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Effect of vericiguat on left ventricular structure and function in patients with heart failure with reduced ejection
Burkert Pieske1, Elisabeth Pieske-Kraigher1, Carolyn S P Lam2
1Charité University Medicine, German Heart Center, Berlin, Germany.
Insights
Vericiguat did not significantly alter left ventricular (LV) structure or function in patients with heart failure with reduced ejection fraction (HFrEF) over 8 months. However, the VICTORIA trial showed vericiguat reduced heart failure hospitalizations and cardiovascular death.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Vericiguat demonstrated efficacy in reducing heart failure (HF) hospitalizations and cardiovascular death in the VICTORIA trial for patients with HF with reduced ejection fraction (HFrEF).
- The impact of vericiguat on reverse left ventricular (LV) remodeling in HFrEF patients remains unclear.
Purpose of the Study:
- To evaluate the effects of vericiguat compared to placebo on LV structure and function after 8 months of therapy in HFrEF patients.
- To investigate potential correlations between LV remodeling and the clinical benefits observed with vericiguat.
Main Methods:
- A subset of HFrEF patients from the VICTORIA trial underwent standardized transthoracic echocardiography (TTE) at baseline and 8 months.
- Co-primary endpoints were changes in LV end-systolic volume index (LVESVI) and LV ejection fraction (LVEF), assessed by a blinded echocardiographic core laboratory.
- 419 patients with high-quality paired TTE data were included, with baseline characteristics well-balanced between the vericiguat (n=208) and placebo (n=211) groups.
Main Results:
- Both vericiguat and placebo groups showed significant improvements in LVESVI and LVEF over 8 months.
- Absolute changes in LVESVI and LVEF were not significantly different between the vericiguat and placebo groups (LVESVI: -3.8 vs. -7.1 ml/m², p=0.07; LVEF: +3.2% vs. +2.4%, p=0.31).
- The rate of the primary composite endpoint showed a trend towards being lower with vericiguat (19.8 per 100 patient-years) compared to placebo (29.6 per 100 patient-years) (p=0.07).
Conclusions:
- Significant improvements in LV structure and function were observed over 8 months in both vericiguat and placebo groups within a high-risk HFrEF population.
- Vericiguat did not demonstrate a significant effect on reverse LV remodeling compared to placebo in this study.
- Further research is needed to elucidate the mechanisms underlying vericiguat's clinical benefits in HFrEF.
Aim:
Vericiguat significantly reduced the primary composite outcome of heart failure (HF) hospitalization or cardiovascular death in the VICTORIA trial. It is unknown if these outcome benefits are related to reverse left ventricular (LV) remodelling with vericiguat in patients with HF with reduced ejection fraction (HFrEF). The aim of this study was to compare the effects of vericiguat versus placebo on LV structure and function after 8 months of therapy in patients with HFrEF.
Methods And Results:
Standardized transthoracic echocardiography (TTE) was performed at baseline and after 8 months of therapy in a subset of HFrEF patients in VICTORIA. The co-primary endpoints were changes in LV end-systolic volume index (LVESVI) and LV ejection fraction (LVEF). Quality assurance and central reading were performed by an echocardiographic core laboratory blinded to treatment assignment. A total of 419 patients (208 vericiguat, 211 placebo) with high-quality paired TTE at baseline and 8 months were included. Baseline clinical characteristics were well balanced between treatment groups and echocardiographic characteristics were representative of patients with HFrEF. LVESVI significantly declined (60.7 ± 26.8 to 56.8 ± 30.4 ml/m2 ; p < 0.01) and LVEF significantly increased (33.0 ± 9.4% to 36.1 ± 10.2%; p < 0.01) in the vericiguat group, but similarly in the placebo group (absolute changes for vericiguat vs. placebo: LVESVI -3.8 ± 15.4 vs. -7.1 ± 20.5 ml/m2 ; p = 0.07 and LVEF +3.2 ± 8.0% vs. +2.4 ± 7.6%; p = 0.31). The absolute rate per 100 patient-years of the primary composite endpoint at 8 months tended to be lower in the vericiguat group (19.8) than the placebo group (29.6) (p = 0.07).
Conclusions:
In this pre-specified echocardiographic study, significant improvements in LV structure and function occurred over 8 months in both vericiguat and placebo in a high-risk HFrEF population with recent worsening HF. Further studies are warranted to define the mechanisms of vericiguat's benefit in HFrEF.
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