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Aims  Historically, cardiac resynchronization therapy (CRT) response in non‐left bundle branch block (non‐LBBB) patients has been suboptimal in comparison with that observed in left bundle branch block patients. The electrical activation pattern of the left ventricle (LV) is different between these two QRS morphologies. Small non‐randomized studies have suggested that targeting the LV wall with greatest electrical delay may be superior to conventional anatomical pacing from the lateral wall in non‐LBBB patients. This article outlines the design and rationale of a prospective, randomized, pilot study, which assesses the effect of a non‐traditional LV lead implant strategy on the clinical composite score after 12 months of follow‐up in a non‐LBBB patient population.    Methods  All patients will receive an Abbott quadripolar CRT‐D system (Quartet 1458Q LV lead with Unify Quadra™, Quadra Assura™ CRT‐D or any market‐approved CRT‐D device with quadripolar pacing capabilities). Patients will be randomized in a 2:1 ratio between a QLV‐based implant strategy vs. standard of care. Up to 250 patients will be enrolled in the study.    Conclusions  If the primary endpoint is achieved, this study will provide important information about reducing the non‐responder rate in non‐LBBB patients and provide further evidence for the QLV‐based implant strategy.

Rationale and design for ENHANCE CRT: QLV implant strategy for non‐left bundle branch block patients