Heart Failure With Reduced Ejection FractionEVERHETT-HFNCT07697365
Vericiguat and Exercise Hemodynamics in Patients With HFrEF
An observational study of Heart Failure With Reduced Ejection Fraction and Chronic Heart Failure, run by Argyrios Ntalianis at 1 site in Greece.
Trial summary
Heart failure with reduced ejection fraction (HFrEF) is associated with impaired exercise capacity and abnormal exercise hemodynamics despite contemporary guideline-directed medical therapy (GDMT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction, Chronic Heart Failure
- What is being tested?
- Vericiguat and Guideline-directed medical therapy (GDMT) for heart failure
- Type of treatment
- Pill or oral medicine
- How many people
- 40 participants
- Where
- 1 siteGreece
- Study dates
- 31 Jan 2024to 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: The study population consisted of consecutive adult patients (≥18 years) with stable chronic heart failure with reduced ejection fraction (LVEF ≤40%) receiving maximally tolerated guideline-directed medical therapy (GDMT). Patients were clinically stable and underwent standardized cardiopulmonary exercise testing (CPET) and exercise right heart catheterization (ERHC) as part of their clinical evaluation at Alexandra General Hospital. Participants were prospectively enrolled and classified according to routine clinical treatment with GDMT alone or GDMT plus vericiguat.
Who may be able to join
- Adults aged ≥18 years. Chronic heart failure with reduced ejection fraction (LVEF ≤40%). Stable chronic heart failure receiving maximally tolerated guideline-directed medical therapy (GDMT).
- Clinically stable for at least 6 months prior to enrollment without hospitalization for worsening heart failure or major modification of heart failure therapy.
- Able to perform symptom-limited cardiopulmonary exercise testing (CPET). Eligible to undergo exercise right heart catheterization (ERHC). Able to provide written informed consent.
Who cannot join
- Acute decompensated heart failure. Recent hospitalization for worsening heart failure (<6 months). Systolic blood pressure <110 mmHg. Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m². Severe hepatic dysfunction. Severe anemia (hemoglobin <9 g/dL). Contraindication to right heart catheterization. Inability to perform CPET. Pregnancy or breastfeeding. Any condition judged by the treating physician to preclude safe participation.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Vericiguat on Exercise Hemodynamics and Exercise Tolerance in Patients With Heart Failure and Reduced Ejection Fraction: The EVERHETT-HF Prospective Observational Cohort Study
Heart failure with reduced ejection fraction (HFrEF) is associated with impaired exercise capacity and abnormal exercise hemodynamics despite contemporary guideline-directed medical therapy (GDMT). Vericiguat, a soluble guanylate cyclase stimulator, has demonstrated clinical benefits in selected patients with HFrEF, but its effects on exercise physiology remain incompletely understood.
The EVERHETT-HF study is a prospective observational cohort study designed to evaluate the effects of treatment with vericiguat on exercise capacity and invasive exercise hemodynamics in patients with stable HFrEF receiving maximally tolerated guideline-directed medical therapy (GDMT). Participants undergo comprehensive cardiopulmonary exercise testing (CPET) and exercise right heart catheterization (ERHC) to assess functional and hemodynamic responses during exercise.
Read the detailed description
Patients with chronic heart failure with reduced ejection fraction (HFrEF) frequently demonstrate persistent impairment in exercise tolerance and abnormal exercise hemodynamics despite contemporary guideline-directed medical therapy (GDMT). Although vericiguat has demonstrated clinical benefits in selected HFrEF populations, the physiological effects of soluble guanylate cyclase stimulation on exercise performance and invasive exercise hemodynamics remain incompletely characterized.
The EVERHETT-HF study is a prospective observational cohort study designed to evaluate the association of vericiguat therapy with changes in exercise capacity and invasive exercise hemodynamics in patients with stable HFrEF receiving maximally tolerated GDMT. Treatment decisions, including the initiation and dose titration of vericiguat, are made according to routine clinical practice and the judgment of the treating physician, independent of the study protocol.
Consecutive eligible adult patients with chronic HFrEF are prospectively enrolled and categorized into two cohorts according to the treatment prescribed by their treating physician: patients receiving guideline-directed medical therapy (GDMT) alone and patients receiving GDMT plus vericiguat. Clinical management is not influenced by study participation.
All participants undergo comprehensive baseline evaluation, including clinical assessment, laboratory testing, cardiopulmonary exercise testing (CPET), and exercise right heart catheterization (ERHC). Follow-up assessments are performed after approximately 12 months using the same standardized evaluation protocol.
Cardiopulmonary exercise testing is performed on a cycle ergometer using a symptom-limited incremental exercise protocol. Functional parameters include peak oxygen uptake (peak VO₂), percentage of predicted peak VO₂, ventilatory efficiency (VE/VCO₂ slope), oxygen uptake efficiency slope (OUES), peak oxygen pulse, anaerobic threshold, respiratory exchange ratio (RER), and exercise duration.
Exercise right heart catheterization is performed using a Swan-Ganz catheter with serial invasive hemodynamic measurements obtained at rest and during standardized supine bicycle exercise. Hemodynamic variables include right atrial pressure (RAP), pulmonary artery systolic, diastolic and mean pressures (sPAP, dPAP, and mPAP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), cardiac index (CI), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), cardiac power output (CPO), cardiac power index (CPI), transpulmonary gradient (TPG), diastolic pressure gradient (DPG), pulmonary artery pulsatility index (PAPi), and other derived exercise hemodynamic indices.
The primary objective of the study is to evaluate the association of vericiguat therapy with longitudinal changes in exercise capacity and invasive exercise hemodynamics in patients with stable HFrEF. Secondary objectives include the assessment of additional cardiopulmonary exercise variables, invasive hemodynamic parameters, laboratory biomarkers, echocardiographic measurements, and overall functional status during follow-up.
This investigator-initiated study aims to provide detailed mechanistic insights into the relationship between vericiguat therapy and exercise physiology in patients with stable HFrEF under routine clinical practice through the combined use of cardiopulmonary exercise testing and invasive exercise hemodynamic assessment.
- Being tested
- Vericiguat, Guideline-directed medical therapy (GDMT) for heart failure
- Keywords
- HFrEF, Vericiguat, Cardiopulmonary Exercise Testing, Exercise Right Heart Catheterization, Exercise Hemodynamics, Heart Failure
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VericiguatDrug
Oral vericiguat prescribed as part of routine clinical care in addition to maximally tolerated guideline-directed medical therapy (GDMT). Dose titration up to 10 mg once daily was performed according to the treating physician's clinical judgment and routine clinical practice.
Guideline-directed medical therapy (GDMT) for heart failureOther
Participants received maximally tolerated guideline-directed medical therapy (GDMT) according to contemporary heart failure management guidelines and routine clinical practice throughout the study period.
| Study group | Role | What they receive |
|---|---|---|
| Vericiguat + GDMT | Participants receiving oral vericiguat in addition to maximally tolerated guideline-directed medical therapy (GDMT) as part of routine clinical care. Treatment decisions were made by the treating physician independently of the study protocol. Receives: Drug: Vericiguat; Other: Guideline-directed medical therapy (GDMT) for heart failure | |
| GDMT Alone | Participants receiving maximally tolerated guideline-directed medical therapy (GDMT) without vericiguat as part of routine clinical care. Treatment decisions were made by the treating physician independently of the study protocol. Receives: Other: Guideline-directed medical therapy (GDMT) for heart failure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in peak oxygen consumption (peak VO2) assessed by cardiopulmonary exercise testing
Assessment of the change in peak oxygen consumption (peak VO₂) measured by cardiopulmonary exercise testing (CPET) between baseline and the 12-month follow-up.
Measured: Baseline to 12 months
Change in pulmonary capillary wedge pressure (PCWP)
Assessment of the change in pulmonary capillary wedge pressure measured during exercise right heart catheterization between baseline and the 12-month follow-up.
Measured: Baseline to 12 months
Secondary outcomes (8)
Change in VE/VCO2 slope
Assessment of the change in VE/VCO₂ slope measured by cardiopulmonary exercise testing (CPET) between baseline and the 12-month follow-up.
Measured: Baseline to 12 months
Change in mean pulmonary artery pressure (mPAP)
Assessment of the change in mean pulmonary artery pressure measured during exercise right heart catheterization between baseline and the 12-month follow-up.
Measured: Baseline to 12 months
Change in cardiac output
Assessment of the change in cardiac output measured during exercise right heart catheterization between baseline and the 12-month follow-up.
Measured: Baseline to 12 months
Change in cardiac index
Assessment of the change in cardiac index measured during exercise right heart catheterization between baseline and the 12-month follow-up.
Measured: Baseline to 12 months
Change in pulmonary vascular resistance (PVR)
Assessment of the change in pulmonary vascular resistance measured during exercise right heart catheterization between baseline and the 12-month follow-up.
Measured: Baseline to 12 months
Change in oxygen uptake efficiency slope (OUES)
Assessment of the change in oxygen uptake efficienc y slope measured during cardiopulmonary exercise testing between baseline and the 12-month follow-up.
Measured: Baseline to 12 months
Change in oxygen pulse
Assessment of the change in oxygen pulse measured during cardiopulmonary exercise testing between baseline and the 12-month follow-up.
Measured: Baseline to 12 months
Change in anaerobic threshold
Assessment of the change in anaerobic threshold measured during cardiopulmonary exercise testing between baseline and the 12-month follow-up.
Measured: Baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2026
- Study start31 Jan 2024
- 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 Heart Failure With Reduced Ejection FractionStudies of the same condition, open and under way.
- 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
- Argyrios Ntalianis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Argyrios Ntalianis, Alexandra Hospital, Athens, Greece
- Investigators
- Argyrios Ntalianis, MD, PhD, Principal investigator, Alexandra General Hospital, Athens, Greece
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07697365
- Sponsor's protocol ID
- EVERHETT-HF
- Acronym
- EVERHETT-HF
- Status last verified
- Jul 2026
- First submitted
- 5 Jul 2026
- Last updated
- 13 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) will not be shared because this is a single-center, investigator-initiated study with a small sample size, and no data-sharing plan has been established.
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Vericiguat on Exercise Hemodynamics and Exercise Tolerance in Patients With Heart Failure and Reduced Ejection Fraction: The EVERHETT-HF Prospective Observational Cohort Study
- ClinicalTrials.gov ID
- NCT07697365
- Acronym / sponsor ID
- EVERHETT-HF / EVERHETT-HF
- Keywords
- HFrEF, Vericiguat, Cardiopulmonary Exercise Testing, Exercise Right Heart Catheterization, Exercise Hemodynamics, Heart Failure
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Argyrios NtalianisUniversity, hospital or other
- Study start
- 31 Jan 2024 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 13 Jul 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.
Heart failure with reduced ejection fraction (HFrEF) is associated with impaired exercise capacity and abnormal exercise hemodynamics despite contemporary guideline-directed medical therapy (GDMT). Vericiguat, a soluble guanylate cyclase stimulator, has demonstrated clinical benefits in selected patients with HFrEF, but its effects on exercise physiology remain incompletely understood.
The EVERHETT-HF study is a prospective observational cohort study designed to evaluate the effects of treatment with vericiguat on exercise capacity and invasive exercise hemodynamics in patients with stable HFrEF receiving maximally tolerated guideline-directed medical therapy (GDMT). Participants undergo comprehensive cardiopulmonary exercise testing (CPET) and exercise right heart catheterization (ERHC) to assess functional and hemodynamic responses during exercise.
Detailed description
Patients with chronic heart failure with reduced ejection fraction (HFrEF) frequently demonstrate persistent impairment in exercise tolerance and abnormal exercise hemodynamics despite contemporary guideline-directed medical therapy (GDMT). Although vericiguat has demonstrated clinical benefits in selected HFrEF populations, the physiological effects of soluble guanylate cyclase stimulation on exercise performance and invasive exercise hemodynamics remain incompletely characterized.
The EVERHETT-HF study is a prospective observational cohort study designed to evaluate the association of vericiguat therapy with changes in exercise capacity and invasive exercise hemodynamics in patients with stable HFrEF receiving maximally tolerated GDMT. Treatment decisions, including the initiation and dose titration of vericiguat, are made according to routine clinical practice and the judgment of the treating physician, independent of the study protocol.
Consecutive eligible adult patients with chronic HFrEF are prospectively enrolled and categorized into two cohorts according to the treatment prescribed by their treating physician: patients receiving guideline-directed medical therapy (GDMT) alone and patients receiving GDMT plus vericiguat. Clinical management is not influenced by study participation.
All participants undergo comprehensive baseline evaluation, including clinical assessment, laboratory testing, cardiopulmonary exercise testing (CPET), and exercise right heart catheterization (ERHC). Follow-up assessments are performed after approximately 12 months using the same standardized evaluation protocol.
Cardiopulmonary exercise testing is performed on a cycle ergometer using a symptom-limited incremental exercise protocol. Functional parameters include peak oxygen uptake (peak VO₂), percentage of predicted peak VO₂, ventilatory efficiency (VE/VCO₂ slope), oxygen uptake efficiency slope (OUES), peak oxygen pulse, anaerobic threshold, respiratory exchange ratio (RER), and exercise duration.
Exercise right heart catheterization is performed using a Swan-Ganz catheter with serial invasive hemodynamic measurements obtained at rest and during standardized supine bicycle exercise. Hemodynamic variables include right atrial pressure (RAP), pulmonary artery systolic, diastolic and mean pressures (sPAP, dPAP, and mPAP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), cardiac index (CI), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), cardiac power output (CPO), cardiac power index (CPI), transpulmonary gradient (TPG), diastolic pressure gradient (DPG), pulmonary artery pulsatility index (PAPi), and other derived exercise hemodynamic indices.
The primary objective of the study is to evaluate the association of vericiguat therapy with longitudinal changes in exercise capacity and invasive exercise hemodynamics in patients with stable HFrEF. Secondary objectives include the assessment of additional cardiopulmonary exercise variables, invasive hemodynamic parameters, laboratory biomarkers, echocardiographic measurements, and overall functional status during follow-up.
This investigator-initiated study aims to provide detailed mechanistic insights into the relationship between vericiguat therapy and exercise physiology in patients with stable HFrEF under routine clinical practice through the combined use of cardiopulmonary exercise testing and invasive exercise hemodynamic assessment.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vericiguat + GDMT | – | Drug: Vericiguat, Other: Guideline-directed medical therapy (GDMT) for heart failureParticipants receiving oral vericiguat in addition to maximally tolerated guideline-directed medical therapy (GDMT) as part of routine clinical care. Treatment decisions were made by the treating physician independently of the study protocol. |
| GDMT Alone | – | Other: Guideline-directed medical therapy (GDMT) for heart failureParticipants receiving maximally tolerated guideline-directed medical therapy (GDMT) without vericiguat as part of routine clinical care. Treatment decisions were made by the treating physician independently of the study protocol. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population consisted of consecutive adult patients (≥18 years) with stable chronic heart failure with reduced ejection fraction (LVEF ≤40%) receiving maximally tolerated guideline-directed medical therapy (GDMT). Patients were clinically stable and underwent standardized cardiopulmonary exercise testing (CPET) and exercise right heart catheterization (ERHC) as part of their clinical evaluation at Alexandra General Hospital. Participants were prospectively enrolled and classified according to routine clinical treatment with GDMT alone or GDMT plus vericiguat.
Key inclusion criteria (3 listed)
- Adults aged ≥18 years. Chronic heart failure with reduced ejection fraction (LVEF ≤40%). Stable chronic heart failure receiving maximally tolerated guideline-directed medical therapy (GDMT).
- Clinically stable for at least 6 months prior to enrollment without hospitalization for worsening heart failure or major modification of heart failure therapy.
- Able to perform symptom-limited cardiopulmonary exercise testing (CPET). Eligible to undergo exercise right heart catheterization (ERHC). Able to provide written informed consent.
Key exclusion criteria (1 listed)
- Acute decompensated heart failure. Recent hospitalization for worsening heart failure (<6 months). Systolic blood pressure <110 mmHg. Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m². Severe hepatic dysfunction. Severe anemia (hemoglobin <9 g/dL). Contraindication to right heart catheterization. Inability to perform CPET. Pregnancy or breastfeeding. Any condition judged by the treating physician to preclude safe participation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VericiguatOral vericiguat prescribed as part of routine clinical care in addition to maximally tolerated guideline-directed medical therapy (GDMT). Dose titration up to 10 mg once daily was performed according to the treating physician's clinical judgment and routine clinical practice. | Drug | Vericiguat + GDMT |
| Guideline-directed medical therapy (GDMT) for heart failureParticipants received maximally tolerated guideline-directed medical therapy (GDMT) according to contemporary heart failure management guidelines and routine clinical practice throughout the study period. | Other | GDMT Alone, Vericiguat + GDMT |
Primary outcome
Change in peak oxygen consumption (peak VO2) assessed by cardiopulmonary exercise testing
Time frame: Baseline to 12 months
Assessment of the change in peak oxygen consumption (peak VO₂) measured by cardiopulmonary exercise testing (CPET) between baseline and the 12-month follow-up.
Change in pulmonary capillary wedge pressure (PCWP)
Time frame: Baseline to 12 months
Assessment of the change in pulmonary capillary wedge pressure measured during exercise right heart catheterization between baseline and the 12-month follow-up.
8 secondary outcomes
Change in VE/VCO2 slope
Time frame: Baseline to 12 months
Change in mean pulmonary artery pressure (mPAP)
Time frame: Baseline to 12 months
Change in cardiac output
Time frame: Baseline to 12 months
Change in cardiac index
Time frame: Baseline to 12 months
Change in pulmonary vascular resistance (PVR)
Time frame: Baseline to 12 months
Change in oxygen uptake efficiency slope (OUES)
Time frame: Baseline to 12 months
Change in oxygen pulse
Time frame: Baseline to 12 months
Change in anaerobic threshold
Time frame: Baseline to 12 months
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 13 Jul 2026.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be shared because this is a single-center, investigator-initiated study with a small sample size, and no data-sharing plan has been established.
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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.
Argyrios Ntalianis, MD, PhD principal investigator
Alexandra General Hospital, Athens, Greece
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 Heart Failure With Reduced Ejection Fraction and Chronic Heart Failure, run by Argyrios Ntalianis at 1 site in Greece.
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 3 inclusion and 1 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 13 Jul 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 Greece. 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?
Change in peak oxygen consumption (peak VO2) assessed by cardiopulmonary exercise testing (time frame: Baseline to 12 months). The study lists 2 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 13 Jul 2026.