A 45 year old male obese patient with a previous history of repaired congenital heart disease developed worsening heart failure making heart transplantation listing mandatory. Unfortunately, due to his anthropometric measures, the search for a suitable brain-dead donor was unsuccessful. For this reason, he accepted to be enrolled in the controlled donation after circulatory death (cDCD) program. According to the Italian Law regulating death declaration after cardiac arrest (no-touch period of 20 minutes—one of the longest in the world), we faced a 34 minute cardiac asystole, after which the heart was recovered through a thoraco-abdominal normothermic regional perfusion excluding the epiaortic vessels. The heart was then preserved by means of cold static storage. Heart transplantation was performed successfully without any signs of primary graft failure. Postoperative endomyocardial biopsies were negative for acute cellular and antibody-mediated rejection. Furthermore, echocardiographic and cardiac magnetic resonance evaluation of the heart did not show any functional abnormalities. The patient was discharged on post-operative day (POD) #39 in good clinical conditions.

Heart transplantation is considered the gold standard for the treatment of advanced end-stage heart failure. However, standard donors after brain death are decreasing, whereas patients on the heart transplant waitlist are constantly rising. The introduction of the ex vivo machine perfusion device has been a turning point; in fact, these systems are able to significantly reduce ischemic times and have a potential effect on ischemia-related damage reduction. From a clinical standpoint, these machines show emerging results in terms of heart donor pool expansion, making marginal donors and donor grafts after circulatory death suitable for donation. This article aims to review mechanisms and preclinical and clinical outcomes of currently available ex vivo perfusion systems, and to explore the future fields of application of these technologies.

Background: Heart transplant rejection, particularly acute cellular rejection (ACR), remains a critical post-operative concern, despite declining incidence rates. Current diagnostic standards rely on invasive endomyocardial biopsy, which presents limitations in sensitivity and reproducibility. There is an unmet need for noninvasive, accurate biomarkers that can detect and monitor rejection. This study aims to evaluate whether extracellular vesicle (EV) surface antigens, analyzed through flow cytometry and interpreted with artificial intelligence (AI), can serve as reliable biomarkers for ACR detection and monitoring in heart transplant recipients. Methods: We conducted a prospective longitudinal cohort study involving 24 heart transplant recipients over a median follow-up of 303 days. A total of 285 blood samples were analyzed for EV surface antigens exploiting two flow cytometry-based protocols. An adaptive AI model (random forest regressor) was developed to interpret EV antigen profiles, dynamically calibrating thresholds per patient. Results: Here we show that 14 EV surface antigens progressively increase with ACR severity. These changes are evident even before histological diagnosis. The AI model achieves an accuracy of 93.3% at leave-one-out testing (AUC 0.968), and 78.9% at validation in an independent cohort (AUC 0.832), with high specificity and negative predictive value. EV profiling outperforms conventional biochemical markers and provides anticipatory insight into rejection dynamics. Conclusions: EV profiling, enhanced by patient-specific AI modeling, offers a powerful noninvasive method for early detection and monitoring of ACR. This approach holds the potential to reduce reliance on biopsies and tailor immunosuppressive strategies more precisely.

Cardiac allograft vasculopathy (CAV) assessment post-heart transplantation (HT) typically relies on invasive coronary angiography (ICA). However, cardiac computed tomography angiography (CCTA) is emerging as a promising alternative due to its potential benefits in economic, safety, and logistical aspects. This study aimed to evaluate the impact of a CCTA program on these aspects in CAV surveillance post-HT. A retrospective single-center study was conducted between March 2021 and February 2023, involving HT patients who underwent either CCTA or ICA. Among 260 patients undergoing CAV surveillance, 115 (44.2%) patients underwent CCTA, and 145 (55.8%) patients underwent ICA. The CCTA group showed incurred lower overall costs (p ​< ​0.0001) and shorter hospitalization times (p ​< ​0.0001) compared to the ICA group. In terms of safety, CCTA surveillance required significantly lower contrast volumes (p ​< ​0.0001) and lower effective doses (p ​= ​0.03). CCTA emerges as a safe and cost-effective non-invasive alternative for CAV surveillance post-HT, outperforming ICA in terms of safety, logistical aspects, and economic burden.