ABSTRACT
BACKGROUND: Although acute cellular rejection after heart transplantation (HTX) can be controlled by full-dose calcineurin inhibitor (CNI)-based immunosuppressive regimens, cardiac allograft vasculopathy (CAV), nephrotoxicity, and malignancy remain ongoing problems. To evaluate the potential beneficial effects of sirolimus and CNI reduction, we compared de novo low-dose tacrolimus and sirolimus with standard tacrolimus and mycophenolate mofetil (MMF)-based immunosuppression after HTX. METHODS: We analyzed a long-term follow-up cohort of 126 patients who underwent HTX during the period 1998-2005 and received either de novo low-dose tacrolimus/sirolimus (lowTAC/SIR; n = 61) or full-dose tacrolimus/MMF (TAC/MMF; n = 64). RESULTS: Freedom from treatment switch was less in the low TAC/SIR group than in the TAC/MMF group (51.7% vs 73.0%, p = 0.038) 8 years after HTX. Freedom from acute rejection was 90.6% in the low TAC/SIR group vs 80.3% in the TAC/MMF group (p = 0.100). There was no difference in freedom from International Society for Heart and Lung Transplantation CAV grade ≥ 1 (55.4% vs 60.0%, p = 0.922), time until CAV diagnosis (4.2 ± 2.0 years vs 3.2 ± 2.4 years, p = 0.087), and CAV severity (p = 0.618). The benefit of reduced early maximum creatinine for low TAC/SIR treatment (1.8 ± 0.9 mg/dl vs 2.4 ± 1.1 mg/dl in TAC/MMF group, p < 0.001) did not continue 5 years and 8 years after HTX (1.4 ± 0.4 mg/dl vs 1.7 ± 1.2 mg/dl, p = 0.333, and 1.6 ± 1.1 mg/dl vs 1.6 ± 0.8 mg/dl, p = 0.957). The trend for superior survival at 5 years with low TAC/SIR treatment (93.1% vs 81.3% in TAC/MMF group, p = 0.051) could not be confirmed after 8 years (84.7% vs 75.0%, p = 0.138). Multivariate analysis at 8 years did not reveal any benefit of low TAC/SIR treatment. CONCLUSIONS: Reduction of de novo CNI did not result in superior long-term renal function. Low-dose mechanistic target of rapamycin inhibition did not achieve any benefit in CAV prevention compared with full-dose TAC/MMF after HTX.
Subject(s)
Graft Rejection/prevention & control , Heart Transplantation , Immunosuppression Therapy/methods , Mycophenolic Acid/analogs & derivatives , Sirolimus/administration & dosage , Tacrolimus/administration & dosage , Acute Disease , Adult , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Follow-Up Studies , Graft Survival/drug effects , Humans , IMP Dehydrogenase/antagonists & inhibitors , Immunosuppressive Agents/administration & dosage , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
The case of a 22-year old male patient who presented with a congenital coronary arterial fistula from the right coronary artery to the right ventricle is described. The arterial fistula had led to an aneurysm of the right sinus of Valsalva and the proximal right coronary artery. The aneurysm was incised from the aorta and the fistula closed with a pericardial patch. The diameter of the aneurysm was reduced by plication. Successful occlusion of the fistula and the competence of the aortic valve were confirmed by transoesophageal echocardiography.
