The Clinical Profile and Pathophysiology of Atrial Fibrillation

Abstract

Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%–26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca 2+ -handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca 2+ -handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of the underlying mechanisms, is needed to develop improved methods for AF prevention and management.

American Heart Association's Life Simple 7 and Risk of Atrial Fibrillation in a Population Without Known Cardiovascular Disease: The ARIC (Atherosclerosis Risk in Communities) Study

“…Ideal physical activity also protected against AF. Although the majority of evidence suggests physical activity reduces AF risk as well, that relationship is more complicated than these for other established risk factors and depends on many factors including individual susceptibility, the environment, and degree of activity 30, 34. In a meta‐analysis of more than 20 studies and 600 000 participants, moderate‐intensity exercise was associated with a lower risk of developing AF, whereas high‐intensity exercise reduced AF risk in women but increased AF risk in men 35.…”

Rates of Atrial Fibrillation in Black Versus White Patients With Pacemakers

“…To account for imbalances in vascular risk factors that may explain racial differences in AF and stroke rates, we used ICD‐9‐CM codes from the index hospitalization to define the following comorbidities that have been reported as risk factors for AF and stroke2, 21: hypertension, diabetes mellitus, coronary heart disease, congestive heart failure, lung disease, chronic kidney disease, valvular disease, obesity, alcohol abuse, and tobacco use. To compare the burden of stroke risk factors between groups, we also used comorbidity data to calculate the CHA 2 DS 2 ‐VASc score 22…”

Clinical Phenotypes in Heart Failure With Preserved Ejection Fraction

“…LA structural remodeling that provides the reentry substrate for AF clearly differs in HFpEF and HFrEF 226, 227. Increased LA stiffness and greater LA pulsatility may result in a higher AF burden in HFpEF than in HFrEF.…”