Abstract Background Left bundle branch area pacing (LBBAP) has been postulated as an alternative to traditional cardiac resynchronization therapy via biventricular pacing (BiV) in heart failure patients with wide QRS. Limited data is available regarding the acute hemodynamic response of LBBAP and the combination of LBBAP and coronary venous (LVcv) pacing (LOT-CRT). Purpose We sought to compare the acute hemodynamic and ECG effects of traditional CRT (BiV or LV-only) versus LBBAP and LOT-CRT in CRT candidates with advanced conduction disease. Methods In this multi-centre study (5 EU and 7 US centres), 48 subjects (mean age 65.8 years, 67% males, LV ejection fraction 29.4%) with either nonspecific interventricular conduction delay (NIVCD, n = 29) or left bundle branch block (LBBB; n =19; based upon strict criteria AHA/ACC/HRS plus Strauss) underwent an acute hemodynamic study to determine the % change in +LV dP/dtmax from baseline atrial pacing versus BiV, LBBAP, or LOT-CRT. Each therapy pacing configuration was applied 4 times at 5 different atrioventricular (AV) delays. QRS shortening was assessed using standard 12-lead ECG. Results Successful LBBAP lead implantation was achieved in 27 patients (56%) using current EHRA criteria. Twenty-one patients (44%) were categorized as deep septal pacing (DSP), due to suboptimal lead penetration or advanced left conduction system disease with broad paced QRS complexes and absent V1-r-wave. The increase in AV-optimized dP/dtmax for the different pacing configurations is displayed in the Figure, left panel. LOT-CRT dP/dtmax % improvement was 25.8%, significantly higher than LBBAP configurations (p&amp;lt;0.01), either unipolar-LBBAP (19.3%), or bipolar-LBBAP (16.4%), but not different from BiV (26.4%). QRS shortening was greater in LOT-CRT (29.5ms) vs. unipolar-LBBAP (11.9ms), bipolar-LBBAP (11.7ms), or BiV (18.5ms), all p&amp;lt;0.01. Sub-group analysis indicated the hemodynamic benefit of adding LVcv pacing when LBBAP strategy was pursued (Figure, right panel) depended on obtaining LBBAP rather than DSP (p &amp;lt; 0.01) and baseline QRS duration (p = 0.03). The largest benefit was observed among subjects with a baseline QRS wider than the observed cohort mean (171ms) and DSP only, where LOT-CRT provided 14.5% (5.0-24.1%) greater dP/dtmax improvement and 20.8ms (12.8-28.8ms) greater QRS duration shortening than unipolar DSP. Conclusions In a CRT cohort with advanced conduction disease, LOT-CRT provided greater acute hemodynamic benefit than LBBAP strategy (i.e. including also DSP cases). Patients with wider QRS or suboptimal outcome of LBBAP strategy (DSP) are more likely to benefit from addition of a LVcv lead to implement LOT-CRT.Figure 1

Multicenter hemodynamic assessment of the LOT-CRT strategy: when is one lead enough for resynchronization?