Mechanisms of Pulmonary Vascular Dysfunction in Heart Failure
Trial ID: NCT06331208
Status: RECRUITING
Study type: OBSERVATIONAL
Start date: 2024-08-23
Completion date: 2026-12-30
Sponsor: Institute for Clinical and Experimental Medicine
Conditions: Heart Failure; Pulmonary Hypertension; Pulmonary Vascular Resistance Abnormality
Interventions: 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
Locations: Institute for Clinical and Experimental Medicine - IKEM
Countries: Czechia
Enrollment: 230
Age range: 18 Years - None
Sex: ALL

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.

Eligibility criteria:
A) 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)

B) 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)

Outcomes:
biomarker of pulmonary vasculopathy in HF; CT characteristics of pulmonary vasculopathy in HF; CT characteristics of presence of heart failure