Atrial Fibrillation Causes and Risk Factors

Cardiac Structural Causes

Valvular heart disease, particularly mitral valve disease, significantly increases atrial fibrillation risk, correlating strongly with left atrial enlargement 1.
Hypertension, especially when left ventricular hypertrophy is present, creates increased left atrial pressure and promotes atrial dilation through altered wall stress 2.
Coronary artery disease is a significant risk factor, occurring predominantly in older patients, males, and those with left ventricular dysfunction 1.
Heart failure creates an arrhythmogenic substrate through structural and electrical remodeling of the atria, with extensive atrial fibrosis 1, 2.
Cardiomyopathies, including hypertrophic cardiomyopathy and dilated cardiomyopathy, are associated with increased atrial fibrillation risk 1.

Alcohol intake, or "holiday heart syndrome," can cause atrial fibrillation through acute consumption or chronic excessive use 3, 1.
Hyperthyroidism must always be evaluated in newly diagnosed atrial fibrillation as a potentially reversible cause 1, 2.
Acute myocardial infarction portends a worse prognosis compared to pre-infarct atrial fibrillation or sinus rhythm 3, 1.
Acute infections, including viral and bacterial infections, myocarditis, and pericarditis, trigger atrial fibrillation through inflammatory processes 1.
Pulmonary conditions, including pulmonary embolism, chronic obstructive pulmonary disease, and sleep apnea syndrome, contribute to atrial fibrillation risk 1, 2.

Atrial fibrosis is the most common structural finding, causing heterogeneous electrical conduction and creating multiple reentry circuits 2.
Renin-angiotensin-aldosterone system activation generates profibrotic factors, including transforming growth factor-beta 1, inflammatory mediators, and oxidative stress 1, 2.
Calcium handling abnormalities result from high atrial rates and early cardiomyocyte reactivation, with elevated diastolic calcium and intracellular calcium storage 2.
Ion channel dysfunction, both acquired and genetic, alters atrial refractoriness and promotes triggered electrical activity 2.
Autonomic dysregulation with elevated vagal tone and increased sympathetic activity contributes to ectopic activity 2.

Obesity promotes atrial fibrillation through left atrial dilation, with progressive enlargement correlating with increasing body mass index 2.
Diabetes mellitus, particularly in women, increases risk through metabolic effects on atrial tissue 2.
Chronic kidney disease contributes through multiple mechanisms, including volume overload and uremic toxins 2.

Approximately 30% to 45% of paroxysmal cases and 20% to 25% of persistent cases occur in younger patients without demonstrable underlying disease 3.
Inflammatory infiltrates and fibrosis may be present even in patients without recognized structural heart disease 2.

Mutations in ion-channel genes associated with long QT syndrome, Brugada syndrome, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy cause atrial fibrillation in structurally normal hearts 2.
Common genetic variants at 17 independent loci, particularly on chromosome 4q25 near the PITX2 gene, predispose to atrial fibrillation 2.

Always screen for reversible causes in new-onset atrial fibrillation: hyperthyroidism, acute alcohol intake, infections, and pulmonary conditions 1, 2.
Do not overlook atrial fibrillation without obvious structural disease on standard imaging, as inflammatory infiltrates and early fibrosis may be present at the cellular level 2.