Multicenter Hemodynamic Assessment of the LOT-CRT Strategy: Primary Results of the CSPOT Study

Authors, Journal, Affiliations, Type, DOI

• Authors: Marek Jastrzębski, Paul Foley, Badrinathan Chandrasekaran, Zachary Whinnett, Pugazhendhi Vijayaraman, Gaurav A. Upadhyay, Robert D. Schaller, Rafał Gardas, Travis Richardson, D'Anne Kudlik, Robert W. Stadler, Patrick Zimmerman, James Burrell, Robert Waxman, Richard N. Cornelussen, Jonathan Lyne, Bengt Herweg
• Journal: Circulation: Arrhythmia and Electrophysiology 2024;17:e013059
• Affiliations: Jagiellonian University (Kraków); Great Western Hospital (Swindon); Imperial College London; Geisinger Heart Institute; University of Chicago; University of Pennsylvania; Medical University of Silesia (Katowice); Vanderbilt Heart (Nashville); Medtronic (Mounds View, MN and Bakken Research Center, Maastricht); Beacon Hospital (Dublin); University of South Florida and Tampa General Hospital
• Type: Prospective, multicentre, acute haemodynamic and electrocardiographic study (CSPOT; NCT04905290)
• DOI: 10.1161/CIRCEP.124.013059

Overview

CSPOT compared the acute haemodynamic and electrical effects of biventricular pacing (BVP), unipolar and bipolar LBBAP, and LOT-CRT (LBBAP plus coronary venous LV pacing) in 48 CRT candidates with advanced conduction disease — 60% non-specific IVCD, 40% LBBB. LOT-CRT produced the greatest QRS shortening (29.5 ms) but BVP and LOT-CRT produced similar improvements in LV dP/dtmax (26.4% and 25.8%), both greater than unipolar (19.3%) or bipolar (16.4%) LBBAP. The incremental benefit of adding an LV lead to LBBAP was concentrated in patients with baseline QRS ≥171 ms and in those in whom LBBAP produced only deep septal pacing (DSP). Anodal capture during bipolar LBBAP, present in 54% of patients, reduced the haemodynamic benefit. The study defines when LOT-CRT adds value over LBBAP alone and cautions that acute electrical and contractile responses are not interchangeable.

Keywords

Bundle-branch block; Cardiac resynchronization therapy; Electrocardiography; Hemodynamics; Pacemaker

Key Takeaways

Design and population

• Prospective, multicentre, global study at 5 European and 5 US sites; 60 enrolled, 48 completed the acute pacing protocol.
• Inclusion: classic CRT indication, with preference for IVCD and non-LBBB; exclusions were persistent/permanent AF or flutter, second- or third-degree AV block, and isolated RBBB without additional block.
• Mean age 65.3 ± 10.3 years; 67% male; ischaemic cardiomyopathy 29%; mean LVEF 30.6% ± 11%; baseline QRS 171 ± 21 ms; PR 200 ± 53 ms.
• Central adjudication: LBBB 19 (40%), IVCD 29 (60%).
• LBBAP capture classification: successful LBBAP 27 (56%), DSP 21 (44%).
• Anodal stimulation during bipolar LBBAP: 25/46 (54%).

Acute haemodynamic response (LV dP/dtmax vs AAI)

• BVP: +26.4% (95% CI 20.2%–32.6%).
• LOT-CRT: +25.8% (95% CI 20.9%–30.7%); BVP vs LOT-CRT P = .45.
• Unipolar LBBAP: +19.3% (95% CI 15.0%–23.7%).
• Bipolar LBBAP: +16.4% (95% CI 12.7%–20.0%).
• BVP and LOT-CRT were superior to both LBBAP configurations (P < .001 except BVP vs unipolar LBBAP P = .005).
• Unipolar LBBAP was superior to bipolar LBBAP (P = .035).
• Bipolar LBBAP with anodal capture: +18.6% vs +23.7% with unipolar LBBAP (P < .001); without anodal capture the two were similar (15.2% vs 14.2%, P = .92).

Acute electrical response (QRS shortening)

• LOT-CRT: 29.5 ms (95% CI 23.4–35.6).
• BVP: 18.5 ms (95% CI 11.0–25.9); LOT-CRT vs BVP P = .005.
• Unipolar LBBAP: 11.9 ms (95% CI 6.1–17.7); LOT-CRT vs unipolar P < .01.
• Bipolar LBBAP: 11.7 ms (95% CI 6.4–17.0); LOT-CRT vs bipolar P < .001.
• BVP vs either LBBAP configuration was not significant (P = .090).

Subgroups

• LBBB vs IVCD: LV dP/dtmax improvement similar (P = .29), but QRS reduction greater in LBBB (P = .026); relative effects of the pacing configurations were similar between conduction types.
• Successful LBBAP vs DSP: overall LV dP/dtmax improvement similar (P = .40), but the relative effect of pacing configuration differed (P < .005). LOT-CRT vs unipolar LBBAP added +12.0% (95% CI 6.2–17.8) in DSP vs +5.1% (0.2–9.9) in successful LBBAP.
• Baseline QRS <171 vs ≥171 ms: overall LV dP/dtmax similar (P = .12), but relative effects differed (P = .031). LOT-CRT vs unipolar LBBAP added 10.4% in QRS ≥171 ms vs 5.5% in QRS <171 ms.
• Combined highest-benefit group: QRS ≥171 ms plus DSP — LOT-CRT added 14.5% (95% CI 5.0–24.1) LV dP/dtmax and 20.8 ms (12.8–28.8) QRS shortening over unipolar LBBAP.
• Ischaemic cardiomyopathy was associated with diminished LV dP/dtmax improvement overall (P = .004), but the relative performance of the three strategies was unchanged.

Interpretation

• The high prevalence of DSP (44%) — distributed across all centres — likely explains why BVP outperformed LBBAP hemodynamically in this cohort, unlike cohorts enriched for typical LBBB and successful LBB capture.
• DSP may be anatomical (shallow lead) or functional (distal conduction disease); both produce a broad paced QRS and less LV lateral wall pre-excitation.
• LOT-CRT is most useful when LBBAP cannot fully resynchronise — wide baseline QRS and DSP capture.
• Anodal capture can be haemodynamically detrimental despite a similar paced QRS; unipolar pacing should be preferred when possible.

Limitations of the document

• Acute study only — LV dP/dtmax and QRS duration are surrogates; long-term clinical outcomes were not assessed.
• Small sample (n = 48) and subgroup analyses are underpowered.
• Population enriched for IVCD and DSP, limiting generalisability to typical LBBB CRT candidates.
• No patients with complete AV block or AF, in whom fusion-based resynchronisation and AV optimisation are not possible.
• LOT-CRT necessarily used bipolar LBBAP, so anodal capture may have blunted the LOT-CRT haemodynamic result.
• Pacing configurations were tested in a fixed order (BVP, unipolar LBBAP, bipolar LBBAP, LOT-CRT), not randomised.
• No diastolic function assessment; LV dP/dtmax reflects systolic contractility only.
• LBBB vs IVCD classification is subjective and the two conditions can coexist.
• Industry sponsorship: Medtronic funded the study and employs several authors; multiple investigators report device-industry honoraria.

Key Concepts Mentioned

• concepts/LOT-CRT — the hybrid strategy
• concepts/Left-Bundle-Branch-Area-Pacing — the pacing lead
• concepts/Left-Bundle-Branch-Area-Pacing — the failed-capture category
• concepts/Cardiac-Resynchronization-Therapy — the clinical context
• concepts/Electrical-Resynchronization-Metrics — QRS duration and LV dP/dtmax
• concepts/Left-Bundle-Branch-Area-Pacing — the pacing-polarity effect

Key Entities Mentioned

• CSPOT (Conduction System Pacing Optimized Therapy) study — the trial
• Medtronic — sponsor and device supplier
• Jagiellonian University — lead site

Wiki Pages Updated

• Created: wiki/sources/lot-crt-circep-2024.md
• Updated: wiki/concepts/LOT-CRT.md
• Updated: wiki/concepts/Left-Bundle-Branch-Area-Pacing.md
• Updated: wiki/concepts/Electrical-Resynchronization-Metrics.md
• Updated: wiki/sourceindex.md
• Updated: log.md