METABolic Deterioration in HTX Determines Outcomes (METAB-HTX)

METAB-HTX: Prospective, Longitudinal Cohort Study Evaluationg Cardiac and Systemic Metabolism After Heart Transplantation

METAB-HTX is a prospective, longitudinal cohort study evaluating cardiac and systemic metabolism in heart transplant recipients.

Study Overview

• Status: Recruiting
• Conditions: Heart Transplantation

Detailed Description

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 (Estimated): 270

Contacts and Locations

• Study Contact: Name: Amin Polzin, Prof.; Phone Number: 0211 81 18801; Email: amin.polzin@med.uni-duesseldorf.de
• Study Contact Backup: Name: Fabian Voß, Dr. med.; Phone Number: 02118118800; Email: fabian.voss@med.uni-duesseldorf.de

Study Locations

• Germany
  • North Rhine-Westphalia
    • Düsseldorf, North Rhine-Westphalia, Germany, 40225
      • Recruiting
      • University-Hospital Düsseldorf Division of Cardiology, Pneumology and Angiology
      • Contact: Daniel Scheiber, MD; Phone Number: +49211811800; Email: daniel.scheiber@med.uni-duesseldorf.de
      • Contact: Amin Polzin, Prof.; Phone Number: +4902118118801; Email: amin.polzin@med.uni-duesseldorf.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients on the heart transplant waiting list, as well as post-heart transplantation

Description

Inclusion Criteria:

• Age: ≥ 18 years
• Planned or already conducted heart transplantation
• Informed consent

Exclusion Criteria:

• Absence of informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Adult advanced heart failure patients listed for HTx; Patients with advanced heat failure (AHF) and listed for heart transplantation (HTx)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf
• Investigators: Study Chair: Malte Kelm, Prof., Clinic of Cardiology, Pneumology and Vascular Medicine at University Hospital Düsseldorf

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2025
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): February 1, 2032

Study Registration Dates

• First Submitted: January 20, 2025
• First Submitted That Met QC Criteria: January 20, 2026
• First Posted (Actual): January 28, 2026

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Type 2 diabetes; heart failure; heart transplant; cardiac function; cardiac metabolism; Systemic Metabolism
• Additional Relevant MeSH Terms: Endocrine System Diseases; Cardiovascular Diseases; Heart Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Heart Failure; Diabetes Mellitus, Type 2
• Other Study ID Numbers: METAB-HTX

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No