Heart Size Corrected Electrical Dyssynchrony and Its Impact on Sex-specific Response to Cardiac Resynchronization Therapy

Background - Women are less likely to receive cardiac resynchronization therapy (CRT), yet, they are more responsive to the therapy and respond at shorter QRS duration. The present study hypothesized that a relatively larger left ventricular (LV) electrical dyssynchrony in smaller hearts contributes to the better CRT response in women. For this the vectorcardiography-derived QRS area is used, since it allows for a more detailed quantification of electrical dyssynchrony compared to conventional electrocardiographic markers. Methods - Data from a multicenter registry of 725 CRT patients (median follow-up: 4.2 years [IQR: 2.7-6.1]) were analyzed. Baseline electrical dyssynchrony was evaluated using the QRS area, and the corrected QRS area for heart size using the LV end-diastolic volume (QRSarea/LVEDV). Impact of the QRSarea/LVEDV-ratio on the association between sex and LV reverse remodeling (end-systolic volume change: ΔLVESV) and sex and the composite outcome of all-cause mortality, LV assist device implantation or heart transplantation was assessed. Results - At baseline, women (n=228) displayed larger electrical dyssynchrony than men (QRS area: 132±55μVs vs 123±58μVs, p=0.043) which was, even more pronounced for the QRSarea/LVEDV-ratio (0.76±0.46μVs/ml vs 0.57±0.34μVs/ml, p<0.001). After multivariable analyses female sex was associated with ΔLVESV (β 0.12, p=0.003) and a lower occurrence the composite outcome (HR 0.59 (0.42-0.85), p=0.004). A part of the female advantage regarding reverse remodeling was attributed to the larger QRSarea/LVEDV-ratio in women (25-fold change in Beta from 0.12 to 0.09). The larger QRSarea/LVEDV-ratio did not contribute to the better survival observed in women. In both volumetric responders and non-responders, female sex remained strongly associated with a lower risk of the composite outcome (adjusted HR 0.59 (0.36-0.97), p=0.036 and 0.55 (0.33-0.90), p=0.018, respectively). Conclusions - Greater electrical dyssynchrony in smaller hearts contributes in part to more reverse remodeling observed in women after CRT, but this does not explain their better long-term outcomes.