SAN DIEGO – For men undergoing heart transplantation, the sex of their donor may mean the difference between life and death, according to a pair of large retrospective cohort studies
The studies, which were reported at the annual meeting of the International Society for Heart and Lung Transplantation (ISHLT), each analyzed data from more than 60,000 recipients over periods spanning several decades.
Dr. Ingo Kaczmarek
Their conclusion: Men were more likely to die if they received a heart from a female donor vs. a male donor, with the elevation in risk largely resulting from excess deaths in the first year. Overall mortality was 13% higher for these men after potential confounders were taken into account.
In contrast, women undergoing heart transplantation had a similar risk of death regardless of whether their donor was male or female.
A possible explanation for the higher risk of death in men with female donors, according to Dr. Ingo Kaczmarek, a cardiac surgeon at the Transplantation Center Munich of Ludwig-Maximilians University of Munich and the lead investigator of one of the studies, is that women’s hearts are smaller than men’s, even given the same body height and weight (J. Am. Coll. Cardiol. 2002;39:1055-60).
Additionally, medication nonadherence may play a part. "In our population ... I can tell you that females take their medication and males don’t," he said. "And that might be a big confounder that you can’t measure."
Although her study took donor characteristics into account, it is still possible that the smaller size of female hearts played a role, agreed Dr. Kiran K. Khush, lead investigator of the other study. "But I think there are probably also some immunological processes involved and sex differences that we don’t completely understand," she added.
This new information helps explain why some patients fare better than others after heart transplantation, but it would not necessarily alter her practice, said Dr. Khush, a cardiologist and instructor in cardiovascular medicine at Stanford (Calif.) University.
"I would worry about it clinically, but I’m not sure that would preclude me from accepting a female graft for a male recipient, because – as we all know – when you have a very sick recipient who is in imminent danger of dying, you just want to have a heart for that patient," she commented.
Dr. Kiran K. Khush
However, she added, perhaps given a situation wherein several highest-priority patients on the waiting list were otherwise similar, sex matching might be something to consider.
Dr. Khush and her colleagues analyzed data from the ISHLT database, the largest repository of heart transplant outcomes, for the years 1990-2008, restricting analyses to 60,584 adult recipients having at least 2 years of follow-up post transplantation.
"The ISHLT database pulls data from a lot of different transplant centers worldwide," she noted, including ones in North America, Europe, Australia, and New Zealand, among others. "So this really represents a truly international experience."
Fully 79% of the heart transplant recipients were men. On average, the men were 52 years old and the women were 49 years old at the time of transplantation.
Men’s odds of acute rejection within 2 years of transplantation were higher if their donor was female vs. male before adjustment for more than a dozen potential confounders (odds ratio, 1.22), although not afterward. Women’s odds of this outcome did not differ by the sex of their donor.
The donor’s sex did not affect the likelihood of cardiac allograft vasculopathy for either group before adjustment. But afterward, men actually had a lower risk of this outcome if their donor was female (OR, 0.77).
Here, Dr. Khush sounded a note of caution about the variability in assessing and defining vasculopathy across centers. "Some use angiography, some use IVUS [intravascular ultrasound], maybe some use clinical suspicion," she explained, and disease extent is often not documented. "So I think this is a really hard end point to interpret because the definition is so vague."
But there is no gray area when it comes to defining death, she noted, and results showed that men were more likely to die after transplantation if their donor was female vs. male, both before statistical adjustment (hazard ratio, 1.18) and afterward (HR, 1.13). The donor’s sex had no influence on this outcome among women.
Temporal patterns, assessed with follow-up out to 20 years, suggested that the poorer survival of men who were given a female heart was largely because of increased mortality in the first year post transplantation.
Men also had a higher risk of graft failure resulting in death or retransplantation (after censoring for death from other causes) if their donor was female (HR, 1.17).