Background/Objectives: Cardiac allograft vasculopathy (CAV) is a major complication following orthotopic heart transplantation (OHT). Graft denervation results in silent ischemia, even when already established, requiring regular screening for early diagnosis. This study explores whether myocardial work (MW) can non-invasively identify OHT patients with obstructive coronary lesions (OCL). Methods: During regular follow-ups, 55 OHT recipients underwent paired, prospective coronary computed tomography angiography (CCTA) and transthoracic echocardiography (TTE) examinations. Additionally, 57 healthy volunteers (HV) provided reference TTE data. Classic echocardiographic parameters, such as left ventricle global longitudinal strain (LV-GLS) and MW indices, were obtained in all individuals. Data from three groups were analyzed: HV, OHT patients without coronary lesions or with <50% lesions on the CCTA (OHT-non-OCL), and OHT patients with ≥50% lesions on the CCTA (OHT-OCL). Results: CCTA identified seven OHT patients with OCL. Significant differences across the groups existed for LV-GLS (OHT-OCL −10.6% CI −14 to −6.8 vs. OHT-non-OCL −15.6% CI −16.5 to −13.4% vs. HV −18% CI −20 to −16, p < 0.01) and global work efficiency (GWE) (OHT-OCL 87% CI 86 to 92 vs. OHT-non-OCL 94% CI 91 to 95 vs. HV 96% CI 95 to 97, p < 0.01). The optimal cut-off values identified using the Youden Index were LV-GLS < −14.4% (AUC 0.80, sensitivity 0.86, specificity 0.71) and GWE < 89% (AUC 0.75, sensitivity 0.71, specificity 0.85). Multivariate analysis showed GWE as the best marker for detecting OCL. Conclusions: GWE is the echocardiographic parameter that best identifies OHT patients that have OCL on CCTA. If validated in larger studies, GWE could become a readily accessible tool for CAV detection.
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