Heart failure patients with preserved ejection fraction (HFpEF) have a higher risk of death, hospitalization, and decreased functional capacity and quality of life. For a study, the researchers determined how well the oral soluble guanylate cyclase stimulator vericiguat affected the Kansas City Cardiomyopathy Questionnaire’s physical limitation score (PLS) (KCCQ). From June 15, 2018, to March 27, 2019, 789 patients with chronic HFpEF and left ventricular ejection fraction 45% or higher with New York Heart Association class II-III symptoms, within 6 months of a recent decompensation (HF hospitalization or intravenous diuretics for HF without hospitalization), and with elevated natriuretic peptides were enrolled at 167 sites in 21 countries in a phase 2b randomized, double-blind, placebo-controlled, multicenter trial. The follow-up was completed on November 4, 2019. Patients were randomised 1:1:1 to receive vericiguat, up-titrated to 15 mg (n=264) or 10-mg (n=263) daily oral dosages, vs placebo (n=262). After 24 weeks of treatment, the primary outcome was a change in the KCCQ PLS (range, 0-100; higher values indicate better functioning). The 6-minute walking distance was measured from baseline to 24 weeks as a secondary result. The average age of the 789 randomized patients was 72.7 (SD, 9.4) years; 385 (49%) were female; the median EF was 56%, and the median N-terminal pro-brain natriuretic peptide level was 1,403 pg/mL; 761 (96.5%) completed the experiment. For the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups, the baseline, and 24-week KCCQ PLS means were 60.0 and 68.3, 57.3 69.0, and 59.0 and 67.1, respectively, while the least-squares mean changes were 5.5, 6.4, and 6.9, respectively. Between the 15-mg/d vericiguat and placebo groups, the least-squares mean difference in scores was -1.5 (95% CI, -5.5 to 2.5; P=0.47), and between the 10-mg/d vericiguat and placebo groups, it was 0.5 (95% CI, -4.6 to 3.5; P=0.80). In the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups, the baseline, and 24-week 6-minute walking distance mean scores were 295.0 m and 311.8 m, 292.1 m and 318.3 m, and 295.8 m and 311.4 m, respectively. In contrast, the least-squares mean changes were 5.0 m, 8.7 m, and 10.5 m, respectively. The least-squares mean the difference between the 15-mg/d vericiguat and placebo groups was -5.5 m (95% Confidence interval, 19.7 m to 8.8 m; P=0.45) and 1.8 m (95% Confidence interval, 16.2 m to 12.6 m; P=0.81), respectively. Symptomatic hypotension occurred in 6.4% of patients in the 15-mg/d vericiguat group, 4.2% in the 10-mg/d vericiguat group, and 3.4% in the placebo group; syncope occurred in 1.5%, 0.8%, and 0.4% of patients, respectively. Compared with placebo, 24-week treatment with vericiguat at either 15-mg/d or 10-mg/d did not enhance the physical limitation score on the KCCQ in patients with HFpEF and recent decompensation.