Paroxysmal Atrioventricular Block

Authors, Journal, Affiliations, Type, DOI

• El-Sherif N, Jalife J
• Heart Rhythm, 2009
• Review article / editorial
• DOI: not available from manuscript

Overview

Paroxysmal AV block (PAVB) is the sudden onset of complete AV block with prolonged ventricular asystole, distinct from gradual AV block. El-Sherif and Jalife review two mechanistic forms — tachycardia-dependent (TD-PAVB) and pause-dependent (PD-PAVB) — both rooted in diseased His-Purkinje tissue with postrepolarization refractoriness. The paper's central argument is that the classical terms "phase 3 block" and "phase 4 block" are mechanistic misnomers that should be abandoned in favor of TD-PAVB and PD-PAVB. Experimental canine models and in vitro Purkinje fiber recordings are used to support the proposed mechanisms.

Keywords

Paroxysmal AV block, tachycardia-dependent AV block, pause-dependent AV block, His-Purkinje system, concealed conduction, postrepolarization refractoriness, phase 4 depolarization

Key Takeaways

Clinical Overview of PAVB

• PAVB presents as sudden complete AV block with ventricular asystole lasting several seconds, causing syncope or near-syncope
• In a series of 22 patients investigated with an implantable loop recorder for syncope, 17 had documented PAVB episodes associated with syncope
• Most patients eventually require permanent pacemaker; in a few, early emergence of a stable escape rhythm prevents significant symptoms
• Association with sudden cardiac death is difficult to ascertain; most patients survive episodes but serious injury from syncope can occur
• Although the majority of PAVB cases are tachycardia-dependent, pause-dependent cases have also been well described

TD-PAVB (Tachycardia-Dependent)

• Since Mobitz's early observations, Mobitz type II AV block has been closely associated with PAVB and Stokes-Adams syndrome
• Atrial rate acceleration — spontaneous or pharmacological (including isoprenaline) — is the classic trigger
• PAVB can also be induced by rapid ventricular pacing ("fatigue" phenomenon): retrograde invasion and repetitive depolarization of Purkinje fibers at the critical block site
• In the authors' series of 42 cases, 10 underwent conduction system study: 7 had intra-Hisian block and only 3 had infra-Hisian block — suggesting the His bundle is the predominant site even when bundle branch block is present
• Intra-His bundle block is frequently misdiagnosed as infra-Hisian or AV nodal block during EPS when the h₁ deflection of a split His potential is overlooked (Figure 1)
• Patients with chronic stable His-Purkinje lesions that respond to rapid atrial pacing with 2:1 or higher-grade block (but NOT PAVB) may lack the propensity for repetitive concealed conduction, or AV nodal refractoriness may prevent the critical short cycle needed for PAVB

Electrophysiological Mechanism of TD-PAVB

• Normal cells (phase 3 refractoriness): resting potential ~−90 mV; refractoriness ends with repolarization; a late-phase-3 stimulus produces a small AP; a post-repolarization stimulus produces a full AP — voltage-dependent block
• Diseased cells (postrepolarization refractoriness): depolarized resting potential; smaller, slower, shorter APs; recovery of excitability extends beyond repolarization due to the increased relative importance of outward repolarizing currents (I_K1, I_Kr, I_Ks) when inward depolarizing currents (I_Na, I_Ca) are reduced; a premature stimulus in early diastole fails even after full repolarization (subthreshold depolarization only) — the cell reaches threshold later in diastole, producing a slow-response AP with poor conduction
• Concealed conduction mechanism: A blocked impulse in the diseased His-Purkinje system leaves sufficient refractoriness that the next one or several impulses also block — self-perpetuating cascade of repetitive block
• This is analogous to concealed AV nodal conduction in AF: flutter at 300/min (2:1 → ventricular rate 150/min) paradoxically slows to lower rate in AF (550/min) because blocked impulses leave residual AV nodal refractoriness
• Experimental model (ischemic canine His-Purkinje after anteroseptal artery ligation): in vitro microelectrode recordings confirm postrepolarization refractoriness and rate-dependent repetitive block at cycle lengths far exceeding action potential duration (Figure 4)
• Conduction failure develops with only minimal increment of conduction delay before block (≤6 ms in experimental series) — the Mobitz type II equivalent

PD-PAVB (Pause-Dependent)

• Onset is ushered by a pause — compensatory pause after APB/VPB, spontaneous sinus slowing, or overdrive suppression of sinus rhythm after a fast atrial rhythm
• Classical (Singer-Lazzara-Hoffman 1967) explanation: phase 4 depolarization in diseased Purkinje fibers → membrane potential drifts to less negative values → reduced Na⁺ channel availability → conduction block. Rosenbaum et al. later defined PD-PAVB as "pause-dependent phase 4 AV block in diseased conduction system"
• Lee-Wellens-Josephson 2009 emphasis: understanding the mechanism and promptly recognizing PD-PAVB is essential to prevent asystole and sudden cardiac death
• Challenge to pure phase 4 explanation (Jalife et al., Circulation 1983): In isolated depressed Purkinje fibers (20 mM KCl, complete absence of phase 4 depolarization), a biphasic time course of excitability was demonstrated — early recovery at intermediate diastolic intervals, then loss of excitability at long diastolic intervals — replicating PD block without phase 4 depolarization (Figure 8)
• Phase 4 depolarization distal to a block zone may FACILITATE conduction (not cause block) by moving membrane potential toward threshold (Figure 6); phase 4 hyperpolarization impairs conduction and leads to block
• Alternative mechanism — source-sink mismatch: frequency-dependent changes in slow inward current (I_Ca) alter action potential amplitude in normally polarized Purkinje fibers proximal to a block zone → reduced electrotonic input → bradycardia-dependent conduction block, independent of maximal upstroke velocity or phase 4 depolarization
• Exit block with slow diastolic depolarization in fibers proximal to an impaired zone (not phase 4 depolarization per se) can cause bradycardia-dependent BBB; block requires absence of phase 4 depolarization in cells distal to the impairment
• Combined TD+PD PAVB exists: biphasic window — block at fast rates (TD), normal conduction at intermediate rates, block again at slow rates (PD)

Epilogue: Terminology

• "Phase 3 block" and "phase 4 block" are MISNOMERS — these terms incorrectly tie the mechanism to action potential phase rather than rate-dependence
• Appropriate terminology: tachycardia-dependent PAVB (TD-PAVB) and pause-dependent PAVB (PD-PAVB)
• "Phase 4 block" is particularly misleading because PD-PAVB can occur in the complete absence of phase 4 depolarization

Limitations of the Document

• Review/editorial format with no systematic methods section
• Only 10 of 42 clinical cases underwent electrophysiology study — site of block is uncertain in most cases
• Experimental data primarily from canine models and isolated Purkinje fiber preparations; extrapolation to intact human His-Purkinje network may not be fully accurate
• Published in 2009 — predates modern mapping and imaging capabilities for conduction system assessment
• No randomized data on management outcomes

Key Concepts Mentioned

• concepts/Paroxysmal-AV-Block — primary topic: TD-PAVB and PD-PAVB mechanisms
• concepts/Atrioventricular-Block — broader context; Mobitz type II association with PAVB
• concepts/Fascicular-Blocks — bundle branch block frequently coexists with PAVB

Key Entities Mentioned

• El-Sherif N — author; pioneered experimental PAVB research in canine ischemic models
• Jalife J — author; co-developed mechanistic framework for depressed Purkinje fiber conduction

Wiki Pages Updated

• wiki/sources/PAVB-HR-2009.md — created
• wiki/concepts/Paroxysmal-AV-Block.md — created
• wiki/concepts/Atrioventricular-Block.md — updated (PAVB section and source added)
• wiki/wikiindex.md — Paroxysmal-AV-Block entry added
• wiki/sourceindex.md — PAVB-HR-2009 entry added