Article

Abstract 11844: Viral Gene Signatures in Patients With Cardiomyopathy After Chemotherapy

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Abstract

Introduction: Chemotherapy for hematologic malignancies can cause severe cardiomyopathy. Chemotherapeutic agents also induce immune suppression increasing the risk of opportunistic infections. Hypothesis: We have hypothesized that immunosuppression after chemotherapy increases opportunistic viral infections, myocarditis and cardiomyopathy. Methods: Viral gene sequences were identified using an unbiased high-throughput sequencing approach of patient blood samples following chemotherapy treatment for hematological malignancies (N = 28). Detected viral sequences were correlated with cardiac ejection fraction (LVEF) measured before and after treatment. Results: In a blinded analysis undertaken by two investigators viral sequences were identified in blood samples from patients after chemotherapy. Low levels of Influenza A, orthomyxovirus and Avian Paramyxovirus sequences were detected but identified individual virus sequences did not have a significant correlation to reduced LVEF post chemotherapy (r = 0.177-0.293). Detected sequences for all RNA viruses combined did indicate some correlation with LVEF, r = 0.621, suggesting potential for nonspecific RNA virus detection ( p < 0.0078). In a secondary broad screen, data mining was performed including all detectable viral sequences without the filtering of human related sequences. In this broad analysis a significant correlation was detected for Paramyxovirus with reduced cardiac LVEF (r = 0.592 post, compared to r = 0.464 prior to chemotherapy; P < .0096). For detected Orthomyxovirus sequences correlations were similar for LVEF pre- and post- chemotherapy (R = 0.483, P < 0.0451). Retroviruses reads were increased but suspect due to human genome retrovirus sequences (R= 0.512; P < 0.0351). No correlation was seen for Anellovirus, a DNA virus. Reduced LVEF did not correlate with chemotherapy (p = NS). Conclusions: This is the first report of screening for RNA viruses in the circulating blood of patients post chemotherapy using a high-throughput sequencing approach. Influenza Orthomyxovirus and Avian Paramyxovirus sequences were detectable in patients with reduced LVEF after chemotherapy. Further analysis for RNA virus infections in cardiomyopathy after chemotherapy is warranted.

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