New Insights Into Pathogenesis, Diagnosis, and Management of Cardiac Allograft Vasculopathy

Despite major advances in short-term outcomes after heart transplantation, long-term survival remains limited by chronic allograft dysfunction, with cardiac allograft vasculopathy (CAV) being the leading cause of late graft failure and an important cause of all-cause mortality. CAV is a unique and multifactorial form of transplant coronary vasculopathy, driven by a complex interplay of alloimmune responses, innate immune activation, and traditional cardiovascular risk factors. Recent insights from deep profiling of human allograft tissue have revealed the key roles of locally sustained T- and B-cell-mediated inflammation, macrophage-natural killer cell interactions, and chronic immune activation within the graft. These discoveries challenge earlier models of systemic immune monitoring and highlight the importance of spatially organised intragraft immune processes. In parallel, the diagnostic landscape of CAV is rapidly evolving. High-resolution imaging techniques, such as optical coherence tomography, and advanced noninvasive tools, including coronary computed tomography angiography and positron emission tomography, not only enable earlier and more precise detection of disease, but also redefine the usual landscape of CAV diagnosis. New methods for individualised risk stratification, including trajectory modelling and machine learning-enhanced biopsy analysis, are paving the way for more personalised surveillance strategies. While current management remains focused on prevention, novel therapeutic targets are emerging, informed by a deeper understanding of CAV immunopathogenesis. This review provides an up-to-date synthesis of recent advances in CAV, with a focus on pathophysiology, individualised risk assessment, diagnostic innovation, and therapeutic perspectives, underscoring a paradigm shift toward more precise and proactive care in heart transplant recipients.