Cardiac reverse remodelling of left heart during vericiguat therapy for high-risk HFrEF
X Yin, V M F Sim, C X Zhao, H Y C Tao, L R Yin, X T Wang, A P W LeeAbstract
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