The significant morbidity and mortality associated with heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF) justify the search for novel therapeutic agents. The nitric oxide (NO)–soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function. This pathway is disrupted in HF resulting in decreased protection against myocardial injury. The sGC activator cinaciguat increases cGMP levels by direct, NO-independent activation of sGC, and may be particularly effective in conditions of increased oxidative stress and endothelial dysfunction, and then reduced NO levels, but this comes at the expense of a greater risk of hypotension. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, and then exert a more physiological action. The phase 3 VICTORIA trial found that vericiguat is safe and effective in patients with HFrEF and recent HF decompensation. Therefore, adding vericiguat may be considered in individual patients with HFrEF, particularly those at higher risk of HF hospitalization; the efficacy of the sacubitril/valsartan-vericiguat combination in HFrEF is currently unknown.

与降低（HFrEF）或保留射血分数（HFpEF）的心力衰竭相关的显着发病率和死亡率证明了寻找新的治疗药物的合理性。一氧化氮 (NO)-可溶性鸟苷酸环化酶 (sGC)-环鸟苷一磷酸 (cGMP) 通路在调节心血管功能中起重要作用。该通路在 HF 中被破坏，导致对心肌损伤的保护降低。sGC 激活剂 cinaciguat 通过直接、不依赖 NO 的 sGC 激活增加 cGMP 水平，并且在氧化应激和内皮功能障碍增加的情况下可能特别有效，然后降低 NO 水平，但这是以降低低血压风险为代价的. 相反，sGC 刺激剂（riociguat 和 vericiguat）增强了 sGC 对内源性 NO 的敏感性，然后发挥更生理的作用。VICTORIA 3 期试验发现，vericiguat 对 HFrEF 和近期 HF 失代偿患者安全有效。因此，可以考虑在个别 HFrEF 患者中添加 vericiguat，特别是那些有较高 HF 住院风险的患者；目前尚不清楚沙库巴曲/缬沙坦-维西卡联合治疗 HFrEF 的疗效。