Authors

• Jana Ljubas Maček — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0001-7171-2206
• Boško Skorić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
• Marijan Pašalić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-3197-2190
• Daniel Lovrić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-5052-6559
• Jure Samardžić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-9346-6402
• Maja Čikeš — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-4772-5549
• Hrvoje Jurin — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-2599-553X
• Ivo Planinc — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0003-0561-6704
• Nina Jakuš — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0001-7304-1127
• Dora Fabijanović — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0003-2633-3439
• Hrvoje Gašparović — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0002-2492-3702
• Davor Miličić — Medicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska — ORCID: 0000-0001-9101-1570

Abstract

**Introduction**: Cytomegalovirus (CMV) infection is known as an external trigger for cardiac allograft vasculopathy (CAV), due to the mechanisms that stimulate graft immunogenicity. (1, 2) The aim of the study was to investigate different aspects of CMV infection and their effect on the development of CAV and cellular rejection (CS) after heart transplantation (HTx). **Patients and methods**: 123 patients after HTx performed in the period from 2005 to 2016 were included, with regular CMV monitoring by PCR method. Follow-up was 3 years (IQR 2-6 years). The presence of CAV was evaluated by coronary angiography and analyzed with respect to pretransplant CMV-immunization and the presence and form of CMV infection, time of the infection (early infection, which was permanently cured within 6 months after HTx, or late with persistence of viremia or viral reactivation after the first 6 months). All patients received CMV-prophylaxis for three months. **Results**: CMV infection was detected in 31.7% of patients, of which 64% had asymptomatic viremia, 25% pneumonitis, 10% enterocolitis and 2.5% myocarditis. There was no difference in CMV seropositivity (91% of patients) compared to later CAV development (p = 0.551) and no effect on reduction of CMV infection after HTx (p=0.485). Significantly higher CAV incidence was associated with higher prevalence of CMV infection (p = 0.013), however early CMV infection had a lower prevalence of CAV than late. The number of viral copies by PCR did not correlate with CAV incidence. Patients with CMV infection did not have a shorter survival rate than CMV-negative patients (p = 0.384) or higher frequency of significant cellular rejection. **Conclusion**: Pretransplant CMV-seropositivity did not affect the ultimate number of CMV infections. CMV infection was confirmed as the trigger for later development of CAV, but it was not related to increased mortality. The number of viral copies was not significant in predicting CAV incidence, but late CMV infection showed higher importance in CAV development than early CMV infection. Despite the high prevalence of CMV infection in our patients (32%), no higher incidence of CAV has been demonstrated, possibly due to effective prophylaxis and thus shorter duration of viremia. The CMV infection did not prove to be the cause of the more frequent cellular graft rejection.

Keywords

heart transplantation, cytomegalovirus infection, cardiac allograft vasculopathy

DOI

Literature

1. Vassalli G, Gallino A, Weis M, von Scheidt W, Kappenberger L, von Segesser LK, et al. Working Group Microcirculation of the Eurpean Society of Cardiology. Alloimmunity and nonimmunologic risk factors in cardiac allograft vasculopathy. Eur Heart J. 2003 Jul;24(13):1180–8. https://doi.org/10.1016/S0195-668X(03)00237-9
2. Delgado JF, Reyne AG, de Dios S, López-Medrano F, Jurado A, Juan RS, et al. Influence of cytomegalovirus infection in the development of cardiac allograft vasculopathy after heart transplantation. J Heart Lung Transplant. 2015 Aug;34(8):1112–9. https://doi.org/10.1016/j.healun.2015.03.015