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METAB-HTX is a prospective, longitudinal cohort study evaluating cardiac and systemic metabolism in heart transplant recipients.
Bankground:
Heart Transplantation (HTS) is the treatment of choice for advanced heart failure, yet long-time survival rates require further improvement. Recent studies highlight obesity, type 2 diabetes, renal dysfunction, and hepatic impairment as key contributors to post-transplant mortality. Furthermore, critical questions persist in understanding the optimal metabolic surveillance post-HTX, the direct association between metabolic dysregulation and cardiac dysfunction, inter-organ interactions linking metabolic decline to hepatic/renal impairment and the timing of therapeutic strategies.
Therefore: METAB-HTX study aims to address these open questions, hypothesizing that metabolic deterioration post-HTX is associated with impaired cardiac function and survival.
Study Design:
The study employs advanced multi-modal phenotyping to investigate interactions between cardiac function, metabolic dysregulation, and systemic organ dysfunction.
Cardiac Phenotyping:
Metabolic phenotyping:
Systemic Organ Evaluation:
Molecular and Multi-Omics Integration:
This innovative study aims to bridge critical gaps in understanding post-transplant metabolic pathophysiology, potentially refining surveillance protocols and guiding targeted therapies to improve long-term survival through precision medicine strategies
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adult advanced heart failure patients listed for HTx | Patients with advanced heat failure (AHF) and listed for heart transplantation (HTx) |
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| Measure | Description | Time Frame |
|---|---|---|
| diastolic and systolic left ventricular function | in cardiac MRI or echocardiography | Baseline, 1 year, and 2 years after heart transplantation |
| CAV diagnosis | coronary angiography, intravascular imaging and intravascular physiology measuraments | Baseline, 1 year, and up to 24 months |
| Allograft rejection will be evaluated by endomyocardial biopsy | Tissue specimens will be collected from the interventricular septum and analyzed by cardiac transplant pathologists. Myocardial inflammation will be assessed in endomyocardial biopsies using immunohistochemistry followed by quantitative digital image analysis. Inflammatory cell infiltration will be quantified as the number of positive cells per square millimeter (mm²), providing a quantitative measure of myocardial inflammatory burden. In addition, biopsy tissue will be used for exploratory molecular analyses. | 1 year and 5 years after heart transplantation |
| Worsening of kidney function | Renal function will be assessed using estimated glomerular filtration rate (eGFR) as the primary quantitative measure. eGFR will be calculated from serum creatinine and cystatin C obtained from periodic blood sampling. Additional renal assessments, including duplex sonography, urinary markers, and immunological parameters, will be used for supportive and exploratory analyses. | Baseline, 1 year, and 2 years after heart transplantation |
| Infection requiring heath care professional interventions | clinical events, labs (CRP) , outpatient contact, hospitalisation. | Baseline, 1 year, and 2 years after heart transplantation |
| Diagnosis of malignencies |
| Measure | Description | Time Frame |
|---|---|---|
| Hospitalisation due to heart transplant events | Number of hospitalisations due to heart transplant-related events after study inclusion | up to 5 years (follow-up in clinical routine) |
| Cardiovascular mortality and all-cause mortality |
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Inclusion Criteria:
Exclusion Criteria:
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Patients on the heart transplant waiting list, as well as post-heart transplantation
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Amin Polzin, Prof. | Contact | 0211 81 18801 | amin.polzin@med.uni-duesseldorf.de | |
| Fabian Voß, Dr. med. | Contact | 02118118800 | fabian.voss@med.uni-duesseldorf.de |
| Name | Affiliation | Role |
|---|---|---|
| Malte Kelm, Prof. | Clinic of Cardiology, Pneumology and Vascular Medicine at University Hospital Düsseldorf | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University-Hospital Düsseldorf Division of Cardiology, Pneumology and Angiology | Recruiting | Düsseldorf | North Rhine-Westphalia | 40225 | Germany |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
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Blood samples:including circulating citrullinated histone H3 (H3cit)-DNA complexes
By whole-body CT scans, screening for occult blood within the stool and if indicated gastroscopy and coloscopy. Analysis of epigenetic alterations in leukocytes which are associated with post HTX events like neoplasia. |
| Baseline, 1 year, and 2 years after heart transplantation |
| Worsening of metabolic derangements | Changes in glucose and lipid metabolism, insulin resistance, HDL function, and body fat distribution will be assessed using blood tests, oral glucose tolerance, and imaging in selected participants. | Baseline, 1 year, and 2 years after heart transplantation |
| Liver deterioration | Liver structure and function will be assessed using blood tests (liver enzymes, bilirubin, albumin, INR), imaging (ultrasound, CT, transient elastography), and fibrosis scores (FIB-4) in selected participants. | Baseline, 1 year, and 2 years after heart transplantation |
Survival and clinical outcomes after study index visit (inclusion)
| up to 5 years (follow-up in clinical routine) |
| Re-transplantation or ventricular assist device implantation | Incidence of re-transplantation or ventricular assist device implantation during follow-up. | Through study completion, up to 5 years after heart transplantation |
| D008659 |
| Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |