Paroxysmal AV Block

Definition

Paroxysmal AV block (PAVB) is the sudden, unexpected development of complete AV block with prolonged ventricular asystole, occurring abruptly without warning in a patient who may have had partial (second-degree) AV block or even 1:1 conduction. It is distinct from gradual, predictable AV block. PAVB is divided into two forms by mechanism: tachycardia-dependent (TD-PAVB) — triggered by an increase in atrial rate — and pause-dependent (PD-PAVB) — paradoxically initiated by a pause. Both arise from diseased His-Purkinje tissue.

Key Concepts

Clinical Presentation

• Presents as syncope or near-syncope from ventricular asystole lasting several seconds
• 17/22 patients investigated with an implantable loop recorder for syncope had documented PAVB sources/PAVB-HR-2009 (high)
• Most patients require permanent pacemaker; in rare cases, an early escape rhythm prevents symptoms
• Association with sudden cardiac death is clinically suspected but difficult to ascertain; most patients survive episodes, though serious injury from syncope can occur

Site of Block

• The His bundle is the most common site of PAVB — demonstrated in 7 of 10 patients undergoing conduction system study in a 42-case series, even when bundle branch block was present on the ECG sources/PAVB-HR-2009 (high)
• Intra-His bundle block is frequently misidentified as infra-Hisian or AV nodal block at EPS when the h₁ component of a split His potential (H1-H2) is overlooked
• Only 3 of 10 cases had confirmed infra-Hisian block

TD-PAVB (Tachycardia-Dependent)

Trigger: Increase in atrial rate — spontaneous, pharmacological (isoprenaline), or via rapid atrial/ventricular pacing

Key association: Closely linked to Mobitz type II AV block — TD-PAVB occurs in close association with pre-existing Mobitz II second-degree block sources/PAVB-HR-2009 (high)

Electrophysiological mechanism (two steps):

1. Postrepolarization refractoriness in diseased His-Purkinje fibers: depolarized resting membrane potential → smaller, slower action potentials → outward repolarizing currents (I_K1, I_Kr, I_Ks) dominate during early diastole because inward currents (I_Na, I_Ca) are reduced → excitability recovery extends beyond the end of repolarization (unlike normal cells). A premature stimulus in early diastole produces only a subthreshold depolarization despite full repolarization. sources/PAVB-HR-2009 (high)

2. Rate-dependent concealed conduction: A blocked impulse in the diseased His-Purkinje system leaves residual refractoriness, causing the next impulse to also block — and so on, creating a self-perpetuating cascade of repetitive block. Directly analogous to concealed AV nodal conduction slowing the ventricular response in AF compared to flutter. sources/PAVB-HR-2009 (high)

• Conduction failure in TD-PAVB occurs with only minimal (≤6 ms) increment of conduction delay before block — the His-Purkinje equivalent of Mobitz II
• "Fatigue" phenomenon: rapid ventricular pacing can also provoke TD-PAVB via retrograde invasion and repetitive depolarization of the critical Purkinje site
• Experimental canine model (ischemic proximal His-Purkinje after anteroseptal artery ligation) replicates TD-PAVB with in vitro microelectrode recordings confirming postrepolarization refractoriness and repetitive block at cycle lengths far exceeding action potential duration sources/PAVB-HR-2009 (high)

PD-PAVB (Pause-Dependent)

Trigger: A pause — compensatory pause after APB or VPB, spontaneous sinus slowing, or overdrive suppression

Classical explanation (Singer-Lazzara-Hoffman 1967; Rosenbaum et al.): Phase 4 depolarization in diseased Purkinje fibers shifts membrane potential toward less negative values → reduced Na⁺ channel availability → conduction block at slow rates sources/PAVB-HR-2009 (high)

Challenge to the phase 4 explanation (Jalife et al., Circulation 1983):

• In isolated depressed Purkinje fibers (20 mM KCl) with confirmed absence of phase 4 depolarization, a biphasic pattern of excitability was observed: early recovery at intermediate diastolic intervals, then re-loss of excitability at long diastolic intervals — reproducing PD block without phase 4 depolarization sources/PAVB-HR-2009 (high)
• Phase 4 depolarization distal to a zone of impaired conductivity may actually facilitate (not block) conduction by moving membrane potential closer to threshold; phase 4 hyperpolarization impairs conduction
• Source-sink mismatch is a sufficient alternative mechanism: frequency-dependent decline in slow inward current (I_Ca) amplitude in proximal Purkinje fibers reduces the electrotonic input to the blocked zone → bradycardia-dependent conduction block, independent of upstroke velocity or phase 4 depolarization

Combined TD+PD PAVB: A biphasic excitability window can produce block at fast rates (TD), normal conduction at intermediate rates, and block again at slow rates (PD) — reported in 8 cases by Rosenbaum et al.

Terminology: Abandoning "Phase 3/Phase 4 Block"

• "Phase 3 block" and "phase 4 block" are misnomers: these terms tie the mechanism to action potential phase rather than to rate-dependence, and "phase 4 block" is particularly misleading because PD-PAVB can occur in the complete absence of phase 4 depolarization sources/PAVB-HR-2009 (high)
• Preferred terminology: TD-PAVB and PD-PAVB

Contradictions / Open Questions

• Relative contribution of phase 4 depolarization vs source-sink mismatch in clinical PD-PAVB remains unresolved — isolated Purkinje fiber data may not fully translate to intact in vivo His-Purkinje network sources/PAVB-HR-2009 (high)
• His bundle as the predominant site of block is based on EPS in only 10 of 42 cases; site is uncertain in the majority
• PAVB and sudden cardiac death: clinically suspected but not established; most studies report syncope, not death, as the outcome

Connections

• Related to concepts/Atrioventricular-Block — PAVB is a specific, paroxysmal subtype of complete AV block
• Related to concepts/Sinus-Node-Dysfunction — sinus slowing/overdrive suppression triggers PD-PAVB
• Related to concepts/Fascicular-Blocks — LBBB/RBBB frequently coexist with PAVB and share diseased His-Purkinje substrate
• Related to concepts/His-Bundle-Pacing — His bundle is the most common site of block in PAVB; conduction system pacing is the logical treatment target
• Related to concepts/Conduction-System-Pacing — physiologic pacing avoids abnormal ventricular activation in patients needing permanent pacing
• Related to concepts/Permanent-Pacing-Indications — PAVB with syncope is a clear PPM indication

Sources

• sources/PAVB-HR-2009 — primary source; El-Sherif/Jalife 2009 mechanistic review of PAVB