The bidirectional association between atrial fibrillation and myocardial infarction

Abstract

Atrial fibrillation (AF) is associated with an increased risk of myocardial infarction (MI) and vice versa. This bidirectional association relies on shared risk factors as well as on several direct and indirect mechanisms, including inflammation, atrial ischaemia, left ventricular remodelling, myocardial oxygen supply-demand mismatch and coronary artery embolism, through which one condition can predispose to the other. Patients with both AF and MI are at greater risk of stroke, heart failure and death than patients with only one of the conditions. In this Review, we describe the bidirectional association between AF and MI. We discuss the pathogenic basis of this bidirectional relationship, describe the risk of adverse outcomes when the two conditions coexist, and review current data and guidelines on the prevention and management of both conditions. We also identify important gaps in the literature and propose directions for future research on the bidirectional association between AF and MI. The Review also features a summary of methodological approaches for the study of bidirectional associations in population-based studies.

Fig. 1 |. Timeline of selected literature on the bidirectional relationship between AF and MI.

Grey boxes refer to studies examining patients with atrial fibrillation (AF) after myocardial infarction (MI), and red boxes refer to studies on patients with MI after AF. REFS.^–. DOAC, direct oral anticoagulant; VKA, vitamin K antagonist.

Fig. 2 |. Inflammatory cells and mediators of inflammation modulate cardiac electrophysiology and structural properties leading to atrial fibrillation.

Calcium homeostasis in cardiomyocytes is regulated by tumour necrosis factor (TNF), IL-2 and platelet-derived growth factor (PDGF), which are associated with increased triggering and shortening of the action potential duration. The atrial expression of connexin 40 (Cx40) and Cx43 is downregulated by inflammation via TNF. Myeloperoxidase (MPO), heat shock proteins (HSPs), PDGF and TNF activate fibroblasts, which express transforming growth factor-β1 (TGFβ1) and matrix metallopeptidases (MMPs), leading to increased collagen synthesis and atrial fibrosis. TNF also increases cardiomyocyte apoptosis and myolysis. These changes contribute to heterogeneous atrial conduction and increased vulnerability to atrial fibrillation. HSPs protect cardiomyocytes against abnormal calcium handling, apoptosis, and myolysis. Adapted with permission from REF., Springer Nature.

Fig. 3 |. Pathophysiology of MI leading to AF and AF leading to MI.

a, Acute myocardial infarction (MI) can initiate several mechanisms that ultimately result in atrial fibrillation (AF). Left ventricular remodelling with wall thinning and left ventricular dysfunction potentiate left atrial dilatation (due to pressure and/or volume overload), electrical remodelling (increases in action potential duration, alterations to K⁺ and Ca²⁺ ion channels and gap junction remodelling) and neurohumoral modulation (stimulation of the renin–angiotensin–aldosterone system (RAAS), vasopressin and atrial natriuretic peptide). In addition, atrial ischaemia caused by MI can lead to cardiomyocyte death and fibrotic replacement, producing an arrhythmogenic substrate that alters electrical conduction and can result in AF. b, In the setting of AF, blood can pool in the left atrial appendage, leading to thrombus formation, which can be dispersed as a coronary artery embolism. During episodes of AF with a rapid ventricular response rate (tachycardia), myocardial oxygen demand increases and can cause a mismatch with oxygen supply, which can lead to type 2 MI.