Response to cardiac resynchronization therapy (CRT) is reduced in patients with posterolateral scar. Multipolar pacing leads offer the ability to select desirable pacing sites and/or stimulate from multiple pacing sites concurrently using a single lead position. Despite this potential, the clinical evaluation and identification of metrics for optimization of multisite CRT (MCRT) has not been performed. The efficacy of MCRT via a quadripolar lead with two left ventricular (LV) pacing sites in conjunction with right ventricular pacing was compared with single-site LV pacing using a coupled electromechanical biophysical model of the human heart with no, mild, or severe scar in the LV posterolateral wall. The maximum dP/dt(max) improvement from baseline was 21%, 23%, and 21% for standard CRT versus 22%, 24%, and 25% for MCRT for no, mild, and severe scar, respectively. In the presence of severe scar, there was an incremental benefit of multisite versus standard CRT (25% vs 21%, 19% relative improvement in response). Minimizing total activation time (analogous to QRS duration) or minimizing the activation time of short-axis slices of the heart did not correlate with CRT response. The peak electrical activation wave area in the LV corresponded with CRT response with an R(2) value between 0.42 and 0.75. Biophysical modeling predicts that in the presence of posterolateral scar MCRT offers an improved response over conventional CRT. Maximizing the activation wave area in the LV had the most consistent correlation with CRT response, independent of pacing protocol, scar size, or lead location.
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