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Mechanisms of Pulmonary Vascular Dysfunction in Heart Failure

ConditionsHeart FailurePulmonary HypertensionPulmonary Vascular Resistance Abnormality
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorInstitute for Clinical and Experimental Medicine

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

age>18y

signed informed consent,

left ventricular (LV) ejection fraction <50%

duration of HF>6 months,

Disqualifiers

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)

Trial 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

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • 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.

  • 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.

  • 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.

  • 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

  • Lung ventilation/perfusion SPECT

    Diagnostic test

    subgroup of HF subjects will undergo ventilation/perfusion SPECT

Treatment groups

230 Participants
are divided into 2 treatment groups
Group A: controls3 interventions
Group B: heart failure5 interventions

Trial outcomes

Primary outcomes

1

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

Time frame
after recruitment and cross-sectional analysis of all enrolled subjects (no later than december 2026-the end of study)
2

CT characteristics of pulmonary vasculopathy in HF

average volume of pulmonary arterioles and venules by non-contrast high resolution CT

Time frame
after recruitment and cross-sectional analysis of all enrolled subjects (no later than december 2026-the end of study)
3

CT characteristics of presence of heart failure

radiographic density of lung parenchyma (lung water estimation) by non-contrast high resolution CT

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

Secondary outcomes

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Institute for Clinical and Experimental Medicine

Lead sponsor

Source ClinicalTrials.gov
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