Mysteries of Heart Failure in Pregnancy

A mysterious and sometimes deadly type of heart failure that can strike otherwise healthy, expectant mothers late in pregnancy and leave them sick for life at last can be traced to faulty blood vessels in the heart, researchers report today.

The team from Beth Israel Deaconess Medical Center in Boston found there's something that puts the brakes on proteins that are supposed to ramp up and produce new blood vessels to meet the extra demand on a heart beating for two ? the mother and her unborn child.

Without those new blood vessels, which are created through a process called angiogenesis, a woman develops shortness of breath and other symptoms, as her heart cannot pump enough blood late in pregnancy and around the time of delivery.

Her weakened heart muscle then becomes more prone to scarring, further compromising its ability to serve her and her baby. About half of women who develop this late-pregnancy complication, called peripartum cardiomyopathy, which can occur through the first five months after delivery, become sicker and may eventually need a heart transplant. The others get better on their own. Peripartum cardiomyopathy can strike up to one in 300 of expectant mothers.

The insights, drawn from a combination of mouse and human studies, are important because they have the potential to help millions of women worldwide who suffer from heart failure that is more common among women with a related late pregnancy complication called preeclampsia, which produces a dangerous rise in blood pressure, and those carrying multiples. With what they now understand, scientists can target women at high-risk of developing pregnancy-related heart failure and test new drugs to treat them.

"It's been a real mystery," said senior study author Dr. Zoltan Arany, an investigator at Beth Israel's CardioVascular Institute. "The majority of women who develop this condition are otherwise healthy, even active."

Given that the "real stressors of pregnancy occur in the first trimester," Zoltan said it's been a big question why these mothers-to-be develop such serious problems at the end of pregnancy.

The new insights build on work done in Arany's lab with a gene that turns on angiogenesis. Mouse studies with that gene "told us that PPCM is indeed a vascular disease, something that was previously not appreciated," said Zoltan, an assistant professor of medicine at Harvard Medical School.

The researchers then used insights from another Beth Israel Deaconess Medical Center scientist, Dr. S. Ananth Karumanchi, who had found that women with preeclampsia had high levels of another gene responsible for blocking angiogenesis, to flesh out their theory further. The angiogenesis blocking gene plays a role in a normal pregnancy to prevent excessive bleeding during delivery. Arany's team then determined that this second gene was also playing a role in development of blood vessel abnormalities setting the stage for heart failure.

The search continues for a still-undiscovered factor that leaves some women's hearts unable to "handle the wave" of blood vessel altering factors late in pregnancy, Arany said. "While we still have a lot to learn, I think we are now close to understanding, and maybe even treating, this devastating disease."

The findings appear in today's online issue of the journal Nature.

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