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CLINICAL STATEMENTS AND GUIDELINES

January 2, 2024 Circulation. 2024;149:e1–e156. DOI: 10.1161/CIR.0000000000001193 e18

Joglar et al 2023 Guideline for the Diagnosis and Management of Atrial Fibrillation

Systemic inflammatory activation, first documented with AF after cardiac surgery,9 has also been associated with nonsurgical AF.10 NLRP3 knockdown prevented AF inducibility in a mouse model, implicating the NLRP3 inflammasome in AF pathophysiology.11 NLRP3-blocking drugs are in development.

2.3.2.2. Persistence of AF In general, persistence of AF reflects the substrate for AF. A suitable substrate for AF has a wavelength (wavelength = refractory period × conduction velocity) that is shorter than the dimensions of the tissue, with heterogenous conduction velocity and/or repolarization duration. Thus, an individual with large, fibrotic, and/or fatty atria is more likely to have persistent AF than one with a normal-sized atria with little interstitial fibrosis or adipose infiltration. Electrophysiologic remodeling is typically a response to persistent AF rather than the trigger. 2.3.3. Role of the Autonomic Nervous System The autonomic nervous system (ANS) has an important role as trigger and substrate (Figure 8).

ANS triggers AF The ANS as AF trigger is detailed in several reviews.1–6 Sympathetic efferent stimulation releases noradrenaline, stimulating G-coupled β-adrenergic receptors, enhancing L-type calcium channels, and increasing inward current (automaticity/early afterdepolarization). Delayed afterdepolarization occurs via calcium overload and ryanodine-2 receptor dysfunction. Parasympathetic stimulation shortens atrial effective refractory period by increasing IKACh (acetyl-choline receptor mediated inward rectifying potassium channel) activity. Atrial effective refractory period heterogeneity follows the pattern of autonomic innervation. Sympathetic and parasympathetic activity, alone or combined, can trigger AF.

Figure 6. Types of Atrial Flutter and Macroreentrant Atrial Tachycardia. The typical, reverse typical, and the lower-loop flutter all have the low right atrial isthmus incorporated in the flutter circuit. Other macroreentrant flutters include scar-mediated reentrant tachycardia and left mitral isthmus flutter. Modified with permission from Wellens et al.3 Copyright 2002 American Heart Association, Inc. Fl indicates flutter; LA, left atrium; and MRT, macroreentrent.

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