HFrEF - Heart Failure With Reduced Ejection FractionNCT07472595
Effect of Vericiguat on cardiAc Remodeling in Patients With Heart faiLure and Reduced Ejection fractioN (HFrEF): A Prospective sTudy usIng NOvel Echocardiographic Imaging Techniques (VALENTINO)
An observational study of HFrEF - Heart Failure With Reduced Ejection Fraction, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
The biological process that underlies the pathogenesis of heart failure (HF) is termed cardiac remodeling. Pathological cardiac remodeling includes structural and functional change of the heart. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HFrEF - Heart Failure With Reduced Ejection Fraction
- How many people
- 40 participants
- Where
- 1 siteHong Kong
- Study dates
- 9 Oct 2023to 31 Dec 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Eligible subjects will be screened and recruited in the Prince of Wales Hospital.
Who may be able to join
- Age ≥ 18y
- Chronic HF; New York Heart Association (NYHA) class II-III, LVEF ≤40% (recent 12 months), and on guideline-directed heart failure therapy
- Recent (6 months) heart failure hospitalization or intravenous diuretic use (without hospitalization) within 3 months
- Elevated NT-proBNP 1000-6000 pg/ml (1600-6000 pg/ml if atrial fibrillation) within 30 days
- Clinically stable (systolic blood pressure ≥100 mm Hg and no intravenous diuretics for 48 hours)
- Meet one of the following criteria:
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- a. Male
- b. Female who is not of reproductive potential, defined as a female who either: (1) postmenopausal (defined as at least 12 months with no menses in women ≥45 years of age); (2) has had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; OR (3) has a congenital or acquired condition that prevents childbearing
- c. Female who is of reproductive potential and agrees to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: (1) practice abstinence from heterosexual activity, OR (2) use (or have her partner use) acceptable contraception during heterosexual activity. Acceptable methods of contraception are:
- i. Single method (one of the following is acceptable):
- • Intrauterine device, vasectomy of a female subject's male partner, or contraceptive rod implanted into the skin
- ii. Combination method (use of two of the following)
- • Diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge, male condom or female condom, or hormonal contraceptive
Who cannot join
- Prior or screening echocardiographic images of suboptimal image quality
- Any addition, discontinuation, or dose modification of heart failure medications (i.e. ARB, ACEi, SGLT2i, ARNI, beta-blocker, MRA) within 4 weeks before vericiguat treatment initiation
- Use of long-acting nitrates, phosphodiesterase type 5 inhibitor, riociguat
- Awaiting heart transplantation, continuous intravenous diuretics, or current/anticipated ventricular assist device
- Chronic kidney disease (estimated glomerular filtration rate <15 ml/min/1.73 m2) or dialysis
- Severe pulmonary disease requiring continuous oxygen
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- Severe hepatic insufficiency
- Has primary valvular heart disease requiring surgery or intervention, or is within 3 months after valvular surgery or intervention
- Has hypertrophic obstructive cardiomyopathy
- Has acute myocarditis, amyloidosis, sarcoidosis, Takotsubo cardiomyopathy
- Has post-heart transplant cardiomyopathy
- Has tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia
- Has acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction [NSTEMI], or ST elevation myocardial infarction [STEMI]) or coronary revascularization (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI]) within 6 months, or indication for coronary revascularization at the time of screening
- Has symptomatic carotid stenosis, transient ischemic attack (TIA) or stroke within 60 days
- Has complex congenital heart disease
- Has active endocarditis or constrictive pericarditis
- Breastfeeding or plans to breastfeed during the course of the trial
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site
Division of Cardiology, Department of Medicine and Therapeutics Faculty of Medicine, The Chinese University of Hong Kong
Hong Kong, New Territories, Sha Tin
About this study
The biological process that underlies the pathogenesis of heart failure (HF) is termed cardiac remodeling. Pathological cardiac remodeling includes structural and functional change of the heart. Structural cardiac remodeling in HF include dilatation and/or hypertrophy of cardiac chambers, in particular the left ventricle (LV), but can also involve the right ventricle (RV) and both atria; moreover, cardiac valves, in particular the mitral valve, have been shown to undergo adaptive enlargement in HF to counteract leaflet tethering that leads to functional regurgitation 1. Functional changes of the heart in HF includes reduction of LV systolic and diastolic function, ischemia, abnormalities in myocardial deformation, and alteration in intracardiac vortex flow formation and energetics. At the tissue level, cardiac remodeling is marked by interstitial reparative and replacement fibrosis and inflammation.
Cyclic guanosine monophosphate (cGMP) is an intracellular second messenger molecule that is important in the pathogenesis of HF. The main kinase effector of cGMP, protein kinase G, counteracts many biological derangements contributing to HF in experimental models. The production of cGMP in the heart, kidney, lung, liver, and brain is triggered by stimulation of either soluble guanylyl cyclase (sGC) or particulate guanylyl cyclase (pGC), and regulated by endogenous receptor ligands such as nitric oxide (NO) and natriuretic peptides (NPs). In the cardiovascular system, cGMP pathway is involved in the pathogenesis of myocardial fibrosis, inflammation, myofilament insensitivity, vascular dysfunction, and cardiomyocyte hypertrophy 2.
Read more
Vericiguat is a direct sGC stimulator with a dual mode of action: it sensitizes sGC to the body's own NO and increases sGC activity in the absence of NO, causing vasorelaxation, antiproliferation, and antifibrotic effects. A recent randomized trial, Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA), found that vericiguat reduced a composite endpoint of hospitalization for HF and cardiovascular death in high-risk patients with HF with LV ejection fraction (LVEF) less than 45 percent 3. The mechanisms underlying the clinical benefit of vericiguat are uncertain but may include effects on fibrosis and inflammation.
Evaluation of LV size by 2D imaging has traditionally be challenging owing to technical limitations, such as foreshortening leading to underestimation of LV volumes using the Simpson's method. Latest advance in 3D echocardiography technology and automated cardiac functional analysis software has revolutionized evaluation and monitoring of LV and LA function in patients with HF. 3D echocardiography allows accurate measurement of LV, LA, and RV volumes and ejection fraction without needing any geometric assumption, with results reproducible and comparable to cardiac magnetic resonance, the imaging gold standard for chamber quantification. Furthermore, speckle tracking echocardiography allows evaluation of cardiac muscle deformation, which are more sensitive and load-independent markers of cardiac function. Echocardiography has the advantage of being wide available, with no harmful effect, and can be repeated in follow-up of patients.
Our group is experienced in the evaluation of the cardiac structure and function in patients with HF using 3D, speckle tracking, and other advanced echocardiographic techniques 4-11. The investigators therefore propose to conduct a pilot study to examine the effect of vericiguat on cardiac remodeling in patients with HF and reduced EF (HFrEF) with particular attention paid to the remodeling of LV and LA, using novel imaging techniques including 3-dimensional (3DE), with automated 3D analysis, and speckle tracking echocardiography.
- Keywords
- Heart Failure, Cardiac Remodeling, Vericiguat
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Vericiguat study | Subjects will be treated for 8 months. A starting dose of Vericiguat 2.5 mg will be initiated. Subjects will be up-titrated to 5 mg and then to the target dose of 10 mg using titration criteria based on mean systolic blood pressure evaluation and clinical symptoms at 2 week intervals. Following the 4-week titration phase, subjects will be evaluated at 4 months (optional) and 8 months. |
What is being measured
The primary outcome is the main question the study is designed to answer.
LV ejection fraction (EF)
Measured using 3D Echocardiography, this assesses the percentage of blood pumped out of the left ventricle with each heartbeat.
Measured: From baseline to 8 months follow-up
LV end-systolic volume index (LVESVI)
Measured using 3D Echocardiography, this reflects the volume of blood in the left ventricle at the end of contraction, indexed to body surface area.
Measured: From baseline to 8 months follow-up
LV end-diastolic volume index (LVEDVI)
Measured using 3D Echocardiography, this represents the volume of blood in the left ventricle at the end of diastole.
Measured: From baseline to 8 months follow-up
LV mass index (LVMI)
Is calculated through measurements obtained via 3D Echocardiography and is representing the left ventricular mass, relative to body surface area.
Measured: From baseline to 8 months follow-up
LV global longitudinal strain (LVGLS)
Is assessed using Speckle Tracking Echocardiography, this provides a comprehensive assessment of the left ventricular function.
Measured: From baseline to 8 months follow-up
Transmitral inflow Doppler velocities
Transmitral Inflow Doppler Velocities (E, A, DT, IVRT) are measured using Pulsed Wave Doppler, assessing blood flow from the left atrium to left ventricle during diastole.
Measured: From baseline to 8 months follow-up
Annular Velocities
Annular Velocities (Septal e', Lateral e') are measured with Tissue Doppler Imaging, indicating myocardial relaxation.
Measured: From baseline to 8 months follow-up
Average E/e'
Is a ratio calculated using Doppler measurements, providing an estimate of left atrial pressure.
Measured: From baseline to 8 months follow-up
Pulmonary Vein Doppler Velocities
Pulmonary Vein Doppler Velocities (S, D, Ar) are measured using 3D Echocardiography and is assessing the blood flow within the pulmonary veins.
Measured: From baseline to 8 months follow-up
TR Velocity
TR Velocity is tricuspid regurgitation velocity measured by Doppler, providing insights into right heart pressures.
Measured: From baseline to 8 months follow-up
LA Maximal Volume Index (LAEF)
Is measured using 3D Echocardiography, this captures left atrial size and function, indexed for body surface area.
Measured: From baseline to 8 months follow-up
LA Phasic Strains (LASr, LAScd, LASc)
Assessed using Speckle Tracking Echocardiography, reflecting the reservoir, conduit, and contraction phases of left atrial function.
Measured: From baseline to 8 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2026
- Study start9 Oct 2023
- Primary completion31 Dec 2025
- Study completion31 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HFrEF - Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Principal investigator, Dr Alex PW Lee, Chinese University of Hong Kong
- Investigators
- Alex PW Lee, Professor, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07472595
- Sponsor's protocol ID
- 2023.078-T
- Status last verified
- Mar 2026
- First submitted
- 10 Mar 2026
- Last updated
- 16 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Vericiguat on cardiAc Remodeling in Patients With Heart faiLure and Reduced Ejection fractioN (HFrEF): A Prospective sTudy usIng NOvel Echocardiographic Imaging Techniques (VALENTINO)
- ClinicalTrials.gov ID
- NCT07472595
- Acronym / sponsor ID
- 2023.078-T
- Keywords
- Heart Failure, Cardiac Remodeling, Vericiguat
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- 9 Oct 2023 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 16 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The biological process that underlies the pathogenesis of heart failure (HF) is termed cardiac remodeling. Pathological cardiac remodeling includes structural and functional change of the heart. Structural cardiac remodeling in HF include dilatation and/or hypertrophy of cardiac chambers, in particular the left ventricle (LV), but can also involve the right ventricle (RV) and both atria; moreover, cardiac valves, in particular the mitral valve, have been shown to undergo adaptive enlargement in HF to counteract leaflet tethering that leads to functional regurgitation 1. Functional changes of the heart in HF includes reduction of LV systolic and diastolic function, ischemia, abnormalities in myocardial deformation, and alteration in intracardiac vortex flow formation and energetics. At the tissue level, cardiac remodeling is marked by interstitial reparative and replacement fibrosis and inflammation.
Cyclic guanosine monophosphate (cGMP) is an intracellular second messenger molecule that is important in the pathogenesis of HF. The main kinase effector of cGMP, protein kinase G, counteracts many biological derangements contributing to HF in experimental models. The production of cGMP in the heart, kidney, lung, liver, and brain is triggered by stimulation of either soluble guanylyl cyclase (sGC) or particulate guanylyl cyclase (pGC), and regulated by endogenous receptor ligands such as nitric oxide (NO) and natriuretic peptides (NPs). In the cardiovascular system, cGMP pathway is involved in the pathogenesis of myocardial fibrosis, inflammation, myofilament insensitivity, vascular dysfunction, and cardiomyocyte hypertrophy 2.
Vericiguat is a direct sGC stimulator with a dual mode of action: it sensitizes sGC to the body's own NO and increases sGC activity in the absence of NO, causing vasorelaxation, antiproliferation, and antifibrotic effects. A recent randomized trial, Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA), found that vericiguat reduced a composite endpoint of hospitalization for HF and cardiovascular death in high-risk patients with HF with LV ejection fraction (LVEF) less than 45 percent 3. The mechanisms underlying the clinical benefit of vericiguat are uncertain but may include effects on fibrosis and inflammation.
Evaluation of LV size by 2D imaging has traditionally be challenging owing to technical limitations, such as foreshortening leading to underestimation of LV volumes using the Simpson's method. Latest advance in 3D echocardiography technology and automated cardiac functional analysis software has revolutionized evaluation and monitoring of LV and LA function in patients with HF. 3D echocardiography allows accurate measurement of LV, LA, and RV volumes and ejection fraction without needing any geometric assumption, with results reproducible and comparable to cardiac magnetic resonance, the imaging gold standard for chamber quantification. Furthermore, speckle tracking echocardiography allows evaluation of cardiac muscle deformation, which are more sensitive and load-independent markers of cardiac function. Echocardiography has the advantage of being wide available, with no harmful effect, and can be repeated in follow-up of patients.
Our group is experienced in the evaluation of the cardiac structure and function in patients with HF using 3D, speckle tracking, and other advanced echocardiographic techniques 4-11. The investigators therefore propose to conduct a pilot study to examine the effect of vericiguat on cardiac remodeling in patients with HF and reduced EF (HFrEF) with particular attention paid to the remodeling of LV and LA, using novel imaging techniques including 3-dimensional (3DE), with automated 3D analysis, and speckle tracking echocardiography.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vericiguat study | – | –Subjects will be treated for 8 months. A starting dose of Vericiguat 2.5 mg will be initiated. Subjects will be up-titrated to 5 mg and then to the target dose of 10 mg using titration criteria based on mean systolic blood pressure evaluation and clinical symptoms at 2 week intervals. Following the 4-week titration phase, subjects will be evaluated at 4 months (optional) and 8 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Eligible subjects will be screened and recruited in the Prince of Wales Hospital.
Key inclusion criteria (13 listed)
- Age ≥ 18y
- Chronic HF; New York Heart Association (NYHA) class II-III, LVEF ≤40% (recent 12 months), and on guideline-directed heart failure therapy
- Recent (6 months) heart failure hospitalization or intravenous diuretic use (without hospitalization) within 3 months
- Elevated NT-proBNP 1000-6000 pg/ml (1600-6000 pg/ml if atrial fibrillation) within 30 days
- Clinically stable (systolic blood pressure ≥100 mm Hg and no intravenous diuretics for 48 hours)
Key exclusion criteria (17 listed)
- Prior or screening echocardiographic images of suboptimal image quality
- Any addition, discontinuation, or dose modification of heart failure medications (i.e. ARB, ACEi, SGLT2i, ARNI, beta-blocker, MRA) within 4 weeks before vericiguat treatment initiation
- Use of long-acting nitrates, phosphodiesterase type 5 inhibitor, riociguat
- Awaiting heart transplantation, continuous intravenous diuretics, or current/anticipated ventricular assist device
- Chronic kidney disease (estimated glomerular filtration rate <15 ml/min/1.73 m2) or dialysis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
LV ejection fraction (EF)
Time frame: From baseline to 8 months follow-up
Measured using 3D Echocardiography, this assesses the percentage of blood pumped out of the left ventricle with each heartbeat.
LV end-systolic volume index (LVESVI)
Time frame: From baseline to 8 months follow-up
Measured using 3D Echocardiography, this reflects the volume of blood in the left ventricle at the end of contraction, indexed to body surface area.
LV end-diastolic volume index (LVEDVI)
Time frame: From baseline to 8 months follow-up
Measured using 3D Echocardiography, this represents the volume of blood in the left ventricle at the end of diastole.
LV mass index (LVMI)
Time frame: From baseline to 8 months follow-up
Is calculated through measurements obtained via 3D Echocardiography and is representing the left ventricular mass, relative to body surface area.
LV global longitudinal strain (LVGLS)
Time frame: From baseline to 8 months follow-up
Is assessed using Speckle Tracking Echocardiography, this provides a comprehensive assessment of the left ventricular function.
Transmitral inflow Doppler velocities
Time frame: From baseline to 8 months follow-up
Transmitral Inflow Doppler Velocities (E, A, DT, IVRT) are measured using Pulsed Wave Doppler, assessing blood flow from the left atrium to left ventricle during diastole.
Annular Velocities
Time frame: From baseline to 8 months follow-up
Annular Velocities (Septal e', Lateral e') are measured with Tissue Doppler Imaging, indicating myocardial relaxation.
Average E/e'
Time frame: From baseline to 8 months follow-up
Is a ratio calculated using Doppler measurements, providing an estimate of left atrial pressure.
Pulmonary Vein Doppler Velocities
Time frame: From baseline to 8 months follow-up
Pulmonary Vein Doppler Velocities (S, D, Ar) are measured using 3D Echocardiography and is assessing the blood flow within the pulmonary veins.
TR Velocity
Time frame: From baseline to 8 months follow-up
TR Velocity is tricuspid regurgitation velocity measured by Doppler, providing insights into right heart pressures.
LA Maximal Volume Index (LAEF)
Time frame: From baseline to 8 months follow-up
Is measured using 3D Echocardiography, this captures left atrial size and function, indexed for body surface area.
LA Phasic Strains (LASr, LAScd, LASc)
Time frame: From baseline to 8 months follow-up
Assessed using Speckle Tracking Echocardiography, reflecting the reservoir, conduit, and contraction phases of left atrial function.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alex PW Lee, Professor principal investigator
Chinese University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HFrEF - Heart Failure With Reduced Ejection Fraction, run by Chinese University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LV ejection fraction (EF) (time frame: From baseline to 8 months follow-up). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2026.