Exercise aNd hEArt Transplant

40 patients who achieved Heart transplantation (HTx) will be randomized in a pilot study to 4 weeks of on-site standard CR (control arm) versus two-four weeks of on-site CR followed by 12 weeks of telerehabilitation (experimental arm). Both surrogate endpoints \[cardiometabolic equivalents (Vo2 peak)\] and clinical endpoint \[primary outcome defined as acute rejection, hospitalization for heart failure, stroke, myocardial infarction, all-cause mortality, at the longest follow-up available (minimum 6-month follow-up)\] will be evaluated.

The rehabilomic approach will be applied in order to identify specific patients' phenotype. To identify the potential variations of circulating molecules levels that could be indicators of the rehabilitation outcome and/or progression of the disease, the research team will focus on the analysis of extracellular vesicles (EVs) isolated from the serum of the 40 patients at admission (T0) and after cardiac rehabilitation (T1). In particular, researchers will detect and analyze the relative amount of serum EVs derived from platelets, endothelium, cardiomyocytes, and macrophages, as their levels are reported to be associated with the occurrence of heart failure.

• telerehabilitation (Other): Telerehabilitation activites will be tested with the aim to provide 1) continuation of rehabilitative care, focused on physical training and patients'monitoring , and 2) information in the mid-term about study goals.
• rehabilomic (Other): blood withdrawal (10 ml of blood, two tubes of 5 ml for serum isolation): at the hospital admission at the Cardiac Rehabilitation Unit of IRCCS Fondazione Don Gnocchi of Milan (T0) and after the rehabilitative treatment (T1)

Primary outcomes

• Cardiovascular events [6-months]: Incidence of acute rejection, Rate of hospitalization for heart failure, Incidence of stroke, Incidence of myocardial infarction and incidence of all-cause mortality

Secondary outcomes

• Vo2 peak [6-months]: cardiometabolic equivalents (Vo2 peak)
• extracellular vesicles (EVs) analysis with Surface Plasmon Resonance imaging (SPRi) [up to 4 weeks]: EVs will be isolated from blood, characterized by standard procedures and injected on the SPRi biosensor for the differential quantification of multiple EV subfamilies. The expression of a secondary antigen will be evaluated on the surface of immobilized EVs.
• EuroQol 5-Dimension (EQ-5D-5L) [6-months]: The EQ-5D-5L is a generic questionnaire measuring five domains of current health-related quality of life, where a higher index score indicates higher health-related quality of life.
• Short Form 36 (SF36) [6-months]: The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures.
• Hospital Anxiety and Depression Scale (HADS) [6-months]: The HADS is a 14-item generic questionnaire measuring symptoms of anxiety and depression within the last week.

Sex: All, ages: 18 Years to any, accepts healthy volunteers

Inclusion Criteria:

* All the patients admitted in the on-site CR after HTx

Exclusion Criteria:

* unable to sign informed consent

• Results publication: Pedersini P, Picciolini S, Di Salvo F, Toccafondi A, Novembre G, Gualerzi A, Cusmano I, Garascia A, Tavanelli M, Verde A, Masciocco G, Ricci C, Mannini A, Bedoni M, Morici N. The Exercise aNd hEArt transplant (ENEA) trial - a registry-based randomized controlled trial evaluating the safety and efficacy of cardiac telerehabilitation after heart transplant. Contemp Clin Trials. 2024 Jan;136:107415. doi: 10.1016/j.cct.2023.107415. Epub 2023 Dec 17. PMID 38114046

• Nuccia Morici, MD, Principal investigator, IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy