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(Circulation. 1999;100:II-211.)
© 1999 American Heart Association, Inc.

Thoracic Transplantation and Ventricular Assist Devices

Quantitative Changes In T-Cell Populations After Left Ventricular Assist Device Implantation

Relationship to T-Cell Apoptosis and Soluble CD95

Hendrik-Jan Ankersmit, MD; Niloo M. Edwards, MD; Michael Schuster, BSc; Ranjit John, MD; Alfred Kocher, MD; Eric A. Rose, MD; Mehmet Oz, MD; Silviu Itescu, MD

From the College of Physicians and Surgeons of Columbia University, New York, NY.

Correspondence to Silviu Itescu, MD, Transplantation Immunology Department of Surgery, College of Physicians & Surgeons of Columbia University, 622 W 168th St, PH 14 W, Room 1485, New York, NY 10032.

Background—Left ventricular assist devices (LVADs) are currently being evaluated as permanent therapy for end-stage heart failure. Because life-threatening infections limit successful long-term device implantation, we investigated the relationship between quantitative T-cell defects in LVAD recipients and CD95-mediated T-cell apoptosis.

Methods and Results—Immunological studies were performed in NYHA class IV patients awaiting cardiac transplantation who received either a TCI Heartmate left ventricular assist device (LVAD) or medical management. Fluorochrome-labeled Mabs were used in T-cell phenotypic analyses. T-cell apoptosis was measured by annexin V binding of T cells cultured in medium for 24 hours. Circulating serum levels of soluble CD95 were measured by ELISA. LVAD recipients had a relative lymphopenia and reduction in CD4 T-cell levels compared with NYHA class IV heart failure controls. These observations were confirmed in a longitudinal study in LVAD recipients, which showed that device implantation was accompanied by progressive and sustained reductions in circulating CD4 T-cell levels. These abnormalities in LVAD recipients were accompanied by increased levels of circulating soluble CD95 and by excessive CD4 and CD8 T-cell apoptosis. Susceptibility to induction of apoptosis was >2-fold greater for CD4 T cells than for CD8 T cells.

Conclusions—These results suggest that the reduction in CD4 T-cell levels accompanying LVAD implantation is a consequence of an augmented pathway of CD95-mediated apoptosis. The clinical consequences of these abnormalities may include increased prevalence of systemic infections.

Key Words: assist devices, left ventricular • heart failure • transplantation • apoptosis