Post-heart transplantation immunosuppression and rejection: what the general cardiologist needs to know

While heart transplantation (HT) is the optimal therapy for end-stage heart failure patients, longevity of HT recipients continues to be limited by rejection and its sequelae. In this review, we provide an overview of current immunosuppressive principles and the prevention, diagnosis and treatment of rejection in HT. All HT recipients are maintained on immunosuppression to prevent rejection and undergo regular surveillance testing to identify rejection episodes that may require treatment. Risk of rejection is highest in the first year-post-HT and so during that period, immunosuppression is maintained at the highest levels and surveillance testing is done most frequently. The current standard triple-drug immunosuppressive regimen for HT consists of tacrolimus, a calcineurin inhibitor, mycophenolate mofetil, an antimetabolite agent and steroids. This regimen, with a calcineurin inhibitor as its cornerstone, has led to significantly decreased rates of rejection, particularly acute cellular rejection (ACR) in the current day compared with the early days of HT. The endomyocardial biopsy is currently the standard for rejection surveillance, but newer technologies such as donor-derived cell-free DNA measurements are changing surveillance practices in the field. While rates of ACR have decreased with current management strategies, antibody-mediated rejection (AMR) continues to pose a challenge. Newer immunosuppressive therapies that more effectively target the humoral and innate immune systems aim to better prevent and treat AMR in HT recipients. Furthermore, ongoing advancements in rejection surveillance strategy offer higher sensitivity and diagnostic accuracy for AMR compared with just histopathology on the endomyocardial biopsy. Ongoing advancements in immunosuppression and rejection surveillance will lead to continued improvement in longevity of HT recipients.