Immune Remodeling Across Advanced Heart Failure, LVAD Support, and Heart Transplantation: From Cellular Activation to Tissue-Resident Memory

Advanced heart failure (HF) left ventricular assist device (LVAD) support and heart transplantation (HTx) are commonly considered distinct clinical stages, although each occurs within an immune system shaped by preceding inflammatory and antigenic exposures. This review introduces the concept of the recipient immune biography, describing the cumulative immunological history that accompanies patients from advanced HF through mechanical circulatory support to transplantation. We examine how HF-associated innate and adaptive immune activation may be modified by mechanical unloading while simultaneously being reshaped by blood–device interactions, hemolysis, complement activation, infection, transfusion, and sensitization during LVAD support. Following transplantation, this preconditioned immune repertoire encounters persistent donor alloantigen through direct, indirect, and semidirect allorecognition. We integrate T-cell effector, regulatory, exhaustion-associated, and memory states with T follicular helper–B-cell interactions, plasma-cell persistence, donor-specific antibodies, and tissue-resident immunity. Emphasis is placed on the limitations of peripheral biomarkers for representing graft-localized immune processes. We propose a Longitudinal Immune Trajectory integrating serial peripheral biomarkers with cellular, clonal, molecular, and spatial profiling to reconstruct patient-specific immune remodeling across the HF–LVAD–HTx continuum.