Hemodynamic effects of vericiguat in symptomaticHFrEF patients: insights from right heart catheterization study

Abstract Background Vericiguat is recommended in the guidelines as Class IIb for patients with heart failure with reduced ejection fraction (HFrEF) who continue to have persistent symptoms despite receiving standard therapy. However, the precise effects of vericiguat on pulmonary and systemic hemodynamics and cardiac performance remain unclear. Purpose This study aimed to investigate the hemodynamic impact of vericiguat in 12 symptomatic HFrEF patients who experienced worsening HF despite receiving standard therapy with the four foundational heart failure medications, using right heart catheterization (RHC). Methods On day 1, RHC was performed via the right internal jugular vein and a balloon-tripped pulmonary artery thermodilution catheter was placed. On day 2 and 3, RHC data were measured at 15min before and 30min, 1hr, 2hr, 3hr and 5hr after intake of 2.5mg vericiguat. RHC data on day 2 and 3 were averaged and the catheter was removed after the RHC measurements on day 3. RHC was repeated on a median day of 105(quartiles 37,168). The acute hemodynamic effects of vericiguat were assessed using a comparison of six RHC measures, including pulmonary artery wedge pressure (PAWP), mean pulmonary artery pressure (MPAP), mean arterial blood pressures (MABP), pulmonary (PVR) and systemic vascular resistances (SVR) and cardiac index (CI), at 15minutes before intake of vericiguat 2.5mg with those at 30minutes to 5hours after that. The chronic hemodynamic effects of vericiguat were evaluated by comparing the six RHC measures on day 1 with those on day 105(37,168). Results Participant characteristics on day 1 were age 63.5(53.5,70)yrs., 16.7%(N=2) women, height 164.3(155,171.3)cm, weight 64.6(54.8,75.1)kg, body mass index 23.8(20,26.3), systolic 101.5(90.5,111.5)mmHg and diastolic blood pressures 60.2(53.5,65)mmHg, heart rate 65.5(56,72)bpm, New York Heart Association functional class Ⅱ 50%(N=6), Ⅲ 16.7%(N=2) and Ⅳ 33.3%(N=4), estimated glomerular filtration rate 44.5(34.5,53.5)mL/min/1.73m2, left-ventricular ejection fraction 19.9(14.5,24.5)% and diastolic diameter 68(60.5,72.5)mm, left-atrial diameter 45(36.5,50.5)mm and brain natriuretic peptide level 419(254,479)pg/mL. Oral intake of vericiguat 2.5mg decreased PAWP (11[7.5,15]mmHg) and MPAP (19.3[14.3,26.8]mmHg) before the intake to PAWP (9.3[6.8,14]mmHg) and MPAP (17.5[12.5,24]mmHg) at 30min after that (both P<0.05[crude P<0.0017])(Figure A) while comparable changes in MABP, PVR, SVR and CI and the other timepoints (all P>0.05[crude P<0.0017]). Vericiguat was titrated to 2.5mg 25% (N=3), 5mg 50% (N=6) and 10mg 25% (N=3) on day 105 (37,168), in which PAWP (9.5[6.5,12.5]mmHg) was decreased from PAWP (14.5[9.5,19.5]mmHg) on day 1 (P<0.05[crude P<0.0083])(Figure B) while comparable changes in the other RHC parameters (all P>0.05[crude P<0.0083]). Conclusions The consistent reduction in PAWP underscores vericiguat's well-tolerated nature and potential to enhance cardiac performance in patients with HFrEF.