Female gender is an independent predictor of clinical benefit from cardiac resynchronisation therapy - results from the BIOWOMEN study
Authors: Van Erven L , Voros G , Calvi V , Osca J , Vernooy K , Quesada A , Martinez J G , Maass A , Nof E , Tolosana J , Pardo M , Barr C , Ellery S , Nurnberg M , Zamorano J L 
Published: November 2023

Abstract

Background
Presently, only indirect evidence indicates that women may benefit more from CRT than men. Since some gender-specific baseline variables are related to CRT benefit, it is unclear whether gender by itself is predictive of CRT benefit after correction for all these differences. We aimed to examine the impact of gender-specific differences on CRT response.

Methods
The BIOWOMEN study is a prospective, multicenter, international study, that enrolled 206 women and 214 men with a standard indication for CRT. The change in left-ventricular ejection fraction (LVEF) at 12 months follow-up after CRT was used as a primary endpoint to measure CRT benefit. The LVEF was quantified by a core lab blinded to gender and other patient characteristics.
We used a median split to dichotomize continuous variables, if required. Uni- and multivariate analyses were used to identify baseline variables that are connected to an increase in LVEF. The latter model allows to estimate the change in LVEF that can be attributed to gender and other baseline variables.

Results
At baseline, women and men had similar LVEF, age and QRS duration, but there was a significant difference in the presence of left bundle branch block (88.3% vs. 79.9%, P=0.023). Women had less often ischemic heart disease (18.4% vs. 51.4%, P&lt;0.001) and previous history of myocardial infarction (MI, 6.8% vs. 32.2%, P&lt;0.001), but more severe heart failure symptoms (NYHA I/II/III 7%/51%/42% vs. 10%/63%/27%, P=0.019) and a shorter 6 minute walk test (345±117 vs. 409±148 m, P&lt;0.001).
In univariate analysis, women presented a significantly larger gain of 3.1 points in LVEF (+14.6±12.4% vs. +11.5±11.6%, P=0.004) compared to men. Additionally, the rate of CRT responders (defined as an improvement in LVEF &gt;5%) was higher in women (82.0% vs. 70.6%, p=0.008). Other variables predictive of larger improvement in LVEF were LBBB (13.9±11.9% vs. 8.4±12.2%, P&lt;0.001), NYHA I compared to NYHA II or III (I: 18.4±11.8%; II: 12.2±12.0%; III: 13.1±12.0%), no history of MI (14.0±11.6% vs. 8.9±13.0%, P&lt;0.001), and an LVEF &lt;32% at baseline (16.9±11.8% vs. 9.7±11.3%, P&lt; 0.001).
In multivariate analysis, female gender remained a significant predictor of a better improvement in LVEF (+2.6% absolute, P=0.036). Other significant predictors were LBBB (+5.2%, P&lt;0.001), NYHA I (+6.9%, P&lt;0.001 vs. NYHA II and +6.3%, P=0.004 vs. NYHA III), no history of MI (+4.1%, P=0.007), baseline LVEF &lt;32% (+7.5%, P&lt;0.001).

Conclusion
Gender has an important impact on the relevant baseline clinical differences that determine CRT response. Whereas women more often have LBBB and no prior-MI, suggesting more benefit from CRT, the BIOWOMEN study shows for the first time that female gender itself is linked to a larger clinical benefit from CRT. These gender-based baseline parameters need to be considered in daily clinical practice when screening patients for CRT, with particular attention to females.