Causes of Prolonged PR Interval
Primary Etiological Categories
Prolonged PR interval most commonly results from delayed conduction at the AV node level, though it can occur anywhere in the conduction system from atria through the His-Purkinje system. 1, 2
Medication-Induced Causes
- Beta-blockers, calcium channel blockers (verapamil, diltiazem), and digoxin are the most common iatrogenic causes of PR prolongation through their negative dromotropic effects on the AV node 2, 3, 4
- Verapamil and diltiazem prolong AV nodal conduction and refractoriness, with verapamil causing minimal PR prolongation at doses below 480 mg/day, typically resulting only in asymptomatic first-degree block 4
- Digoxin produces PR prolongation as an expected pharmacologic effect and can cause therapeutic doses to precipitate heart block in patients with pre-existing sinoatrial or AV conduction disorders 3
- Combination therapy with both a calcium channel blocker and beta-blocker rarely causes second-degree AV block but carries additive effects on AV nodal conduction that can result in advanced or complete heart block 3, 4
Cardiac Structural and Ischemic Causes
- Acute myocardial infarction and coronary ischemia can cause PR prolongation through damage to the conduction system 2
- Cardiomyopathies including idiopathic, valvular, and hypertrophic subtypes lead to PR prolongation 2
- Congenital heart defects such as L-transposition of great arteries are associated with prolonged PR intervals 2
Infectious and Inflammatory Causes
- Lyme carditis, bacterial endocarditis, and acute rheumatic fever represent important infectious etiologies that require specific treatment 2
- Myocarditis and infiltrative conditions such as amyloidosis cause PR prolongation through direct involvement of the conduction system 2
Degenerative and Genetic Causes
- Lev's and Lenegre's diseases represent progressive degenerative processes affecting the conduction system 2
- SCN5A mutations and other genetic abnormalities can manifest as isolated PR prolongation 2
Physiologic and Metabolic Causes
- Increased vagal tone and sleep represent physiologic causes that are typically benign 2
- Metabolic derangements including acid-base disorders and thyroid disease (particularly hypothyroidism) can prolong the PR interval 2
- Highly trained athletes may demonstrate physiologic PR prolongation that should not be confused with pathologic bradyarrhythmias 1
Anatomic Localization Considerations
- When the QRS complex is narrow, the conduction delay is usually in the AV node and rarely within the His bundle 1
- When the QRS is wide, the conduction delay may be either in the AV node or in the His-Purkinje system, and only a His bundle electrogram can locate it precisely 1
- In the setting of bifascicular block with PR prolongation, the delay is often at the AV node level and does not necessarily predict progression to higher-degree AV block 1, 2
Critical Clinical Pitfalls
- Do not assume all first-degree AV block is benign—PR intervals ≥300 ms can cause hemodynamic compromise similar to pacemaker syndrome, with atrial contraction occurring before complete atrial filling, compromising ventricular filling and increasing pulmonary capillary wedge pressure 1, 5
- Exercise-induced first-degree AV block occurring at the end of exercise or during recovery is uncommon and may indicate underlying conduction system disease requiring further evaluation 1
- Digoxin-induced PR prolongation and ST segment depression should not by themselves be considered digoxin toxicity, though therapeutic doses can cause heart block in patients with pre-existing conduction disorders 3