Abstract 12149: Vericiguat May Improve Conduit Vessel Function and Exercise Functional Capacity in Heart Failure With Reduced Ejection Fraction

Background: The treatment of heart failure with reduced ejection fraction (HFrEF) has advanced considerably in recent years with the advent of novel agents; however, limitations, such as blood pressure and renal dysfunction, limit the number of patients who can benefit from this treatment in practice. Vericiguat, a novel heart failure treatment, has been found to be efficacious in patients with HFrEF while maintaining a good safety profile. Unfortunately, its mechanisms remain largely unknown. Objective and Methods: A total of 11 patients with HFrEF who were determined to be inadequately treated underwent right heart catheterization, echocardiography, flow-mediated dilatation (FMD) testing, 6-min walking distance (6MWD) test, and blood sampling at a median interval of 70 ± 13 days before and after vericiguat treatment. Results: Participating patients were 73 ± 9.3 years old with a mean of 2.5 repeated heart failure hospitalizations, ejection fraction (EF) of 31.2% ± 8.7%, BNP of 328.7 ± 282, and New York Heart Association classification of mostly II. No significant changes in systolic blood pressure or pulse rate were observed before and after vericiguat introduction (115 ± 64 vs. 105 ± 52 mmHg and 70 ± 5 vs. 75 ± 12 bpm; P = 0.533 and 0.960, respectively). No significant changes in the mean pulmonary artery pressure and pulmonary artery wedge pressure were also observed before or after drug administration (19 ± 5 vs. 17 ± 10 mmHg and 7 ± 5 vs. 9 ± 3 bpm; P = 0.177 and 0.240 respectively). However, cardiac output was significantly increased and vascular resistance was significantly decreased after vericiguat treatment (4.0 ± 1.0 vs. 4.3 ± 1.1 L/min and 1719 ± 462 vs. 1467 ± 377 dynes·sec·cm-5; P = 0.016 and 0.002, respectively). FMD test results improved significantly after treatment (4.5 ± 5% vs. 8.1± 8%: P = 0.027), with the 6MWD increasing significantly by 42 m (311 ± 100 vs. 353 ± 50 m; P = 0.035). BNP also decreased significantly, whereas eGFR remained unchanged (317 ± 274 vs. 221.5 ± 200 pg/mL and 51.7 ± 21 vs. 51.5 ± 25.3 mL/min/1.73 m 2 ; P = 0.015 and 0.967, respectively). Conclusion: Vericiguat may improve exercise tolerance by improving vascular endothelial function and cardiac output.