Age-associated changes in electrophysiologic remodeling: a potential contributor to initiation of atrial fibrillation

Abstract

Objective: Although the incidence of atrial fibrillation (AF) increases with age, the cellular electrophysiological changes that render the atria of aged individuals more susceptible to AF remain poorly understood. We hypothesized that dispersion of atrial repolarization increases with aging, creating a substrate for initiation of AF. Methods: Four groups of dogs were studied: adult and old dogs in normal sinus rhythm (SR) and adult and old dogs with chronic AF (CAF) induced by rapid atrial pacing. In each dog, action potentials (AP) were recorded with microelectrodes from isolated endocardial preparations of four regions of right atrium and three regions of left atrium. Two indices of AP duration (APD) heterogeneity were obtained in each dog by calculating standard deviation (SD) and the coefficient of variation (COV=[SD/mean]Â100%). Results: In SR groups, APD averaged across all regions was significantly longer in old than in adult tissues. Both indices of APD heterogeneity were higher in old dogs in comparison to adult. At both ages, CAF was associated with significant APD shortening and a decrease in APD adaptation to rate. While CAF significantly increased both indices of APD heterogeneity in adult dogs, it significantly decreased them in old dogs. Conclusions: The increase of spatial variability in repolarization in old atria may contribute to the initiation of AF in the aged. CAF-induced APD shortening and a decrease in APD adaptation appear to be important for the maintenance of sustained AF in both adult and old atria. The CAF-induced increase in dispersion of repolarization may be important for AF stabilization in adults, while previously reported fibrosis and slowed conduction of premature beats may be important in the old for both AF initiation during SR and subsequent stabilization of AF.

EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication

“…165,166 Clinical mapping studies have also demonstrated similar findings of conduction abnormalities, prolonged refractoriness, reduced myocardial voltage, and a greater number of double potentials and fractionated electrograms. 167,168 Perhaps as a result of these atrial changes, alteration of wavefront propagation velocities has been described with an inverse correlation to age.…”

Alterations in the expression of atrial calpains in electrical and structural remodeling during aging and atrial fibrillation

“…Fibrosis preferentially affects lateral (or transverse) connections, rather than longitudinal cell-cell connections (29,30), resulting in a slower, zigzag transverse propagation (31,32). Thus, a premature response occurring in the aged atrial myocardium has a higher probability of undergoing unidirectional block from an imbalance between source/sink currents and initiating re-entry due to the underlying arrhythmogenic substrate, which is produced as a result of electrical and/or structural remodeling (5,14,33).…”

“…It affects millions of individuals worldwide and the incidence increases with age (1,2). The increased number of cases of AF in the elderly may be due to several factors, including disease, fibrosis and/or age-related changes in cellular electrophysiological properties, which are likely to lead to a disturbance in atrial activation and repolarization (3)(4)(5)(6). Calcium regulation is commonly implicated in numerous forms of injury that may occur during cellular aging.…”

“…Calcium regulation is commonly implicated in numerous forms of injury that may occur during cellular aging. Altered calcium homeostasis has been correlated with age-related phenomena (5,7,8). Calpains are calcium-dependent enzymes that are readily activated by elevated cellular calcium levels.…”

A Caveat Emptor for myocardial regeneration: Mechanical without electrical recovery will not suffice

“…They may also enhance survival via angiogenesis or promote myocyte proliferation in the infarct by secretion of paracrine factors. The cartoon describes a localized region and is intended only to illustrate the basis of enhanced electrical conduction, not the diffuse (MSC) or punctuate (SKMB) distribution of the delivered cells as proposed by Mills et al [23]; EPI and ENDO from [24]; Atrial AP from [25]; Skeletal myoblast from [26]. (B) When induced to differentiate, all of the cell types currently under investigation for cardiac repair yield heterogenous populations of cardiac myocytes.…”