Causes of Atrial Fibrillation
Atrial fibrillation is primarily caused by structural heart disease, cardiovascular risk factors, and age-related changes, with valvular heart disease, hypertension, and coronary artery disease being the most common underlying conditions. 1
Cardiovascular Conditions Associated with AF
Structural Heart Disease
- Valvular heart disease: Most commonly mitral valve disease 1, 2
- Coronary artery disease: Causes ischemia and scarring 1, 2
- Hypertension: Particularly when left ventricular hypertrophy is present 1, 2
- Causes ventricular diastolic abnormalities and increased left atrial pressure
- Found in a significant proportion of AF patients
- Cardiomyopathies: 1, 2
- Hypertrophic cardiomyopathy
- Dilated cardiomyopathy
- Restrictive cardiomyopathies (amyloidosis, hemochromatosis, endomyocardial fibrosis)
- Congenital heart disease: Especially atrial septal defect in adults 1, 2
- Other cardiac conditions: 1
- Mitral valve prolapse (with or without regurgitation)
- Calcification of the mitral annulus
- Cardiac tumors
- Constrictive pericarditis
- Idiopathic dilation of the right atrium
Pathophysiological Mechanisms
Atrial fibrosis and remodeling: 1
- Progressive structural changes in atrial tissue
- Loss of atrial muscle mass
- Patchy fibrosis juxtaposed with normal atrial fibers
- Age-dependent loss of atrial myocardium (0.5-1.0% per year)
Altered calcium homeostasis: 1
- High atrial rates elevate diastolic calcium levels
- Changes in ion channels controlling calcium reuptake and release
- Spontaneous electrical activity due to abnormal calcium handling
- Genetic or acquired changes in ion channel expression
- Altered post-translational regulation of ion channels
Non-Cardiac Conditions
- Alcohol intake ("holiday heart syndrome")
- Surgery
- Electrocution
- Acute infections
- Myocardial infarction
- Pericarditis/myocarditis
- Pulmonary embolism or other pulmonary conditions
Metabolic and systemic conditions: 1, 2
- Hyperthyroidism
- Obesity (found in 25% of AF patients)
- Diabetes mellitus (found in 20% of AF patients)
- Chronic kidney disease (present in 10-15% of AF patients)
- Sleep apnea syndrome
- Chronic obstructive pulmonary disease (COPD) (found in 10-15% of AF patients)
Autonomic nervous system imbalance: 2
- Vagal predominance (common in athletes)
- Adrenergic predominance
Age-Related Factors
- Aging: 1, 2
- Increases risk of developing AF
- Associated with left atrial enlargement
- Reduced left atrial appendage flow velocity
- Spontaneous echo contrast
- Age-related prothrombotic diathesis
- Increased atrial fibrosis and stiffness
Lone Atrial Fibrillation
- Approximately 30-45% of paroxysmal cases and 20-25% of persistent cases occur without demonstrable underlying disease 1
- May present as isolated or familial arrhythmia
- Underlying disease may appear over time
Risk Factors for Progression
- The presence of multiple risk factors has an additive effect on perpetuation of AF 1
- Successful treatment of underlying conditions may eliminate AF in some cases 1, 2
- Early intervention targeting modifiable risk factors may slow or prevent progression 2
Clinical Implications
- Understanding the underlying cause is crucial for effective management 2
- Treatment should target both the arrhythmia and underlying causes when possible 2
- AF can lead to tachycardiomyopathy, a reversible cause of heart failure 2
- Patients with AF have significantly increased risk of stroke, heart failure, myocardial infarction, dementia, chronic kidney disease, and mortality 3
Understanding these causes and mechanisms is essential for implementing effective prevention strategies and treatment approaches tailored to the specific underlying pathophysiology in each patient with atrial fibrillation.