Causes of Atrial Fibrillation and Atrial Flutter
Atrial fibrillation and atrial flutter develop due to a combination of structural abnormalities, electrical remodeling, and triggering factors that create an arrhythmogenic substrate in the heart tissue, leading to chaotic electrical activity that disrupts normal cardiac contraction.
Pathophysiological Mechanisms
Structural Changes
- Atrial fibrosis: A common feature in both experimental and human AF, making the atria more sensitive to profibrotic signaling 1
- Atrial dilatation: Progressive enlargement of the atria creates more space for reentrant circuits 2
- Inflammation: Contributes to structural remodeling and heterogeneous conduction 1
- Hypertrophy: Increases atrial wall thickness and alters conduction properties 1
Electrical Remodeling
- Shortened refractory periods: Progressive shortening of atrial effective refractory periods supports the concept that "atrial fibrillation begets atrial fibrillation" 1
- Ion channel dysfunction: Alters impulse formation and propagation 1
- Abnormal calcium handling: Disrupts normal electrical activity and promotes triggered activity 2
Risk Factors and Triggers
Cardiac Conditions
- Valvular heart disease: Particularly mitral valve disease 2
- Heart failure: Promotes atrial structural and electrical changes through hemodynamic and mechanical mechanisms 1
- Coronary artery disease: Causes ischemia and scarring 2
- Hypertension: Increases left atrial pressure and promotes structural remodeling 2
- Cardiomyopathies: Alter cardiac structure and function 1
- Congenital heart disease: Creates abnormal hemodynamics 1
Acute Temporary Causes
- Alcohol intake ("holiday heart syndrome"): Acute toxic effect on cardiac electrophysiology 2
- Surgery: Particularly cardiac and thoracic surgery 2
- Electrocution: Causes electrical injury to the heart 2
- Myocardial infarction: Acute ischemia and inflammation 2
- Pericarditis and myocarditis: Inflammatory processes affecting the heart 2
- Pulmonary embolism: Increases right heart pressures 2
- Pulmonary diseases: Alter cardiac hemodynamics and oxygenation 2
Systemic Factors
- Hyperthyroidism: Increases heart rate and shortens action potential duration 3, 4
- Metabolic disorders: Disrupt normal cardiac function 2
- Obesity: Associated with LA enlargement and increased risk of AF 2
- Weight reduction has been linked to regression of LA enlargement 2
- Diabetes mellitus: Contributes to atrial fibrosis and remodeling 2
- Chronic kidney disease: Alters electrolyte balance and promotes fibrosis 2
- Sleep apnea: Causes intermittent hypoxia and autonomic changes 1
- Aging: Associated with increased atrial fibrosis and stiffness 2
- AF prevalence increases with age, reaching 9% in octogenarians 2
Drug-Induced Causes
- Cardiovascular drugs: Can exacerbate risk of developing AF 2
- Non-cardiovascular drugs: May trigger AF through various mechanisms 2
- Anticancer drugs: Associated with increased risk of AF 2
- Antiarrhythmic drugs: Can paradoxically promote conversion of AF to atrial flutter 5
Autonomic Influences
- Changes in sympathetic or parasympathetic tone: Alter atrial action potential and refractory periods 1
- Vagal stimulation: Shortens atrial refractory periods, potentiating initiation and maintenance of AF 1
Other Factors
- Long-term endurance exercise: May increase incidence of AF and atrial flutter in younger populations 6
- Genetic factors: Mutations in ion-channel genes and common genetic variants increase susceptibility 1
- Lone AF: Occurs in approximately 30-45% of paroxysmal AF and 20-25% of persistent AF cases without demonstrable underlying disease 2
Clinical Implications
- AF is often progressive, with paroxysmal episodes becoming more frequent and longer over time
- Structural heart disease and other risk factors accelerate progression
- Early intervention targeting modifiable risk factors may slow or prevent progression
- Treatment of underlying causes (e.g., hyperthyroidism, sleep apnea, obesity) can reduce AF burden
- Male sex, increasing age, ischemic heart disease, congestive heart failure, and heart valve disease are associated with increased risk of AF in patients with hyperthyroidism 4
Understanding these mechanisms is crucial for effective prevention and treatment strategies, including rhythm control, rate control, and upstream therapy targeting structural remodeling.