Heart FailureLUNG-HFNCT06331208
Mechanisms of Pulmonary Vascular Dysfunction in Heart Failure
An observational study of Heart Failure and Pulmonary Hypertension, run by Institute for Clinical and Experimental Medicine at 1 site in Czechia.
Trial summary
Heart failure (HF) patients often develop pulmonary hypertension (PH) that leads to transition into a biventricular HF with poor prognosis. There are two PH components: 1) passive transmission of increased left atrial pressure, 2) heart failure (HF) related pulmonary vascular dysfunction (PVD) with increased vascular… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Pulmonary Hypertension, Pulmonary Vascular Resistance Abnormality
- What is being tested?
- non-contrast chest CT, spirometry with diffusing lung capacity for carbon monoxide (DLCO) analysis and Omics analysis of blood plasma obtained from pulmonary artery or peripheral blood
- How many people
- 230 participants
- Where
- 1 siteCzechia
- Study dates
- 23 Aug 2024to 30 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: HF: Patients with HFrEF reffered to Institute for Clinical and Experimental Medicine, Prague (IKEM) for diagnostic evaluation Controls non-HF controls reffered to IKEM for diagnostic or therapeutic procedure
- Inclusion Criteria
HF group:
- age>18y
- signed informed consent,
- left ventricular (LV) ejection fraction <50%
- duration of HF>6 months,
- loop diuretic use,
- clinical indication to right heart catheterisation
Control group:
- Age >18years
- Signed informed consent
- Non-HF subjects referred to Institute for Clinical and Experimental Medicine (IKEM) in Prague for an invasive procedure (PFO closure, arrhythmia ablation, for subjects undergoing RHC) or non-invasive diagnostic evaluation (controls without invasive sampling)
- Exclusion Criteria:
Heart Failure group:
- Patients with hemodynamic instability requiring inotropic support
- Severe renal insufficiency (estimated glomerular filtration rate <0.6 ml/s)
- Acute coronary syndrome
- High cardiac output (cardiac index >4 l/m2)
- Known pulmonary hypertension of other type than II (type I, III, IV)
- Active infection
- Respiration insufficiency
- Large pleural effusion
- Severe intrinsic lung disease (treated chronic obstructive pulmonary disease (COPD)
- asthma, known interstitial lung disease)
Control group:
- Pulmonary hypertension (RV systolic pressure estimate on screening > 45 mmHg)
- History of recent pulmonary embolism < 1 year
- Echocardiographic evidence of reduced function of right or left ventricle
- Treated asthma/COPD, known intersticial lung disease
- Significant exercise intolerance (NYHA > II)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Czechia1 site, 1 recruiting
- Recruiting
Institute for Clinical and Experimental Medicine - IKEM
Prague, 140 21
Vojtech Melenovsky, MD, PhD, 420 236055190, vome@ikem.cz
About this study
Heart failure (HF) patients often develop pulmonary hypertension (PH) that leads to transition into a biventricular HF with poor prognosis.
There are two PH components: 1) passive transmission of increased left atrial pressure, 2) heart failure (HF) related pulmonary vascular dysfunction (PVD) with increased vascular resistance. Intriguingly, only some, but not all HF patients develop heart failure-related PVD. The mechanisms and non-invasive detection of HF-PVD are poorly understood and are the focus of the current grant application. Development of PVD is linked to insufficiently characterized metabolic factors that may be mediators of HF-PVD.
Read more
Untargeted metabolomics is an emerging powerful platform for the discovery of pathways linked to diseases. Its specificity can be further enhanced using transpulmonary gradient sampling.
Part A of the project aims to identify novel metabolites associated with the presence of PVD in patients with HF that can serve as biomarkers or targets and will provide biologic insights into PVD. Part C will assess the effects of reverting of metabolic alterations (identified in part A) by a drug/diet on pulmonary vasculature in experimental HF-related PVD. The "gold standard" for the detection of PVD is right heart catheterization, which is invasive and risky. Heart failure-related PVD is therefore often diagnosed late.
There is a need for noninvasive tests that may help to detect PVD in early stages and can be done repeatedly. Recent advances in artificial intelligence (AI)-assisted automated quantitative analysis of lung texture from low-dose contrast-free high-resolution CT images allow to quantify lung water content, interstitial changes or vessel volume, and may provide clues for detection of heart failure-related PVD. Such an approach, not tested yet, will be utilized for the detection of HF-PVD (part B). Clinical and functional characteristics of lung circulation (exercise hemodynamics, diffusion capacity, perfusion) will be analyzed in relation to quantitative CT data.
Read the detailed description
Goals of the project are:
- To identify metabolic factors associated with the development of heart failure related pulmonary vascular disease (PVD) using unbiased metabolomic analysis of blood samples obtained before and after passage through lungs (transpulmonary metabolome), obtained during medically indicated right heart catheterization of HF patients with variable degree of pulmonary vasculopathy. Findings from discovery cohort A1 (200 HF, 30 controls) will be prospectively validated in validation cohort A2 (200 HF, 30 controls). Clinical data (medication, comorbidities, nutritional intake) will be analyzed to identify explanatory links to transpulmonary metabolome and increased pulmonary vascular resistance. The goal is to discover metabolic factors and pathways critical for PVD development, that might be targeted by pharmaco-intervention.
- To identify structural and functional characteristics of heart failure (HF) related PVD using advanced imaging (cohort B, 60 HF patients, 30 controls). Advanced non-invasive imaging methods (high resolution non-contrast CT, SPECT) will be used to identify early changes in lung structure indicating the presence of pulmonary vascular disease. HF subjects with variable elevation of pulmonary vascular resistance will be extensively phenotyped using novel automated AI-augmented analysis of CT data texture, and by SPECT perfusion imaging. These morphologic characteristics will be linked to functional parameters (diffusion capacity, pulmonary vascular resistance change during exercise). The goal is to develop non-invasive imaging markers of early PVD due to HF.
- To test the impact of the correction of metabolic abnormalities on heart failure-related PVD in animal model. Animal model mimicking PVD due to HF will be characterized and the impact of the dietary or pharmacological intervention (based on findings from part A) on pulmonary hemodynamics will be tested in rats with myocardial infarction by left anterior descending (LAD) artery ligation combined with low-dose toxin to pulmonary circulation (monocrotaline or substance Sugen 5416).
- Being tested
- non-contrast chest CT, spirometry with diffusing lung capacity for carbon monoxide (DLCO) analysis, Omics analysis of blood plasma obtained from pulmonary artery or peripheral blood, supine bike exercise during right heart catheterisation, Lung ventilation/perfusion SPECT
- Keywords
- heart failure, pulmonary Hypertension, pulmonary Vasculopathy, Type 2 pulmonary Hypertension, right heart catheterisation, metabolomics, computed tomography of the lungs, AI-assisted quantitative lung CT
- Medical subject headings
- Heart Failure, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
non-contrast chest CTDiagnostic test
patients who undergo clinically indicated evaluation of pulmonary circulation (right heart catheterisation - RHC) will undergo non-contrast CT of the chest, blood sampling from pulmonary artery and spirometry with DLCO analysis.
spirometry with diffusing lung capacity for carbon monoxide (DLCO) analysisDiagnostic test
patients who undergo clinically indicated evaluation of pulmonary circulation (RHC) will undergo non-contrast CT of the chest, blood sampling from pulmonary artery and spirometry with DLCO analysis.
Omics analysis of blood plasma obtained from pulmonary artery or peripheral bloodDiagnostic test
patients who undergo clinically indicated evaluation of pulmonary circulation (RHC) will undergo non-contrast CT of the chest, blood sampling from pulmonary artery and spirometry with DLCO analysis.
supine bike exercise during right heart catheterisationDiagnostic test
subgroup of HF subjects who undergo right heart catheterisation will perform short supine bike exercise during RHC
Lung ventilation/perfusion SPECTDiagnostic test
subgroup of HF subjects will undergo ventilation/perfusion SPECT
| Study group | Role | What they receive |
|---|---|---|
| controls | Subjects without heart failure or pulmonary hypertension undergoing clinically indicated diagnostic evaluation or therapeutic procedure Receives: Diagnostic Test: non-contrast chest CT; Diagnostic Test: spirometry with diffusing lung capacity for carbon monoxide (DLCO) analysis; Diagnostic Test: Omics analysis of blood plasma obtained from pulmonary artery or peripheral blood | |
| heart failure | Subjects with chronic heart failure due to reduced ejection fraction (EF), undergoing clinically indicated right heart catheterisation (evaluation for left ventricular assist device (LVAD)/transplantation (TX) or other decision) Receives: Diagnostic Test: non-contrast chest CT; Diagnostic Test: spirometry with diffusing lung capacity for carbon monoxide (DLCO) analysis; Diagnostic Test: Omics analysis of blood plasma obtained from pulmonary artery or peripheral blood; Diagnostic Test: supine bike exercise during right heart catheterisation; Diagnostic Test: Lung ventilation/perfusion SPECT |
What is being measured
The primary outcome is the main question the study is designed to answer.
biomarker of pulmonary vasculopathy in HF
putative biomarker (protein or metabolite) identified by omics analysis of from plasma of HF patients (with low and high pulmonary vascular resistance) or controls
Measured: after recruitment and cross-sectional analysis of all enrolled subjects (no later than december 2026-the end of study)
CT characteristics of pulmonary vasculopathy in HF
average volume of pulmonary arterioles and venules by non-contrast high resolution CT
Measured: after recruitment and cross-sectional analysis of all enrolled subjects (no later than december 2026-the end of study)
CT characteristics of presence of heart failure
radiographic density of lung parenchyma (lung water estimation) by non-contrast high resolution CT
Measured: after recruitment and cross-sectional analysis of all enrolled subjects (no later than december 2026-the end of study)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2024
- Study start23 Aug 2024
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies 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
- 230 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Institute for Clinical and Experimental Medicine
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Vojtech Melenovsky, MD, PhD, Institute for Clinical and Experimental Medicine
- Investigators
- Vojtech Melenovsky, Principal investigator, Institute for Clinical and Experimental Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06331208
- Sponsor's protocol ID
- LUNG-HF:16181/21; G-21-57
- Acronym
- LUNG-HF
- Status last verified
- Aug 2024
- First submitted
- 23 Feb 2024
- Last updated
- 27 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Melenovsky V, Jarolim P, Kutilkova E, Jenca D, Binova J, Al-Hiti H, Franekova J, Kikerlova S, Yarnykh S, Adamova M, Miklovic M, Borlaug BA. Transpulmonary Proteome Gradients Identify Pathways Involved in Pulmonary Vascular Disease Due To Heart Failure. Circ Heart Fail. 2025 Dec;18(12):e013208. doi: 10.1161/CIRCHEARTFAILURE.125.013208. Epub 2025 Sep 23.
PubMed 40985143
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Pulmonary Vascular Dysfunction in Heart Failure
- ClinicalTrials.gov ID
- NCT06331208
- Acronym / sponsor ID
- LUNG-HF / LUNG-HF:16181/21; G-21-57
- Keywords
- heart failure, pulmonary Hypertension, pulmonary Vasculopathy, Type 2 pulmonary Hypertension, right heart catheterisation, metabolomics, computed tomography of the lungs, AI-assisted quantitative lung CT
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 230 participants (estimated)
- Lead sponsor
- Institute for Clinical and Experimental MedicineOther government
- Study start
- 23 Aug 2024 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 26 Mar 2024 (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 (HF) patients often develop pulmonary hypertension (PH) that leads to transition into a biventricular HF with poor prognosis.
There are two PH components: 1) passive transmission of increased left atrial pressure, 2) heart failure (HF) related pulmonary vascular dysfunction (PVD) with increased vascular resistance. Intriguingly, only some, but not all HF patients develop heart failure-related PVD. The mechanisms and non-invasive detection of HF-PVD are poorly understood and are the focus of the current grant application. Development of PVD is linked to insufficiently characterized metabolic factors that may be mediators of HF-PVD.
Untargeted metabolomics is an emerging powerful platform for the discovery of pathways linked to diseases. Its specificity can be further enhanced using transpulmonary gradient sampling.
Part A of the project aims to identify novel metabolites associated with the presence of PVD in patients with HF that can serve as biomarkers or targets and will provide biologic insights into PVD. Part C will assess the effects of reverting of metabolic alterations (identified in part A) by a drug/diet on pulmonary vasculature in experimental HF-related PVD. The "gold standard" for the detection of PVD is right heart catheterization, which is invasive and risky. Heart failure-related PVD is therefore often diagnosed late.
There is a need for noninvasive tests that may help to detect PVD in early stages and can be done repeatedly. Recent advances in artificial intelligence (AI)-assisted automated quantitative analysis of lung texture from low-dose contrast-free high-resolution CT images allow to quantify lung water content, interstitial changes or vessel volume, and may provide clues for detection of heart failure-related PVD. Such an approach, not tested yet, will be utilized for the detection of HF-PVD (part B). Clinical and functional characteristics of lung circulation (exercise hemodynamics, diffusion capacity, perfusion) will be analyzed in relation to quantitative CT data.
Detailed description
Goals of the project are:
- To identify metabolic factors associated with the development of heart failure related pulmonary vascular disease (PVD) using unbiased metabolomic analysis of blood samples obtained before and after passage through lungs (transpulmonary metabolome), obtained during medically indicated right heart catheterization of HF patients with variable degree of pulmonary vasculopathy. Findings from discovery cohort A1 (200 HF, 30 controls) will be prospectively validated in validation cohort A2 (200 HF, 30 controls). Clinical data (medication, comorbidities, nutritional intake) will be analyzed to identify explanatory links to transpulmonary metabolome and increased pulmonary vascular resistance. The goal is to discover metabolic factors and pathways critical for PVD development, that might be targeted by pharmaco-intervention.
- To identify structural and functional characteristics of heart failure (HF) related PVD using advanced imaging (cohort B, 60 HF patients, 30 controls). Advanced non-invasive imaging methods (high resolution non-contrast CT, SPECT) will be used to identify early changes in lung structure indicating the presence of pulmonary vascular disease. HF subjects with variable elevation of pulmonary vascular resistance will be extensively phenotyped using novel automated AI-augmented analysis of CT data texture, and by SPECT perfusion imaging. These morphologic characteristics will be linked to functional parameters (diffusion capacity, pulmonary vascular resistance change during exercise). The goal is to develop non-invasive imaging markers of early PVD due to HF.
- To test the impact of the correction of metabolic abnormalities on heart failure-related PVD in animal model. Animal model mimicking PVD due to HF will be characterized and the impact of the dietary or pharmacological intervention (based on findings from part A) on pulmonary hemodynamics will be tested in rats with myocardial infarction by left anterior descending (LAD) artery ligation combined with low-dose toxin to pulmonary circulation (monocrotaline or substance Sugen 5416).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| controls | – | Diagnostic Test: non-contrast chest CT, Diagnostic Test: spirometry with diffusing lung capacity for carbon monoxide (DLCO) analysis, Diagnostic Test: Omics analysis of blood plasma obtained from pulmonary artery or peripheral bloodSubjects without heart failure or pulmonary hypertension undergoing clinically indicated diagnostic evaluation or therapeutic procedure |
| heart failure | – | Diagnostic Test: non-contrast chest CT, Diagnostic Test: spirometry with diffusing lung capacity for carbon monoxide (DLCO) analysis, Diagnostic Test: Omics analysis of blood plasma obtained from pulmonary artery or peripheral blood, Diagnostic Test: supine bike exercise during right heart catheterisation, Diagnostic Test: Lung ventilation/perfusion SPECTSubjects with chronic heart failure due to reduced ejection fraction (EF), undergoing clinically indicated right heart catheterisation (evaluation for left ventricular assist device (LVAD)/transplantation (TX) or other decision) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HF: Patients with HFrEF reffered to Institute for Clinical and Experimental Medicine, Prague (IKEM) for diagnostic evaluation Controls non-HF controls reffered to IKEM for diagnostic or therapeutic procedure
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 |
|---|---|---|
| non-contrast chest CTpatients who undergo clinically indicated evaluation of pulmonary circulation (right heart catheterisation - RHC) will undergo non-contrast CT of the chest, blood sampling from pulmonary artery and spirometry with DLCO analysis. | Diagnostic test | controls, heart failure |
| spirometry with diffusing lung capacity for carbon monoxide (DLCO) analysispatients who undergo clinically indicated evaluation of pulmonary circulation (RHC) will undergo non-contrast CT of the chest, blood sampling from pulmonary artery and spirometry with DLCO analysis. | Diagnostic test | controls, heart failure |
| Omics analysis of blood plasma obtained from pulmonary artery or peripheral bloodpatients who undergo clinically indicated evaluation of pulmonary circulation (RHC) will undergo non-contrast CT of the chest, blood sampling from pulmonary artery and spirometry with DLCO analysis. | Diagnostic test | controls, heart failure |
| supine bike exercise during right heart catheterisationsubgroup of HF subjects who undergo right heart catheterisation will perform short supine bike exercise during RHC | Diagnostic test | heart failure |
| Lung ventilation/perfusion SPECTsubgroup of HF subjects will undergo ventilation/perfusion SPECT | Diagnostic test | heart failure |
Primary outcome
biomarker of pulmonary vasculopathy in HF
Time frame: after recruitment and cross-sectional analysis of all enrolled subjects (no later than december 2026-the end of study)
putative biomarker (protein or metabolite) identified by omics analysis of from plasma of HF patients (with low and high pulmonary vascular resistance) or controls
CT characteristics of pulmonary vasculopathy in HF
Time frame: after recruitment and cross-sectional analysis of all enrolled subjects (no later than december 2026-the end of study)
average volume of pulmonary arterioles and venules by non-contrast high resolution CT
CT characteristics of presence of heart failure
Time frame: after recruitment and cross-sectional analysis of all enrolled subjects (no later than december 2026-the end of study)
radiographic density of lung parenchyma (lung water estimation) by non-contrast high resolution CT
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2024.
- Derived from this study: PubMed 40985143Melenovsky V, Jarolim P, Kutilkova E, Jenca D, Binova J, Al-Hiti H, Franekova J, Kikerlova S, Yarnykh S, Adamova M, Miklovic M, Borlaug BA. Transpulmonary Proteome Gradients Identify Pathways Involved in Pulmonary Vascular Disease Due To Heart Failure. Circ Heart Fail. 2025 Dec;18(12):e013208. doi: 10.1161/CIRCHEARTFAILURE.125.013208. Epub 2025 Sep 23.
- Individual participant dataSharing planned: Undecided
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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.
Vojtech Melenovsky principal investigator
Institute for Clinical and Experimental Medicine
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 and Pulmonary Hypertension, run by Institute for Clinical and Experimental Medicine at 1 site in Czechia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: looking for participants now, as of the sponsor's last update on 27 Aug 2024. 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 Czechia. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vojtech Melenovsky, MD, PhD (420 236055190, vome@ikem.cz), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
biomarker of pulmonary vasculopathy in HF (time frame: after recruitment and cross-sectional analysis of all enrolled subjects (no later than december 2026-the end of study)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06331208, which also lists 1 linked publication.
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 27 Aug 2024.