Cytomegalovirus Donor Seropositivity Negatively Affects Survival After Heart Transplantation

Abstract

Background. Prior studies have shown that cytomegalovirus (CMV) infection is a risk factor for the development of cardiac allograft vasculopathy (CAV) and is associated with reduced long-term survival after heart transplantation (HTx). The aim of this International Society for Heart and Lung Transplantation Transplant Registry study was to compare posttransplant survival in different CMV donor:recipient serologic combinations. Methods. We performed a retrospective cohort study, using the International Society for Heart and Lung Transplantation Thoracic Transplant Registry, on 15 885 adult primary heart transplant recipients with known CMV serologic status between July 2004 and June 2014. Posttransplant survival and risk of developing CAV were compared across 4 groups: CMV-seronegative recipients (R–) receiving CMV-positive grafts (D+), intermediate-risk patients (D+R+ and D–R+), and low-risk patients (D–R–). Results. Baseline characteristics (donor/recipient age, body mass index, recipient serum creatinine, blood group, donor cause of death, recipient diagnosis, and ischemic time) were mostly balanced between the groups. Kaplan-Meier survival analyses over a follow-up of 10 y revealed significantly worse survival for both D+ groups as compared to the CMV low-risk group (D+R+: 56.61% [95% confidence interval, 53.94-59.41] versus D–R–: 63.09% [59.74-66.64] P < 0.01 and D+R–: 57.69% [56.03-59.39] versus D–R–; P < 0.001), whereas recipient seropositivity alone was not associated with reduced survival (D–R+ versus D–R– P = 0.178). The risk of developing CAV after HTx was not significantly increased in D+ as compared to D– groups. Conclusions. In a large contemporary cohort, CMV status at the time of HTx was not associated with CAV development. However, there was a significant association between donor CMV seropositivity and reduced short- and long-term survival after HTx. Approaches to mitigate the impact of CMV on posttransplant survival are needed.

Increasing Proportion of High-risk Cytomegalovirus Donor-positive/Recipient-negative Serostatus in Solid Organ Transplant Recipients

“…We did not specifically assess patient outcomes in this cohort, but the association between CMV D+R-status and worse allograft and patient survival has been previously well-established across multiple organ types. [1][2][3][4] In summary, our study demonstrated that the proportion of high-risk CMV D+R-SOTs has increased significantly from 2000 to 2020, most notably among liver, heart, and lung SOTs, and is projected to be >25% among nonkidney SOTs by 2040 if current trends continue. This increase in the proportion of D+R-SOTs appears to be driven largely by decreasing CMV seroprevalence among candidates rather than increased seroprevalence among donors.…”

“…We did not specifically assess patient outcomes in this cohort, but the association between CMV D+R– status and worse allograft and patient survival has been previously well-established across multiple organ types. 1-4…”

“…Donor-positive/recipient-negative (D+R-) CMV serostatus is a major risk factor for CMV disease and is independently associated with worse long-term patient and graft survival among kidney, liver, heart, and lung transplant recipients despite current prevention and treatment strategies. [1][2][3][4] The factors associated with CMV serostatus are complex, include a range of socioeconomic and demographic parameters, and have been assessed in population-representative cohorts such as those surveyed with the National Health and Nutrition Examination Survey. [5][6][7] The association of these factors with D/R serostatus have not previously been reported among solid organ transplant (SOT) candidates or donors, who may differ substantially from the general population with regard to risk factors.…”

Cytomegalovirus Matching in Deceased Donor Kidney Allocation: Results From a U.S. National Simulation Model

“…Numerous calls have been made 10 , 41 , 42 for actions to mitigate the impact of CMV on post-SOT. In addition to the aforementioned approaches, several prevention measures have been proposed.…”

“… 15 , 16 , 32 , 40 , 43 , 44 This article focuses on one such proposal: CMV serological matching while allocating deceased donor organs. 10 , 16 , 17 , 45 CMV matching has been advocated and practiced as early as 1988 in the United States 46 and the United Kingdom, 47 , 48 despite some contradictory findings. 15 , 30 , 35 , 42 , 49 A recent U.S. pilot study 16 documented that successful CMV matching is possible without adversely affecting local transplant rates and waitlisted times.…”