Mechanisms of Pulmonary Vascular Dysfunction in Heart Failure

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

Interventions

DIAGNOSTIC_TEST

non-contrast chest CT

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.

DIAGNOSTIC_TEST

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

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.

DIAGNOSTIC_TEST

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

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.

DIAGNOSTIC_TEST

supine bike exercise during right heart catheterisation

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

DIAGNOSTIC_TEST

Lung ventilation/perfusion SPECT

subgroup of HF subjects will undergo ventilation/perfusion SPECT

Sponsors & Collaborators

• Institute for Clinical and Experimental Medicine

  lead OTHER_GOV

Principal Investigators

• Vojtech Melenovsky · Institute for Clinical and Experimental Medicine

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-08-23

Primary Completion

2026-12-30

Completion

2026-12-30

Countries

• Czechia

Study Locations