Influence of cytomegalovirus infection in the development of cardiac allograft vasculopathy after heart transplantation

https://doi.org/10.1016/j.healun.2015.03.015Get rights and content

Background

Cardiac allograft vasculopathy (CAV) is a major cause of long-term morbidity and mortality after heart transplantation (HTx), whose relationship with CMV infection is uncertain. This study evaluated the influence of CMV infection in the development of CAV.

Methods

We enrolled 166 consecutive HTx recipients who underwent their first transplant from January 1995 to July 2002. All patients received 14 days of intravenous ganciclovir and were prospectively monitored for CMV infection during the first year after HTx. CAV was diagnosed by coronary angiography performed at 1, 5, and 10 years after HTx, following the new criteria of the International Society for Heart and Lung Transplantation. We collected all variables potentially related with the development of CAV. Risk factors were studied using a complementary log-log model.

Results

After a median follow-up of 11 years (range, 1–17 years), 72 patients (43%) developed CAV (63.8% CAV1, 15.2% CAV2, 20.8% CAV3). Symptoms secondary to CAV were present in 32% of these patients, and 8% died because of it. In the regression multivariate analysis, independent variables associated with the development of CAV were donor age (hazard ratio [HR], 1.028; 95% confidence interval [CI], 1.002–1.053; p < 0.028), presence of cellular acute rejection ≥ 2R (HR, 1.764; 95% CI, 1.011–3.078; p < 0.0414), CMV infection (HR, 2.334; 95% CI, 1.043–5.225; p < 0.0354), and not having been treated with a calcium channel blocker (HR, 0.472; 95% CI, 0.275–0.811; p < 0.0055).

Conclusions

Standardized angiographic criteria show CMV infection is associated with the development of CAV.

Section snippets

Methods

The Local Ethical Committee approved this investigation.

Results

Overall, 213 patients received their first HTx at our institution during the study period. We excluded 4 patients who underwent re-HTx, 31 who died during the first year after HTx, 5 whose CMV sampling was inadequate, and 7 without angiographic studies due to vascular access problems. Thus, we finally included 166 HTx recipients.

Table 1 describes the main baseline characteristics of the cohort. Most patients received induction therapy with OKT3 and triple therapy with cyclosporine,

Discussion

Our study shows that CMV infection, including asymptomatic replication, is an independent risk factor associated with the development of CAV.

We were able to demonstrate it through a special scenario that occurred during the interval we chose for the study: a homogeneous cohort who received intense immunosuppressive therapy, a short course of intravenous ganciclovir prophylaxis, standardized blood sampling to search for CMV replication, and a long-term angiographic follow-up. Of course, our

Disclosure statement

None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.

The authors are grateful to David Lora-Pablos (Research Institute, Clinical Research Unit, University Hospital 12 de Octubre) for the statistical analyses and to Martin J. Smyth, BA, for revision of the English version of this manuscript.

This study was partially supported by the Spanish Cardiovascular Research

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