What causes P-R (P-R interval) prolongation?

Causes of P-R Prolongation

P-R interval prolongation (>200 ms) can be caused by numerous conditions affecting the conduction system, most commonly involving the AV node, with both pathological and physiological etiologies. 1

Anatomical Classification of P-R Prolongation

P-R prolongation, also known as first-degree AV block, represents delayed conduction that can occur at different levels:

• Most commonly occurs at the level of the AV node 1
• Can also occur within the His bundle (intra-Hisian) 1
• Less commonly occurs below the His bundle (infra-Hisian) 1

Etiological Categories

Congenital/Genetic Causes

• Congenital heart defects (e.g., L-transposition of great arteries) 1
• Genetic mutations (e.g., SCN5A mutations) 1

Infectious Causes

• Lyme carditis 1
• Bacterial endocarditis with perivalvar abscess 1
• Acute rheumatic fever 1
• Chagas disease 1
• Toxoplasmosis 1

Inflammatory/Infiltrative Conditions

• Myocarditis 1
• Amyloidosis 1
• Cardiac sarcoidosis 1
• Rheumatologic diseases:
  • Systemic sclerosis 1
  • Systemic lupus erythematosus 1
  • Rheumatoid arthritis 1
  • Reactive arthritis (Reiter's syndrome) 1

Cardiomyopathies

• Idiopathic cardiomyopathy 1
• Valvular cardiomyopathy 1
• Hypertrophic cardiomyopathy 1

Ischemic Causes

• Acute myocardial infarction 1
• Coronary ischemia without infarction (unstable angina, variant angina) 1
• Chronic ischemic cardiomyopathy 1

Degenerative Causes

• Lev's and Lenegre's diseases (progressive cardiac conduction disease) 1
• Age-related degeneration (more common after the sixth decade) 2

Vagotonic-Associated Causes

• Increased vagal tone 1
• Sleep, obstructive sleep apnea 1
• High-level athletic conditioning 1
• Neurocardiogenic mechanisms 1

Metabolic/Endocrine Disorders

• Acid-base disorders 1
• Poisoning/overdose (e.g., mercury, cyanide, carbon monoxide, mad honey) 1
• Thyroid disease (both hypothyroidism and hyperthyroidism) 1
• Adrenal disease (e.g., pheochromocytoma, hypoaldosteronism) 1

Other Diseases

• Neuromuscular diseases (e.g., myotonic dystrophy, Kearns-Sayre syndrome, Erb's dystrophy) 1
• Lymphoma 1

Iatrogenic/Medication-Related Causes

• Beta blockers 1
• Calcium channel blockers (verapamil, diltiazem) 1
• Digoxin 1, 3
• Antiarrhythmic drugs 1
• Nutraceuticals 1
• Post-catheter ablation (especially slow pathway ablation for AVNRT) 1, 4, 5
• Post-cardiac surgery, especially valve surgery 1
• Transcatheter aortic valve replacement (TAVR) 1
• Alcohol septal ablation 1

Clinical Significance

• PR prolongation may be benign in many cases, especially in younger individuals 6
• Can be associated with increased risk of atrial arrhythmias, heart failure, and mortality in some populations 2
• May cause symptoms resembling pacemaker syndrome (pseudo-pacemaker syndrome) when severely prolonged 5
• In the setting of bifascicular block, PR prolongation is often at the AV node level and does not necessarily predict progression to higher-degree AV block 1
• In patients taking digoxin, PR prolongation may be an early sign of toxicity, especially in children 3

Special Considerations

• PR prolongation after slow pathway ablation for AVNRT is generally associated with a benign prognosis 4
• In acute coronary syndromes, PR prolongation may be associated with more extensive coronary disease but doesn't consistently predict adverse outcomes 7
• In patients with pre-existing conduction system disease, medications that prolong PR interval should be used with caution 3