Causes of Atrial Fibrillation
Atrial fibrillation results from a combination of cardiac structural disease, systemic conditions, and reversible triggers that create an arrhythmogenic substrate through atrial remodeling, fibrosis, and electrical dysfunction.
Cardiac Structural Causes
Valvular heart disease, particularly mitral valve disease, significantly increases AF risk regardless of severity but correlates strongly with left atrial enlargement 1. The risk is present with both mitral stenosis and mitral regurgitation 2.
Hypertension is the most commonly encountered risk factor in patients with incident AF, associated with a 1.8-fold increase in developing new-onset AF 1, 3. The mechanism involves left ventricular hypertrophy and atrial structural remodeling 1, 4.
Heart failure creates an arrhythmogenic substrate through structural and electrical remodeling of the atria, with extensive atrial fibrosis 1, 5. This represents one of the strongest predictors of AF development 1, 2.
Coronary artery disease increases AF risk, particularly in older patients, males, and those with left ventricular dysfunction 1, 5, 2.
Cardiomyopathies including hypertrophic cardiomyopathy, dilated cardiomyopathy, and restrictive cardiomyopathies (amyloidosis, hemochromatosis) all significantly elevate AF risk 5, 2.
Reversible and Acute Causes
Hyperthyroidism must be evaluated in every patient with newly diagnosed AF as a potentially reversible cause 1. This is a Class I recommendation requiring thyroid function testing 5.
Acute alcohol intake ("holiday heart syndrome") or chronic excessive alcohol use can trigger AF 1, 5. This represents a modifiable risk factor.
Acute medical conditions that can precipitate AF include:
- Myocardial infarction (portends worse prognosis when AF develops acutely) 1, 5
- Pulmonary embolism 1, 5
- Pneumonia and acute infections 5
- Pericarditis and myocarditis 1, 5
Cardiothoracic surgery commonly causes postoperative AF as an early complication 1.
Non-Cardiac Systemic Conditions
Obesity is found in 25% of AF patients and increases risk through left atrial dilation, with graded increase in atrial size as body mass index rises 1. Weight reduction may decrease AF risk 1.
Diabetes mellitus requiring medical treatment is present in 20% of AF patients and contributes to atrial damage 1, 2, 4. In women specifically, diabetes is an important predictive factor 4.
Sleep apnea, especially with concurrent hypertension, diabetes, and structural heart disease, contributes to AF through apnea-induced increases in atrial pressure, atrial size, and autonomic changes 1, 5.
Chronic obstructive pulmonary disease is found in 10-15% of AF patients, though it may be more a marker for general cardiovascular risk than a specific AF trigger 1.
Chronic kidney disease is present in 10-15% of AF patients and may increase risk of AF-related cardiovascular complications 1.
Pathophysiological Mechanisms
Structural atrial remodeling is the fundamental mechanism, characterized by:
- Fibrosis with proliferation of fibroblasts into myofibroblasts 1, 5
- Enhanced connective tissue deposition creating electrical dissociation between muscle bundles 1
- Local conduction heterogeneities facilitating multiple small reentrant circuits 1, 5
- Atrial dilation, hypertrophy, and altered wall stress 5, 6
Renin-angiotensin-aldosterone system activation promotes AF through:
- Stimulation of fibrosis and production of growth-related factors 1, 6
- Increased intracellular calcium, hypertrophy, and apoptosis 1
- Cytokine release, inflammation, and oxidative stress 1, 6
- Modulation of ion channel and gap-junction dynamics 1
In primary hyperaldosteronism, AF incidence is significantly increased due to aldosterone's profibrotic and proinflammatory effects 1, 6.
Age and Demographic Factors
Advancing age is the strongest predictor, with AF prevalence increasing from <0.5% at ages 40-50 years to 5-15% at age 80 years 1. The mechanism involves age-dependent loss and isolation of atrial myocardium with associated conduction disturbances 1.
Male sex confers higher risk, with men affected more often than women 1.
European ancestry and family history represent genetic risk factors 1.
Lone Atrial Fibrillation
Approximately 30% of paroxysmal AF and 20-25% of persistent AF occurs in patients without demonstrable underlying disease ("lone AF") 1, 2, 4. However, underlying cardiac structural changes related to aging may still be present even in elderly patients classified as having lone AF 1.
Clinical Pitfalls
A critical caveat: sparse data support the notion that AF occurring with "reversible" causes is truly cured after treating the underlying condition 1. Even after successful treatment of precipitating factors, AF may recur, requiring careful long-term follow-up 1.
The population-attributable risk analysis shows that 56% of AF cases could be explained by one or more common modifiable risk factors 1. This suggests prevention through blood pressure control, weight loss, and management of other risk factors may reduce AF incidence 1.