Aging Modulates the Substrate and Triggers Remodeling in Atrial Fibrillation

Abstract

how aging and AF are connected and highlight the potential role of aging in AF substrate and triggered remodeling. Effects of Aging on Structural RemodelingStructural remodeling is characterized by histopathological changes, such as cellular hypertrophy, apoptosis, or myocardial fibrosis, and anatomical changes, such as chamber dilatation. 5 Anatomical Changes With Dilation of PV and Atria in AgingThe left atrium (LA) anteroposterior diameter and wall thickness increase with aging, and the 4 PVs become dilated in patients older than 50 years (Figure 1), 3 which suggests mechanical effects of aging on AF triggers and substrates. 3 Clinical data indicate that PV size correlates with PV arrhythmogenesis. Therefore, larger PVs may correlate with a higher PV arrhythmogenesis resulting in AF. Histopathological Changes With AgingBoth animal and human studies had shown that loss of cardiomyocytes by apoptosis and necrosis produces compensatory cellular hypertrophy, which may represent the structural basis of the aged heart, and contribute to cardiac dysfunction in the elderly. 5 Aging increases the rate of ventricular cardiomyocyte death caused by enhanced vulnerability to stress such as oxidative stress. 6 These histopathological changes at the microscopic level potentially T he prevalence and severity of arrhythmias increase with age. Advancing age is independently associated with the prevalence of atrial fibrillation (AF). 1 Aging and aging-related underlying diseases frequently result in structural remodeling as cardiac morphological changes either grossly or at the histological and ultrastructural levels, or they induce electrophysiological remodeling with changes in cardiac electrical properties in response to a functional insult, or as a result of a structural alteration. Aging-associated cardiac anatomical and functional remodeling may enhance the occurrence or the persistence of AF.Ectopic impulses generated from the pulmonary veins (PVs) play a key role in the genesis and maintenances of AF. 2 Elimination of PV arrhythmogenic foci or targeting atrial substrate abnormalities reduces the AF burden or cures AF. 2 PVs contain complex electrical activity because of their distinctive anatomical and physiological characteristics. 3 Aging-associated electrophysiological or structural changes in the atria or PVs may facilitate AF occurrence. 3 Age is an independent predictor of AF recurrence in lone AF patients after undergoing the first circumferential PV isolation. 4 AF may coexist with cardiovascular disorders, which may potentiate its occurrence, and these are also more prevalent with increased age. Together with agingrelated myocardial degeneration or anatomical changes, both inflammation and oxidative stress, as consequences of aging, enhance the occurrence and maintenance of AF. The aim of this review is to update the understanding of Aging plays a critical role in the genesis of atrial fibrillation (AF) and also increases the risks of cardiac dysfunction and stroke in AF patients. AF is caused by increased AF t...

Atrial Fibrillation Initiated by Early Afterdepolarization-Mediated Triggered Activity during Acute Oxidative Stress: Efficacy of Late Sodium Current Blockade

“…These findings are consistent with our previous findings in aged rats and rabbits atria [1,7,20,22] as well as in aged human atria [23]. …”

“…However as stressed previously [40] levels 100–150 μM concentrations of H 2 O 2 have been suggested to be clinically relevant to mimic reversible pro-oxidant pathological states [41]. Indeed H 2 O 2 has been used successfully to assess the influence of oxidative stress in AF in diverse animal models [23,25,42,43]. …”

Atrial Cardiomyopathy: An Unexplored Limb of Virchow's Triad for AF Stroke Prophylaxis

“…Aging is the most common risk factor for atrial fibrosis. Given that aging is associated with oxidative stress, Ca 2+ dysregulation, and apoptosis, it is not surprising that age is directly associated with the extent of both atrial fibrosis and apopotosis (49). Matrix metalloproteins are highly expressed in AF and positively correlate to extent of atrial fibrosis in AF; in particular matrix metalloprotein 9 (MMP-9) has been described as a circulating serum biomarker suggestive of atrial fibrosis (47).…”

Atrial Cardiopathy and Sympatho-Vagal Imbalance in Cryptogenic Stroke: Pathogenic Mechanisms and Effects on Electrocardiographic Markers

“…Oxidative stress occurs when the formation of reactive oxygen species (ROS) and reactive nitrogen species exceeds the body's ability to metabolize them. These reactive molecules are able to determine cardiac damage by means of different molecular pathways ( 94 ): direct oxidative damage of myofibrillar proteins ( 95 ), increased inflammation by NF-κB and c-jun activation ( 96 ), TGF-β, MAPK and ERK1/ERK2 activation ( 96 ), increased activity of MMPs in cardiac fibroblasts ( 97 ), regulation of cardiomyocyte apoptosis ( 98 ). Therefore, oxidative stress represents a pathogenic mechanism promoting atrial fibrosis and structural cardiac remodeling ( 99 ).…”