Study: Two-sizes-too-small 'Grinch' effect hampers heart transplant success

Study: Two-sizes-too-small 'Grinch' effect hampers heart transplant success

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22 years of data suggest need for new heart-size matching strategy to improve outcomes

Current protocols for matching donor hearts to recipients foster sex mismatching and heart size disparities, according to a first-of-its kind analysis by physicians at the University of Maryland School of Medicine and the University of Iowa. Matching instead by donor heart size may provide better outcomes for recipients, who already face a scarcity of resources as they await a transplant.

The analysis of 22 years of adult heart transplant data in the U.S., published this week in "JACC: Heart Failure" by the American College of Cardiology, critically re-appraises the current practice of matching donors and recipients by body weight rather than heart size. While two people may weigh the same, their hearts could have vastly different sizes—often requiring a smaller donor heart to strain to do the necessary work. The researchers dubbed this the “Grinch” effect, referring to the Dr. Seuss character whose heart was “two sizes too small.”

The contrast is especially amplified when a match based on body weight doesn’t factor in sex differences.

“Men who receive women’s hearts are 32 percent more likely to die in the first year after transplantation, and this is entirely because of suboptimal sizing,” says the study’s principal author, Dr. Robert M. Reed, assistant professor of medicine at the University of Maryland School of Medicine and a transplant pulmonologist at the University of Maryland Medical Center. “Even if the weights of donor and recipient are similar, the female heart is considerably smaller, while women are more often given men’s hearts that are larger.”

According to study co-author Dr.Keshava Rajagopal, a University of Maryland heart and lung transplant surgeon, the research emphasizes the peril of undersizing.

“Undersizing a donor heart is very dangerous. It’s like putting a motorcycle engine into a truck,” says Rajagopal, assistant professor of surgery at the University of Maryland School of Medicine. “We need to figure out a better way to reliably ascertain heart size to best match donor and recipient. Some of the heart size models we utilize in this study may provide those predictive tools.”

This research complements prior work on lung sizing in transplantation done by Reed in collaboration with the study’s senior author, Dr. Michael Eberlein, an assistant professor of internal medicine at the University of Iowa Roy J. and Lucille A. Carver College of Medicine and transplant pulmonologist at UI Hospitals and Clinics.

Eberlein notes that lung transplant candidates in the United States are listed for acceptable donor height ranges, with body height used as a surrogate for lung size. A series of studies conducted by Eberlein and Reed have shown that the body height standard for lungs has shortcomings similar to the body weight standard for hearts.

“This thoracic transplantation research tells us there are better ways to manage the organ size- matching process,” Eberlein says. “Instead of body weight for hearts and body height for lungs, we show that such parameters of estimated organ size as the predicted heart mass and predicted total lung capacity are clinically more relevant for the size-matching decision.”

Transplant centers typically limit the pool of acceptable heart donors to those whose body weight is within 30 percent of the recipient’s body weight. “This research shows that the current system allows some less-than-optimal matches to occur, while simultaneously reducing access to an already very limited resource for people waiting for heart transplants,” Reed says. He and his team propose a new strategy to determine compatibility based on the predicted total heart mass for recipient and donor pairs.

The research conclusions are based on a retrospective analysis of more than 31,000 donor-recipient adult heart transplant pairings from the United Network for Organ Sharing transplant registry between October 1989 and June 2011. The study focused on heart size matching, comparing outcomes based on body weight, predicted heart mass, and sex. The study evaluated risk of death at one year and five years after transplantation.

The body weight sizing analysis reflected the prevailing weight-based matching criteria: 86 percent of donor weights were within 30 percent of the corresponding recipient’s weight. Donor-recipient weight differences were distributed similarly across categories of sex matching. Survival was similar among groups with weight mismatches when compared against the best weight-matched group. “These findings confirm that weight differences are not associated with any difference in survival,” Reed says.

The sex comparison revealed that 77 percent of recipients were male (median age 55) and 71 percent of donors were male (median age 29). Overall death rates at one and five years post-transplant were 12 percent and 23 percent respectively. Nearly 71 percent were sex-matched recipient-donor pairs, while 29 percent were sex-mismatched pairs. Differences in predicted cardiac size accounted for the survival differences associated with donor-recipient sex mismatch.

The comparison of predicted heart mass shows the risk of death rose markedly when the donor heart’s predicted mass was 10 to 15 percent below the predicted mass of the recipient’s heart.

The group that had the most undersized hearts was 25 percent more likely to die in the first year after transplant.

Finally, the study found that heart size plays a role in the need to treat acute organ rejection during the first year after transplant. Rejection was treated nearly 50 percent more often in the most undersized compared to the most oversized heart pairings.

The study did not pinpoint why undersized hearts produce worse outcomes, but Reed speculates that problems result because the heart has to grow to meet the needs of its new body. “The undersized donor heart has to bulk up to deal with the work load of a body it was never meant for. I suspect this growth occurs in an unhealthy way.”

More than 3,700 people undergo heart transplantation annually in the United States. About 3,570 people are currently on the heart transplant waiting list, according to the Organ Procurement and Transplantation Network.

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Editors note: This media release was adapted from a release written at the University of Maryland.

Contacts

Molly Rossiter, UI Health Care Marketing and Communications, 319-356-7127

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