Left ventricular ejection fraction, ventricular remodelling and outcomes after sacubitril - valsartan in a real-life cohort

Background

Sacubitril/valsartan (SV) has shown to improve prognosis in patients with heart failure with reduced ejection fraction (HFrEF). Beyond its impact on clinical outcomes, SV also promotes ventricular reverse remodelling. However, in real-world, the left ventricular ejection fraction (LVEF) trajectories and clinical impact after SV started remains not fully stablished.

Aims

To assess the LVEF trajectories after SV and long-term clinical outcomes in patients with HFrEF treated with SV in real life cohort.

Methods

We conducted an observational study including patients with HFrEF who initiated SV between 2017 and 2019. Ventricular reverse remodelling was defined as an increase in LVEF > 5% between baseline and follow-up echocardiography. Based on follow-up LVEF, patients were classified into: ≤40%, 41–49% and ≥50%. The primary endpoint was a composite of all-cause mortality, HF admission and visit to emergency department. A survival analyses was performed using Kaplan–Meier curves and log-rank tests.

Results

A total of 379 patients were included (mean age 69±12 years, 25% women), with a median follow-up of 6.5 years. The main aetiology was ischemic (49%) and most patients were in NYHA functional class II (66.4%) and III (33.1%) before SV started. The median LVEF was 34% (28 ; 39).

According to baseline guideline directed medical therapy (GDMT) patients had high use of betablockers (84.1%), MRA (68.6%) and low use of SGLT2i (19%). SV was predominantly initiated at lower doses (77.2%, n=292) (Figure 1).

Ventricular reverse remodelling occurred in 166 patients (54%). Patients who experienced remodelling were younger, had more likely a non-ischemic aetiology, higher baseline LVEF and showed a trend toward better renal function. Patients who achieved higher SV dose were more likely to undergo ventricular remodelling during follow-up.

When stratified by LVEF group at follow-up, a progressive risk reduction was observed across increasing LVEF categories (p<0.001) in the composite endpoint (HF admission or death during follow-up). The main cause of death in the LVEF <40% group was HF and unknown cause, while patients with higher LVEF tended to die from non-cardiac causes (Figures 1 and 2).

Conclusions

In this real-world cohort of HFrEF patients treated with sacubitril-valsartan, ventricular reverse remodelling was associated with better long-term outcomes, fewer HF admissions and lower mortality. These findings highlight the clinical value of echocardiographic monitoring after treatment initiation.Clinical characteristics and outcomesFor image description, please refer to the figure legend and surrounding text.LVEF trajectories and survivalFor image description, please refer to the figure legend and surrounding text.