title: Recent Advances in Mammalian Target of Rapamycin Inhibitor Use in Heart and Lung Transplantation.
abstract: The mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus are increasingly used in cardiothoracic transplantation. Several recent clinical trials have demonstrated their efficacy in combination with reduced cyclosporine dosing in de novo heart transplant recipients, in particular with everolimus. A number of other studies have demonstrated their efficacy for improving renal function and reducing calcineurin inhibitor use, attenuating cardiac allograft vasculopathy progression and reducing cytomegalovirus infections in maintenance heart transplant populations. A growing body of literature, including a small number of clinical trials, now describes the use mTOR inhibitors in lung transplant recipients. The benefits in this population include improved lung and renal function in limited studies. Considerably less evidence is available in pediatric heart transplantation, though similar indications in the maintenance therapy population have been described. The benefits of mTOR inhibitors must be weighed against the increased risk of adverse events and drug intolerance compared with other primary immunosuppressants, and discontinuation rates are particularly high in lung transplant recipients. The risks of surgical wound healing complications in transplant recipients receiving mTOR inhibitors previously or actively supported by mechanical circulatory support devices remains poorly described in the current literature. The current role and recent evidence for mTOR inhibitor use in heart and lung transplantation is examined in this review.
authors: 1 Division of Cardiology, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada.2 Department of Cardiovascular Diseases and the William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN.
authors: Nowell M
authors: NM
authors: Fine
authors: Sudhir S
authors: SS
authors: Kushwaha
mesh_terms: D064591:Allografts; D000970:Antineoplastic Agents / Q000627:therapeutic use; D065095:Calcineurin Inhibitors / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000627:therapeutic use; D003586:Cytomegalovirus Infections; D000068338:Everolimus / Q000627:therapeutic use; D006084:Graft Rejection; D016027:Heart Transplantation / Q000639:trends*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007668:Kidney / Q000601:surgery; D016040:Lung Transplantation / Q000639:trends*; D011183:Postoperative Complications / Q000209:etiology; D020123:Sirolimus / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D066027:Transplant Recipients; D014945:Wound Healing
chemical_list: D000970:Antineoplastic Agents; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus