Cardiac Conduction System Pacing: A Comprehensive Update

Authors, Journal, Affiliations, Type, DOI

• Authors: Pugazhendhi Vijayaraman, Mihal G. Chelu, Karol Curila, Gopi Dandamudi, Bengt Herweg, Shumpei Mori, Marek Jastrzebski, Parikshit S. Sharma, Kalyanam Shivkumar, Roderick Tung, Gaurav Upadhyay, Kevin Vernooy, Allan Welter-Frost, Zachary Whinnett, Francesco Zanon, Kenneth A. Ellenbogen
• Journal: JACC: Clinical Electrophysiology, Vol. 9, No. 11, November 2023: 2358–2387
• Affiliations: Multi-institutional (Geisinger, Baylor, UCLA, Jagiellonian, Rush, Imperial College London, and others)
• Type: State-of-the-Art Review
• DOI: https://doi.org/10.1016/j.jacep.2023.06.005

Overview

This state-of-the-art review from JACC:EP provides a comprehensive update on conduction system pacing (CSP), covering new anatomical insights, hemodynamic comparisons (CSP vs RVP vs BVP), ventricular synchronization measurement techniques (V6RWPT, V6-V1 interpeak interval, UHF-ECG), and LBB capture confirmation criteria. LBBAP is consolidating its dominance over HBP due to superior technical characteristics, while hybrid approaches (HOT-CRT, LOT-CRT) show promise for complex LBBB/IVCD cases. Seven published small RCTs suggest non-inferiority or superiority to BVP, with landmark trials (Left vs Left: n=2,136; PROTECT-HF: n=2,600) underway to define CSP's definitive role.

Keywords

Conduction system pacing • His bundle pacing • Left bundle branch area pacing • Cardiac resynchronization therapy • Ventricular synchrony • Hemodynamics

Key Takeaways

New Insights into Cardiac Anatomy

• Tawara's original description of the AV conduction system remains foundational; modern 3D reconstruction (micro-CT, pressure-perfused hearts) now allows virtual simulation of pacing lead placement relative to the conduction system
• AV node is an epicardial structure located on the right side of the central fibrous body (right fibrous trigone); dissection of the triangle of Koch reveals 3D relationships between AV node, His bundle, membranous septum, and tricuspid leaflets
• Lead position near the commissure between septal and anterosuperior tricuspid leaflets minimises risk of TR from lead–leaflet interaction during HBP
• McAlpine's pressure-perfused heart model reveals that the membranous septum (site of His bundle penetration) carries perforation risk during HBP

Hemodynamics of CSP

CSP vs Right Ventricular Pacing (Bradycardia Indications)

• HBP vs RVP (Keene et al, n=18): HBP produced shorter QRS duration (–56 ms; 95% CI –67 to –46 ms; P<0.0001) and improved acute systolic BP by +5.0 mmHg (95% CI 2.8–7.1 mmHg; P<0.0001)
• Myocardial perfusion (Zanon et al): HBP significantly better than RVP by scintigraphy at 3 months (0.44 ± 0.5 vs 0.71 ± 0.53; P=0.011)
• Global longitudinal strain (Michalik et al): GLS declined and peak systolic dispersion increased after 6 months of RVP vs unchanged/improved with HBP

CSP vs Biventricular Pacing (CRT Indications)

• HBP-CRT vs BVP-CRT (n=18/23 patients): HBP-CRT shortened LVAT by –26 ms more than BVP-CRT and produced ~60% greater improvement in acute systolic BP (+4.6 mmHg; P=0.04)
• HOT-CRT vs BVP-CRT (Zweerink et al, n=19): HOT-CRT produced 24% greater reduction in LVAT than BVP-CRT (–22 ms; P=0.002) in patients where HBP alone failed to narrow QRS
• LBBAP vs BVP (Liang et al): LBBAP produced greater QRS reduction (–11 ms; P=0.003) and 6% greater increase in LV dP/dt (P=0.002)
• HBP-CRT vs LBBAP-CRT (Ali et al, n=19): HBP achieves faster total biventricular activation; LBBAP non-inferior for LVAT reduction; delayed RV activation with LBBAP did not adversely affect hemodynamic response
• Anodal capture during LBBAP: Produces shorter QRS but no additional hemodynamic benefit; RV septal myocardial capture (not right bundle capture) is the mechanism of earlier RV activation
• HBP in long PR interval + LV impairment (Sohaib/HOPE-HF): AV-optimised HBP improved acute hemodynamics (~60% of BVP benefit); HOPE-HF trial (n=167, crossover): no change in peak VO₂ or LVEF, but significant improvement in QoL and symptomatic preference

Techniques to Measure Ventricular Synchronisation

Ultra-High Frequency ECG (UHF-ECG)

• UHF-ECG measures electrical dyssynchrony (e-DYS): time difference between first and last ventricular activation under leads V1–V8
• nsHBP = sHBP in e-DYS; both equivalent to normal intrinsic narrow QRS rhythm; para-Hisian myocardial pacing significantly worsens e-DYS (32 ms)
• nsLBBP and LVSP are on average less physiological than nsHBP; LVSP preserves absolute synchrony level but produces left-to-right activation pattern with broader LV lateral wall depolarisation map
• nsLBBP delays RV activation and worsens left-to-right interventricular dyssynchrony vs both HBP and LVSP

QRS Area

• Vectorcardiographic QRS area (X, Y, Z leads) predicts CRT response in large cohorts
• During LVSP without LBB capture, QRS area slightly higher than during LBBP, but absolute difference small
• QRS area during LBBAP in patients with normal ventricular activation is close to intrinsic QRS values (near-physiologic synchrony)

Criteria for LBB Capture

V6 R-Wave Peak Time (V6RWPT)

• Activation of LV lateral wall is faster during nsLBBP than LVSP (average difference ~20 ms)
• V6RWPT <75 ms = ~100% specific for LBB capture in narrow QRS/isolated RBBB
• V6RWPT 80–85 ms = best sensitivity/specificity balance in standard patients
• In LBBB/IVCD, wide escape rhythms, or asystole: use adjusted cutoffs of 80 ms (high specificity) and 90–100 ms (optimal diagnostic accuracy)
• Low sensitivity remains a major limitation, especially in heart failure and diffuse conduction disease

V6–V1 Interpeak Interval

• During LVSP: activation spreads bidirectionally → V6 and V1 R-peaks occur nearly simultaneously → short V6–V1 interval
• During nsLBBP: RV activation delayed → longer V6–V1 interval
• >44 ms: highly specific for LBB capture; 33–40 ms = optimal sensitivity/specificity balance
• Less influenced by initial latency, LV dilatation, or diseased HPS (affects both V1 and V6 equally)
• Combined use of V6RWPT + V6–V1 interpeak interval increases diagnostic yield

QRS Transition During Threshold Test

• Sensitivity 30–70% at implant; 15–30% at follow-up
• For ns-LBBP → LVSP transition: V6RWPT prolongs ≥10 ms
• For ns-LBBP → s-LBBP transition: V1RWPT prolongs; S wave deepens in I, V5, V6; isoelectric latency appears; discrete LBB potential on endocardial channel
• Conduct threshold test in unipolar mode at constant rate; decrease output slowly while monitoring 12-lead QRS and endocardial recordings

Lead-Position-Dependent QRS Transition

• Real-time capture confirmation during lead rotation into the septum
• Beat-to-beat QRS change at moment of LBB capture: V6RWPT shortens suddenly ≥10 ms; R′ amplitude increases in V1; repolarisation normalises in V5–V6; S waves appear in I, V5, V6
• Requires electrophysiology recording system (difficult to confirm in real time; review consecutive QRS complexes retrospectively)
• Requires rotational adapter connecting distal lead pin to external pacemaker

Distal vs Proximal LBBAP: LVAT–QRS Trade-off

• Distal LBB stimulation: shorter LVAT (shorter local Purkinje-to-ventricle interval) but wider QRS (longer retrograde path to activate RBB → more interventricular dyssynchrony)
• Whether shorter LVAT or narrower QRS is more important physiologically is unresolved

CSP Implant Technique Updates

Delivery Sheaths

• C315 preshaped sheath (Medtronic): standard for most centres; comparable success to Selectra 3D (Biotronik) in 151-patient comparison
• Multiple new sheaths available (SSPC series from Boston Scientific) for dilated hearts, right-sided implants, enlarged RA
• No dedicated CSP pacing lead approved yet; Medtronic 3830 (4.1 Fr lumenless) FDA-approved for both HBP and LBBAP
• Stylet-driven leads: 87–89% implant success, comparable thresholds; long-term performance data lacking

Implant Technique Updates

• Liu et al. contrast-based tricuspid valve visualisation technique: reduced procedural and fluoroscopy time, fewer repositioning attempts
• Jastrzebski et al. fixation beats (template beats): improve specificity of LBB capture at implant
• Ponnusamy et al. "M" beats: improve specificity of LBB capture

Fluoroless and 3D Mapping

• HBP feasible without fluoroscopy in 79% of patients (Zanon et al., n=41; 95% success rate); guided purely by electrograms
• 3D electroanatomical mapping (Sharma et al., Richter et al.): safe, feasible, dramatically reduces radiation exposure
• LBBAP with 3D mapping: real-time visualisation of lead penetrating septum; measures distance from His cloud; enables perpendicular lead orientation assessment

Hybrid Approaches to CSP

HOT-CRT (His-Optimized CRT)

• Combines HBP with coronary vein LV pacing, optimised to produce narrowest fused QRS
• Indicated when HBP alone fails to resynchronise (block distal to His capture site, or myocardial IVCD)
• Observational data (Vijayaraman et al., n=27): QRS reduced from 183 ms (baseline) to 120 ms (HOT-CRT) vs 162 ms (BVP) vs 151 ms (HBP); LVEF 24%→38%; NYHA improved
• Currently investigational; ongoing RCT (HOT-CRT trial, NCT04561778, n=100)

LOT-CRT (Left Bundle–Optimized CRT)

• Combines LBBP with coronary vein LV pacing when LBBP alone insufficient
• Multicentre series (Jastrzebski et al., n=112, 81% success): QRS 182→144 ms (21% reduction) vs 7% with BVP; LVEF 28.5→37.2%; NYHA 2.9→1.9
• CSPOT trial (NCT04905290): ongoing acute hemodynamic crossover comparing BVP, LBBP, LOT-CRT
• Currently investigational; no large RCT data

Clinical Trials

Published Randomised Controlled Trials (Table 3)

Seven small RCTs (29–167 patients) with short follow-up (6–18 months):

Key Ongoing Trials

• PROTECT-HF (NCT pending, n=2,600): CSP vs RVP; high VP burden; primary: CV death + HFH + QoL + upgrade; 48-month follow-up; UK/worldwide
• Left vs Left (NCT05650658, n=2,136): HBP/LBBAP vs BVP; LVEF ≤50%; primary composite: death + HFH; 66-month follow-up; USA/Canada
• LEAP (NCT04595487, n=470): LVSP vs RVP; unique: tests whether CS capture is required
• OptimPacing (NCT04624763, n=683): LBBP vs RVP; AVB or permanent AF; primary: death + HFH + pacing-induced CM

Future Perspectives

• Is LBBAP as good as HBP? Uncertain — HBP achieves superior biventricular synchrony; LBBAP has better technical parameters; no outcomes RCT
• Is LBB capture (vs LVSP) necessary for maximal benefit? LEAP trial directly addresses this
• Clinical impact of delayed RV activation with LBBAP in HF: not fully characterised
• Leadless pacemakers for CSP: under development; may enable leadless HBP/LBBAP
• AI-assisted capture detection: in development
• Long-term lead extraction from deep septal LBBAP position: requires prospective evaluation

Limitations of the Document

• No large RCTs with hard outcomes (mortality/hospitalisation); all published trials underpowered or short-term
• Most hemodynamic comparisons use acute surrogate endpoints (SBP, LV dP/dt); chronic remodelling data sparse
• Optimal criteria for LBB capture confirmation (V6RWPT, V6-V1 interval, QRS transition) have variable sensitivity/specificity depending on substrate
• LOT-CRT and HOT-CRT remain investigational; predominantly observational data
• Lead extraction data for LBBAP leads in deep septal position very limited

Key Concepts Mentioned

• concepts/Conduction-System-Pacing — central topic; hemodynamics, ventricular synchrony, RCT evidence
• concepts/His-Bundle-Pacing — hemodynamic data vs RVP and BVP; HOPE-HF; fluoroless techniques
• concepts/Left-Bundle-Branch-Area-Pacing — LBB capture criteria; lead-position-dependent QRS transition; anodal capture; LOT-CRT

Key Entities Mentioned

• entities/Heart-Failure — HOT-CRT/LOT-CRT for LBBB + HF; multiple RCTs; ongoing PROTECT-HF/Left vs Left
• entities/Atrial-Fibrillation — HBP in AF + AVJ ablation (ALTERNATIVE AF trial); LBBAP preferred post-AVNA

Wiki Pages Updated

• wiki/sources/csp-jaccep-2023.md (created)
• wiki/concepts/Conduction-System-Pacing.md (updated)
• wiki/concepts/His-Bundle-Pacing.md (updated)
• wiki/concepts/Left-Bundle-Branch-Area-Pacing.md (updated)
• wiki/sourceindex.md (updated)
• wiki/wikiindex.md (updated)
• log.md (appended)