https://doi.org/10.1007/s00392-025-02625-4
1IKDT - Institut Kardiale Diagnostik und Therapie GmbH Berlin, Deutschland; 2Deutsches Herzzentrum der Charite (DHZC) Klinik für Kardiologie, Angiologie und Intensivmedizin | CBF Berlin, Deutschland; 3Universitätsklinikum Düsseldorf Klinik für Kardiologie, Pneumologie und Angiologie Düsseldorf, Deutschland
Background: Viral infections of the heart muscle are associated with inflammation and cardiac dysfunction. Chronic immunosuppression in heart transplant recipients (HTX) can lead to reactivation of viral infections, which can be associated with an increased risk of inflammation and rejection. This study investigates the prevalence of cardiotropic viruses in endomyocardial biopsies (EMB) from HTX patients and their involvement in transplant rejection, intramyocardial inflammation and cardiac dysfunction.
Methods: EMB from 1,200 HTX patients (70 % men, age 59±12 years) were analyzed for viral genomes (parvovirus B19 (B19V), enterovirus, human herpesvirus 6 (HHV-6), cytomegalovirus (CMV) and Epstein-Barr virus (EBV)). B19V and EBV activity were assessed using RNA transcript quantification and next generation sequencing (NGS) to differentiate latent from active infections. Viral findings were correlated with rejection, inflammation and left ventricular ejection fraction (LVEF).
Results: Viral genomes were detected in 71% of EMB (N=851). B19V was detected in 61% (N=726), with 16% (N=186) having an active infection. HHV-6 and CMV genomes were found in 5% (N=58) and 2% (N=24) of cases, respectively. EBV was detected in 8% (N=97), significantly more than in patients with heart failure without HTX (2.4%, P<0.0001). Virus-positive patients had increased T lymphocytes (38±98 vs. 25±47 cells/mm², P=0.019) and macrophages (56±97 vs. 40±61 cells/mm², P=0.009) compared to patients without evidence of viral infection. EBV-positive patients also had a reduced LVEF (45±20 vs. 55±11%, P=0.001) and an increased incidence of rejection (P=0.001). The number of immune cells, including T lymphocytes (81±166 vs. 32±84 cells/mm², P<0.0001), T helper cells (147±202 vs. 81±131 cells/mm², P<0.0001) and macrophages (94±170 vs. 51±82 cells/mm², P<0.0001) was significantly increased in EMB from EBV-positive patients, and inflammation was more frequently observed in HTX patients with EBV detection (P=0.040). Subgroup analysis of RNA transcripts by NGS confirmed that approximately 50% of EBV infections were of lytic origin.
Conclusion: Active viral infections, particularly EBV, are prevalent in HTX patients and associated with rejection, inflammation and cardiac dysfunction. These findings emphasize the importance of routine viral monitoring and timely interventions to manage virus-related complications in HTX patients.