Association of elevated cyclic GMP levels with hemodynamic changes in HFrEF patients treated with

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Takumi Inoue1, Hiroyuki Takahama1, Hideaki Suzuki1

  • 1Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

International Journal of Cardiology. Heart & Vasculature
|May 11, 2026
PubMed

Insights

Treatments like sacubitril/valsartan and vericiguat boost cyclic guanosine monophosphate (cGMP) levels in heart failure patients. This cGMP increase is linked to improved heart function and hemodynamics.

Area of Science:

  • Cardiology
  • Pharmacology
  • Biochemistry

Background:

  • Heart failure (HF) patients often exhibit a relative cyclic guanosine monophosphate (cGMP) deficiency despite elevated B-type natriuretic peptide (BNP).
  • The drugs sacubitril/valsartan and vericiguat target the cGMP pathway, but the balance of cardiac versus systemic cGMP production is unclear.
  • This study investigated the relationship between cGMP alterations and hemodynamic changes in heart failure with reduced ejection fraction (HFrEF) patients undergoing treatment.

Purpose of the Study:

  • To assess the association between changes in cyclic guanosine monophosphate (cGMP) levels and hemodynamic improvements in patients with heart failure with reduced ejection fraction (HFrEF).
  • To explore the impact of sacubitril/valsartan and vericiguat on the cGMP pathway in HFrEF.
  • To determine if cardiac or systemic cGMP production is more relevant to treatment response.

Main Methods:

  • Fourteen symptomatic HFrEF patients and 20 controls were enrolled.
  • HFrEF patients underwent right heart catheterization before and after two months of treatment with sacubitril/valsartan and/or vericiguat.
  • Blood samples were analyzed from the coronary sinus, arteries, and veins to measure cGMP and BNP levels.

Main Results:

  • HFrEF patients had higher coronary sinus cGMP but a lower cGMP/BNP ratio compared to controls, indicating relative cGMP deficiency.
  • Treatment significantly increased the cGMP/BNP ratio, with changes in coronary sinus cGMP correlating with improved cardiac index.
  • cGMP levels increased systemically across all sampling sites, suggesting augmented cGMP pathway activity.

Conclusions:

  • Elevated cGMP levels correlate with hemodynamic improvements in HFrEF patients treated with sacubitril/valsartan and vericiguat.
  • Augmenting the cGMP pathway is therapeutically relevant for HFrEF.
  • Findings provide mechanistic insights into the clinical efficacy of these agents in HFrEF.
Abstract

Keywords:
Cyclic GMPHeart failureHemodynamic testNatriuretic peptide

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