Abstract 13892: Therapeutic Suppression of Parvovirus B19 Replication with the Thymidine Analog Telbivudine Improves Clinical Outcome in Chronic Myocarditis and Reduces Apoptosis in Circulating Angiogenic Cells
Parvovirus B19 (B19V) is a causative agent of inflammatory cardiomyopathy and impaired cellular endothelial regeneration with consecutive endothelial dysfunction and microvascular disease. B19V was recently identified as strong inductor of apoptosis with impaired function of circulating angiogenic cells. Since as yet no therapeutic option for chronic B19V infection exists, we tested whether antiviral treatment with the thymidine analog telbivudine was effective on clinical outcome in B19V-cardiomyopathy and in suppressing B19V replication in vitro. Patients (6 male, 2 female) with B19V associated chronic myocarditis were enrolled in a pilot trail to receive 600 mg o.d. of telbivudine for 6 months. Transcriptional activity of B19V was silenced in all but one patient after end of telbivudine therapy resulting in a significant suppression of B19V load in endomyocardial biopsies (EMB; 2245 to 629 genome equivalents (GE/µg isolated nucleic acids; p<0.05). Patients under treatment reported early improvement of angina and physical disability within the first weeks. At 6 months NYHA classification (median 3 to 2; p<0.05), quality-of-life score (38.5 to 14.5; p<0.05), and 6-min-walking distance (486 m to 563 m; p<0.005) had improved significantly. Inflammatory lymphocyte count was reduced from 8.75 to 4.5 cells per mm2 on immunohistochemical analysis. Left ventricular ejection fraction improved significantly from 45% to 55% (p<0.05). Confirming reduced B19V replication in EMB of patients our in vitro data showed suppressed B19V replication after 48 hours. Pretreatment of early outgrowth endothelial progenitor cells and endothelial colony forming cells with telbivudine resulted in a significant reduction of apoptosis in vitro (39% and 60%, both p<0.005), as measured by activate caspase-3. Currently, the underlying cellular pathways are being scrutinised. In conclusion, the data of this first antiviral trial for B19V infection indicate functional benefit of telbivudine on symptomatic B19V-chronic myocarditis, paving the way for a randomised controlled clinical study. Both, suppression of B19V replication and reduction of apoptosis of circulating angiogenic cells represent attractive treatment approaches for this so far untreatable disease.
- © 2012 by American Heart Association, Inc.