Impact of guideline-directed medical therapy on LVEF-recovery in de novo HFrEF in females: analysis from a bicentric patient cohort

Aim: 

Patients with heart failure (HF) and severely reduced left ventricular ejection fraction (LVEF) ≤ 35% (HFrEF) are at elevated risk for arrhythmias and sudden cardiac death (SCD). SCD prevention in this population at risk can be achieved by prescribing the Wearable Cardioverter Defibrillator (WCD) According to the latest ESC-HF guideline (HF-GL) GDMT consists of the well-known “fantastic four” combination. It is known that less females are diagnosed with HFrEF than men and also experience under-treatment with GDMT. The aim of this analysis was to evaluate in a real-word patient cohort the prescription of GDMT in females and the influence on ICD-indication, LVEF recovery and ventricular arrhythmia. 

Methods: 

We performed a retrospective bi-centric cohort study at 2 tertiary care centres, examining 262 patients fitted with a WCD from 03/2015 until 03/2024 for primary prevention due to de novo HFrEF. We included 114 before and 148 patients after implementation of the HF-GL in 09/2021. For every patient we calculated Quad Medical Score (QMS) as surrogate of guideline adherence. LVEF was assessed at baseline and 3 months (FU) after GDMT initiation. 

Results:

A total of 262 patients were analysed: 18% female (n = 48; 18 before and 30 females after GL-update), ischemic heart disease (ICM) in 55% (n=144). In patients, treated before HF-GL update, m-LVEF was 25% at baseline with Δ-LVEF of +10% at FU, while patients treated after HF-GL update showed a recovery up to m-LVEF 35% resulting in a Δ-LVEF of 10% at FU (p<0.05; BL vs. FU). In total 3% of patients showed ventricular tachycardia during the FU. Mean QMS in all patients before and after HF-GL update was 9 vs. 18, (p<0.001). Median QMS of the cohor0 was 12. Dividing the groups in QMS < 12 and QMS ≥ 12 showed a significantly higher LVEF at FU in higher QMS values (36% vs. 32%, p<0.01). In line with this, a higher QMS resulted in lower rate of ICD indications (48% vs. 67%, p=0.01).

In females the data show no difference in treatment adherence of GDMT as there is also significant improvement in the prescription of SGLT-2 inhibitors (6% before GL vs. 90% after GL; p < 0.001), in ARNI (22% before GL vs. 63% after GL; p < 0.01) and improvement in QMS (9 at BL vs. 20 at FU; p < 0.001).  There is no significant difference, but trend towards reduced ICD indication (p=0.18) and higher LVEF after three months (p=0.43) in this small subgroup of patients.

Conclusion: 

The HF GL update had a significant impact on the medication prescribed for patients with HFrEF in our centres. Females showed also a high prevalence of GDMT with high QMS after GL-update and no-undertreatment in our patient cohort. 

Our data also suggest that adequate implementation of the current guidelines resulted in lower rate of ICD indications and larger LVEF recovery. We showed that a higher QMS was correlated with greater LVEF recovery. Ventricular arrhythmias occurred during the GMDT initiation, indicating the need for WCD, also in females. 

A: Distribution of ICD-indication in females after three months, divided before and after guideline update in females (p = 0.18). B: LVEF recovery after three months of FU, p=0.43. C: Distribution of QMS in women before (blue) and after (red) guideline update (pre vs. post p < 0.001). D: Occurrence of ventricular tachycardia or ventricular fibrillation (black) in women treated before and after guideline update. p = 0.43. BL: baseline, FU: follow up, QMS: Quad medication score.