Development in Left Ventricular Mass After Early and Late Conversion From Calcineurin Inhibitors to Everolimus in Heart Transplant Recipients-Results From Two Randomized Controlled Trials.

Left ventricular hypertrophy in heart transplant recipients has been attributed to the use of calcineurin inhibitors. We assessed left ventricular mass across treatment arms in 83 heart transplant recipients in the Scandinavian heart transplant everolimus de novo study with early calcineurin inhibitors avoidance (SCHEDULE), and in 75 maintenance recipients in the Nordic Certican Trial in Heart and Lung Transplantation (NOCTET). In SCHEDULE, we randomized participants to treatment with calcineurin inhibitors or replacement with everolimus within 7-11 weeks after transplant. In NOCTET, participants were randomized to treatment with calcineurin inhibitors or a combination of low dose calcineurin inhibitors and everolimus. We followed patients with echocardiography for 3 years in the SCHEDULE trial and for 5 years in NOCTET. In SCHEDULE, left ventricular mass diminished with time, particularly across the first year of follow-up (everolimus arm: -10 ± 18 g/m2, cyclosporine arm: -9 ± 13 g/m2). However, there was no between-group difference in this development (p = 0.91). In NOCTET, there was no significant change in LVM over time and no between-group difference in the change (p = 0.27). In conclusion, the replacement of calcineurin inhibitors with everolimus or a reduction in the calcineurin inhibitor dose did not mitigate left ventricular hypertrophy after heart transplantation. TRIAL REGISTRATION: SCHEDULE-ClinicalTrials.gov Identifier: NCT01266148; NOCTET-ClinicalTrials.gov Identifier: NCT00377962.