Peripheral blood mononuclear cell transcriptome profiles suggest T-cell immunosuppression after uncomplicated mechanical circulatory support device surgery.

Mechanical circulatory support device (MCSD) surgery in patients with advanced heart failure patients is often complicated by infections that are linked to altered cell-mediated immunity. Using a transcriptome-wide peripheral blood mononuclear cell (PBMC) gene expression profiling approach, we analyzed expression patterns directly before and after MCSD implantation in 11 patients who had an uncomplicated course after MCSD implantation (Day 0-24 hours before, Day 1-24 hours after, and Day 7-1 week after implantation). Data were analyzed using Significance Analysis of Microarrays (SAM) and High-Throughput GoMiner on post-implantation profiles (Day 1, Day 7) in comparison with baseline (Day 0). Day1 profiles included differential expression of 821 genes (SAM, FDR <0.1, fold change >1.5), enriching >60 Gene Ontology (GO) categories. Grouping by component genes revealed GO clusters, which we term "interleukin related" (primarily upregulated), "T-cell related" (primarily downregulated), and "apoptosis related" (both up- and down-regulated genes). Day 7 profiles included GO categories related to repair processes. In conclusion, transcriptome-wide expression profiling of PBMCs suggests a response pattern to MCSD implantation of inflammatory activation and simultaneous T-cell suppression.

Cardiac transplantation: any role left?

The authors analyze the question of whether heart transplantation still has a role in the current era of complex technologies. To achieve this objective, the authors first discuss the known benefits of different therapeutic modalities currently available for patients who have end-stage heart failure, including pharmacologic management, electrophysiologic therapies, high-risk surgical strategies, implantation of mechanical circulatory support device therapy, and heart transplantation. The authors then evaluate the current developments and future perspectives in the field that may influence the likelihood of heart transplantation to remain the therapeutic modality of choice for end-stage heart failure.

Destination therapy: does progress depend on left ventricular assist device development?

The role of therapy using mechanical circulatory support devices has evolved rapidly over the last two decades. New developments in the field achieved smaller adverse events, but, currently, only minor improvements in survival were observed in published observational data. The authors discuss the development of mechanical circulatory support devices as a "destination therapy" option for patients who have end-stage heart failure and are ineligible for heart transplantation as it relates to left ventricular assist device development.

Cellular coating of the left ventricular assist device textured polyurethane membrane reduces adhesion of Staphylococcus aureus.

OBJECTIVE: Infections are among the most common and serious complications of ventricular assist device implantation. These infections generally occur within the first 2 months after surgery. The basis for this high incidence of infection is not well established, so a murine intravascular infection model was developed with aortic implantation of the textured polyurethane patch material currently used in HeartMate ventricular assist devices (Thoratec Corporation Pleasanton, Calif). METHODS: Polyurethane patch material was placed in the wall of the mouse descending aorta. Mice were then infected with Staphylococcus aureus 1 or 14 days after implantation. In vitro adhesion studies were conducted with polyurethane membranes coated with endothelial cells and membranes coated with fibrinogen. RESULTS: Mice were susceptible to infection in both dose- and time-dependent fashions. The patch material was significantly more susceptible to infection at day 1 than day 14. Immunohistologic and morphologic studies demonstrated that the CD31+ cells deposited on the membrane surface phenotypically appeared to be endothelial cells. In vitro adhesion studies of polyurethane membranes coated with endothelial cells showed them to be less susceptible to S. aureus binding than were membranes coated with fibrinogen. CONCLUSION: Textured polyurethane membranes are less susceptible to infection as cellular deposition occurs. The time frame within which these membranes become populated with cellular material is consistent with the time-dependent clinical incidence of infection. Cellular coating of polyurethane may provide a strategy for reducing the risk of infection.