Causes of Atrial Fibrillation
Atrial fibrillation results from a combination of cardiac structural abnormalities, systemic conditions, and acute triggers that create an arrhythmogenic substrate through atrial fibrosis, electrical remodeling, and ectopic firing mechanisms. 1
Cardiac Structural Causes
The most common cardiac causes involve conditions that increase atrial pressure, promote dilation, and trigger structural remodeling:
Valvular heart disease, particularly mitral valve disease, significantly increases AF risk regardless of severity but correlates strongly with left atrial enlargement 1. The occurrence is unrelated to the severity of mitral stenosis or regurgitation but is more common with enlarged left atrium and heart failure 2.
Hypertension, especially when left ventricular hypertrophy is present, creates increased left atrial pressure and promotes atrial dilation through altered wall stress 3. This represents one of the most important predictive factors for developing AF 2.
Coronary artery disease is a significant risk factor, occurring predominantly in older patients, males, and those with left ventricular dysfunction 1, 2.
Heart failure creates an arrhythmogenic substrate through structural and electrical remodeling of the atria, with extensive atrial fibrosis 1, 3.
Cardiomyopathies, including hypertrophic cardiomyopathy and dilated cardiomyopathy, are associated with increased AF risk 1.
Acute and Reversible Causes
These triggers can cause AF that may resolve with treatment of the underlying condition:
Alcohol intake ("holiday heart syndrome") through acute consumption or chronic excessive use 4, 1.
Hyperthyroidism must always be evaluated in newly diagnosed AF as a potentially reversible cause 1, 3.
Acute myocardial infarction, which portends a worse prognosis compared to pre-infarct AF or sinus rhythm 4, 1.
Acute infections, including viral and bacterial infections, myocarditis, and pericarditis, trigger AF through inflammatory processes 1.
Pulmonary conditions, including pulmonary embolism, chronic obstructive pulmonary disease, and sleep apnea syndrome 1, 3.
Post-surgical states and electrocution 4.
Pathophysiological Mechanisms
The underlying mechanisms that perpetuate AF involve:
Atrial fibrosis is the most common structural finding, causing heterogeneous electrical conduction and creating multiple reentry circuits 3. The aging heart loses cardiomyocytes at approximately 0.5-1.0% per year, with fibrous tissue replacing lost myocytes 3.
Renin-angiotensin-aldosterone system activation generates profibrotic factors including transforming growth factor-beta 1, inflammatory mediators, and oxidative stress 1, 3.
Calcium handling abnormalities result from high atrial rates and early cardiomyocyte reactivation, with elevated diastolic calcium and intracellular calcium storage 3.
Ion channel dysfunction, both acquired and genetic, alters atrial refractoriness and promotes triggered electrical activity 3.
Autonomic dysregulation with elevated vagal tone and increased sympathetic activity contributes to ectopic activity 3.
Non-Cardiac Systemic Causes
Obesity promotes AF through left atrial dilation, with progressive enlargement correlating with increasing body mass index 3.
Diabetes mellitus, particularly in women, increases risk through metabolic effects on atrial tissue 3.
Chronic kidney disease contributes through multiple mechanisms including volume overload and uremic toxins 3.
Lone Atrial Fibrillation
Approximately 30% to 45% of paroxysmal cases and 20% to 25% of persistent cases occur in younger patients without demonstrable underlying disease 4. However, inflammatory infiltrates and fibrosis may be present even in patients without recognized structural heart disease 3.
Genetic Factors
Mutations in ion-channel genes associated with long QT syndrome, Brugada syndrome, hypertrophic cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy cause AF in structurally normal hearts 3.
Common genetic variants at 17 independent loci, particularly on chromosome 4q25 near the PITX2 gene, predispose to AF 3.
Critical Clinical Pitfalls
Always screen for reversible causes in new-onset AF: hyperthyroidism, acute alcohol intake, infections, and pulmonary conditions 1, 3.
Do not overlook AF without obvious structural disease on standard imaging, as inflammatory infiltrates and early fibrosis may be present at the cellular level 3.
Recognize that multiple factors often coexist, with aging, hypertension, and structural heart disease frequently combining to increase AF risk 2, 5.