Left Bundle Branch Area vs Biventricular Pacing for Cardiac Resynchronization Therapy: The LEFT-BUNDLE-CRT Trial

Authors, Journal, Affiliations, Type, DOI

• Authors: Óscar Cano, Víctor Pérez-Roselló, Andrea Di Marco, Javier Ramos-Maqueda, Pablo Moriña, Thomas Brouzet, Daniel Rodríguez-Muñoz, Víctor Castro, Sebastian Giacoman, Pablo Peñafiel, María Rodríguez-Serrano, Manuel Molina-Lerma
• Journal: European Heart Journal 2026;00:1–13 (online)
• Affiliations: 11 Spanish centres — Hospital Universitari i Politècnic La Fe (Valencia), Hospital General Universitari de Castelló, Hospital Universitari de Bellvitge, Hospital Clínico Universitario Lozano Blesa (Zaragoza), Hospital Universitario Juan Ramón Jiménez (Huelva), Hospital General Universitario Dr. Balmis (Alicante), Hospital Universitario 12 de Octubre (Madrid), Hospital Universitario Puerta de Hierro (Majadahonda), Hospital Universitario Clínico San Cecilio (Granada), Hospital Clínico Universitario Virgen de la Arrixaca (Murcia), Hospital Universitario Virgen de las Nieves (Granada)
• Type: Multicentre, randomised, investigator-initiated, non-inferiority trial (NCT05434962)
• DOI: 10.1093/eurheartj/ehag225

Overview

LEFT-BUNDLE-CRT randomised 176 patients with typical LBBB (Strauss criteria) and a guideline CRT indication to biventricular pacing (BiVP) or LBBAP in 11 Spanish centres. The primary endpoint — CRT response at 6 months, defined as an improved clinical composite score or ≥15% reduction in LV end-systolic volume — occurred in 94.6% of BiVP and 89.7% of LBBAP patients in the intention-to-treat analysis (RR 0.95, 95% CI 0.88–1.02), so the prespecified 10% non-inferiority margin was not met (P = .12). In the on-treatment analysis, response rates were 92.8% vs 91.3% (RR 0.98, 95% CI 0.91–1.06; P = .03 for non-inferiority), suggesting comparable efficacy when the pacing modality actually delivered is considered, but the authors label this exploratory. Both strategies produced high response rates and similar clinical outcomes; the trial's interpretation is complicated by a 14.9% crossover rate, asymmetrically concentrated in the BiVP arm.

Keywords

Conduction system pacing; Biventricular pacing; Left bundle branch area pacing; Cardiac resynchronization therapy

Key Takeaways

Design and population

• Multicentre, randomised (1:1), investigator-initiated, non-inferiority trial; patients blinded to allocation; echocardiographic core laboratory blinded; independent clinical events committee.
• 176 patients randomised June 2022–June 2024: BiVP 84, LBBAP 92.
• Inclusion: age ≥18, class I or IIa CRT indication (ESC or ACC/AHA/HRS), typical LBBB by Strauss criteria, sinus rhythm (transient atrial arrhythmias allowed if sinus rhythm restored).
• Exclusions: permanent/persistent AF, previous CRT or >10% ventricular pacing, conventional pacemaker indication, non-specific IVCD, recent acute coronary syndrome/revascularisation/valve surgery, life expectancy <12 months.
• Baseline: median age 68 vs 67 years; 68% vs 66% male; LVEF 29% vs 30%; median QRS 165 ms (BiVP) vs 171 ms (LBBAP) (P = .04); ischaemic cardiomyopathy 28% vs 27%.
• All centres had ≥100 prior implants of both techniques; maximum two implanters per centre.
• Primary endpoint evaluated in 161 patients (74 BiVP, 87 LBBAP) with 6-month data.

Implantation and crossovers

• CS lead successfully implanted in 65/82 (79%) randomised to BiVP.
• LBBAP implant success 83/92 (90%).
• Crossovers: 26 patients (14.9%) — 17/82 (20.7%) from BiVP to LBBAP (inability to cannulate CS n = 3, no target vein n = 4, high threshold or phrenic capture n = 10), and 9/92 (9.8%) from LBBAP to BiVP (inability to penetrate septum n = 3, failure to correct LBBB despite appropriate septal deployment n = 6).
• Final LBBAP capture pattern: left bundle branch capture 38 (41%), LV septal capture 50 (54%), deep septal pacing 4 (4%).
• Procedure time: median 105 min BiVP vs 92 min LBBAP (P = .23).
• Fluoroscopy: median 19 min BiVP vs 11 min LBBAP (P = .01).
• Final paced QRS: 130 ms (IQR 124–140) vs 130 ms (IQR 122–138) (P = .45).
• Pacing threshold higher for the CS lead than the LBBAP lead at implant and at 6 and 12 months; unipolar impedance lower for LBBAP.

Primary endpoint

• Intention-to-treat: CRT response 94.6% BiVP vs 89.7% LBBAP; RR 0.95 (95% CI 0.88–1.02); P = .12 — non-inferiority not established.
• On-treatment (actual pacing modality: 69 BiVP, 92 LBBAP): 92.8% vs 91.3%; RR 0.98 (95% CI 0.91–1.06); P = .03 — non-inferiority met, but exploratory.
• Absolute difference in the ITT analysis was small (−4.9%) with narrow confidence intervals.

Secondary endpoints

• LVEF improvement: +16.3% ± 10.4% BiVP vs +14.4% ± 11.3% LBBAP at 6 months (P = .29); comparable at 12 months.
• ≥15% LVESV reduction: 84.9% vs 79.1% (P = .34) in ITT; 84.1% vs 80.0% (P = .51) on-treatment.
• Super-responders (LVEF gain ≥20 points or final LVEF >50%): 47% vs 45% at 6 months (P = .87); 63% vs 49% at 12 months (P = .07).
• 6-minute walk distance and EQ-5D severity index improved in both groups without significant differences.
• Deaths: 3, all originally allocated to BiVP (2 crossed to LBBAP at implant), none cardiovascular.
• Death or HF hospitalisation: 7.8 vs 5.8 per 100 patient-years (P = .56).
• Ventricular arrhythmia: 1 patient in the LBBAP group received appropriate shocks.

Complications

• Acute complications: 12.2% BiVP vs 10.9% LBBAP (P = .81).
• Lead-related complications: 9.8% vs 10.9% (P = .81).
• Septal perforation: 0 vs 6 (6.5%) (P = .03), none clinically consequential.
• CS dissection: 7 (8.5%) vs 1 (1.1%) (P = .03).
• Follow-up device complications: 2.7 vs 5.7 per 100 patient-years (P = .34).
• Re-intervention: 6.1% vs 3.3% (P = .48).
• One LBBAP patient with DSP at index implantation and non-response underwent re-intervention to achieve LBB capture.

Interpretation

• The very high response rates (>90% in both arms) reflect the strict selection of typical LBBB, a predominantly electrical substrate; this ceiling effect limits the ability to demonstrate non-inferiority.
• The asymmetric crossover rate — driven by a pragmatic policy of not accepting suboptimal CS lead performance — complicates the ITT analysis.
• Exploratory analysis by capture pattern suggested that confirmed LBB capture produced more reverse remodelling and functional improvement than LVSP, supporting the concept that true conduction-system capture matters.
• The authors conclude LBBAP is a feasible alternative, particularly when BiVP is not achievable, but that adequately powered randomised trials are still needed to define its role.

Limitations of the document

• Primary non-inferiority endpoint was not met in the ITT analysis; the on-treatment result is exploratory and cannot support a formal non-inferiority claim.
• High, asymmetric crossover rate (20.7% in the BiVP arm) — the trial does not compare the strategies as randomly assigned.
• Modest sample size (176) and short follow-up (12 months), underpowered for mortality and heart failure hospitalisation.
• Restricted population — only typical LBBB by Strauss criteria, excluding IVCD, RBBB, AF, and patients with prior pacing; results may not generalise to the broader CRT population.
• Quality of life measured with EQ-5D, a generic rather than heart-failure-specific instrument.
• Blinding was incomplete — lead position may reveal allocation despite blinded core-lab echocardiography.
• Capture-pattern subgroups are small and exploratory.
• Funding and conflicts: Medtronic provided an external research programme; the Spanish Society of Cardiology sponsored the trial. Multiple authors report consultancy fees from Medtronic, Abbott, Biotronik, Boston Scientific and MicroPort.

Key Concepts Mentioned

• concepts/Left-Bundle-Branch-Area-Pacing — the randomised intervention
• concepts/Cardiac-Resynchronization-Therapy — the indication
• concepts/Cardiac-Resynchronization-Therapy — the comparator
• concepts/LBBB-Criteria — the inclusion criterion
• concepts/Left-Bundle-Branch-Area-Pacing — the most common capture pattern in the LBBAP arm
• concepts/Left-Bundle-Branch-Area-Pacing — the failed-capture category

Key Entities Mentioned

• Hospital Universitari i Politècnic La Fe (Valencia) — coordinating centre
• Spanish Society of Cardiology — sponsor
• Medtronic — external research programme funding and device supplier
• Galaxia Empírica S.L. — contract research organisation

Wiki Pages Updated

• Created: wiki/sources/left-bundle-crt-ehj-2026.md
• Updated: wiki/concepts/Left-Bundle-Branch-Area-Pacing.md
• Updated: wiki/concepts/Conduction-System-Pacing.md
• Updated: wiki/entities/CRT.md
• Updated: wiki/sourceindex.md
• Updated: log.md