Circulating Biomarkers Predictive of Postoperative Atrial Fibrillation

Abstract

Postoperative atrial fibrillation (PoAF), a common complication of cardiac surgery, contributes significantly to morbidity, mortality, and increasing health care costs. Despite advances in surgical and medical management, the overall incidence of PoAF has not changed significantly, partly due to the limited understanding of mechanisms underlying acute surgery-related factors, such as myocardial injury, inflammation, sympathetic activation, and oxidative stress, which play an important role in the initiation of PoAF, while a preexisting atrial substrate appears to be more important in the maintenance of this dysrhythmia. Thus, in a majority of patients, PoAF becomes a manifestation of an underlying arrhythmogenic substrate that is unmasked following acute surgical stress. As such, the ability to identify which patients have this proarrhythmic substrate and are, therefore, at high risk for developing AF postoperatively, is important for the improved selection for prophylactic interventions, closer monitoring for complications, and establishing the probability of AF in the long term. This review highlights the role of the underlying substrate in promoting PoAF, proposed mechanisms, and the potential role of serum biomarkers to identify patients at risk for PoAF.

Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation

“…The incidence and prevalence of AF increase with advancing age and aging-associated diseases such as hypertension, ischemic heart disease, and heart failure (2, 40) and contribute to increased morbidity, particularly an increased risk for stroke, heart failure, and death (25,52). Although the pathophysiology of AF has been well characterized, the underlying mechanisms that contribute to the progression of AF in human atria have not been fully defined (33,35,57,58,60). Mitochondria, occupying 30% of cardiomyocyte volume, are critical for maintaining normal energetics of the heart, a highly aerobic organ dependent on oxidative phosphorylation (OXPHOS) for maintenance of its normal electrical and mechanical function (1, 61).…”

Atrial Fibrillation and Stroke 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.…”

“…This is particularly evident in the elderly with aging-associated diseases, including diabetes, heart failure and hypertension, which further increase thrombogenicity. 6,28,[32][33][34] In addition, atrial stretch associated with AF and myocardial dysfunction leads to downregulation of thrombomodulin, which renders a defective anticoagulant defense in AF patients and, thus, predisposes these patients to stroke. 35 fibrillation]) trial, 38 and the AF-CHF (Atrial Fibrillation and Congestive Heart Failure) 39 trial demonstrated that AF patients who had a high risk of thromboembolism did no better when treated with a strategy of pharmacologic rhythm control than did AF patients treated with rate control in regard to reducing overall or cardiovascular mortality, hospitalization or risk of stroke.…”

“…Additional circulating biomarkers of fibrosis or cardiac stress, including high levels of troponin and brain natriuretic peptide, increase the risk of stroke in the setting of AF independent of those well-established clinical characteristics. 6,7 Women accounted for 58% of U.S. stroke deaths in 2013. 2 More women than men die of stroke each year because of the larger number of elderly women.…”

“…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.…”