Cyclosporine may affect improvement of cognitive brain function after successful cardiac transplantation

Background The effects of cardiac transplantation on cognitive brain function are uncertain. Methods and Results We measured cognitive brain function and quality of life in out-of-hospital cardiac transplant candidates (n=55; ejection fraction, 19.9%; age, 54.8 years [means]). After transplantation, the patients were serially reevaluated at 4 months (n=25) and at 12 months (n=19). Brain function was measured objectively by cognitive P300 evoked potentials. Additionally, standard psychometric tests (Trail Making Test A, Mini-Mental State Examination, and Profile of Mood State test) were performed. Cognitive P300 evoked potentials were impaired in cardiac transplant candidates (359 ms, recorded at vertex) compared with 55 age- and sex-matched healthy subjects (345 ms, P<.01). Trail Making Test A was also abnormal (45 versus 31 seconds in 55 healthy subjects, P<.01). After transplantation, P300 measures were normalized at 4 months (345 ms, P<.05 versus before transplantation) but declined again at 12 months (352 ms, P=NS versus before transplantation). Stepwise multiple regression analysis revealed that cumulative cyclosporine dosage was the only predictor of individual cognitive brain function 4 months (753 mg/kg body wt, P<.05) and 12 months: (2006 mg/kg body wt, P<.01) after transplantation, respectively. Conclusions Objective cognitive P300 auditory evoked potential measurements indicate that cognitive brain function is significantly impaired in patients suffering from stable endstage heart failure. Successful cardiac transplantation is effective to fully normalize impaired br ain function. Subsequent relative long-term decline of cognitive brain function after successful cardiac transplantation is strongly suggested to be related to cumulative cyclosporine neurotoxicity.