Cardiac transplantation: drug regimens for the 21st century

Survival with congestive heart failure has improved significantly over the last 20 years. However, many patients continue to progress to end-stage disease and suffer unacceptable morbidity and mortality. In the current era, survival after cardiac transplantation approaches 88% to 90% by 1 year at most centers, with more than 50% of patients surviving more than 10 years. Thus, for end-stage patients who are acceptable candidates, cardiac transplantation remains the treatment of choice. The majority of the early (<30-day) postoperative mortality relates to allograft quality and surgical issues, whereas the majority of deaths after 30 days relates to issues of "over" or "under" immunosuppression. With an early mortality rate of less than 10%, the majority of deaths occur after 30 days. Thus a "perfect" immunosuppression regimen would save more lives than a "perfect" donor heart or surgical procedure. Immunosuppression continues to improve but we are all striving for the "perfect" regimen: one free of adverse side effects with perfect graft function. Only a protocol with no chronic immunosuppressive drugs, in other words, complete allograft tolerance, will accomplish this. Many fascinating tolerance-inducing strategies are currently under development.