NEW ORLEANS — A person who receives a heart transplant from someone of the same gender is more likely to survive the subsequent few years than someone getting a new heart from a donor of the opposite sex, researchers reported November 12 at the American Heart Association’s annual Scientific Sessions meeting.

“This was something that was speculated” based on smaller studies from single institutions, says surgeon Eric Weiss of Johns Hopkins University in Baltimore. With the new findings, he says, “we basically supported the hypothesis.”

To do so, he and his colleagues tapped into a nationwide database of every adult heart transplant in the United States from 1998 to 2007—18,240 recipients. The researchers were able to track heart recipients’ progress for 3.4 years on average, with data for some people stretching out over 10 years.

One-fourth of heart recipients died during the study. The records show that people who got a heart from a donor of the opposite sex were 15 percent more likely to die during the study period than people who got a gender-matched heart. The female donor/male recipient combination yielded the greatest risk, a 23 percent increase of death.

Sex-mismatched recipients were also more likely to develop transplant immune rejection during the first year. Female recipients getting gender-mismatched hearts had the highest rejection rates.

In rejection, the recipient’s immune system identifies the new organ as foreign and attacks it. The greatest risk of transplant rejection occurs during the first year after the transplant, although the danger never goes away fully, Weiss says.

Both risks — of death or immune rejection — remained about the same at the three-year and five-year points after transplant, Weiss says.

The authors accounted for differences between donors and recipients, other than gender, that might influence how well a transplant progresses. These differences included age, race, diabetes status, kidney function, immunological match and recipient frailty.

“This is evidence that these investigators identified a signal where gender mismatch was in fact a concern,” says Clyde Yancy, a transplant cardiologist at Baylor University Medical Center at Dallas.

The biological reasoning behind the seeming risk of a gender-mismatched donor heart — and particularly for women receiving one — might rest with the Y chromosome, which only men have, Weiss says.

But the full explanation probably goes deeper, says Yancy. “A woman’s immune system is sensitized to a larger array of common antigens in the donor pool after pregnancy,” he says. That may include antigens — any compounds that elicit an immune reaction — found on the Y chromosome, he says, and could account for the higher rejection rate in women seen here and in smaller studies.

At present, transplant teams do their best to match donors and recipients by body size and blood type.

Moving beyond current methods and even beyond gender, Yancy says these findings also add credence to the argument that transplant centers need to develop a rapid system for identifying better immune matches between donors and recipients.

The usefulness of sex-based matching would come up only if there were more than one heart available, Yancy says. And he cautions that any benefit of gender matching might be lost if it means waiting for a matched heart and delaying a transplant.

Weiss says he and his colleagues are interested in developing a formula that would clarify for doctors how to match up the best possible donors with recipients, also assuming more than one heart is available.

For the time being, Weiss says patients “are still much better off receiving an organ than trying to live with end-stage heart failure, whether [the heart] is from a male or female.”

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