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, 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 cardiac resynchronization therapy response in women. For this, the vectorcardiography-derived QRS area is used, since it allows for a more detailed quantification of electrical dyssynchrony compared with conventional electrocardiographic markers. Methods: Data from a multicenter registry of 725 cardiac resynchronization therapy patients (median follow-up, 4.2 years [interquartile range, 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 (LV end-systolic volume change) 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±55 versus 123±58 μVs; P=0.043), which was even more pronounced for the QRSarea/LVEDV ratio (0.76±0.46 versus 0.57±0.34 μVs/mL; P<0.001). After multivariable analyses, female sex was associated with LV end-systolic volume change (β=0.12; P=0.003) and a lower occurrence of the composite outcome (hazard ratio, 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 β 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 nonresponders, female sex remained strongly associated with a lower risk of the composite outcome (adjusted hazard ratio, 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 cardiac resynchronization therapy, but this does not explain their better long-term outcomes.