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CLINICAL RESEARCH: HEART FAILURE

Pre-Transplant Toxoplasma gondii Seropositivity Among Heart Transplant Recipients Is Associated With an Increased Risk of All-Cause and Cardiac Mortality

Satish Arora, MD^_*,_*, Pål A. Jenum, MD, PhD^,||, Pål Aukrust, MD, PhD, Halvor Rollag, MD, PhD^,¶, Arne K. Andreassen, MD, PhD^_*, Svein Simonsen, MD, PhD^_*, Einar Gude, MD^_*, Arnt E. Fiane, MD, PhD, Odd Geiran, MD, PhD^,¶ and Lars Gullestad, MD, PhD^_*

^_* Department of Cardiology, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
Institute of Medical Microbiology, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
Section of Clinical Immunology and Infectious Diseases, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
Department of Thoracic and Cardiovascular Surgery, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
^|| Department of Microbiology, Central Laboratory, Hospital of Asker and Baerum, Oslo, Norway
^¶ Faculty Division Rikshospitalet, University of Oslo, Oslo, Norway.

Manuscript received April 10, 2007; revised manuscript received June 22, 2007, accepted July 30, 2007.

^_* Reprint requests and correspondence: Dr. Satish Arora, Department of Cardiology, Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway. (Email: satish.arora{at}medisin.uio.no).

Objectives: We evaluated the risk of mortality, development of cardiac allograft vasculopathy (CAV), and acute cellular rejection among Toxoplasma gondii (T. gondii) seropositive heart transplant (HTx) recipients and the 4 donor/recipient seropairing groups.

Background: Chronic T. gondii infection is known to trigger potentially adverse immunoregulatory changes, but the long-term implication for HTx recipients has not been assessed previously.

Methods: Frozen pre-HTx serum samples of 288 recipients and 246 donors were evaluated for T. gondii serostatus using Platelia immunoglobulin G immunoassay. Patients had undergone prospective serotesting using alternative assays, and results determined by the 2 methods were compared. Data regarding mortality, CAV, and acute cellular rejection were available for all patients.

Results: Overall, 211 recipients (73%) were seronegative and 77 (27%) were seropositive. In total, 82 recipients died, 76 developed CAV, and 82 had 1 or more episode of treated cellular rejection. Recipient seropositivity was associated with a significantly higher risk of all-cause (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.1 to 3.4; p = 0.02) and CAV mortality (HR 4.4, 95% CI 1.3 to 15.6; p = 0.02) and a higher risk of developing advanced CAV (HR 2.7, 95% CI 1.2 to 5.8; p = 0.01). Seropositivity did not influence the number of rejection episodes, and donor/recipient seropairing was not a risk factor for any end point.

Conclusions: T. gondii seropositivity among HTx recipients is associated with an increased risk of all-cause and CAV mortality and of development of advanced CAV. This may be mediated via immunoregulatory changes triggered by chronic T. gondii infection and needs to be explored further.

Abbreviations and Acronyms   CAV = cardiac allograft vasculopathy   CMV = cytomegalovirus   EIA = enzyme immunoassay   HTx = heart transplant/transplantation   IFN = interferon   IL = interleukin   R = recipient   T. gondii = Toxoplasma gondii

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