Chronic Heart Failure, Heart Failure With Reduced Ejection Fraction
Conditions
Keywords
HFrEF, Vericiguat, Cardiopulmonary Exercise Testing, Exercise Right Heart Catheterization, Exercise Hemodynamics, Heart Failure
Brief 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). 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.
Interventions
DRUGVericiguat
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.
Participants received maximally tolerated guideline-directed medical therapy (GDMT) according to contemporary heart failure management guidelines and routine clinical practice throughout the study period.
Sponsors
Argyrios Ntalianis
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in peak oxygen consumption (peak VO2) assessed by cardiopulmonary exercise testing | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in VE/VCO2 slope | Baseline to 12 months | Assessment of the change in VE/VCO₂ slope measured by cardiopulmonary exercise testing (CPET) between baseline and the 12-month follow-up. |
| Change in mean pulmonary artery pressure (mPAP) | Baseline to 12 months | Assessment of the change in mean pulmonary artery pressure measured during exercise right heart catheterization between baseline and the 12-month follow-up. |
| Change in cardiac output | Baseline to 12 months | Assessment of the change in cardiac output measured during exercise right heart catheterization between baseline and the 12-month follow-up. |
| Change in cardiac index | Baseline to 12 months | Assessment of the change in cardiac index measured during exercise right heart catheterization between baseline and the 12-month follow-up. |
| Change in pulmonary vascular resistance (PVR) | Baseline to 12 months | Assessment of the change in pulmonary vascular resistance measured during exercise right heart catheterization between baseline and the 12-month follow-up. |
| Change in oxygen uptake efficiency slope (OUES) | Baseline to 12 months | Assessment of the change in oxygen uptake efficienc y slope measured during cardiopulmonary exercise testing between baseline and the 12-month follow-up. |
| Change in oxygen pulse | Baseline to 12 months | Assessment of the change in oxygen pulse measured during cardiopulmonary exercise testing between baseline and the 12-month follow-up. |
| Change in anaerobic threshold | Baseline to 12 months | Assessment of the change in anaerobic threshold measured during cardiopulmonary exercise testing between baseline and the 12-month follow-up. |
Countries
Greece
Contacts
PRINCIPAL_INVESTIGATORArgyrios Ntalianis, MD, PhD
Alexandra General Hospital, Athens, Greece
Outcome results
None listed