Cytomegalovirus infection and disease reduce 10-year cardiac allograft vasculopathy-free survival in heart transplant recipients

Abstract

BackgroundCytomegalovirus (CMV) is associated with an increased risk of cardiac allograft vasculopathy (CAV), the major limiting factor for long-term survival after heart transplantation (HTx). The purpose of this study was to evaluate the impact of CMV infection during long-term follow-up after HTx.MethodsA retrospective, single-centre study analyzed 226 HTx recipients (mean age 45 ± 13 years, 78 % men) who underwent transplantation between January 1988 and December 2000. The incidence and risk factors for CMV infection during the first year after transplantation were studied. Risk factors for CAV were included in an analyses of CAV-free survival within 10 years post-transplant. The effect of CMV infection on the grade of CAV was analyzed.ResultsSurvival to 10 years post-transplant was higher in patients with no CMV infection (69 %) compared with patients with CMV disease (55 %; p = 0.018) or asymptomatic CMV infection (54 %; p = 0.053). CAV-free survival time was higher in patients with no CMV infection (6.7 years; 95 % CI, 6.0–7.4) compared with CMV disease (4.2 years; CI, 3.2–5.2; p < 0.001) or asymptomatic CMV infection (5.4 years; CI, 4.3–6.4; p = 0.013). In univariate analysis, recipient age, donor age, coronary artery disease (CAD), asymptomatic CMV infection and CMV disease were significantly associated with CAV-free survival. In multivariate regression analysis, CMV disease, asymptomatic CMV infection, CAD and donor age remained independent predictors of CAV-free survival at 10 years post-transplant.ConclusionsCAV-free survival was significantly reduced in patients with CMV disease and asymptomatic CMV infection compared to patients without CMV infection. These findings highlight the importance of close monitoring of CMV viral load and appropriate therapeutic strategies for preventing asymptomatic CMV infection.

Elevated serum vascular endothelial growth factor and development of cardiac allograft vasculopathy in children

“…CMV disease and infection predispose adult heart transplant recipients to development of CAV 30 and there have been conflicting reports regarding the association between pre-transplant CMV positivity and risk of CAV in pediatric recipients. 31,32 Our study did not identify any significant differences in VEGF concentration based on recipient and donor cytomegalovirus status at transplant.…”

Cytomegalovirus reactivation in liver transplant recipients due to hepatitis C cirrhosis is associated with higher cardiovascular risk - an observational, retrospective study

“…More specifically, cardiovascular complications are the main cause of non‐graft‐related deaths, accounting for approximately 21% of deaths among patients who survive at least 3 years . The association between CMV reactivation and CVE has been described in other solid organ transplants, such as heart, lung, or kidney transplantation , but had not been previously assessed in LT patients. In our study, 16 of 26 patients who developed a CVE during the follow‐up period had a prior history of CMV reactivation after LT, 12 of whom considered clinically significant.…”

“…In the post‐transplant setting, experimental studies with murine models have provided compelling evidence that CMV plays an important role in the vascular disease process due to the alloreactive immune response to CMV inducing an acceleration of transplant vascular sclerosis . In clinical studies, CMV reactivation has been associated with higher incidence of CVE, especially in heart transplant patients due to cardiac allograft vasculopathy and/or direct endothelial injury; some studies have also reported a significant increase in medium‐term mortality in different organ transplant patients with CMV reactivation . In addition, recently, Desai and cols have reported that positive CMV serology has an impact on long‐term mortality, specifically due to CVE deaths in renal, cardiac, and pulmonary transplant patients, but not in LT patients.…”

Recent advances in allograft vasculopathy

“…A recent large retrospective study in patients following long-term following heart transplantation demonstrated that those with either asymptomatic or symptomatic CMV infection had significantly increased AV and reduced 10-year graft survival (64). While the exact mechanism in which CMV infection leads to AV has not been elucidated, the ability of subclinical infection to directly activate graft endothelium or enhance innate immune responses are two mechanisms which have been proposed (4).…”