I27.0
Conditions
Interventions
Group 1: frequently iron deficient patients with pulmonary arterial hypertension will be investigated via iron resorption test and stool sample (at baseline and after 5-7 days)
Group 2: non-iron defic
Sponsors
Thoraxklinik am Universitätsklinikums Heidelberg - Zentrum für pulmonale Hypertonie
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Patients • Patients, diagnosed with heritable PAH, idiopathic PAH, drug and toxin associated PAH (PAH), PAH associated with congenital heart disease with simple heart defects (such as ventricle septal defect, atrial septal defect, patent ductus arteriosus and patent foramen ovale), PAH with comorbidities not affecting iron metabolism or microbiome • Baseline haemodynamics showing mPAP >20 mmHg at rest, PVR >2 WU, PAWP =15 mmHg • Optimized, unchanged targeted PAH therapy since at least 2 months • Ability to understand and willing to sign the informed consent form Healthy controls (control group will be age and sex matched to non-iron deficient PAH patients, n=15) • Ability to understand and willing to sign the informed consent form
Exclusion criteria
Exclusion criteria: General • Patients with connective tissue disease associated PAH (gastrointestinal bleeding cannot be excluded in these patients) • Patients with Morbus Osler associated PAH (gastrointestinal bleeding cannot be excluded in these patients) • Pregnancy or lactation • Malignancy • Severe kidney disease with glomerular filtration rate 3x upper limit of normal or bilirubin levels >50 µmol/l (equivalent to >2.9 mg/dl) ) and aminotransferases >3x upper limit of normal at the same time • Intravenous or oral iron supplementation within the preceding 2 months • Patients with prior determined transferrin saturation >90% as plasma iron is not expected to rise in these patients (Kobune et al., 2011) • Comorbidities affecting iron metabolism such as haemolytic anaemias, genetic disorders of haemoglobin, sickle cell disease, thalassemia or any known iron overload syndrome • Comorbidities affecting the gut microbiome such as inflammatory bowel disease, Crohn’s disease or other gastrointestinal diseases • Acute infection 5 days prior to enrollment • Intake of antibiotics in the past 2 weeks (If this case occurs, the stool sampling will be omitted) • Diarrhoea • Any haemolytic samples will be disregarded as iron values can be falsely elevated Healthy controls • Significant cardiovascular or lung diseases
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the difference in iron absorption in PAH patients with and without iron deficiency and healthy controls measured by a standardized iron absorption test | — |
Secondary
| Measure | Time frame |
|---|---|
| blood and/or stool and urine as well as clinical characteristics: • Iron in stool and urine • Ferritin • Transferrin • Transferrin saturation • Ferroportin • Erythroferrone • Soluble transferrin receptor concentration • Erythropoietin • Hepcidin • Peripheral blood monocyte levels • Erythrocytes • Myoglobin • Haemoglobin • Haematocrit • Red blood distribution cell width • Hypochromic erythrocytes • Mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC) • Bilirubin Laboratory parameters independent of iron metabolism in blood: • C-reactive protein levels • Creatinine • Interleukin 6 (IL6) • NT-proBNP • Glomerular filtration rate • Urea • Leukocytes • Additional urine parameters contained on multistix 10SG system test strip • Peripheral blood mononuclear cells levels and iron-related proteins therein Metagenome of gut microbiome • Alpha-diversity (species diversity within a sample): richness (number of different species/sample), evenness (species abundance), dominance (species with high share in total species abundance) • Beta-diversity (species diversity differences between the two groups) Plasma proteome • Changes before and 3 h after iron resorption test in the same patient • Changes between the two groups with a focus on proteomic iron homeostasis regulators Clinical and demographic parameters include • Age • Height • Weight • Sex • Age at diagnosis • Oxygen saturation • 6-minute walking distance (6-MWD) • WHO functional class • Data of last lung function tests • Diffusion capacity of carbon monoxide • Data of first and most recent right heart catheterisation • Echocardiographic parameters of the right ventricle regarding size and pump function • Targeted PAH therapy (dose & type of medication) • Comorbidities • Dietary & activity habits (with influence on iron levels) | — |
Countries
Germany
Contacts
Public ContactChristina Eichstaedt
Thoraxklinik am Universitätsklinikum Heidelberg - Zentrum für pulmonale Hypertonie
Outcome results
None listed