What is the main cause of atrial fibrillation?

Main Cause of Atrial Fibrillation

There is no single "main" cause of atrial fibrillation—rather, it results from multiple interacting cardiovascular and systemic conditions, with hypertension, structural heart disease (particularly valvular disease), and advancing age being the most prevalent contributors in clinical practice. 1, 2

Most Common Associated Conditions

The epidemiological reality is that approximately 70-80% of AF patients have underlying organic heart disease, while only 20-30% present without demonstrable structural abnormalities ("lone AF"). 1, 3, 4

Cardiac Structural Causes (Most Prevalent)

• Hypertension is the single most common associated condition, particularly when left ventricular hypertrophy is present, creating increased left atrial pressure and promoting atrial dilation through altered wall stress. 1, 2

• Valvular heart disease, especially mitral valve disease, significantly increases AF risk regardless of severity but correlates strongly with left atrial enlargement. 1, 2, 5

• Coronary artery disease represents a significant risk factor, occurring predominantly in older patients, males, and those with left ventricular dysfunction. 2, 5, 3

• Heart failure creates an arrhythmogenic substrate through structural and electrical remodeling of the atria, with extensive atrial fibrosis. 2, 5

• Cardiomyopathies (hypertrophic and dilated) are associated with increased AF risk through direct atrial structural changes. 1, 5

Age as a Fundamental Risk Factor

• Advancing age is multifactorial in its effect: aging is associated with LA enlargement, reduced left atrial appendage flow velocity, age-related prothrombotic changes, and progressive atrial fibrosis with loss of atrial myocardium. 1

• The prevalence increases from <0.5% at age 40-50 years to 5-15% at age 80 years. 1

Acute and Reversible Causes (Critical to Identify)

Always screen for these reversible triggers in new-onset AF, as successful treatment often eliminates the arrhythmia:

• Hyperthyroidism must always be evaluated in newly diagnosed AF as a potentially reversible cause. 2, 5, 6

• Alcohol intake ("holiday heart syndrome") can trigger AF through acute consumption or chronic excessive use. 1, 5

• Acute myocardial infarction portends a worse prognosis compared to pre-infarct AF or sinus rhythm. 1, 5

• Acute infections, including myocarditis and pericarditis, trigger AF through inflammatory processes. 2, 5

• Pulmonary conditions (pulmonary embolism, COPD, sleep apnea) contribute through hemodynamic and hypoxic stress. 1, 2

• Post-cardiac or thoracic surgery AF is a common early complication. 1

Underlying Pathophysiological Mechanisms

Understanding the mechanisms helps explain why multiple conditions lead to the same arrhythmia:

• Atrial fibrosis is the most common structural finding, causing heterogeneous electrical conduction and creating multiple reentry circuits. 2, 6

• Renin-angiotensin-aldosterone system activation generates profibrotic factors (transforming growth factor-beta 1), inflammatory mediators, and oxidative stress. 2, 6

• Calcium handling abnormalities result from high atrial rates with elevated diastolic calcium and intracellular calcium storage. 2, 6

• Ion channel dysfunction (both acquired and genetic) alters atrial refractoriness and promotes triggered electrical activity. 2, 6

• Autonomic dysregulation with elevated vagal tone and increased sympathetic activity contributes to ectopic activity. 2, 6

Non-Cardiac Systemic Contributors

• Obesity promotes AF through left atrial dilation, with progressive enlargement correlating with increasing body mass index. 1, 2

• Diabetes mellitus, particularly in women, increases risk through metabolic effects on atrial tissue. 1, 2, 6

• Chronic kidney disease contributes through multiple mechanisms including volume overload and uremic toxins. 1, 2, 6

• Chronic obstructive pulmonary disease is found in 10-15% of AF patients and may be more a marker for cardiovascular risk than a specific predisposing factor. 1

• Sleep apnea, especially with hypertension and diabetes, may be pathophysiological through apnea-induced increases in atrial pressure and size. 1

Drug-Induced Atrial Fibrillation

• A progressively increasing number of cardiovascular, non-cardiovascular, and anticancer drugs may cause or exacerbate AF risk, though this is often overlooked in clinical practice. 1

Lone Atrial Fibrillation (Without Obvious Structural Disease)

• Approximately 30-45% of paroxysmal cases and 20-25% of persistent cases occur in younger patients without demonstrable underlying disease. 1, 2

• Critical pitfall: Do not overlook AF without obvious structural disease on standard imaging, as inflammatory infiltrates and early fibrosis may be present at the cellular level. 2, 6

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. 2, 6

• Common genetic variants at 17 independent loci, particularly on chromosome 4q25 near the PITX2 gene, predispose to AF. 2, 6

Clinical Approach to Identifying the Cause

In every new AF patient, systematically evaluate:

1. Reversible causes first: thyroid function, recent alcohol intake, active infection, pulmonary embolism, recent surgery. 2, 5, 6

2. Structural heart disease: echocardiography for valvular disease, LV function, chamber sizes, wall thickness. 1, 2

3. Cardiovascular risk factors: hypertension, diabetes, obesity (BMI), coronary disease history. 1, 2

4. Systemic conditions: renal function, pulmonary disease, sleep apnea screening. 1, 2

5. Medication review: identify potentially arrhythmogenic drugs. 1