Ventricular assist devices as bridge to heart transplantation: impact on post-transplant infections

English version České info

Background:
Ventricular assist devices (VAD) are valuable options for patients with heart failure awaiting cardiac transplantation. We assessed the impact of pre-transplant VAD implantation on the incidence of post-transplant infections in a nationwide cohort of heart transplant recipients.

Methods:
Heart transplant recipients included in the Swiss Transplant Cohort Study between May 2008 and December 2012 were analyzed. Cumulative incidence curves were used to calculate the incidence of bacterial or Candida infections (primary endpoint) and of other infections (secondary endpoint) after transplant. Cox regression models treating death as a competing risk were used to identify risk factors for the development of infection after transplant.

Results:
Overall, 119 patients were included in the study, 35 with a VAD and 84 without VAD. Cumulative incidences of post-transplant bacterial or Candida infections were 37.7 % in VAD patients and 40.4 % in non-VAD patients. In multivariate analysis, the use of cotrimoxazole prophylaxis was the only variable associated with bacterial/Candida infections after transplant (HR 0.29 [95 % CI 0.15-0.57], p < 0.001), but presence of a VAD was not (HR 0.94, [95 % CI 0.38-2.32], p = 0.89, for continuous-flow devices, and HR 0.45 [0.15 – 1.34], p = 0.15, for other devices). Risk for post-transplant viral and all fungal infections was not increased in patients with VAD. One-year survival was 82.9 % (29/35) in the VAD group and 82.1 % (69/84) in the non-VAD group. All 6 patients in the VAD group that died after transplant had a history of pre-transplant VAD infection.

Conclusion:
In this nationwide cohort of heart transplant recipients, the presence of VAD at the time of transplant had no influence on the development of post-transplant infections.

Keywords:
Outcome, Cardiac transplantation, Mechanical heart support

Autoři: Delphine Héquet† ^1,2; Georg Kralidis† ³; Thierry Carrel ⁴; Alexia Cusini ⁵; Christian Garzoni ^5,6; Roger Hullin ⁷; Pascal R. Meylan ^2,8; Paul Mohacsi ⁹; Nicolas J. Mueller ¹⁰; Frank Ruschitzka ¹¹; Piergiorgio Tozzi ¹²; Christian Van Delden ¹³; Maja Weisser ¹⁴; Markus J. Wilhelm ¹⁵; Manuel Pascual ¹; Oriol Manuel ^1,2,16*; Swiss Transplant Cohort Study (stcs)
Působiště autorů: Transplantation Center, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland. ¹; Infectious Diseases Service, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland. ²; Institute for Clinical Epidemiology and Biostatistics, University Hospital of Basel, Basel, Switzerland. ³; Clinic for Cardiovascular Surgery, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland. ⁴; Department of Infectious Diseases, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland. ⁵; Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese, Lugano, Switzerland. ⁶; Department of Medicine, Service of Cardiology, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland. ⁷; Institute of Microbiology, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland. 9Bern University Hospital and University of Bern, Bern, Switzerland. ⁸; Division of Infectious Diseases and Hospital Epidemiology, University Hospital, University of Zurich, Zurich, Switzerland. ¹⁰; Department of Cardiology, Cardiovascular Center, University Hospital, University of Zurich, Zurich, Switzerland. ¹¹; Department of Cardiovascular Surgery, University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland. ¹²; Transplant Infectious Diseases Unit, University Hospitals Geneva, Geneva, Switzerland. ¹³; Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland. ¹⁴; Clinic for Cardiovascular Surgery, University Hospital Zurich, Zurich, Switzerland. ¹⁵; Infectious Diseases Service and Transplantation Center, University Hospital and University of Lausanne, BH 10/553, CHUV, Lausanne, Switzerland. ¹⁶
Vyšlo v časopise: BMC Infectious diseases 2016, 16:321
Kategorie: Research article
prolekare.web.journal.doi_sk: https://doi.org/10.1186/s12879-016-1658-0

© 2016 The Author(s).
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
The electronic version of this article is the complete one and can be found online at: http://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-1658-0

Souhrn

Conclusion:
In this nationwide cohort of heart transplant recipients, the presence of VAD at the time of transplant had no influence on the development of post-transplant infections.

Keywords:
Outcome, Cardiac transplantation, Mechanical heart support

Zdroje

1. Miller LW, Pagani FD, Russell SD, John R, Boyle AJ, Aaronson KD, Conte JV, Naka Y, Mancini D, Delgado RM, et al. Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med. 2007;357(9):885–96.

2. Baddour LM, Bettmann MA, Bolger AF, Epstein AE, Ferrieri P, Gerber MA, Gewitz MH, Jacobs AK, Levison ME, Newburger JW, et al. Nonvalvular cardiovascular device-related infections. Circulation. 2003;108(16):2015–31.

3. Nienaber JJ, Kusne S, Riaz T, Walker RC, Baddour LM, Wright AJ, Park SJ, Vikram HR, Keating MR, Arabia FA, et al. Clinical manifestations and management of left ventricular assist device-associated infections. Clin Infect Dis. 2013;57(10):1438–48.

4. Simon D, Fischer S, Grossman A, Downer C, Hota B, Heroux A, Trenholme G. Left ventricular assist device-related infection: treatment and outcome. Clin Infect Dis. 2005;40(8):1108–15.

5. Monkowski DH, Axelrod P, Fekete T, Hollander T, Furukawa S, Samuel R. Infections associated with ventricular assist devices: epidemiology and effect on prognosis after transplantation. Transpl Infect Dis. 2007;9(2):114–20.

6. Goldstein DJ, El-Amir NG, Ashton Jr RC, Catanese K, Rose RA, Levin HR, Oz MC. Fungal infections in left ventricular assist device recipients. Incidence, prophylaxis, and treatment. ASAIO J. 1995;41(4):873–5.

7. 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):664–71.

8. Koval CE, Rakita R, Practice ASTIDCo. Ventricular assist device related infections and solid organ transplantation. Am J Transplant. 2013;13 Suppl 4:348–54.

9. Deng MC, Loebe M, El-Banayosy A, Gronda E, Jansen PG, Vigano M, Wieselthaler GM, Reichart B, Vitali E, Pavie A, et al. Mechanical circulatory support for advanced heart failure: effect of patient selection on outcome. Circulation. 2001;103(2):231–7.

10. Wozniak CJ, Stehlik J, Baird BC, McKellar SH, Song HK, Drakos SG, Selzman CH. Ventricular assist devices or inotropic agents in status 1A patients? Survival analysis of the United Network of Organ Sharing database. Ann Thorac Surg. 2014;97(4):1364–71. discussion 1371–1362.

11. Stehlik J, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dipchand AI, Dobbels F, Kirk R, Rahmel AO, Hertz MI, et al. The Registry of the International Society for Heart and Lung Transplantation: 29th official adult heart transplant report–2012. J Heart Lung Transplant. 2012;31(10):1052–64.

12. Poston RS, Husain S, Sorce D, Stanford E, Kusne S, Wagener M, Griffith BP, Kormos RL. LVAD bloodstream infections: therapeutic rationale for transplantation after LVAD infection. J Heart Lung Transplant. 2003; 22(8):914–21.

13. Healy AH, Baird BC, Drakos SG, Stehlik J, Selzman CH. Impact of ventricular assist device complications on posttransplant survival: an analysis of the United network of organ sharing database. Ann Thorac Surg. 2013;95(3):870–5.

14. Schulman AR, Martens TP, Russo MJ, Christos PJ, Gordon RJ, Lowy FD, Oz MC, Naka Y. Effect of left ventricular assist device infection on post-transplant outcomes. J Heart Lung Transplant. 2009;28(3):237–42.

15. Yamani MH, Chuang HH, Ozduran V, Avery RK, Mawhorter SD, Cook DJ, Zilka C, Zeroske K, Buda T, Hobbs RE, et al. The impact of hypogammaglobulinemia on infection outcome in patients undergoing ventricular assist device implantation. J Heart Lung Transplant. 2006;25(7):820–4.

16. Kimball PM, Flattery M, McDougan F, Kasirajan V. Cellular immunity impaired among patients on left ventricular assist device for 6 months. Ann Thorac Surg. 2008;85(5):1656–61.

17. Koller MT, van Delden C, Muller NJ, Baumann P, Lovis C, Marti HP, Fehr T, Binet I, De Geest S, Bucher HC, et al. Design and methodology of the Swiss Transplant Cohort Study (STCS): a comprehensive prospective nationwide long-term follow-up cohort. Eur J Epidemiol. 2013;28(4):347–55.

18. Kirklin JK, Naftel DC, Kormos RL, Stevenson LW, Pagani FD, Miller MA, Ulisney KL, Baldwin JT, Young JB. Third INTERMACS Annual Report: the evolution of destination therapy in the United States. J Heart Lung Transplant. 2011;30(2):115–23.

19. Manuel O, Kralidis G, Mueller NJ, Hirsch HH, Garzoni C, van Delden C, Berger C, Boggian K, Cusini A, Koller MT, et al. Impact of antiviral preventive strategies on the incidence and outcomes of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2013;13(9):2402–10.

20. Humar A, Michaels M, Monitoring AIWGoID. American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation. Am J Transplant. 2006;6(2):262–74.

21. Hannan MM, Husain S, Mattner F, Danziger-Isakov L, Drew RJ, Corey GR, Schueler S, Holman WL, Lawler LP, Gordon SM, et al. Working formulation for the standardization of definitions of infections in patients using ventricular assist devices. J Heart Lung Transplant. 2011;30(4):375–84.

22. Billingham ME, Cary NR, Hammond ME, Kemnitz J, Marboe C, McCallister HA, Snovar DC, Winters GL, Zerbe A. A working formulation for the standardization of nomenclature in the diagnosis of heart and lung rejection: Heart Rejection Study Group. The International Society for Heart Transplantation. J Heart Transplant. 1990;9(6):587–93.

23. Allignol A, Beyersmann J. Software for fitting nonstandard proportional subdistribution hazards models. Biostatistics. 2010;11(4):674–5.

24. Koller MT, Raatz H, Steyerberg EW, Wolbers M. Competing risks and the clinical community: irrelevance or ignorance? Stat Med. 2012;31(11–12):1089–97.

25. Ruan PK, Gray RJ. Analyses of cumulative incidence functions via nonparametric multiple imputation. Stat Med. 2008;27(27):5709–24.

26. R Development Core Team. A Language and Environment for Statistical Computing [http://www.R-project.org. 2012]

27. Cleveland Jr JC, Grover FL, Fullerton DA, Campbell DN, Mitchell MB, Lindenfeld J, Wolfel EE, Lowes BD, Shakar SF, Brieke A, et al. Left ventricular assist device as bridge to transplantation does not adversely affect one-year heart transplantation survival. J Thorac Cardiovasc Surg. 2008;136(3):774–7.

28. Russo MJ, Hong KN, Davies RR, Chen JM, Sorabella RA, Ascheim DD, Williams MR, Gelijns AC, Stewart AS, Argenziano M, et al. Posttransplant survival is not diminished in heart transplant recipients bridged with implantable left ventricular assist devices. J Thorac Cardiovasc Surg. 2009; 138(6):1425–32. e1421-1423.

29. Pal JD, Piacentino V, Cuevas AD, Depp T, Daneshmand MA, Hernandez AF, Felker GM, Lodge AJ, Rogers JG, Milano CA. Impact of left ventricular assist device bridging on posttransplant outcomes. Ann Thorac Surg. 2009;88(5): 1457–61. discussion 1461.

30. Drakos SG, Kfoury AG, Long JW, Stringham JC, Gilbert EM, Moore SA, Campbell BK, Nelson KE, Horne BD, Renlund DG. Effect of mechanical circulatory support on outcomes after heart transplantation. J Heart Lung Transplant. 2006;25(1):22–8.

31. Gordon RJ, Weinberg AD, Pagani FD, Slaughter MS, Pappas PS, Naka Y, Goldstein DJ, Dembitsky WP, Giacalone JC, Ferrante J, et al. Prospective, multicenter study of ventricular assist device infections. Circulation. 2013; 127(6):691–702.

32. Entenza JM, Betrisey B, Manuel O, Giddey M, Sakwinska O, Laurent F, Bizzini A. Rapid detection of Staphylococcus aureus strains with reduced susceptibility to vancomycin by isothermal microcalorimetry. J Clin Microbiol. 2014;52(1):180–6.

33. Bucheli E, Kralidis G, Boggian K, Cusini A, Garzoni C, Manuel O, Meylan PR, Mueller NJ, Khanna N, van Delden C, et al. Impact of enterococcal colonization and infection in solid organ transplantation recipients from the Swiss transplant cohort study. Transpl Infect Dis. 2014;16(1):26–36.