Left Bundle Branch Area Pacing Compared With Biventricular Pacing for CRT in Patients With LVEF ≤50% (I-CLAS)

Authors, Journal, Affiliations, Type, DOI

• Authors: Ramez Morcos, Pugazhendhi Vijayaraman, Oscar Cano, Francesco Zanon, Shunmuga Sundaram Ponnusamy, Bengt Herweg, Parikshit S. Sharma, Marek Jastrzebski, Manuel Molina-Lerma, Zachary I. Whinnett, Kevin Vernooy, Jiangang Zou, Girish M. Nair, Rajeev K. Pathak, Roderick Tung, Gaurav A. Upadhyay, Karol Curila, Mihail G. Chelu, Kenneth A. Ellenbogen
• Journal: Heart Rhythm 2025;22(8):2028–2037
• Affiliations: 18 international centres in North America, Asia, Australia and Europe, including Geisinger Heart Institute, Hospital Universitari i Politècnic La Fe (Valencia), Santa Maria della Misericordia (Rovigo), Velammal Medical College (Madurai), USF Morsani, Cleveland Clinic Weston, Jagiellonian University, Hospital Universitario Virgen de las Nieves, Imperial College, Maastricht UMC, Nanjing Medical University, University of Ottawa Heart Institute, Canberra Heart Rhythm, University of Arizona, University of Chicago, Charles University, Baylor College of Medicine, VCU Medical Center
• Type: Retrospective, multicentre, observational case-control study with propensity-score matching
• DOI: 10.1016/j.hrthm.2025.04.005

Overview

This I-CLAS analysis combines the programme's HFrEF (LVEF <35%) and HFmrEF (36%–50%) cohorts into 2,579 patients with LVEF ≤50% undergoing CRT at 18 centres, then performs 1:1 propensity-score matching to create a balanced cohort of 1,560 (780 LBBAP, 780 BVP). In the matched cohort LBBAP produced narrower paced QRS (129 vs 143 ms), a lower composite of death or heart failure hospitalisation (22.2% vs 30.8%; HR 0.81), and a 37% relative reduction in heart failure hospitalisation (13.6% vs 21.8%), with no significant difference in all-cause mortality (12.4% vs 18.2%). LBBAP also produced greater LVEF improvement (+11.5% vs +8.9%) and higher echocardiographic response and hyper-response rates, with fewer procedural complications (3.5% vs 6.5%). The paper is the largest matched comparison of LBBAP and BVP in CRT-eligible patients and is explicitly hypothesis-generating pending randomised trials.

Keywords

Cardiac resynchronization therapy; Left bundle branch area pacing; Biventricular pacing; Heart failure hospitalization; Mortality

Key Takeaways

Population and matching

• 2,579 patients: BVP 1,118, LBBAP 1,461; mean age 70 ± 13 years; 32% women; mean LVEF 32% ± 9%; mean QRS 156 ± 29 ms; LBBB 52%.
• Before matching, the LBBAP group had more women, more non-ischaemic cardiomyopathy and more non-LBBB, with higher LVEF and shorter QRS; the BVP group had lower LVEF and longer QRS.
• Propensity matching (1:1, caliper 0.001) matched on age, sex, hypertension, cardiomyopathy cause, LVEF, LBBB, QRS duration and medications → 1,560 patients (780/780).
• Matched cohort: mean age 70 ± 13 years; 34% women; LVEF 29% ± 8%; QRS 159 ± 28 ms; LBBB 54%; ischaemic 33%.
• Device use: single/dual-chamber devices in 38% of LBBAP patients; all BVP patients received CRT devices; defibrillators in 71% BVP vs 65% LBBAP (P = .01).

Procedural outcomes (matched cohort)

• Procedure duration similar: 117 ± 42 min BVP vs 113 ± 45 min LBBAP (P = .09).
• Fluoroscopy similar: 15.4 ± 11 vs 15.7 ± 14 min (P = .59).
• Implant thresholds lower with LBBAP: 0.7 ± 0.4 V vs 1.1 ± 0.6 V (P < .001).
• Paced QRS narrower with LBBAP: 129 ± 19 vs 143 ± 22 ms (P < .001).
• Complications lower with LBBAP: 3.5% vs 6.5% (P = .004), driven by fewer acute lead dislodgements and infections.
• Lead revisions 4.3% overall, no significant difference.
• Follow-up 34 ± 15 months; thresholds remained stable.

Clinical outcomes (matched cohort)

• Primary composite (death or first HFH): 22.2% LBBAP vs 30.8% BVP; HR 0.81 (95% CI 0.66–0.98), log-rank P = .048.
• Multivariable adjustment: HR 0.75 (95% CI 0.61–0.93), P = .008.
• HFH: 13.6% vs 21.8%; HR 0.63 (95% CI 0.49–0.82), P < .001; competing-risk analysis HR 0.63 (0.49–0.80).
• All-cause mortality: 12.4% vs 18.2%; HR 0.82 (95% CI 0.63–1.07), P = .156 — not significant.
• Unmatched cohort showed a mortality difference (11.7% vs 17.4%; HR 0.76, P = .012), which disappeared after matching.
• Independent predictors of worse outcome: male sex (HR 1.37), diabetes (1.49), AF (1.29), diuretics (1.83). ACEI/ARB (0.50) and ARNI (0.50) were associated with better outcomes.

Echocardiographic outcomes

• Available in 85% of the matched cohort.
• LVEF improved from 29% ± 8% to 41% ± 13% with LBBAP vs 38% ± 13% with BVP (P < .001).
• Change in LVEF greater with LBBAP: +11.5% ± 12% vs +8.9% ± 12% (P < .001).
• Echocardiographic response (≥5% absolute LVEF gain): 69% vs 61% (P < .001).
• Hyper-response (≥15% absolute gain): 37% vs 30% (P = .004).

Subgroups and arrhythmias

• Composite and HFH benefits were significant in LVEF ≤30% and 31%–40% subgroups but not in the 41%–50% subgroup.
• Benefits were present in both LBBB and non-LBBB, but not in the specific subgroup of LVEF 36%–50% with non-LBBB.
• Sustained ventricular arrhythmias and ICD shocks were lower with LBBAP.
• New-onset AF >30 seconds was lower with LBBAP, including in the LVEF 36%–50% subgroup.

Limitations of the document

• Retrospective, non-randomised, on-treatment analysis — treatment allocation by operator/institution; true success rates not analysed.
• Residual confounding after propensity matching, including unmeasured variables and centre effects.
• The matched cohort is a selected subset of the overall cohort; matching discarded 1,019 patients and may have altered the effect estimate.
• Mortality difference was not significant after matching, so the composite benefit is driven by HFH; the authors appropriately do not claim a mortality benefit.
• Heterogeneous device configurations — many LBBAP patients received single- or dual-chamber pacemakers rather than CRT devices, and the proportion receiving defibrillators differed between groups.
• Subgroup analyses are underpowered and should be considered exploratory.
• Echocardiography was not core-laboratory adjudicated.
• Industry funding and conflicts: authors report extensive Medtronic, Abbott, Boston Scientific and Biotronik relationships; no specific funding was declared.

Key Concepts Mentioned

• concepts/Left-Bundle-Branch-Area-Pacing — the intervention
• concepts/Cardiac-Resynchronization-Therapy — the clinical context
• concepts/Cardiac-Resynchronization-Therapy — the comparator
• entities/Heart-Failure — most of the cohort
• entities/Heart-Failure — the remainder

Key Entities Mentioned

• International Collaborative LBBAP Study (I-CLAS) Group — multicentre consortium
• Geisinger Heart Institute — coordinating centre
• Medtronic, Abbott, Boston Scientific, Biotronik, MicroPort — device manufacturers

Wiki Pages Updated

• Created: wiki/sources/iclas-lbbap-crt-hrs-2025.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