title: Rejection after conversion to a proliferation signal inhibitor in chronic heart transplantation.
abstract: We sought to determine the incidence, risk factors, and consequences of acute rejection (AR) after conversion from a calcineurin inhibitor (CNI) to a proliferation signal inhibitor (PSI) in maintenance heart transplantation. Relevant clinical data were retrospectively obtained for 284 long-term heart transplant recipients from nine centers in whom CNIs were replaced with a PSI (sirolimus or everolimus) between October 2001 and March 2009. The rejection rate at one yr was 8.3%, stabilizing to 2% per year thereafter. The incidence rate after conversion (4.9 per 100 patient-years) was significantly higher than that observed on CNI therapy in the pre-conversion period (2.2 per 100 patient-years). By multivariate analysis, rejection risk was associated with a history of late AR prior to PSI conversion, early conversion (<5 yr) after transplantation and age <50 yr at the time of conversion. Use of mycophenolate mofetil was a protective factor. Post-conversion rejection did not significantly influence the evolution of left ventricular ejection fraction, renal function, or mortality during further follow-up. Conversion to a CNI-free immunosuppression based on a PSI results in an increased risk of AR. Awareness of the clinical determinants of post-conversion rejection could help to refine the current PSI conversion strategies.
authors.affiliation: Heart Failure and Cardiac Transplantation Unit, Cardiology Service, Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), University Hospital Marques de Valdecilla, Santander, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: González-Vílchez
authors.forename: José A
authors.initials: JA
authors.lastname: Vázquez de Prada
authors.forename: María J
authors.initials: MJ
authors.lastname: Paniagua
authors.forename: Luis
authors.initials: L
authors.lastname: Almenar
authors.forename: Sonia
authors.initials: S
authors.lastname: Mirabet
authors.forename: Manuel
authors.initials: M
authors.lastname: Gómez-Bueno
authors.forename: Beatriz
authors.initials: B
authors.lastname: Díaz-Molina
authors.forename: Jose M
authors.initials: JM
authors.lastname: Arizón
authors.forename: Juan
authors.initials: J
authors.lastname: Delgado
authors.forename: Félix
authors.initials: F
authors.lastname: Pérez-Villa
authors.forename: María G
authors.initials: MG
authors.lastname: Crespo-Leiro
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Dolz
authors.forename: Eulalia
authors.initials: E
authors.lastname: Roig
authors.forename: Javier
authors.initials: J
authors.lastname: Segovia
authors.forename: José L
authors.initials: JL
authors.lastname: Lambert
authors.forename: Amador
authors.initials: A
authors.lastname: Lopez-Granados
authors.forename: Pilar
authors.initials: P
authors.lastname: Escribano
authors.forename: Marta
authors.initials: M
authors.lastname: Farrero
mesh_terms: D000368:Aged; D065095:Calcineurin Inhibitors; D049109:Cell Proliferation / Q000187:drug effects; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology*; D006085:Graft Survival; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D013030:Spain / Q000453:epidemiology; D015996:Survival Rate
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus
keywords: cardiac transplantation; complications; everolimus; rejection; sirolimus