Heart transplantation incidence

Cyclosporine has been approved for use in allogeneic kidney, liver, and heart transplant patients and is under study for use in pancreas, bone marrow, single lung, and heart-lung transplant procedures. It is recommended that corticosteroids, such as prednisone, be used concomitantly, although at half or less of their usual dose. Such combined therapy leads to fewer side effects, a decreased incidence of infectious complications, efficacy of lower doses of cyclosporine, and a better history of patient survival. 

Mycophenolic acid (Figure 3.36) is produced by fermentation cultures of the fungus Penicillium brevicompactum. It has been known for many years to have antibacterial, antifungal, antiviral, and antitumour properties. It has recently been introduced into medicine as an immunosuppressant drug, to reduce the incidence of rejection of transplanted organs, particularly kidney and heart transplants. It is formulated as the /V-morpholinoethyl ester mycophenolate mofetil (Figure 3.37), which is metabolized after ingestion to mycophenolic... 

Toxicities are numerous and frequently include nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, and hirsutism. A significant increase in the incidence of cholelithiasis has been observed in children treated with cyclosporine after heart transplantation. Cyclosporine causes very little bone marrow toxicity. While an increased incidence of lymphoma and other cancers (Kaposi s sarcoma, skin cancer) has been documented in transplant recipients receiving cyclosporine, other immunosuppressive agents may also predispose recipients to cancer. Some evidence suggests that tumors may arise after cyclosporine treatment because it induces TGF-3, which promotes tumor invasion and metastasis. 

Opelz G, Henderson R. Incidence of non-Hodgkin lymphoma in kidney and heart transplant recipients. Lancet 1993 342(8886-8887) 1514-16. 

The introduction of CSA signiflcantly improved the outcomes of transplantation. Since its approval and widespread use, patient and graft survival rates have improved secondary to a lower incidence of acute rejection episodes and severe infectious complications. In heart transplant recipients, for example, 1 -year survival rates increased from 56% to 85%, and 5-year survival rates increased from 31% to 15%P The efficacy of CSA is well established in aU types of solid-organ transplants. Currently, CSA is approved for use in kidney, liver, and heart transplantation. 

In heart transplantation, induction with daclizumab produced favorable results with a lower incidence of acute rejection 18% in the daclizumab-treated patients compared with 63% in the group receiving CSA, MMF, and prednisone with no induction therapy (P = 0.04). The time to occurrence of the first rejection episode also was significantly longer in the daclizumab-treated patients. There were no adverse reactions to daclizumab and no significant differences between the groups in the incidence of infection or cancer dnr-ing follow-up. Data for basiliximab in heart transplant recipients are lacking. 

However, in one clinical study in heart transplant patients taking ciclosporin, mycophenolate, and corticosteroids, use of daclizumab with another antilymphocyte (such as mnromonab-CD3 or antithymocyte immunoglobniin) appeared to be associated with a higher incidence of fatal infection 8 of 40 patients died, compared with 2 of 37 who received an antilymphocyte and placebo. The manufacturer suggests that concurrent use of daclizumab with another antilymphocyte antibody in patients receiving intensive immunosuppression may be a factor leading to fatal infection. Caution may be warranted, and more study is needed. 

Derumeaux G, Habib G, Schleifer DM et al (1995) Standard orthotopic heart transplantation versus total orthotopic heart transplantation. A transesophageal echocardiography study of the incidence of left atrial thrombosis. Circulation 9211 196-201... 

In longer term survivors, the incidence of malignancy increases. By 7 years, 24% of heart transplant... 

The incidence, clinical features, consequences, and management of ciclosporin-induced hjq)ertension have been reviewed (9). The prevalence was 29-54% in nontransplant patients and 65-100% in heart and hver transplant patients also taking glucocorticoids. Disturbed circadian rhythm with a loss of nocturnal blood pressure fall was the main characteristic, and patients therefore had higher risks of left ventricular hjq)ertrophy. 

Lake K, Anderson D, Mihred S, Love K, Pritzker M, Emery R. The incidence of cytomegalovirus disease is not increased after OKT3 induction therapy. J Heart Lung Transplant 1993 12(3) 537-8. 

Pattison JM, Petersen J, Kuo P, Valantine V, Robbins RC,Theodore J.The incidence of renal failure in one hundred consecutive heart-lung transplant recipients. Am J Kidney Dis 1995 26 643-648. 

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