Left Bundle Branch–Optimized Cardiac Resynchronization Therapy (LOT-CRT): Results From an International LBBAP Collaborative Study Group

Authors, Journal, Affiliations, Type, DOI

• Authors: Marek Jastrzębski, Paweł Moskal, Wim Huybrechts, Karol Curila, Praveen Sreekumar, Leonard M. Rademakers, Shunmuga Sundaram Ponnusamy, Bengt Herweg, Parikshit S. Sharma, Agnieszka Bednarek, Marek Rajzer, Pugazhendhi Vijayaraman
• Journal: Heart Rhythm 2022;19(1):13–21
• Affiliations: Jagiellonian University (Kraków); University Hospital Antwerp; Charles University and University Hospital Královské Vinohrady (Prague); Aster Medcity (Kochi); Catharina Ziekenhuis (Eindhoven); Velammal Medical College (Madurai); University of South Florida (Tampa); Rush University Medical Center (Chicago); Geisinger Heart Institute (Wilkes-Barre)
• Type: Prospective, multicentre, observational feasibility study
• DOI: 10.1016/j.hrthm.2021.07.057

Overview

This international multicentre study introduced and evaluated LOT-CRT — replacing the right ventricular lead of a conventional CRT system with a left bundle branch area pacing lead, while retaining the coronary venous LV lead. Among 112 patients with advanced heart failure and broad QRS (42% LBBB, 22% non-specific IVCD, 23% RV-paced, 12% RBBB), LOT-CRT was feasible in 81%. It narrowed QRS from 182 ms at baseline to 144 ms, significantly more than BVP (170 ms) or LBBAP alone (162 ms), and produced LVEF improvement from 28.7% to 37.2%, LV reverse remodelling, a fall in NT-proBNP, and clinical improvement in 76% at a mean follow-up of 7.8 months. Patients with confirmed LBB capture had better electrical and echocardiographic outcomes than those with LV septal capture only. The paper is the foundational description of the LOT-CRT concept and its rationale — combining proximal conduction-system engagement with distal lateral-wall resynchronisation.

Keywords

Biventricular pacing; Cardiac resynchronization therapy; Left bundle branch area pacing; QRS narrowing; Heart failure

Key Takeaways

Rationale

• Proximal LBB pacing cannot restore physiological lateral wall activation when the delay is distal — in the distal LBB, LV Purkinje network, or myocardium.
• Conventional BVP is limited by the desynchronising effect of RV myocardial pacing, single-site epicardial LV pacing, latency, and suboptimal LV lead position.
• Combining LBBAP (in place of the RV lead) with coronary venous LV pacing addresses both limitations: direct conduction-system engagement plus lateral wall pre-excitation.
• In this cohort the mean V6 R-wave peak time during LBBAP was 99.6 ± 21 ms, indicating residual LV conduction delay despite proximal capture — the substrate LOT-CRT is designed to correct.

Population and feasibility

• 112 patients at 9 centres (4 European, 3 American, 2 Indian); non-consecutive, selected by operator judgment for suboptimal QRS with BVP or LBBAP alone.
• Mean age 70.5 ± 11.4 years; 20% female; ischaemic cardiomyopathy 61%.
• Baseline LVEF 28.7% ± 9.8%; LVEDD 61.9 ± 8.6 mm; NT-proBNP 5821 ± 8193 pg/mL; QRS 180 ± 24 ms.
• Conduction disease: LBBB 47 (42%), RBBB 14 (12.5%), non-specific IVCD 25 (22%), RV-paced 26 (23%).
• LOT-CRT successful in 91/112 (81%): LBBAP lead could not be placed in 16, CS lead failed in 4.
• Devices: BiV defibrillator in 83, pacemaker in 29.
• Mean fluoroscopy 27.3 ± 22 min; LBBAP threshold 0.8 ± 0.4 V at 0.5 ms; R-wave 10 ± 5 mV; stable at follow-up.
• Early complications: 2 lead dislocations, 1 intraprocedural septal perforation, 2 pocket haematomas; follow-up: 1 infection, 1 CS threshold rise, 1 atrial lead dislodgement.

Electrical outcomes

• QRS: 181 ± 26 → 144 ± 22 ms with LOT-CRT (P < .0001).
• LOT-CRT QRS was narrower than BVP (170 ± 30 ms; P < .0001) and LBBAP alone (162 ± 23 ms; P < .0001).
• Lack of QRS narrowing occurred in 20.6% with BVP vs 4.4% with LOT-CRT.
• LBB capture was diagnosed in 68 (75%), LV septal capture in 23 (25%).

Echocardiographic and clinical outcomes

• LVEF: 28.5% ± 9.9% → 37.2% ± 12% (P < .0001).
• LVEDD: 62.0 ± 8.9 → 59.1 ± 9.1 mm (P = .0442).
• LVEDV: 209.8 ± 99 → 171.4 ± 83 mL (P < .0001).
• LVESV: 149.5 ± 84 → 110.6 ± 69 mL (P < .0001).
• Echocardiographic response 62.8%; super-response 24.4%.
• NYHA class: 2.9 ± 0.6 → 1.9 ± 0.6 (P < .0001); clinical response 76% overall, 87% in baseline NYHA III–IV.
• NT-proBNP: 5668 ± 8249 → 2561 ± 3555 pg/mL (P < .0001).
• Mean follow-up 7.8 ± 2.3 months; 1 heart failure death, 2 non-cardiac deaths, 1 lost to follow-up.

LBB capture vs LV septal capture

• LOT-CRT with confirmed LBB capture vs LV septal capture only:
  • Paced QRS 141 ± 20 vs 152 ± 25 ms (P = .028).
  • LVEF improvement +11.1 ± 11.3 vs +4.7 ± 7.5 points (P = .0196).
  • Echocardiographic response 71% vs 45% (P = .039).
  • Clinical response 82% vs 61% (P = .035).
• No difference in NT-proBNP reduction.

Interpretation

• LOT-CRT achieved roughly three times the acute QRS narrowing of BVP in this selected, advanced cohort.
• The benefit was greatest in patients with more advanced conduction disease and wider baseline QRS.
• The authors argue for an individualised, mechanism-based CRT approach rather than empirical BVP.
• The LBB capture comparison supports pursuing true LBB capture rather than accepting LV septal capture.

Limitations of the document

• Non-consecutive, observational design with no randomisation and no uniform criteria for selecting LOT-CRT over BVP or LBBAP — substantial selection and operator bias.
• Small sample (n = 112) and short, non-uniform follow-up (mean ~8 months); the COVID-19 pandemic forced remote follow-up in 12 patients.
• ECG comparison was acute only; clinical outcomes are uncontrolled before–after comparisons rather than a randomised comparison with BVP.
• No core-laboratory echocardiography and no blinded outcome assessment.
• LBB capture criteria vary between centres, and 25% of patients had only LV septal capture.
• Additional hardware and procedural complexity — an extra lead, capping of the RV pace/sense lead, and loss of MRI conditionality in some configurations.
• Industry conflicts: multiple authors report Medtronic consultancy fees; one author has a His-bundle pacing delivery-tool patent.

Key Concepts Mentioned

• concepts/LOT-CRT — the technique defined by this study
• concepts/Left-Bundle-Branch-Area-Pacing — the pacing lead replacing the RV lead
• concepts/Cardiac-Resynchronization-Therapy — the clinical context
• concepts/Cardiac-Resynchronization-Therapy — the comparator
• concepts/Left-Bundle-Branch-Area-Pacing — the capture pattern associated with inferior outcomes
• concepts/Electrical-Resynchronization-Metrics — QRS duration and V6 R-wave peak time

Key Entities Mentioned

• International LBBAP Collaborative Study Group — the multicentre consortium
• Jagiellonian University — lead site
• Medtronic — 3830 SelectSecure lead, C315HIS/C304 sheaths

Wiki Pages Updated

• Created: wiki/sources/lot-crt-hrs-2021.md
• Updated: wiki/concepts/LOT-CRT.md
• Updated: wiki/concepts/Left-Bundle-Branch-Area-Pacing.md
• Updated: wiki/sourceindex.md
• Updated: log.md