Mechanisms of Pulmonary Vascular Dysfunction in Heart Failure

NCT06331208 | Recruiting

• 1 other identifier: LUNG-HF:16181/21; G-21-57
• Study Type: observational
• Target: 230
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Heart Failure; Pulmonary Hypertension; Pulmonary Vascular Resistance Abnormality

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

Outcome Measures

Primary Outcomes (3)

• 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

  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

  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

  after recruitment and cross-sectional analysis of all enrolled subjects (no later than december 2026-the end of study)

Study Arms (2)

controls

Subjects without heart failure or pulmonary hypertension undergoing clinically indicated diagnostic evaluation or therapeutic procedure

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)

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

Interventions

non-contrast chest CT DIAGNOSTIC_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.

controls; heart failure

spirometry with diffusing lung capacity for carbon monoxide (DLCO) analysis DIAGNOSTIC_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.

controls; heart failure

Omics analysis of blood plasma obtained from pulmonary artery or peripheral blood DIAGNOSTIC_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.

controls; heart failure

supine bike exercise during right heart catheterisation DIAGNOSTIC_TEST

subgroup of HF subjects who undergo right heart catheterisation will perform short supine bike exercise during RHC

heart failure

Lung ventilation/perfusion SPECT DIAGNOSTIC_TEST

subgroup of HF subjects will undergo ventilation/perfusion SPECT

heart failure

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Institute for Clinical and Experimental Medicine: lead

Study Sites (1)

Institute for Clinical and Experimental Medicine - IKEM

Prague, 140 21, Czechia

RECRUITING

Related Publications (1)

• 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.

  PMID: 40985143 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

blood plasma samples obtained A) during right heart catheterisation from wedged and non-wedged position of pulmonary artery catheter B) during morning fasting blood sampling from peripheral vein

MeSH Terms

Conditions

Heart Failure; Hypertension, Pulmonary

Interventions

Spirometry; Respiration

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases

Intervention Hierarchy (Ancestors)

Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Vojtech Melenovsky

  Institute for Clinical and Experimental Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vojtech Melenovsky, MD, PhD

CONTACT

420 236055190; vome@ikem.cz

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof, MD, PhD

Study Record Dates

• First Submitted: February 23, 2024
• First Posted: March 26, 2024
• Study Start: August 23, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: August 27, 2024

Record last verified: 2024-08

Locations

CZ (1)