous ion channel expression changes were observed in the AVJ with aging. For the first time, we have shown that HCN and RyR2 play an important role in AVN dysfunction with aging. [ABSTRACT FROM AUTHOR]

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder which usually presents in the first or second decade of life with syncope, which is typically induced by emotional stress or exercise. We describe a large family with a history of three sudden unexpected deaths. Investigations in the sibling of a deceased individual affected by emotion-induced syncope revealed ventricular bigeminy. Molecular genetic testing was performed on one symptomatic individual and a missense mutation in RYR2 was identified consistent with a diagnosis of CPVT. Subsequent cascade testing of family members excluded 37 of 43 individuals from risk and facilitated preventative intervention. This case highlights the value of genotyping in sudden cardiac death by defining the precise diagnosis and through the identification and exclusion of at-risk individuals. < Learning objective: The diagnosis of CPVT should be considered in families with a history of sudden death in a previously asymptomatic young person. Cascade molecular genetic testing should be undertaken as, if a pathogenic mutation is found, this can distinguish it from other arrhythmogenic disorders and can identify at-risk individuals allowing treatment to be targeted at those in need, thus helping to reduce the mortality associated with the condition.> [ABSTRACT FROM AUTHOR]

Background Electrogram fractionation and atrial fibrosis are both thought to be pathophysiological hallmarks of evolving persistence of atrial fibrillation (AF), but recent studies in humans have shown that they do not colocalize. The interrelationship and relative roles of fractionation and fibrotic change in AF persistence therefore remain unclear. Objective The aim of the study was to examine the hypothesis that electrogram fractionation with increasing persistence of AF results from localized conduction slowing or block due to changes in atrial connexin distribution in the absence of fibrotic change. Methods Of 12 goats, atrial burst pacemakers maintained AF in 9 goats for up to 3 consecutive 4-week periods. After each 4-week period, 3 goats underwent epicardial mapping studies of the right atrium and examination of the atrial myocardium for immunodetection of connexins 43 and 40 (Cx43 and Cx40) and quantification of connective tissue. Results Despite refractoriness returning to normal in between each 4-week period of AF, there was a cumulative increase in the prevalence of fractionated atrial electrograms during both atrial pacing (control and 1, 2, and 3 months period of AF 0.3%, 1.3% ± 1.5%, 10.6% ± 2%, and 17% ± 5%, respectively; analysis of variance, P < .05) and AF (0.3% ± 0.1%, 2.3% ± 1.2%, 14% ± 2%, and 23% ± 3%; P < .05) caused by colocalized areas of conduction block during both pacing (local conduction velocity <10 cm/s: 0.1% ± 0.1%, 0.3% ± 0.6%, 6.5% ± 3%, and 6.9% ± 4%; P < .05) and AF (1.5% ± 0.5%, 2.7% ± 1.1%, 10.1% ± 1.2%, and 13.6% ± 0.4%; P < .05), associated with an increase in the heterogeneity of Cx40 and lateralization of Cx43 (lateralization scores: 1.75 ± 0.89, 1.44 ± 0.31, 2.85 ± 0.96, and 2.94 ± 0.31; P < .02), but not associated with change in connective tissue content or net conduction velocity. Conclusion Electrogram fractionation with increasing persistence of AF results from slow localized conduction or block associated with changes in atrial connexin distribution in the absence of fibrotic change. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the world's most common cardiac arrhythmia. Due to the complexity of the heart and highly irregular electrical activity during AF it is a grand challenge to underpin the mechanisms underlying the initiation and maintenance of AF. Complimentary to experimental physiology, biophysically detailed models of the heart provide a powerful platform for investigating the substrates that prompt and perpetuate AF. In the last decade, there has been significant progress in the development of atrial models at the cellular, tissue and whole organ levels. This article presents a review of recent advances in modelling of the human atria and their application to understanding AF. [ABSTRACT FROM AUTHOR]

Abstract: Background: Heart failure (HF) and atrial fibrillation (AF) are common disorders that frequently occur together and are associated with an increased risk of thromboembolism. This thromboembolic risk may be reduced by anticoagulation with warfarin but not without introducing new hemorrhagic risks. Methods and Results: Current guidelines recommend the use of anticoagulation in patients with HF and chronic AF and paroxysmal AF (PAF) that is symptomatic or frequent and prolonged enough to be detected by electrocardiogram. However, the evidence supporting these recommendations is weak and does not take account of research indicating that the prothrombotic risk is higher in more severe HF. Conclusions: An area not addressed by current guidelines is anticoagulation in patients with HF and short, asymptomatic episodes of AF. These issues need to be resolved with further studies using implanted devices to detect such asymptomatic PAF. [Copyright &y& Elsevier]

Ventricular rate adaptive pacemakers are the pacing systems of choice in patients with atrioventricular block and permanent or persistent atrial arrhythmias. A number of different pacemaker models are available, relying on different sensors of activity or metabolic demand. None of the sensors are perfect, each having its own advantages and disadvantages. Rate adaptive pacing is possible in the atrium as well as the ventricle, and atrial systems have a role in the management of patients with a poor sinus node response to exercise (chronotropic incompetence). The major groups of rate adaptive pacemakers are discussed in the following article, together with indications pr use and possible future developments. [ABSTRACT FROM AUTHOR]