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Ann Thorac Surg 2006;82:893-894
© 2006 The Society of Thoracic Surgeons

Original article: Cardiovascular

Invited commentary

Hendrik Jan Ankersmit, MD, Bernhard Moser, MD, Ernst Wolner, MD

Department of Cardiothoracic Surgery, General Hospital Vienna, Meduniwien, Währinger Gürtel 18-20, Vienna, A-1090 Austria

(Email: hjankersmit{at}hotmail.com).

Pulsatile and axial ventricular assist devices (VADs) have found acceptance as life sustaining pumps in regard to the "bridge to transplantation concept" or "destination therapy" in patients with terminal heart failure. Immunologic consequences have been described regarding increased susceptibility to acquire infections [1] and B-cell hyper-reactivity [2, 3], as determined by HLA antibody production. This process was termed sensitization, and the latter finding was described in patients who received pulsatile VAD systems. Recent reports have linked this laboratory finding to increased rejection rates and worsened transplant outcome in this patient cohort. Intravenous immunoglobulin (IVIG) was suggested to be beneficial in order to "desensitize" these patients under VAD support [4]. Based on these results Drakos and colleagues [5] designed a study in the recipients of pulsatile VADs with the goal to precondition the immune system with a "preemptive strike" to prevent or attenuate HLA antibody formation. The success (as seen in the Results section of this article) was meek. However this attempt of systematic immune-modulation in VAD recipients represents the first and most farsighted innovation as of yet presented in the literature. Other potential immune modulating drugs, such as mycophenolate mofetil (Cell Cept), have been able to attenuate human leucocyte antigen (HLA) antibody formation, and in my opinion deserve further clinical evaluation [6]. In conclusion, it has to be clearly stated in this Invited Commentary the following: (1) that increasing the dosage of IVIG to prevent HLA sensitization will also heighten known incidences of anaphylactic shock and transitory renal failure in VAD patients. In addition, increased infection rates will be seen. In this context it has to be mentioned that IVIG is a highly immunosuppressive drug that finds its use with great effect in patients suffering from autoimmune diseases such as Kawasaki, dermatomyositis, lupus erythematosus, polyradiculoneuritis, Guillain-Barre syndrome, and toxic epidermal necrolysis [7, 8]. Nachbaur and colleagues [9] have even demonstrated in the in vitro assays that IVIG has a tremendous dose-dependent immunosuppressive effect. Therefore it seems unwise to use higher IVIG dosages to prevent HLA-antibody production in VAD patients. (2) Recent reports have demonstrated that recipients of "novel" axial flow pumps (VADs) evidence no HLA sensitization [10]. In this context it is of interest to mention that patients who received DeBakey axial flow pumps evidenced only a transitory immunologic response [11]. (3) In our institution, HLA sensitization is not followed in a regular fashion due to complete absence of life-threatening rejections in our VAD recipients who underwent heart transplantation. This is due to our routine application of rabbit ATG (thymoglobuline), passive and active cytomegalovirus prophylaxis and initiation of triple therapy after heart allograft implantation [12, 13]. In conclusion, Drakos and colleagues have evidenced in this important contribution that low-dose IVIG is not capable to prevent sensitization in recipients of pulsatile VADs. It will be the future task of high-volume VAD centers, such as the University of Utah Health Sciences Center, to define and refine the best treatment option for our VAD recipients bridged heart transplantation.


   References
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 References
 

  1. Ankersmit HJ, Tugulea S, Spanier T, et al. Activation- induced T-cell death and immune dysfunction after implantation of left-ventricular assist device Lancet 1999;354:550-555.[Medline]
  2. Smith JD, Danskine AJ, Laylor RM, Rose ML, Yacoub MH. The effect of panel reactive antibodies and the donor specific crossmatch on graft survival after heart- and lung transplantation Transpl Immunol 1993;1:60-65.[Medline]
  3. Tyan DB, Li VA, Lawrence C, Trento A, Stanley CJ. Intravenous immunoglobulin suppression of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histoincompatible organ Transplantation 1994;57:553-562.[Medline]
  4. John R, Lietz K, Ankersmit J, et al. Intravenous immunoglobulin reduces anti-HLA alloreactivity and shortens waiting time to cardiac transplantation in highly sensitized left ventricular assist device recipients Circulation 1999;100(19 Suppl):II229-II235.
  5. Drakos SG, Kfoury AG, Long JW, et al. Low-dose prophylactic intravenous immunoglobulin does not prevent HLA sensitization in left ventricular assist device recipients Ann Thorac Surg 2006;82:889-894.[Abstract/Free Full Text]
  6. Lederer SR, Friedrich N, Banas B, Welser G, Albert ED, Sitter T. Effects of mycophenolate mofetil on donor-specific antibody formation in renal transplantation Clin Transplant 2005;19:168-174.[Medline]
  7. French LE, Trent JT, Kerdel FA. Use of intravenous immunoglobulin in toxic epidermal necrolysis and Stevens-Johnson syndromeour current understanding. Int Immunopharmacol 2006;6:543-549.[Medline]
  8. Sapir T, Shoenfeld Y. Facing the enigma of immunomodulatory effects of intravenous immunoglobuline Clin Rev Allergy Immunol 2005;29:185-199.[Medline]
  9. Nachbaur D, Herold M, Eibl B, Glassl H, et al. A comparative study of the in vitro immunomodulatory activity of human intact immunoglobulin (7S IVIG), F(ab')2 fragments (5S IVIG) and Fc fragments. Evidence for post-transcriptional IL-2 modulation Immunology 1997;90:212-218.[Medline]
  10. Grinda JM, Bricourt MO, Arnrein C, et al. Human leukocyte antigen sensitization in ventricular assist device recipientsa lesser risk with the DeBakey axial pump. Ann Thorac Surg 2005;80:945-949.[Abstract/Free Full Text]
  11. Ankersmit HJ, Wieselthaler G, Moser B, Gerlitz S, Roth G, Wolner E. Transitory immunologic response after implantation of the DeBakey VAD continuous-axial-flow pump JTCVS 2002;123:557-561.
  12. Zuckermann A, Dunkler D, Deviatko E, et al. Long-term survival (>10 years) of patients >60 years with induction therapy after cardiac transplantation Eur J Cardiothorac Surg 2003;24:283-291.[Abstract/Free Full Text]
  13. Syeda B, Roedler S, Schukro C, Yahya N, Zuckermann A, Glogar D. Transplant coronary artery diseaseincidence, progression and interventional revascularization. Int J Cardiol 2006;104:269-274.




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