Atrial Fibrillation: A Review.
JAMA
Importance:In the US, approximately 10.55 million adults have atrial fibrillation (AF). AF is associated with significantly increased risk of stroke, heart failure, myocardial infarction, dementia, chronic kidney disease, and mortality. Observations:Symptoms of AF include palpitations, dyspnea, chest pain, presyncope, exertional intolerance, and fatigue, although approximately 10% to 40% of people with AF are asymptomatic. AF can be detected incidentally during clinical encounters, with wearable devices, or through interrogation of cardiac implanted electronic devices. In patients presenting with ischemic stroke without diagnosed AF, an implantable loop recorder (ie, subcutaneous telemetry device) can evaluate patients for intermittent AF. The 2023 American College of Cardiology (ACC)/American Heart Association (AHA)/American College of Clinical Pharmacy (ACCP)/Heart Rhythm Society (HRS) Guideline writing group proposed 4 stages of AF evolution: stage 1, at risk, defined as patients with AF-associated risk factors (eg, obesity, hypertension); stage 2, pre-AF, signs of atrial pathology on electrocardiogram or imaging without AF; stage 3, the presence of paroxysmal (recurrent AF episodes lasting ≤7 days) or persistent (continuous AF episode lasting >7 days) AF subtypes; and stage 4, permanent AF. Lifestyle and risk factor modification, including weight loss and exercise, to prevent AF onset, recurrence, and complications are recommended for all stages. In patients with estimated risk of stroke and thromboembolic events of 2% or greater per year, anticoagulation with a vitamin K antagonist or direct oral anticoagulant reduces stroke risk by 60% to 80% compared with placebo. In most patients, a direct oral anticoagulant, such as apixaban, rivaroxaban, or edoxaban, is recommended over warfarin because of lower bleeding risks. Compared with anticoagulation, aspirin is associated with poorer efficacy and is not recommended for stroke prevention. Early rhythm control with antiarrhythmic drugs or catheter ablation to restore and maintain sinus rhythm is recommended by the 2023 ACC/AHA/ACCP/HRS Guideline for some patients with AF. Catheter ablation is first-line therapy in patients with symptomatic paroxysmal AF to improve symptoms and slow progression to persistent AF. Catheter ablation is also recommended for patients with AF who have heart failure with reduced ejection fraction (HFrEF) to improve quality of life, left ventricular systolic function, and cardiovascular outcomes, such as rates of mortality and heart failure hospitalization. Conclusions and Relevance:AF is associated with increased rates of stroke, heart failure, and mortality. Lifestyle and risk factor modification are recommended to prevent AF onset, recurrence, and complications, and oral anticoagulants are recommended for those with an estimated risk of stroke or thromboembolic events of 2% or greater per year. Early rhythm control using antiarrhythmic drugs or catheter ablation is recommended in select patients with AF experiencing symptomatic paroxysmal AF or HFrEF.
10.1001/jama.2024.22451
Molecular and Cellular Mechanisms of Atrial Fibrosis in Atrial Fibrillation.
Nattel Stanley
JACC. Clinical electrophysiology
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Atrial fibrosis has emerged as an important pathophysiological contributor and has been linked to AF recurrences, resistance to therapy and complications. Here, the author reviews the molecular and cellular mechanisms that control atrial fibrosis. It is important to note that not all tissue fibrosis is identical. For example, reactive (interstitial) fibrosis increases the amount of collagen between cardiac muscle bundles without fundamentally altering muscle bundle architecture. Replacement (reparative) fibrosis replaces dead cardiomyocytes with extracellular matrix tissue and fibroblasts, preserving tissue integrity at the expense of muscle bundle continuity. Replacement fibrosis may be much more disruptive to electric conduction and more difficult to reverse than reactive fibrosis. The author reviews the complex signaling systems that cause fibrosis, including those connected to connective tissue growth factor, angiotensin-II, platelet-derived growth factor, and transforming growth factor-β. The author then considers the molecular constitution of fibrous tissue, including the production and maturation of collagen and the roles of important extracellular matrix proteins such as fibronectin, tenascin-C, and thrombospodin-1. The author then discusses the evolving evidence for an important role of Ca entry in the profibrotic activation of fibroblasts, along with evidence that dysregulation of Ca-transporting transient potential receptor channels and inward rectifier K channels in AF fibroblasts is profibrotic. Finally, the author reviews the evidence for micro-ribonucleic acid involvement in atrial fibrotic signaling and AF promotion. It is hoped that an improved understanding of the mechanisms controlling atrial fibrosis will open up new opportunities for AF prevention and management.
10.1016/j.jacep.2017.03.002