Next generation sequencing analysis reveals large proportions of undetected viral infections in patients with unexplained heart failure

Abstract Background Heart failure (HF) is often triggered by preceding or persisting viral infections, which can lead to irreversible cardiac damage when the causative etiology is not rapidly identified and adequately treated. While virus detection has been restricted by polymerase chain reaction (PCR) limitations, metagenomic sequencing has gained attention in advanced diagnostics of viral genomes. Here, we investigate the use of new targeted next generation sequencing (NGS) to detect viral genomes and transcripts in endomyocardial biopsies (EMBs) of patients with unexplained HF. Methods A total of n=80 patients with unexplained HF were enrolled in this study who underwent EMB. In all patients, coronary artery disease and other possible causes of myocardial dysfunction were excluded prior to EMB. EMBs were taken from the left or right ventricle and were examined for viral infections by routine PCR. In state-of-the-art qPCR-based analysis of the EMBs, all patients were virus-negative. Subsequently, the cohort was analyzed by NGS using an Illumina MiSeqTM. Results In contrast to PCR, in 52% of total cohort, viral genomes were detected using targeted NGS, of which the majority revealed parvovirus B19 (B19V) DNA (N=28), Epstein-Barr Virus (EBV) (N=10), Human Herpes Virus 6 (N=2), and Herpes-Simplex Virus (HSV) (N=2). Moreover, in N=8, transcriptional virus activity of B19V and EBV were detected. Conclusions Our work highlights metagenomic NGS as a sensitive and powerful tool in EMB analyses. Our data clearly demonstrate the need for advanced EMB-based diagnosis and emphasize the applicability of targeted NGS in EMB diagnostics as a basis for potential specific treatment.