METABolic Deterioration in HTX Determines Outcomes

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

• Hospitalisation due to heart transplant events [Срок оценки: up to 5 years (follow-up in clinical routine)]
• Cardiovascular mortality and all-cause mortality [Срок оценки: up to 5 years (follow-up in clinical routine)]
• Re-transplantation or ventricular assist device implantation [Срок оценки: Through study completion, up to 5 years after heart transplantation]