Vericiguat for right‑ventricular function and heart remodeling in HFrEF

Vericiguat's Effects on Reverse Remodeling Indices: Pathophysiologic Approach to Treatment of Heart Failure With Reduced Ejection Fraction

This study will test whether adding vericiguat to usual heart‑failure treatment helps adults with stable HFrEF improve right‑ventricular function and heart remodeling over 12 months.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Medical Centre Ljubljana (other)
• Locations: 1 site (Ljubljana)
• Trial ID: NCT07405944 on ClinicalTrials.gov

What this trial studies

Adults with stable HFrEF on guideline‑directed medical therapy are randomized to vericiguat plus usual care or usual care alone and followed for 12 months. The trial measures right ventricular systolic function by TAPSE and evaluates myocardial structure and biology using cardiac MRI, blood biomarkers, metabolomics, genomics, transcriptomics, OGTTs, and platelet function testing. Outcomes include imaging markers of remodeling, fibrosis, angiogenesis, inflammation, metabolic and renal measures, and hematologic balance, with exploration of genetic and oxidative stress modifiers of response. Approximately 60 participants will be enrolled at a single center in Ljubljana, Slovenia.

Who should consider this trial

Good fit: Adults (≥18) with chronic stable HFrEF (LVEF ≤40%) who have had no heart‑failure worsening requiring hospitalization or outpatient diuretics in the prior 6 months and are on stable guideline‑directed medical therapy for at least 3 months.

Not a fit: People with recent decompensation, systolic blood pressure <100 mmHg, current or planned use of long‑acting nitrates or PDE5 inhibitors, certain infiltrative or inflammatory cardiomyopathies, awaiting transplant, or dependent on continuous inotropes are unlikely to be eligible or to receive benefit from this protocol.

Why it matters

Potential benefit: If effective, vericiguat could improve right‑ventricular function and reverse maladaptive remodeling, potentially reducing symptoms and future heart‑failure events.

How similar studies have performed: Large randomized trials such as VICTORIA demonstrated that vericiguat reduces worsening heart‑failure events after recent decompensation, and smaller or emerging analyses suggest possible benefits in stable HFrEF, but its direct effects on remodeling and right‑ventricular function remain incompletely defined.

Eligibility criteria

Inclusion Criteria:

* Written informed consent from an adult patient (≥ 18 years old) to participate in the clinical study,
* Stable HFrEF defined as no heart failure worsening in the 6 months before randomization that required hospitalization or outpatient diuretic treatment,
* Confirmed diagnosis of chronic heart failure with reduced ejection fraction (LVEF ≤ 40%, confirmed by echocardiography) within 12 months before randomization,
* Stable GDMT for HFrEF for at least 3 months prior to randomisation.

Exclusion Criteria:

* Systolic blood pressure \< 100 mmHg or symptomatic hypotension,
* Current or planned use of long-acting nitrates, soluble guanylate cyclase stimulators, or phosphodiesterase type V inhibitors,
* Known allergy/hypersensitivity to soluble guanylate cyclase stimulators,
* Awaiting heart transplantation or dependence on continuous inotropic therapy
* Cardiac amyloidosis, sarcoidosis, myocarditis, stress cardiomyopathy, or tachycardic cardiomyopathy,
* Acute coronary syndrome, coronary artery bypass grafting, or percutaneous coronary intervention in the past three months before randomisation,
* Long-term mechanical circulatory support of the left ventricle,
* Active infection,
* Chronic kidney disease stage 4 or 5, and
* Advanced liver failure classified as Child-Pugh B or C.

Where this trial is running

Ljubljana

• University Medical Centre Ljubljana — Ljubljana, Slovenia (RECRUITING)

Study contacts

• Principal investigator: Gregor Poglajen, MD, PhD — Advanced Heart Failure and Transplantation Center, Department of Cardiology, University Medical Centre Ljubljana, Ljubljana, Slovenia
• Study coordinator: Tine Bajec, MD

Conditions: Heart Failure With Reduced Ejection Fraction, Chronic Heart Failure, Vericiguat, Soluble Guanylate Cyclase, Cyclic GMP, Reverse Remodeling, Cardiac Magnetic Resonance Imaging, Myocardial Perfusion Imaging