Size Matters

Abstract

Background: In patients with left bundle branch block (LBBB), QRS duration (QRSd) depends on left ventricular (LV) dimension. Previously, we demonstrated that normalizing QRSd to LV dimension, to adjust for variations in LV size, improved prediction of hemodynamic response to cardiac resynchronization therapy (CRT). In addition, sex-specific differences in CRT outcome have been attributed to normalized QRSd. The present study evaluates the effect of normalization of QRSd to LV dimension on prediction of survival after CRT implantation. Methods: In this 2-center study, we studied 250 heart failure patients with LV ejection fraction ≤35% and QRSd ≥120 ms who underwent cardiac magnetic resonance imaging before CRT implantation. LV end-diastolic volumes were used for QRSd normalization (ie, QRSd/LV end-diastolic volumes). The primary end point was a combined end point of death, LV assist device, or heart transplantation. Results: During a median follow-up of 3.9 years, 79 (32%) patients reached the primary end point. Using univariable Cox regression, unadjusted QRSd was unrelated to CRT outcome ( P =0.116). In contrast, normalized QRSd was a strong predictor of survival (hazard ratio, 0.81 per 0.1 ms/mL; P =0.008). Women demonstrated higher normalized QRSd than men (0.62±0.17 versus 0.55±0.17 ms/mL; P =0.003) and showed better survival after CRT (hazard ratio, 0.52; P =0.018). A multivariable prognostic model included normalized QRSd together with age, atrial fibrillation, renal function, and heart failure cause, whereas sex, diabetes mellitus, strict left bundle branch block morphology, and LV end-diastolic volumes were expelled from the model. Conclusions: Normalization of QRSd to LV dimension improves prediction of survival after CRT implantation. In addition, sex-specific differences in CRT outcome might be attributed to the higher QRSd/LV end-diastolic volumes ratio that was found in selected women, indicating more conduction delay.

The relationship between ECG predictors of cardiac resynchronization therapy benefit

“…The definition of proper predictors and the analysis of their contribution represent a present challenge. The QRS narrowing index (QI) [25] and QRS duration normalized to LV end-diastolic volume [26] have been recently introduced and are potentially promising parameters. Other suggested parameter is the interventricular conduction delay [27–29] or the multi-parametric models, based on different properties including biomarkers [30].…”

“…The result is limited by access to corresponding data. According to review in Cardiac Electrophysiology [31], the promising predictors defined in the 2018 year are the QRS duration normalized to LV end-diastolic volume [26]; VED [9]; and interventricular delay [30]. The different imaging methods such as tissue Doppler imaging, 2D speckle echocardiography, cardiac computed tomography (CCT), single positron emission computed tomography (SPECT), and cardiac magnetic resonance (CMR) are being extensively studied in relation to CRT, but are still far from wide use due to their various limitations [32].…”

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

“…Varma et al 7 demonstrated in 130 patients that sex differences in volumetric CRT response resolved by normalization of the QRSd for heart size using LV mass or volumes. In addition to these findings, Zweerink et al 14 suggested that a higher QRS/LVEDV ratio in women might explain their better long-term survival. This hypothesis, however, should be interpreted with caution because the study was not designed to investigate sex-based differences in CRT outcomes and because the authors failed to index LVEDV to BSA or transform serum creatinine values to kidney function.…”

“…The notion that women may have greater LV dyssynchrony than men is not new. 3,7,14,26 Two large patient cohort studies displayed that female CRT recipients more frequently show mechanical dyssynchrony on 2-dimensional echocardiography than their male counterparts. 10,26 Moreover, because women have smaller hearts, any single QRSd may represent greater retardation of myocardial conduction.…”

“…12,13 It has been suggested that because female hearts are smaller, they may experience, on a relative basis, greater left ventricular (LV) dyssynchrony compared with male hearts at identical QRSd, hence the greater CRT benefit. 7,14 While the extent of electrical dyssynchrony is, in part, reflected by the QRSd, recent work displayed that quantification of electrical dyssynchrony may better be achieved with the vectorcardiographic QRS area. [15][16][17][18] By normalizing the QRS area for LV dimensions using the LV end-diastolic volume (LVEDV), the impact of a relatively larger electrical dyssynchrony in women can be assessed for the involvement in their better CRT outcomes.…”