Incidence and severity of cytomegalovirus infection in seropositive heart transplant recipients

Abstract

Background The frequency and significance of cytomegalovirus (CMV) infection in seropositive (R+) heart transplant recipients (HTR) is unclear, with preventative recommendations mostly extrapolated from other groups. We evaluated the incidence and severity of CMV infection in R+ HTR, to identify risk factors and describe outcomes. Methods R+ HTR from 2010 to 2019 were included. Antiviral prophylaxis was not routinely used, with clinically guided monitoring the local standard of care. The primary outcome was CMV infection within one‐year post‐transplant; secondary outcomes included other herpesvirus infections and mortality. Results CMV infection occurred in 27/155 (17%) R+ HTR. Patients with CMV had a longer hospitalization (27 vs. 20 days, unadjusted HR 1.02, 95% CI 1.00–1.02, p = .01), higher rate of intensive care readmission (26% vs. 9%, unadjusted HR 3.46, 1.46–8.20, p = .005), and increased mortality (33% vs. 8%, unadjusted HR 10.60, 4.52–24.88, p < .001). The association between CMV and death persisted after adjusting for multiple confounders (HR 24.19, 95% CI 7.47–78.30, p < .001). Valganciclovir prophylaxis was used in 35/155 (23%) and was protective against CMV (infection rate 4% vs. 27%, adjusted HR .07, .01–.72, p = .025), even though those receiving it were more likely to have received thymoglobulin (adjusted OR 10.5, 95% CI 2.01–55.0, p = .005). Conclusions CMV infection is common in R+ HTR and is associated with a high burden of disease and increased mortality. Patients who received valganciclovir prophylaxis were less likely to develop CMV infection, despite being at higher risk. These findings support the routine use of antiviral prophylaxis following heart transplantation in all CMV R+ patients.

Multicenter study of universal prophylaxis versus pre‐emptive therapy for patients at intermediate risk (R+) for CMV following heart transplantation

“…These results build upon those of a recent, smaller, single-center analysis of CMV R+ HT recipients from Australia, in which valganciclovir prophylaxis was associated with significantly reduced incidence of CMV infection (HR .07, .01-.72, p = .025). 18 In our cohort, there was also a trend towards decreased 18-month survival amongst PET treated patients which did not meet statistical significance. Of further interest, pre-HT induction therapy with basiliximab was also associated with increased risk of CMV infection, and CMV-related hospitaliza- and possibly with cellular rejection.…”

“…Evidence is limited to predominantly single-center retrospective studies, in many of which only one preventive strategy was applied uniformly to all R+ patients, preventing any analysis on the comparative efficacy of UP versus PET. 3,17,18 While randomized studies of PET versus UP in R+ renal transplant recipients have shown largely equivalent outcomes between the two strategies, the applicability of such data to the HT population is limited, given the increased levels of immunosuppression required in HT patients. 19,20 This evidence gap has contributed to the current consensus guidelines which do not provide a strong recommendation for use of either strategy over the other in CMV R+ HT patients.…”

Reliability of QuantiFERON®‐CMV in predicting CMV recurrence in heart transplant recipients: A single‐center retrospective study

“…The study published by Chiereghin et al 11 CMV infection has been associated with ICU admission in some reports. 15 The study by Chiereghin et al 11 with mostly ATG-based induction, also showed more preemptive than prophylactic regimens, and as expected, CMV infections were more frequent (55%), with no data on recurrences in this specific group. For these reasons, the risk-benefit ratio might still favor secondary prophylaxis in our population.…”

“…Nevertheless, in contrast to this study, recurrences among positive QF‐CMV patients showed fast replication kinetics, with one patient experiencing severe colitis requiring ICU admission. Particularly in HTR and with ATG‐based induction, CMV infection has been associated with ICU admission in some reports 15 . The study by Chiereghin et al 11 .…”