8/9/2019 Professor Hannah Valantine, MD: Heart transplant failure higher in women with common virus

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Acute rejection of a transplanted heart is higher in women than in men. A recent study

by a Stanford cardiologist shows that women who have been exposed to

cytomegalovirus (CMV), a common virus that lies dormant in many adults, may be part of 

the reason.

About 75 percent of all adults have been exposed to the virus. Although the virus causes

no or mild symptoms in adults, it is dangerous to fetuses whose mothers acquire the

disease when pregnant and to people with suppressed immune systems. Because CMV

stays alive in the body indefinitely, the body develops antibodies against the virus, even

while the disease is dormant.

In a multi-site study funded by the National Institutes for Health (NIH), Hannah Valantine,

MD, a Stanford professor of cardiovascular medicine and a Clayman Institute 2009-10

Faculty Research Fellow, helped to clarify the relationship between the virus and transplant failure, and now hopes

to expand the study to determine how CMV affects women in particular.

“Women with the virus are more likely to develop problems, including acute rejection of the transplanted heart,”said Valantine, who has spent much of her career studying the mechanisms behind heart transplant failure. “The

question is, do sex differences affect the relationship between the virus and transplant outcome?” 

Heart transplant patients require immunosuppressant drugs to keep their T cells from attacking the new heart.

However, the B cells that make CMV antibodies are produced in the bone marrow and have an indefinite capacity

for memory. Once the B cells that normally produce protective antibodies against the virus have been suppressed

by drugs, the virus is more likely to be reactivated and cause serious side effects.

Valantine’s studies have shown that even in the presence of CMV antibodies, immunosuppression can reactivate

the virus and cause rejection. Her research points to the possibility that CMV activation leads to increased

numbers of antibodies directed against the transplanted heart by the recipient. Further study is required since

heart biopsies have conventionally looked for inflammatory cells, not antibodies.

“The antibodies mount an attack against the transplanted heart,” said Valantine. “Women are most prone to

producing these antibodies since they may be more likely to be exposed to the virus when pregnant.” 

Valantine also is participating in the Clinical Trials in Organ Transplantation project, a new interdisciplinary, multi-

site NIH study, to assess several drugs in reducing presensitization of patients to human leukocyte antigens (HLA)

before a transplant.

“It’s routine to look at HLA antibodies before a transplant to avoid certain donors,” she said. “However, we’re

Heart transplant failure higher in women with

common virus by Ruth Schechter on 08/02/10 at 7:00am 

8/9/2019 Professor Hannah Valantine, MD: Heart transplant failure higher in women with common virus

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Copyright 2010 Board of Trustees of Leland Stanford Junior University. All rights reserved.

Hannah Valantine, MD, speaks on gender in

cardiovascular medicine on iTunes

finding that the rates of presensitization are higher in

women, so they may be at greater risk for transplant

failure. That means that women are more l ikely to wait

for a match. We need to see if woman are being treated

differently—there’s a huge emphasis to see how we can

better select patients for transplant to prevent

rejections.” 

Valantine, who is also the medical school’s senior

associate dean for diversity and leadership, has been

conscious of the role of gender in medicine throughout

her career. “I found my gender and race were actually an

advantage when I was starting out because women were

so rare in cardiology at the time,” she said. “Today,

however, we need a robust pipeline for women in

medicine to shape research on gender differences in

disease outcomes. At the very least, doctors should

represent the proportions of minorities and women

among their patients.”