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CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2024;149:e1–e156. DOI: 10.1161/CIR.0000000000001193 January 2, 2024 e17

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

loss of calcium currents. Shunt closure reverses electrophysiological changes.3 Clinically, the hemodynamic structural changes are difficult or impossible to reverse.

2.3.2.1. Upstream Pathways Upstream pathways include inflammatory, oxidative stress, fibrosis, calcium handling, genetic, metabolic, obesity, and other mechanisms implicated in increasing susceptibility to or progression of AF. The renin-angiotensin-aldosterone system (RAAS), oxidative stress, inflammatory signaling, and calcium overload are discussed here and in Section 2.3.1 (“Electrophysiological Mechanisms and Electrical Remodeling”). Upstream therapies are discussed in Section 8.3.4 (“Upstream Therapy”). The RAAS regulates blood pressure (BP) and is activated in hypertension and obesity. RAAS activation promotes vascular smooth muscle constriction (increasing BP), activates fibroblasts (increasing atrial intersti- tial collagen), and increases reactive oxygen species in the sympathetic nervous system. BP and weight control, including treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-II receptor blockers, attenuate pathologic changes.

Oxidative stress is associated with: (1) activation of calcium-dependent calmodulin kinase II1,2 and jun kinase 2,3 which promotes ryanodine receptor phosphorylation and leads to spontaneous calcium release4; (2) increased late sodium current, INa,L, and lower calcium current amplitude; (3) formation of reactive lipid products (isolevuglandins) in hypertension5 and AF6; (4) activation of the redox-sensitive transcription factor nuclear factorkappa B and the NLRP3 inflammasome7; (5) increase in mitochondrial and metabolic stress; (6) inflammatory changes; and (7) myofilament protein degradation, impairing atrial contractility, which may increase thromboembolism risk.8

Table 4.  Definitions Term Definition AF A supraventricular tachyarrhythmia with uncoordinated atrial activation and ineffective atrial contraction

Electrocardiographic characteristics include (1) irregular R-R intervals (when atrioventricular conduction is present), (2) absence of distinct P waves, and (3) irregular atrial activity also known as fibrillatory waves. AF can be documented by, for example, 12-lead ECG, rhythm strips, wearables, intracardiac electrograms, but will always require visual confirmation that the diagnosis is accurate.

Clinical AF With the increasing availability of wearable devices and other continuous monitoring technologies, the distinction between clinical and subclinical AF has become increasingly blurred, thus the writing committee felt the term clinical AF has become less useful. Yet, the term was kept because most of the evidence from randomized trials that have led to guideline recommendations for the treatment of AF refer to “clinical AF.” These trials required electrocardiographic documentation of the arrhythmia for inclusion and most patients presented for clinical evaluation and/or therapy of the arrhythmia. Subclinical AF Subclinical AF refers to this arrhythmia identified in individuals who do not have symptoms attributable to AF and in whom there are no previous ECGs documenting AF This includes AF identified by implanted devices (pacemakers, defibrillators, or implantable loop recorders) or wearable monitors Atrial high-rate episodes These are defined as atrial events exceeding the programmed detection rate limit set by the device. These are recorded by implanted devices but require visual inspection to confirm AF and exclude other atrial arrhythmias, artifact or oversensing. AF burden AF burden encompasses both frequency and duration and refers to the amount of AF that an individual has. AF burden has been defined differently across studies. For the purpose of this guideline, AF burden will be defined as the durations of an an episode or as a percentage of AF duration during the monitoring period depending on how it was defined in the individual studies. First detected AF The first documentation of AF, regardless of previous symptoms Paroxysmal AF AF that is intermittent and terminates within ≤7 d of onset Persistent AF AF that is continuous and sustains for >7 d and requires intervention. Of note, patients with persistent AF who, with therapy, become paroxysmal should still be defined as persistent as this reflects their original pattern and is more useful to predict outcomes and define substrate. Long-standing persistent AF AF that is continuous for >12 mo in duration Permanent AF A term that is used when the patient and clinician make a joint decision to stop further attempts to restore and/or maintain sinus rhythm Acceptance of AF represents a therapeutic decision and does not represent an inherent pathophysiological attribute of AF Terms considered obsolete Chronic AF This historical term has had variable definitions and should be abandoned. It has been replaced by the “paroxysmal,” “persistent,” “longstanding persistent,” and “permanent” terminology. Valvular and nonvalvular AF The distinction between “valvular” and “nonvalvular “AF remains a matter of debate. Their definitions may be confusing. Recent trials comparing vitamin K antagonists with non-vitamin K antagonist oral anticoagulants in AF were performed among patients with so-called “nonvalvular” AF. These trials have all allowed native valvular heart disease other than mitral stenosis (mostly moderate and severe) and prosthetic heart valves to be included. We should no longer consider the classification of AF as ‘‘valvular’’ or “nonvalvular” for the purpose of defining the etiology of AF, since the term was specific for eligibility of stroke risk reduction therapies. Valvular and nonvalvular terminology should be abandoned. Lone AF This term has been used in the past to identify AF in younger patients without structural heart disease who are at a lower risk for thromboembolism. This term does not enhance patient care, is not currently used, and should be abandoned. AF indicates atrial fibrillation.

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