Reduced cardiac signaling efficiency remains a hallmark of heart failure progression, driving the need for therapies that restore hemodynamic stability. At the European Society of Cardiology (ESC) Congress 2025, a study published in the European Heart Journal demonstrated that cardiac cyclic guanosine monophosphate (cGMP) augmentation is closely linked to improved hemodynamics in patients with heart failure with reduced ejection fraction (HFrEF).

The investigation enrolled 15 HFrEF patients (median ejection fraction 24.5%) and 20 controls, with simultaneous blood sampling from the coronary sinus, artery, and vein. Compared to controls, patients had higher coronary sinus cGMP levels (15.9±1.6 vs. 10.9±1.2 nM) but a markedly reduced cGMP-to-BNP ratio (0.09 vs. 1.72). 

After treatment with sacubitril/valsartan or vericiguat, both pulmonary artery and wedge pressures declined significantly, while cGMP levels rose in cardiac and peripheral blood. Importantly, changes in coronary sinus cGMP positively correlated with improved cardiac index. An inverse relationship between pro-B-type natriuretic peptide percentage and cGMP levels highlighted impaired pro-BNP processing as a potential regulator of cGMP signaling. These findings strengthen the rationale for targeting cGMP pathways to improve cardiac performance in HFrEF.