Sex differences in trajectory of left ventricular reverse remodelling under contemporary GDMT in recent-onset dilated cardiomyopathy

Background Emerging evidence suggests sex differences in clinical characteristics and outcomes in dilated cardiomyopathy (DCM), e.g. females are less likely to develop the disease, have more favorable left ventricular remodeling, yet paradoxically have worse survival than males. However, the sex-specific trajectories of LV reverse remodeling (LVRR) under contemporary guideline-directed medical therapy (GDMT) remain poorly understood. Objectives To explore sex differences in the trajectory of LVRR in patients with recent-onset DCM (RODCM) after contemporary GDMT. Methods This was a single-center cohort study conducted from January 2021 to June 2024 which enrolled patients with RODCM (diagnosed < 6 months). All patients received GDMT and dose titration following guidelines. All patients were followed at 6- and 12-month. The LV volumes were adjusted for body mass index (BMI). LVRR was defined as an absolute increase in left ventricular ejection fraction (LVEF) ≥10% and a reduction in left ventricular end-diastolic volume index (LVEDVi) ≥15%. Results Of the 134 patients, 28.4% were females (n=38) and 71.6% were males (n=96). Females were older (55 ± 11 vs. 48 ± 13 years, P=0.002) with a lower BMI (24.1 ± 4.1 vs. 25.8 ± 4.1 kg/m², P=0.037) but a higher baseline LVEF (35 ± 7% vs. 30 ± 7%, P<0.001). Baseline blood pressure, heart rate, comorbidities, NT-proBNP level and LV volumes were comparable between sexes (Table 1). The use rates of each component of GDMT were similar at baseline and follow-up, except for fewer use of beta-blocker (BB) in females at 12 months (81.6% vs. 93.8%, P=0.032). The females had comparable initial doses of ARNI and BB at baseline (ARNI: 122 ± 61 mg vs. 128 ± 96 mg, P = 0.667; BB: 26 ± 20 mg vs. 32 ± 22 mg, P = 0.181), but lower dose at follow-ups (ARNI: 211 ± 114 mg vs. 277 ± 111 mg, P=0.002 at 6-month; 216 ± 131 mg vs. 299 ± 114 mg, P<0.001 at 12-month; BB: 40 ± 31 mg vs. 57 ± 36 mg, P<0.001 at 6 months; 44 ± 30 mg vs. 62 ± 38 mg, P<0.001 at 12-month) compared to males . From baseline to follow-up, both groups showed comparable changes in LVEDVi (ΔLVEDVi6m-baseline and ΔLVEDVi12m-6m) (Figure 1A). However, females demonstrated smaller improvement in LVEF at 6 months [ΔLVEF6m-baseline: 10% (6-22)% vs. 19% (8-28)%, P=0.001], with less females achieving LVRR (39.5% vs. 63.5%, P=0.011). Subsequently, the improvement in LVEF attenuated, with comparable ΔLVEF12m-6m between groups [2% (-1-7) vs. 3% (0-9), P=0.848]. As a result, a comparable LVEF was observed at both 6-month and 12-month follow-up (Figure 1B). Conclusions Females with RODCM exhibited smaller early improvement in LVEF at 6 months after GDMT compared to males, despite higher baseline LVEF. This sex difference may be attributed to lower doses of GDMT, inherent biological differences, or other unidentified factors. The attenuated LVEF improvement observed in both sexes beyond 6 months suggests that early therapeutic optimization may be critical.