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(Circulation. 1995;91:1029-1035.)
© 1995 American Heart Association, Inc.

Articles

Increased Early Mortality in Women Undergoing Cardiac Transplantation

Presented in part at the 65th Scientific Sessions of the American Heart Association, New Orleans, La, November 17, 1992.

Mindy E. Wechsler, MD; Elsa-Grace V. Giardina, MD; Robert R. Sciacca, ScD, Eng; Eric A. Rose, MD; Mark L. Barr, MD

From the Cardiovascular Clinical Pharmacology Laboratory and Center for Women's Health, Department of Medicine (M.E.W., E.-G.V.G., R.R.S.), and the Division of Cardiothoracic Surgery, Department of Surgery (E.A.R., M.L.B.), College of Physicians and Surgeons, Columbia University, New York, NY, and Health Care Consultation Center (M.L.B.), USC School of Medicine, Los Angeles, Calif.

Background To evaluate factors that explain sex differences affecting mortality after cardiac transplantation, a retrospective analysis of adult patients undergoing orthotopic cardiac transplantation was undertaken at the Columbia-Presbyterian Medical Center.

Methods and Results The study population consisted of 379 patients (75 women, 304 men) 18 years of age who survived for 48 hours after undergoing orthotopic cardiac transplantation between March 1985 and March 1992. The following were analyzed: incidence of death and treated rejection episodes, donor and recipient cytomegalovirus (CMV) matches, use of OKT3 induction therapy, and donor and recipient HLA mismatches. Women 49±12 years old and men 47±12 years old were characterized by differences in race and diagnosis. Women were more likely to be nonwhite (P<.01) and have idiopathic cardiomyopathy than were men (P<.01). A trend toward an increase in first-year rejection frequency was seen in women compared with men (P=.08). Overall actuarial survival was significantly reduced in women after transplantation (P<.05). At 36 months, female actuarial survival was 64±7% versus 76±3% for men (P<.05). The majority of patients in this study did not receive CMV prophylaxis. Univariate analysis revealed that only CMV(+) donor status and the use of OKT3 induction therapy affected survival in women. Multivariate analysis revealed a marked reduction in survival in female recipients of CMV(+) donors given OKT3 induction therapy. At 36 months, only 25% of women were still alive compared with 86% of women with neither risk factor (P<.001). Even without OKT3 induction there was markedly reduced survival in women with mismatched CMV status, ie, CMV(-) recipients of CMV(+) donors; 17% survival after 36 months versus 86% in women who were CMV(+) recipients (P<.05). Although at this institution during the study time period, CMV prophylaxis was not routinely employed and OKT3 induction was selectively used in higher-risk patients, conclusions regarding differences in outcome that are sex dependent are valid.

Conclusions (1) Women are at risk for reduced actuarial survival up to 3 years after cardiac transplantation. (2) Univariate analysis shows that women are selectively at risk for death when receiving hearts from CMV(+) donors and after receiving OKT3 induction therapy. (3) Multivariate analysis reveals that women are at even greater risk for death when receiving hearts from CMV(+) donors in conjunction with OKT3 induction therapy. (4) In the absence of OKT3 use, the greatest risk of death occurs in CMV(-) women transplanted with CMV(+) donor hearts. (5) When female to male survival curves are compared, factors that influenced survival in women did not appear to be problematic in men.

Key Words: risk factors • transplantation • clinical trials • rejection

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