PURPOSE OF REVIEW: The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic 
guanosine monophosphate (cGMP) pathway plays an important role in the regulation 
of cardiovascular function, and it is disrupted in heart failure (HF), resulting 
in decreased protection against myocardial injury. Impaired NO-sGC-cGMP 
signaling in HF is secondary to reduced NO bioavailability and altered redox 
state of sGC, which becomes less responsive to NO. 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 therefore reduced NO levels, at the expense of a 
greater risk of hypotension. Conversely, sGC stimulators (riociguat and 
vericiguat) enhance sGC sensitivity to endogenous NO, thus exerting a more 
physiological action.
RECENT FINDINGS: Clinical trials have suggested the benefit of vericiguat in 
patients with high-risk HF; in particular, a lower incidence of death from 
cardiovascular causes or HF hospitalization. Adding vericiguat may be considered 
in individual patients with HF, and reduced left ventricular ejection fraction 
(HFrEF) particularly those at higher risk of HF hospitalization.