Mechanisms of Arrhythmias and Conduction Disorders in Older Adults

Abstract

Synopsis Aging is associated with an increased prevalence of cardiac arrhythmias, which contribute to higher morbidity and mortality in the elderly. The frequency of cardiac arrhythmias, particularly atrial fibrillation and ventricular tachyarrhythmia, is projected to increase as the population ages, greatly impacting health care resource utilization. Several clinical factors associated with the risk of arrhythmias have been identified in the population, yet the molecular bases for the increased predisposition to arrhythmogenesis in the elderly are not fully understood. Therefore, only limited therapeutic strategies directed at pathophysiological processes that enhance cardiac vulnerability to arrhythmias are available. This is further compounded by the paucity of outcome studies providing evidence on which optimal management guidelines can be formulated for the very elderly. This review highlights the epidemiology of cardiac dysrhythmias, changes incardiac structure and function associated with aging, and the basis for arrhythmogenesis in the elderly, the understanding of which is critical to formulate preventive strategies.

Atrial Fibrillation and Stroke in Elderly Patients

“…12 Further research is needed to identify initiating factors and critical mediators of thromboembolism and to delineate pathways altered by aging that potentiate the risk for AF and thromboembolism. 11,95 With better patient risk-stratification and the design of more appropriate therapeutic strategies, AF-associated thromboembolic risk could be further reduced in elderly patients.…”

“…12 Episodes of AF themselves promote a procoagulant state with an increase in markers of platelet activation (betathromboglobulin and platelet factor 4), thrombogenesis (elevated fibrinogen, prothrombin fragment F1 + 2, thrombin-antithrombin complexes, D-dimer levels) and endothelial dysfunction or injury (elevated von Willebrand factor, soluble E-selectin levels), independent of the presence of structural heart disease, increasing the likelihood of thromboembolism. 6,11,16,22,23,[25][26][27][28][29][30] Evidence also points to endocardial or endothelial dysfunction with decreased anticoagulant mechanisms --such as expression of nitric oxide synthase, tissue factor pathway inhibitor and thrombomodulin --and an increase in procoagulant factors such as plasminogen activator inhibitor-1 22,23,31 as a possible mechanism for thromboembolism in the setting of AF. Inflammation with elevated C-reactive protein and interleukin-6 is associated with a prothrombotic state and an increase in reactive oxygen species production that promotes platelet hyperactivity and additional susceptibility to thrombosis, contributing to an overall hypercoagulable state in AF.…”

“…2,10 There is a growing need to better understand the mechanisms that underlie aging-associated changes in the cardiovascular system that predispose people to AF and thromboembolism. 6,11 Active research in these areas has focused on identification of novel therapeutic targets for prevention to reduce the incidence of AF and its associated thromboembolic risk. 12,13 This overview highlights the pathogenesis and management of stroke and thromboembolism associated with AF in elderly patients.…”

Essentials of Herb-Drug Interactions in the Elderly With Cardiovascular Disease

“…15 Drugs with a narrow therapeutic index, such as anticoagulants, chemotherapeutics, organ antirejection agents and antiarrhythmic compounds, are particularly vulnerable to interaction.…”

Age-dependent myocardial transcriptomic changes in the rat. Novel insights into atrial and ventricular arrhythmias pathogenesis

“…Aging is associated with significantly increased prevalence of both atrial and ventricular arrhythmias (1,2), likely due to age-associated changes in heart structure and function (3). Factors such as DNA and/or protein damage due to increased oxidative stress or late-acting mutations could account for the adverse effects of aging on myocyte structure and function (4)(5)(6)(7)(8).…”