Strain-based staging as a unifying concept in cardiac resynchronization therapy

Abstract Aims Left bundle branch block (LBBB) septal strain patterns are associated with left ventricular (LV) reverse remodeling after cardiac resynchronization therapy (CRT). However, their prognostic value and impact in patients undergoing CRT, as well as in CRT-eligible patients receiving conservative treatment remains underexplored. This study aimed to validate the prognostic significance of LBBB strain patterns and elucidate the mechanisms underlying CRT response by evaluating their interaction with myocardial scar and clinical outcomes. Methods and results In this multicenter study, 267 CRT patients underwent pre-implantation speckle-tracking strain analysis, with 155 also undergoing cardiac magnetic resonance imaging. CRT-treated patients were compared to 116 CRT-eligible conservatively treated patients. LBBB septal strain curves were categorized into five stages (LBBB-0 to LBBB-4). Endpoints included all-cause mortality, heart transplantation, and volumetric response in CRT recipients. CRT outcomes showed a stepwise improvement across LBBB stages in volumetric response (p<0.001) and survival (log-rank p=0.002). Myocardial scar, present in 52% of CRT patients, inversely correlated with LBBB stages (p=0.003). After multivariable adjustment, LBBB stages independently predicted volumetric response (OR 2.30, p<0.001) and survival (HR 0.64, p=0.038), while scar burden did not. Survival benefits were greater in CRT-treated patients than in conservatively treated patients, ranging from HR 1.42 (p=0.436) in LBBB-0 to HR 16.49 (p<0.001) in LBBB-4. Conclusions LBBB strain stages independently predict CRT outcomes, with lower stages associated with attenuated benefits, possibly due to higher scar burden. This classification provides a framework for understanding LBBB pathophysiology and CRT response.