Key result
Vericiguat linked to ~29 mL/m² LVESVI reduction in high-risk HFrEF at 8 months.
Why the study?
Vericiguat is approved for high-risk HFrEF, yet its left ventricular and left atrial reverse remodelling profile remained incompletely characterised.
Does vericiguat therapy improve left ventricular and left atrial reverse remodelling in adults with high-risk HFrEF and a recent worsening heart failure event?
Observational (n=41)
No
Does vericiguat therapy improve left ventricular and left atrial reverse remodelling in adults with high-risk HFrEF and a recent worsening heart failure event?
In patients with high-risk HFrEF, 8 months of vericiguat therapy was associated with significant left ventricular and left atrial reverse remodelling, reductions in cardiac biomarkers, and improved health status.
Vericiguat was associated with reverse remodelling in high-risk HFrEF; hypothesis-generating and requires randomized confirmation before practice change.
Background Vericiguat is approved for high-risk heart failure with reduced ejection fraction (HFrEF), yet its left heart reverse remodelling profile remains incompletely characterised. Purpose This study aimed to characterise left ventricular (LV) and left atrial (LA) reverse remodelling during vericiguat therapy in adults with HFrEF. Methods Prospective single-centre, single-arm study of adults with HFrEF (New York Heart Association class II-III; left ventricular ejection fraction [LVEF] ≤40%) receiving guideline-directed medical therapy (GDMT) and experiencing recent worsening heart failure (HF) event (HF hospitalisation within 6 months or outpatient intravenous diuretics within 3 months). Eligibility required stable GDMT (no initiation/discontinuation or dose change in the prior 4 weeks). Participants received vericiguat, initiated at 2.5 mg once daily and uptitrated to 10 mg as tolerated. Baseline and 8-month echocardiography (three-dimensional volumetry; two-dimensional speckle-tracking) quantified LVEF, LV end-diastolic and end-systolic volume indices (LVEDVI/LVESVI), mass index (LVMI), global longitudinal strain (LVGLS), LA volume index (LAVI), emptying fraction (LAEF) and strain (reservoir/conduit/contractile; LASr/LAScd/LASc), NT-proBNP, high-sensitivity cardiac troponin T (hs-cTnT) and Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) were assessed; paired analyses were used. Results Among 41 enrolled patients, 36 (87.8%) completed 8-month echocardiography; 30/36 (83.3%) achieved the 10 mg dose. Of these, 25/36 (69%) were on ≥2 foundational GDMT classes for ≥60 days. LV remodelling was observed, with LVESVI decreased by 29.1 mL/m² (95% CI -37.81 to -20.28; P<0.001) and LVEF increased by 12.8 percentage points (95% CI 8.96 to 16.62; P<0.001). LVEDVI decreased by 26.7 mL/m² (95% CI -36.65 to -16.68; P<0.001), LVGLS improved (change -3.51%, 95% CI -4.67 to -2.34; P<0.001), and LVMI decreased by 11.23 g/m² (95% CI -27.40 to -4.20; P<0.001). LA function improved, with LAEF increased by 5.92 percentage points (95% CI 0.51 to 11.32; P=0.033) and LASr increased by 6.12% (95% CI 3.27 to 8.97; P<0.001). Conduit and contractile strain also improved (LAScd change -3.69%, 95% CI -5.54 to -1.83; P<0.001; LASc change -2.67%, 95% CI -4.76 to -0.58; P=0.014). Biomarkers decreased: NT-proBNP geometric mean ratio (GMR; 8-month/baseline) 0.323 (95% CI 0.210 to 0.498; P<0.001), mean change −1348.8 pg/mL, hs-cTnT GMR 0.827 (95% CI 0.708 to 0.966; P=0.016) with median change -1.8 ng/L (IQR -8.75 to 0.00). KCCQ-12 increased by 10.23 points (95% CI 2.22 to 18.24; P=0.014). Conclusion In high-risk HFrEF, 8 months of vericiguat therapy was associated with left-heart reverse remodelling (reduced LVESVI, increased LVEF, improved LVGLS and reduced LVMI) and enhanced LA function (increased LAEF and improved LA phasic strain), accompanied by biomarker reductions and improved patient-reported health status.figure1figure2
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Yin et al. (2026) conducted an observational in High-risk heart failure with reduced ejection fraction (HFrEF) (n=41). Vericiguat vs. Baseline (paired single-arm comparison) was evaluated on Change in left ventricular end-systolic volume index (LVESVI) and left ventricular ejection fraction (LVEF) at 8 months (MD -29.1 mL/m² for LVESVI; MD +12.8 percentage points for LVEF, 95% CI -37.81 to -20.28, p=<0.001). Vericiguat therapy for 8 months in high-risk HFrEF decreased LVESVI by 29.1 mL/m² (P<0.001) and increased LVEF by 12.8 percentage points (P<0.001).
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