Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Dutch Research Council (NWO) Background Left bundle branch area pacing (LBBAP) has been introduced as an alternative, more physiological pacing strategy to biventricular pacing (BiVP). LBBAP can result in selective LBB pacing (sLBBP), non-selective LBB pacing (nsLBBP), or LV septal pacing (LVSP). Direct comparison between the different pacing strategies is challenging due to the practical implications of performing multiple pacing procedures within the same patients, as well as the large heterogeneity of underlying disease in patients. Computational models can be used to perform controlled in silico experiments and to compare all possible pacing modalities under the same conditions. Aim To investigate the effects of LBBAP strategies versus BiVP on cardiac mechanics and hemodynamics in a set of well-defined virtual heart failure patients. Methods An electrophysiological model was used to calculate biventricular electrical activation maps during LBBB and the different pacing strategies. The resulting regional activation times were imposed to the well-validated CircAdapt model of the human four-chamber heart and circulation. A set of virtual patients at different stages of heart failure are then defined within the CircAdapt framework, which is achieved by decreasing the contractility of the LV myocardium, such that LVEF≤35%. The CircAdapt model is then used to compute regional ventricular strain patterns and myocardial work as well as global ventricular pump function during LBBB, BiVP and the different LBBAP modalities. Results Selective LBBP is best at restoring mechanical homogeneity in LV contraction as evidenced by simulated wall strains waveforms (Fig 1, Left). NsLBBP increases septal dyssynchrony and introduces small pre-stretch in the LVfw (1.3±0.3%). This effect is more pronounced in LVSP (2.4±1.4%). In BiVP, pre-stretch occurs only in a single LV free wall (LVfw) segment, but all septal segments display a distinct oscillatory pattern. Work load homogeneity (Fig 1, Center) was best restored in sLBBP (4.9±1.1 kPa). NsLBBP lead to reduced homogeneity (4.9±1.8 kPa). LVSP reduced this further (4.8±2.6kPa), while BiVP performed similarly (4.6±2.6kPa) to LVSP. All modalities vastly improved on the baseline LBBB (4.06±5.6 kPa). Hemodynamically (Fig 1, Right), sLBBP showed greatest improvement in LV function (LVESV:-8.1%; LVEF:+6.8%; MLAP:-16.4%; LVdp/dtmax:+12.8%), followed by nsLBBP (LVESV:-7.2%; LVEF:+6.0%; MLAP:-14.5%; LVdp/dtmax:+12.5%), LVSP (LVESV:-5.6%; LVEF:+4.6%; MLAP:-11.7%; LVdp/dtmax:+12.358%) and finally BiVP (LVESV: -4.6%; LVEF:+3.8%; MLAP:-9.3%; LVdp/dtmax:+9.8%) Conclusion We were able to simulate LBBB and subsequent pacing strategies in virtual heart failure patients. This approach allowed direct comparison of mechanical and hemodynamic effects of BiVP and LBBAP modalities without confounding variables. Our results indicate that all LBBAP modalities perform at least similar to bi-ventricular pacing regardless of mechanical viability.
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