Heart Transplantation in 2076: From Scarcity to Cardiac Restoration

Heart transplantation has historically been defined by the scarcity of donor organs and the uncertainties surrounding them. Over the past 50 years, advances in immunosuppression, surgical techniques, and posttransplant surveillance have improved outcomes, yet the fundamental paradigm remains unchanged: the replacement of a failing heart still depends on the death of another person. In this Perspective, we argue that this paradigm is beginning to shift, with early evidence emerging from molecular diagnostics that enable noninvasive detection of graft injury. Over the coming decades, regenerative therapies, immune engineering, and advances in organ preservation are poised to shift the trajectory of advanced heart failure, reducing progression to end-stage disease, whereas evolving mechanical circulatory support technologies may provide durable alternatives or bridges. As biologic restoration becomes feasible, artificial intelligence may integrate molecular, physiologic, and clinical data into adaptive systems of care. By 2076, heart transplantation will be characterized by a spectrum of cardiac-restoration strategies, including regeneration, engineered tissues, xenografts, and targeted immune therapies to promote graft tolerance. In this evolving model of care, equity will be strengthened through integration of data, decision-making, and care delivery. Collectively, these advances mark a shift from the incremental progress of the past 50 years toward an accelerating pace of scientific and clinical innovation that will redefine heart failure care, moving beyond donor-dependent transplantation.