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

Ashley Darlington,Mark D Mccauley

doi:10.3389/fcvm.2020.00011

Abstract

The most dreaded complication of atrial fibrillation is stroke, and 70–80% of patients with AF-related stroke die or become disabled. The mechanisms of thromboembolism in AF are multifactorial, with evidence demonstrating that all three criteria of Virchow's triad are satisfied in AF: abnormal stasis of blood, endothelial damage, and hypercoagulability. Mechanistic insights into the latter two limbs have resulted in effective stroke prophylactic therapies (left atrial appendage occlusion and oral anticoagulants); however, despite these advances, there remains an excess of stroke in the AF population that may be due, in part, to a lack of mechanistic understanding of atrial hypocontractility resulting in abnormal stasis of blood within the atrium. These observations support the emerging concept of atrial cardiomyopathy as a cause of stroke. In this Review, we evaluate molecular, translational, and clinical evidence for atrial cardiomyopathy as a cause for stroke from AF, and present a rationale for further investigation of this largely unaddressed limb of Virchow's triad in AF.

Highlights

The atria play an integral role in the initiation of the cardiac cycle, maintenance of sinus rhythm, ventricular filling, and cardiac output [1]
Several clinical observations suggest that in addition to electrical ion channel remodeling in atrial fibrillation (AF), atrial contractile dysfunction forms a substrate for stroke risk: [1] atrial hypocontractility persists for 6–8 weeks following conversion from AF to sinus rhythm [14, 15]; [2] atrial dilation and hypocontractility may progress despite catheter ablation of AF, leading to stroke [16, 17]; [3] there is a temporal dissociation between the occurrence of AF and the development of stroke [18]; and [4] atrial hypocontractility alone is an independent risk factor for stroke [19, 20]
This treatment resulted in overexpression of angiotensin converting enzyme and angiotensin-1 receptors, a signaling pathway that is known to contribute to remodeling of the myocardium [57]. This adverse angiotensin II signaling was reversed when treated with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) [57]. These results suggest that inhibition of coagulation may reduce stroke risk by reducing thromboembolism, and by limiting progression of the atrial cardiomyopathy (AC) substrate for AF

Summary

Introduction

The atria play an integral role in the initiation of the cardiac cycle, maintenance of sinus rhythm, ventricular filling, and cardiac output [1]. Atrial hypocontractility and atrial dilation are associated with increased risk of stroke [1]. Several clinical observations suggest that in addition to electrical ion channel remodeling in AF, atrial contractile dysfunction forms a substrate for stroke risk: [1] atrial hypocontractility persists for 6–8 weeks following conversion from AF to sinus rhythm [14, 15]; [2] atrial dilation and hypocontractility may progress despite catheter ablation of AF, leading to stroke [16, 17]; [3] there is a temporal dissociation between the occurrence of AF and the development of stroke [18]; and [4] atrial hypocontractility alone is an independent risk factor for stroke [19, 20].

Results

Conclusion