The Role of Renin Angiotensin System Blockade in the Treatment of Atrial Fibrillation

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical practice. The understanding of the pathophysiology of AF has changed drastically during the last several decades. Recent observations have challenged the concept of the multiple circuit reentry model in favor of single focus or single circuit reentry models. Atrial electrical dysfunction provides a favorable substrate and transmembrane ionic currents are key determinants. Recent research is focusing increasingly on the atrial structural remodeling, which underlies the development of AF in different pathological conditions. This has led to concepts about how interfering with the substrate might prevent AF development and recurrence. Particular interest has been generated in the role of renin angiotensin system (RAS) blockade in reversing the electrical and structural remodeling of diseased atria. The mechanisms for the preventive effect of angiotensin converting enzyme inhibitors (ACEi) or angiotensin-II (AT-II) type 1 receptor blockers (ARB) in AF are probably complex. They may comprise general haemodynamic changes leading to lower intra-atrial pressure and wall-stress, or reduce in atrial fibrosis, connexin43 over-expression and conduction delay. The promising results of several clinical trials concerning RAS blockade may herald a whole new era of AF treatment, where AF is prevented and treated by modifying its substrate rather than fighting it electrically. This review centers on the pathophysiology of the structural and electrical remodeling in AF, the possible mechanisms by which RAS blockade may reverse electrical and structural remodeling of diseased atria and on the role of ACEi or ARB blockers in AF prevention and treatment that has already been postulated both experimentally and clinically.

Functionally Selective AT1Receptor Activation Reduces Ischemia Reperfusion Injury

“…They found that myocardial infarct size was signi�icantly smaller in the losartan and captopril groups than in the control group [21]. Several other experimental models have similarly demonstrated the protective effects of both ACE inhibitors and AT 1 R antagonists in I/R studies [22,24,26]. There is thus solid evidence of a deleterious effect connected with particularly G protein-dependent signaling from the AT 1 R in the setting of Ischemia and Reperfusion.…”

Redox Regulation, NF-κB, and Atrial Fibrillation

“…This may help explain the efficacy of RAS inhibitors to prevent AF (24,26). The reduction in sodium current seen with AngII is similar to its effect on other cardiac ion channels, including the transient outward current a-subunit Kv4.3 (60), the gap junction protein connexin 43 (47), connexin 40 (31,47), and the calcium current (31), which may be mediated by comparable mechanisms and also may contribute to enhanced arrhythmic risk in states of increased oxidative stress.…”

Use of vitamins C and E as a prophylactic therapy to prevent postoperative atrial fibrillation

“…Nevertheless, the underlying etiology of AF is likely different in quite different patient subpopulations. In the postoperative state, a number of mechanisms play a pivotal role in its genesis and perpetuation; among them, the increase of adrenergic tone [15], the activation of the renin-angiotensin system (RAS) [16,17], inflammation, fibrosis and the pre-operative injuries associated with cardiac diseases (ventricular hypertrophy, atrial dilatation, hypertension and necrotic zones secondary to atherosclerotic injuries) are the most significant elements underlying atrial remodeling. Specific mechanisms involved in long-term structural remodeling include activation of calcium dependent proteases [18,19], phosphatases or kinases and/or inflammatory mechanisms [20].…”