Mechanism of Prolonged Electro-Mechanical Delay in Late Activated

Abstract Word count: 250 26 27 During left bundle branch block (LBBB) electromechanical delay (EMD), defined as 28 time from regional electrical activation (REA) to onset shortening, is prolonged in the late 29 activated left ventricular (LV) lateral wall compared to the septum. This leads to greater 30 mechanical relative to electrical dyssynchrony. The aim of this study was to determine the 31 mechanism of the prolonged EMD. We investigated this phenomenon in an experimental 32 LBBB dog model (n=7), in patients (n=9) with bi-ventricular pacing devices, in an in vitro 33 papillary muscle study (n=6), and a mathematical simulation model. Pressures, myocardial 34 deformation, and REA were assessed. In the dogs, there was a greater mechanical than 35 electrical delay (82±12 vs. 54±8 ms, p =0.002) due to prolonged EMD in the lateral wall vs. 36 septum (39±8 vs.11±9 ms, p =0.002). The prolonged EMD in later activated myocardium 37 could not be explained by increased excitation-contraction coupling time or increased 38 pressure at the time of REA, but was strongly related to dP/dt at the time of REA (r=0.88). 39 Results in humans were consistent with experimental findings. The papillary muscle study 40 and mathematical model showed that EMD was prolonged at higher dP/dt because it took 41 longer for the segment to generate active force at a rate superior to the load rise which is a 42 requirement for shortening. We conclude that during LBBB prolonged EMD in late activated 43 myocardium is caused by a higher dP/dt at the time of activation, resulting in aggravated 44 mechanical relative to electrical dyssynchrony. These findings suggest that LV contractility 45 may modify mechanical dyssynchrony. 46 47 48 49 50