Safety and Feasibility of Induction Immunosuppression When Driveline Infection Is an Indication for Cardiac Transplantation

Abstract

Background There is a paucity of data on the use of induction immunosuppression in patients with active infections undergoing orthotopic heart transplantation (OHT). We hypothesized that induction immunosuppression in patients with ventricular assist device (VAD) undergoing OHT with localized active driveline infection (DLI) does not lead to worse outcomes.

Materials and Methods We retrospectively analyzed our database for bridge-to-transplant VAD patients who underwent OHT and received induction therapy. Patients were stratified into those with and without active DLI at the time of OHT and followed up till death or at least 30 months after OHT. Posttransplant length of stay (LOS), frequency of infections, and mortality were compared between the two groups.

Results Thirty-eight patients (30 males) with mean age of 57.5 ± 13 years with VAD underwent OHT during the study period. Twelve had active DLI. Mean follow-up was 46.4 ± 23.1 months. In the DLI versus non-DLI group, there was no difference in mortality (17 vs. 23%, p = NS), LOS (16.3 ± 5.4 vs. 17.2 ± 13.7, p = NS), postoperative renal function, incidence of hyperacute or late rejection or infection either in the first month (25 vs. 23%, p = NS) or during entire follow-up (92 vs. 88%, p = NS). No patient in the DLI group had infections attributable to the same organism responsible for pretransplant DLI.

Conclusion In patients with active DLI, induction immunosuppression after OHT did not increase LOS, infections, or mortality after at least 30 months of follow-up and therefore it appears to be a safe and feasible therapeutic option.

Keywords

induction immunosuppression - driveline infection - orthotopic heart transplantation

Note

This study was presented as a poster in American College of Cardiology Scientific Sessions 2014, Washington D.C.[34]

• References

• 1 Shapiro R, Young JB, Milford EL, Trotter JF, Bustami RT, Leichtman AB. Immunosuppression: evolution in practice and trends, 1993-2003. Am J Transplant 2005; 5 (4, Pt 2): 874-886
• 2 Hawksworth JS, Leeser D, Jindal RM, Falta E, Tadaki D, Elster EA. New directions for induction immunosuppression strategy in solid organ transplantation. Am J Surg 2009; 197 (4) 515-524
• 3 Rosenberg PB, Vriesendorp AE, Drazner MH , et al. Induction therapy with basiliximab allows delayed initiation of cyclosporine and preserves renal function after cardiac transplantation. J Heart Lung Transplant 2005; 24 (9) 1327-1331
• 4 Cantarovich M, Giannetti N, Barkun J, Cecere R. Antithymocyte globulin induction allows a prolonged delay in the initiation of cyclosporine in heart transplant patients with postoperative renal dysfunction. Transplantation 2004; 78 (5) 779-781
• 5 Yamani MH, Taylor DO, Czerr J , et al. Thymoglobulin induction and steroid avoidance in cardiac transplantation: results of a prospective, randomized, controlled study. Clin Transplant 2008; 22 (1) 76-81
• 6 Lund LH, Edwards LB, Kucheryavaya AY , et al; International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: thirtieth official adult heart transplant report–2013; focus theme: age. J Heart Lung Transplant 2013; 32 (10) 951-964
• 7 Higgins R, Kirklin JK, Brown RN , et al; Cardiac Transplant Research Database (CTRD). To induce or not to induce: do patients at greatest risk for fatal rejection benefit from cytolytic induction therapy?. J Heart Lung Transplant 2005; 24 (4) 392-400
• 8 Uber PA, Mehra MR. Induction therapy in heart transplantation: is there a role?. J Heart Lung Transplant 2007; 26 (3) 205-209
• 9 Hershberger RE, Starling RC, Eisen HJ , et al. Daclizumab to prevent rejection after cardiac transplantation. N Engl J Med 2005; 352 (26) 2705-2713
• 10 Kirklin JK, Naftel DC, Pagani FD , et al. Sixth INTERMACS annual report: a 10,000-patient database. J Heart Lung Transplant 2014; 33 (6) 555-564
• 11 Go AS, Mozaffarian D, Roger VL , et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation 2014; 129 (3) 399-410
• 12 Miller LW, Pagani FD, Russell SD , et al; HeartMate II Clinical Investigators. Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med 2007; 357 (9) 885-896
• 13 Sharma V, Deo SV, Stulak JM , et al. Driveline infections in left ventricular assist devices: implications for destination therapy. Ann Thorac Surg 2012; 94 (5) 1381-1386
• 14 Zierer A, Melby SJ, Voeller RK , et al. Late-onset driveline infections: the Achilles' heel of prolonged left ventricular assist device support. Ann Thorac Surg 2007; 84 (2) 515-520
• 15 Poston RS, Husain S, Sorce D , et al. LVAD bloodstream infections: therapeutic rationale for transplantation after LVAD infection. J Heart Lung Transplant 2003; 22 (8) 914-921
• 16 Hannan MM, Husain S, Mattner F , et al; International Society for Heart and Lung Transplantation. Working formulation for the standardization of definitions of infections in patients using ventricular assist devices. J Heart Lung Transplant 2011; 30 (4) 375-384
• 17 Simon D, Fischer S, Grossman A , et al. Left ventricular assist device-related infection: treatment and outcome. Clin Infect Dis 2005; 40 (8) 1108-1115
• 18 Raymond AL, Kfoury AG, Bishop CJ , et al. Obesity and left ventricular assist device driveline exit site infection. ASAIO J 2010; 56 (1) 57-60
• 19 Aliabadi A, Grömmer M, Zuckermann A. Is induction therapy still needed in heart transplantation?. Curr Opin Organ Transplant 2011; 16 (5) 536-542
• 20 Smart FW, Naftel DC, Costanzo MR , et al. Risk factors for early, cumulative, and fatal infections after heart transplantation: a multiinstitutional study. J Heart Lung Transplant 1996; 15 (4) 329-341
• 21 Aziz T, el-Gamel A, Krysiak P , et al. Risk factors for early mortality, acute rejection, and factors affecting first-year survival after heart transplantation. Transplant Proc 1998; 30 (5) 1912-1914
• 22 Kubo SH, Naftel DC, Mills Jr RM , et al; Cardiac Transplant Research Database Group. Risk factors for late recurrent rejection after heart transplantation: a multiinstitutional, multivariable analysis. J Heart Lung Transplant 1995; 14 (3) 409-418
• 23 Al Aly Z, Abbas S, Moore E, Diallo O, Hauptman PJ, Bastani B. The natural history of renal function following orthotopic heart transplant. Clin Transplant 2005; 19 (5) 683-689
• 24 Segovia J, Rodríguez-Lambert JL, Crespo-Leiro MG , et al. A randomized multicenter comparison of basiliximab and muromonab (OKT3) in heart transplantation: SIMCOR study. Transplantation 2006; 81 (11) 1542-1548
• 25 Møller CH, Gustafsson F, Gluud C, Steinbrüchel DA. Interleukin-2 receptor antagonists as induction therapy after heart transplantation: systematic review with meta-analysis of randomized trials. J Heart Lung Transplant 2008; 27 (8) 835-842
• 26 Schulman AR, Martens TP, Christos PJ , et al. Comparisons of infection complications between continuous flow and pulsatile flow left ventricular assist devices. J Thorac Cardiovasc Surg 2007; 133 (3) 841-842
• 27 Gordon RJ, Quagliarello B, Lowy FD. Ventricular assist device-related infections. Lancet Infect Dis 2006; 6 (7) 426-437
• 28 Arrecubieta C, Asai T, Bayern M , et al. The role of Staphylococcus aureus adhesins in the pathogenesis of ventricular assist device-related infections. J Infect Dis 2006; 193 (8) 1109-1119
• 29 Aslam S, Hernandez M, Thornby J, Zeluff B, Darouiche RO. Risk factors and outcomes of fungal ventricular-assist device infections. Clin Infect Dis 2010; 50 (5) 664-671
• 30 Gómez-Moreno S, Lage E, Jiménez-Jambrina M , et al. Infections in cardiac transplant recipients: clinical and microbiological characteristics and consequences. Transplant Proc 2006; 38 (8) 2555-2557
• 31 González-Vílchez F, de Prada JA, Exposito V , et al. Avoidance of calcineurin inhibitors with use of proliferation signal inhibitors in de novo heart transplantation with renal failure. J Heart Lung Transplant 2008; 27 (10) 1135-1141
• 32 Schulman AR, Martens TP, Russo MJ , et al. Effect of left ventricular assist device infection on post-transplant outcomes. J Heart Lung Transplant 2009; 28 (3) 237-242
• 33 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 (9178) 550-555
• 34 Bhatia N, Voelkel A, Sharma U, Birks E, McCants K. Safety and outcomes of induction immunosuppression for cardiac transplantation in patients with active driveline infection. J Am Coll Cardiol 2014; 63 (12) A857