After adjustment for other factors, gender-matched transplantation was associated with 24% lower 30-day mortality (P=0.05), 16% to 23% lower one-year mortality, and 19% lower risk of rejection (P=0.04), Eric S. Weiss, M.D., of Johns Hopkins, and colleagues reported at the American Heart Association meeting here.
In their multicenter study, female recipients of a male heart were at the greatest cumulative risk of death, whereas male hearts paired with male recipients had the highest rate of success.
These findings support long-standing speculation that donor-recipient sex pairing improves transplantation outcomes for many organs, including the heart, Dr. Weiss said.
A prior study of kidney transplants gender matching likewise showed the lowest graft survival for women receiving male grafts both at one year (hazard ratio 1.08, P=0.003) and from two to 10 years (HR 1.06, P=0.008) compared with all other gender combinations. (See: Graft-Success Risk Higher for a Woman Getting Male Kidney )
One reason for these associations, despite major histocompatability matching of all organs, may be the minor histocompatability antigen present on the Y chromosome, Dr. Weiss noted.
But one issue unique to heart transplantation is the issue of size in hemodynamic stability, he said. "The heart, unlike most other organs that are transplanted, is really vulnerable to the mechanical constraints of the chest."
But the scarcity of donor hearts means physicians don't often get to choose the gender of the donor, Dr. Weiss said. Men account for the majority of heart transplants with 76% of recipients, and more than half of donors in his study were male, he noted.
Patients shouldn't be overly concerned about receiving a gender-mismatched heart, he cautioned. "If you have end-stage heart failure, you're still much better off receiving a heart -- assuming you're a candidate -- than going on to live with end-stage heart failure."
His group retrospectively reviewed the United Network for Organ Sharing (UNOS) database for outcomes of all 18,240 adults who were first-time orthotopic heart transplant recipients from 1998 through 2007.
Overall mortality at 30 days and one year varied significantly across the donor-recipient gender combinations (both P<0.001).
Survival curves showed the best cumulative survival rates were for male-male grafts both overall through nine years' follow-up (61%, P<0.001) and when censored for one-year mortality (69%, P<0.001).
After adjusting for 18 predictors of mortality, cumulative mortality was highest for female recipients of male donor hearts. The mortality risks compared with male-male transplantation were:
- 25% lower for female-donor to female-recipient transplantation (HR 0.75, 95% confidence interval 0.89 to 1.19).
- 23% higher for women receiving a male donor heart (HR 1.23, P=0.004).
- 15% higher for men receiving a female donor heart (HR 1.15, P=0.01).
Mismatch appeared to be more important than gender alone because neither donor gender nor recipient gender were significant predictors of mortality in the multivariate analysis (HR 0.95 and 0.84, respectively).
Mismatch in the physical size of donors appeared to contribute to the effects of gender mismatch overall. The hazard ratio for death was 1.29 with a low donor-to-recipient body mass index ratio but fell to 1.01 as the ratio flipped to reflect a larger donor-to-smaller recipient.
Graft rejection risk was elevated with sex-mismatched transplantation (odds ratio 1.19, P=0.04) and particularly high for female recipients (OR 1.5, P<0.001).
Gender is just one of many factors in transplant outcomes, such as level of histocompatability matching, donor organ health, and age.
"We still have sort of a rudimentary understanding of all the factors," Dr. Weiss noted, "We're putting together some of the pieces but we still don't have the puzzle together."