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

Abstract

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.

LBBB and heart failure—Relationships among QRS amplitude, duration, height, LV mass, and sex

“…Normalization of QRSd to LV mass resulted in the widest separation of sexes (24% greater), in the direction of sex‐specific responses (women greater than men) (Figure 3). Other studies have demonstrated that QRSd/LV mass (and also normalized QRS area, which integrates QRS amplitude as well as duration) may be sex‐independent metrics for superior patient selection 4,27–29 . We observed no correlation between QRSd and height but LV mass correlated with height (Figure 2A) indicating that body size also affects LV size in HF patients as well as normals.…”

“…More prolonged (>150 ms QRS duration [QRSd]) is favored. QRS area, which reflects voltage amplitude as well as QRSd, may add value 4 . Larger areas predicate CRT response.…”

“…QRS amplitude is traditionally linked to LV mass and/or loss of canceling electrocardiographic forces 7 . Notably, recent guidelines propose that characteristics such as female sex, body size and/or LV size should be considered, since women gain more from CRT 4,8,9 . It is curious why such nonelectrical factors should modulate CRT efficacy.…”

Aetiology of Heart Failure, Rather than Sex, Determines Reverse LV Remodelling Response to CRT

“…It has however been reported that in patients with LBBB, women more frequently have true LBBB morphology and more mechanical dyssynchrony at shorter QRS durations compared to men, indicating that also dyssynchrony should be interpreted differently between women and men [ 32 ]. Using a sophisticated approach were QRS area was normalized to heart size, using the QRS area/LVEDV ratio, Salden and colleagues showed that women have a larger QRS area/LVEDV ratio and this contributes to a greater change in LVESV in women after CRT [ 33 ]. This association remained significant after adjusting for, among other things, ischemic etiology (classified by medical history of myocardial infarction or revascularization).…”

2023 HRS/APHRS/LAHRS guideline on cardiac physiologic pacing for the avoidance and mitigation of heart failure

“…Similar results were seen in a single-center retrospective analysis 117 The potential mechanisms for sex differences in CRT response in terms of QRS duration may be related to anatomic differences, especially patient height, with a greater CRT benefit seen in shorter patie nts. 112,113,[115][116][117][118]121,129,130 In a meta-analysis, 122 longer QRS duration and shorter height (mean 163.8 cm [64 in] in the shortest tercile),…”