What is the pathophysiology of bradycardia?

Pathophysiology of Bradycardia

Bradycardia results from complex electrophysiologic and structural remodeling affecting the cardiac conduction system, primarily involving dysfunction in the sinoatrial node, atrioventricular node, or His-Purkinje system. 1

Sinus Node Dysfunction (SND)

The sinoatrial node consists of specialized tissue with unique properties:

• Cellular composition: Complex matrix of pacemaker cells, transitional cells, endothelial cells, fibroblasts, and extracellular scaffolding 1
• Electrical properties: Characterized by unique ion channel and connexin expression profiles that generate chronotropic automaticity 1
• Structural support: Connective tissue strands electrically insulate pacemaker cells from atrial myocardial tissue, protecting them from hyperpolarization effects of adjacent myocytes 1

Age-Related Changes

• Increased cardiac fibrosis correlates with slower heart rates and prolonged sinoatrial conduction times 1
• Histopathologic studies show association between extensive fibrosis and sinus node dysfunction 1
• Fibrosis of the sinus node often correlates with fibrosis in the atrioventricular node 1

Genetic Factors

• Genome-wide association analyses have identified multiple loci in ion channel and channel-interacting proteins related to heart rate regulation 1
• Genetic variants in multiple genes contribute to inherited sinus node dysfunction or progressive cardiac conduction disorders 2

Atrioventricular Conduction Disorders

Bradycardia can result from:

• First-degree AV block
• Second-degree AV block (types I and II)
• Third-degree (complete) heart block 3

These conduction disturbances may occur due to:

• Myocardial ischemia/infarction with necrosis of conduction system 4
• Fibrosis of the AV node 1
• Altered autonomic influence 4
• Structural heart disease

Autonomic Nervous System Regulation

Heart rate is regulated through a complex interplay between:

• Parasympathetic system: Dominant during expiration, causing heart rate deceleration via the vagus nerve 5

  • Produces high-frequency oscillations (0.15-0.45 Hz) in heart rate variability
  • Primarily affects the sinoatrial node

• Sympathetic system: More active during inspiration, contributing to heart rate acceleration 5

  • Influences low-frequency oscillations (0.04-0.15 Hz) in heart rate variability

Central Nervous System Integration

• The prefrontal cortex and amygdala regulate heart rate through pathways involving the nucleus ambiguus, dorsal nucleus of the vagus nerve, and the vagus nerve itself 1
• This neurovisceral integration model explains how central and autonomic nervous systems interact to control heart rate 5

Clinical Manifestations

Symptoms of bradycardia correlate with the severity of rate reduction and include:

• Syncope (present in 50% of patients with SND requiring pacemakers) 1
• Dizziness or lightheadedness
• Fatigue and exercise intolerance
• Dyspnea
• Heart failure 1

Common Etiologies

1. Intrinsic causes:

   • Age-related degeneration and fibrosis
   • Ischemic heart disease/myocardial infarction
   • Congenital heart disease
   • Infiltrative diseases

2. Extrinsic causes:

   • Drug toxicity (e.g., digitalis)
   • Electrolyte abnormalities
   • Inflammatory conditions (e.g., Lyme disease)
   • Transient injury during cardiac surgery 1
   • Increased vagal tone (common in athletes)

Prognostic Implications

• Asymptomatic sinus bradycardia has not been associated with adverse outcomes 1
• Symptomatic bradycardia is associated with increased risk of cardiovascular events including syncope, atrial fibrillation, and heart failure 1
• Chronotropic incompetence (inability to increase heart rate with exertion) correlates with increased risk of cardiovascular death and overall mortality 1

Key Considerations in Evaluation

• Correlation between symptoms and bradycardia is considered the "gold standard" for diagnosis 1
• Distinguish pathological bradycardia from physiological sinus bradycardia (as occurs in athletes) 1
• Identify potentially reversible causes before considering permanent pacing therapy 1

Understanding the pathophysiology of bradycardia is essential for appropriate clinical management, as treatment approaches differ based on underlying mechanisms, symptom severity, and whether the cause is reversible or permanent.