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: * Imaging: Serial echocardiography, cardiac MRI (cMRI), and magnetic resonance spectroscopy (MRS) for myocardial structure, perfusion, and metabolic profiling. * Vascular Evaluation: Coronary angiography to detect macro- and microvascular coronary allograft vasculopathy (CAV). * Rejection Monitoring: Protocol-driven endomyocardial biopsies for histopathological grading. Metabolic phenotyping: * Serial oral glucose tolerance tests, homeostasis model assessment, type 2 diabetes endotyping and muscle biopsies. * Advanced lipid panels, HDL functional assays and plasma membrane lipid fluidity analyses. * MRI/MRS-based quantification of adipose tissue distribution and ectopic fat deposition. Systemic Organ Evaluation: * renal and liver function. Molecular and Multi-Omics Integration: * Myocardial Energy Metabolism, Genomic/Transcriptomic Profiling, Thromoboinflammation and Neoplasia Risk. 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
Study Type
OBSERVATIONAL
Enrollment
270
University-Hospital Düsseldorf Division of Cardiology, Pneumology and Angiology
Düsseldorf, North Rhine-Westphalia, Germany
RECRUITINGdiastolic and systolic left ventricular function
in cardiac MRI or echocardiography
Time frame: Baseline, 1 year, and 2 years after heart transplantation
CAV diagnosis
coronary angiography, intravascular imaging and intravascular physiology measuraments
Time frame: 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.
Time frame: 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.
Time frame: Baseline, 1 year, and 2 years after heart transplantation
Infection requiring heath care professional interventions
clinical events, labs (CRP) , outpatient contact, hospitalisation.
Time frame: Baseline, 1 year, and 2 years after heart transplantation
Diagnosis of malignencies
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.
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Time frame: 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.
Time frame: 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.
Time frame: Baseline, 1 year, and 2 years after heart transplantation
Hospitalisation due to heart transplant events
Number of hospitalisations due to heart transplant-related events after study inclusion
Time frame: up to 5 years (follow-up in clinical routine)
Cardiovascular mortality and all-cause mortality
Survival and clinical outcomes after study index visit (inclusion)
Time frame: 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.
Time frame: Through study completion, up to 5 years after heart transplantation