Lone atrial fibrillation: what is known and what is to come

Abstract

Summary Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in adults, affecting > 1% of general population. Atrial fibrillation is commonly associated with structural heart disease and is a major cause of significant cardiovascular morbidity and mortality. AF sometimes develops in a subset of young patients (e.g. aged ≤ 60 years), with no evidence of associated cardiopulmonary or other comorbid disease (including hypertension), and has been referred to as ‘lone AF’. The latter generally has a favourable prognosis; the prognostic and therapeutic implications of an accurate identification of patients with truly lone AF (that is, truly at low risk of complications), if any, would be of the utmost importance. The true prevalence of lone AF is unknown, varying between 1.6% and 30%, depending on the particular study population. Nonetheless, novel risk factors for AF, including obesity, metabolic syndrome, sleep apnea, alcohol consumption, endurance sports, anger, hostility, subclinical atherosclerosis and others, have been increasingly recognised. Also, various underlying pathophysiological mechanisms predisposing to AF, including increased atrial stretch, structural and electrophysiological alterations, autonomic imbalance, systemic inflammation, oxidative stress and genetic predisposition, have been proposed. The growing evidence of these diverse (and numerous) pathogenic mechanisms and factors related to AF inevitably raises the question of whether ‘lone AF’ does exist at all. In this review article, we summarise the current knowledge of the epidemiology, pathophysiology, clinical course and treatment of patients with so‐called ‘lone AF’ and outline emerging insights into its pathogenesis and the potential therapeutic implications of a diagnosis of lone AF.

Impaired endothelial function in lone atrial fibrillation

“…obesity, metabolic syndrome, sleep apnea, excessive alcohol consumption and competitive sports) [2][3][4][5] . Lone AF is defined as the occurrence of AF in subjects younger than < 60 years without associated comorbidities (including hypertension) or recognized risk factors 6,7 . AF is considered a benign condition with favorable long-term prognosis 8,9 .…”

Atrial Fibrillation and the Risk of Ischemic Stroke

“…1 It is an independent risk factor for stroke and is associated with marked morbidity, mortality, and socioeconomic burden. [2][3][4] Although the knowledge about the pathogenesis and treatment of AF has greatly advanced in recent years, stroke prevention with appropriate thromboprophylaxis remains central to AF management.…”

Lone Atrial Fibrillation: Where Are We Now?

“…20 A number of genetic loci and causal mutations, mostly of genes encoding components of sodium, potassium, or L-type calcium ion channels, have been identifi ed in patients with apparently lone AF, with signifi cant overlap of AF with congenital long QT, short QT, or Brugada syndrome, or with inherited dilated cardiomyopathy; however, these channel mutations are not a major cause of AF according to the results of large-scale sequencing in lone AF cohorts. 21,22 In addition, genome-wide association studies that compared non-familial cases of AF with age-related, gender-matched controls have provided some insight into the genetics of acquired AF, suggesting that some common gene or singlenucleotide polymorphisms, including those encoding the renin-angiotensin-aldosterone system, calcium handling, neurohumoral and lipoprotein pathways, gap junction proteins, ion channels, interleukins, signaling molecules, and mediators of various molecular pathways, could contribute to a genetically determined "AF diathesis." 21,22 Overall, it is most likely that variable individual vulnerability to AF arises from the infl uence of multiple genes, which could alter the atrial structural and functional properties to a variable extent, either alone or in combination, and further insights into the genetics of AF could perhaps facilitate a pharmacogenomic treatment approach to AF in the future.…”