What causes left atrial enlargement in the absence of atrial fibrillation (AF)?

Causes of Left Atrial Enlargement in the Absence of Atrial Fibrillation

Left atrial enlargement in the absence of atrial fibrillation is most commonly caused by conditions that create pressure or volume overload on the left atrium, including valvular heart disease (especially mitral valve disease), hypertension with left ventricular hypertrophy, heart failure, and cardiomyopathies.

Primary Cardiovascular Causes

Valvular Heart Disease

• Mitral valve disease is a leading cause of left atrial enlargement 1
  • Mitral stenosis causes pressure overload
  • Mitral regurgitation causes volume overload
  • Mitral valve prolapse (with or without regurgitation)
  • Calcification of the mitral annulus

Hypertension and Left Ventricular Changes

• Hypertension, particularly when associated with left ventricular hypertrophy 1, 2
  • Creates increased left ventricular filling pressures
  • Leads to diastolic dysfunction
  • Activates RAAS (renin-angiotensin-aldosterone system) which promotes fibrosis and remodeling

Heart Failure

• Left ventricular systolic dysfunction 1
• Heart failure with preserved ejection fraction (HFpEF) 1
  • Characterized by diastolic dysfunction
  • Increased left ventricular end-diastolic pressure transmits backward to the left atrium

Cardiomyopathies

• Hypertrophic cardiomyopathy 1, 2
• Dilated cardiomyopathy 1, 2
• Restrictive cardiomyopathies 1
  • Amyloidosis
  • Hemochromatosis
  • Endomyocardial fibrosis

Congenital Heart Disease

• Atrial septal defect in adults 1, 2
• Other congenital heart defects with left-to-right shunting

Non-Cardiac and Systemic Causes

Metabolic and Endocrine Disorders

• Obesity 1, 2
  • Strong association between increasing BMI and left atrial size
  • Weight reduction has been linked to regression of LA enlargement

Pulmonary Conditions

• Pulmonary hypertension 1
• Sleep apnea syndrome 1, 2
  • May cause LA enlargement through multiple mechanisms:
    • Hypoxia
    • Changes in pulmonary dynamics
    • Autonomic tone alterations
    • Associated systemic hypertension

Other Conditions

• Coronary artery disease 1, 3
  • Particularly when associated with left ventricular dysfunction
• Pericardial disease (constrictive pericarditis) 1
• Cardiac tumors (atrial myxoma) 1, 3
• Idiopathic dilation of the right atrium 3

Pathophysiological Mechanisms

The primary mechanisms leading to left atrial enlargement include:

1. Pressure overload - increased afterload on the left atrium due to:

   • Mitral stenosis
   • Left ventricular diastolic dysfunction
   • Increased left ventricular end-diastolic pressure

2. Volume overload - increased preload due to:

   • Mitral regurgitation
   • Left-to-right shunts
   • High output states

3. Myocardial changes 1:

   • Fibrosis
   • Inflammation
   • Remodeling due to activation of RAAS

Clinical Significance

Left atrial enlargement is an important finding even in the absence of AF because:

• It serves as a marker of chronic elevated left ventricular filling pressures 4
• It's a negative prognostic factor for survival in patients with stroke, heart failure, and myocardial infarction 4
• It may be a precursor to the development of atrial fibrillation 1
• LA volume progressively increases with worsening diastolic dysfunction 4

Diagnostic Considerations

When evaluating left atrial enlargement without AF, it's important to:

• Assess for valvular heart disease, especially mitral valve pathology
• Evaluate left ventricular systolic and diastolic function
• Screen for hypertension and left ventricular hypertrophy
• Consider obesity as a potential contributing factor
• Evaluate for sleep apnea, particularly in patients with obesity or hypertension

By identifying and addressing the underlying cause of left atrial enlargement, progression to atrial fibrillation may potentially be prevented in some cases.