Phenotyping of the Out-of-proportion Pulmonary Hypertension

Study Purpose

Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions and may be associated with a variety of cardiovascular and respiratory diseases. The complexity of managing PH requires a multidisciplinary approach, with active involvement of patients with PH in partnership with clinicians.(1) All age groups are affected. Present estimates suggest a PH prevalence of 1% of the global population. Due to the presence of cardiac and pulmonary causes of PH, prevalence is higher in individuals aged 65 years. Globally, LHD is the leading cause of PH. Lung disease, especially chronic obstructive pulmonary disease (COPD), is the second most common cause. In the UK, the observed PH prevalence has doubled in the last 10 years and is currently 125 cases/million inhabitants.

(2) Pulmonary hypertension is defined by a mean pulmonary arterial pressure (mPAP) more than 20 mmHg at rest according to the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension .

It is essential to include PVR and pulmonary arterial wedge pressure (PAWP) in the definition of pre-capillary PH, in order to discriminate elevated PAP due to pulmonary vascular disease (PVD) from that due to left heart disease (LHD), elevated pulmonary blood flow, or increased intrathoracic pressure.(3) Clinical classification of pulmonary hypertension includes GROUP 1 Pulmonary arterial hypertension (PAH), GROUP 2 PH associated with left heart disease, GROUP 3 PH associated with lung diseases and/or hypoxia, GROUP 4 PH associated with pulmonary artery obstructions and GROUP 5 PH with unclear and/or multifactorial mechanisms.

(3) Pulmonary hypertension is frequently observed in patients with COPD and/or emphysema, diffuse parenchymal lung diseases and hypoventilation syndromes.

Pulmonary hypertension is uncommon in obstructive sleep apnoea unless other conditions coexist, such as COPD or daytime hypoventilation. In patients with lung disease, PH is categorized as non-severe or severe, Whereas non-severe PH is common in advanced COPD and ILD defined by spirometric criteria, severe PH is uncommon, occurring in 1-5% of cases of COPD and ,10% of patients with advanced ILD, with limited data in obesity hypoventilation syndrome.(4) Pulmonary hypertension presenting in patients with lung disease may be due to a number of causes, including undiagnosed CTEPH or PAH. A number of distinct phenotypes of PH in patients with lung disease, including a pulmonary vascular phenotype, have been proposed. The pulmonary vascular phenotype is characterized by better preserved spirometry, low DLCO, hypoxaemia, a range of parenchymal involvement on lung imaging, and a circulatory limitation to exercise.(5) Cardiac comorbidities are also common in patients with lung disease and may contribute to increased risk for hospitalization, longer length of stay, pulmonary hypertension and CVD-related mortality.(6) A vast category of patients suffering from parenchymal lung diseases (often accompanied by minor pulmonary impairment on pulmonary function test and/or CT scan) with an unexplained severe degree of PH was brought to the attention of physicians. In these patients, the development of moderate to severe PH, which is disproportionate to the degree of parenchymal lung disease and hypoxia, has been termed "out-of-proportion" PH, and an arbitrary value of . 35 mm Hg mean pulmonary artery pressure has been selected to identify this category of patients.(7) and there is limited data about the Out-of proportion PH and it different phenotypes

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years - 70 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- All Patients presented with severe pulmonary hypertension (PASP > 70mmHg by echocardiographic assessment) (8) associated with chronic lung diseas will be included in the study.

Exclusion Criteria:

- 1- Age under 18 years.

2- Severe PH proportional to the disease. 3- Hemodynamically unstable condition requiring inotropic or vasoactive drugs. 4- Severe chest wall deformity. 5- Pregnant women. 6- Right-sided endocarditis, right-sided tumor, or thrombus. 7- Severe coagulopathy or bleeding diathesis

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06051396
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Assiut University
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Mahmoud Badwy, specialist
Principal Investigator Affiliation	Assiut University
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Egypt
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	1- Haemodynamic Phenotyping of the Out - of - Proportion PH to Guide Different Therapeutic Lines

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