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Researchers Probe Cardiomyopathy in Pregnant Women

Condition Can Threaten Lifelong Health


Zoltan Arany, MD, PhD (right), a scientist in the CardioVascular Institute at BIDMC, with Sarosh Rana, MD.

Heart failure develops when the heart's muscle becomes weak and is unable to effectively pump blood throughout the rest of the body. Peripartum cardiomyopathy is a specific type of heart failure that, for unknown reasons, affects pregnant women just before or after delivery. Cardiologist Zoltan Arany, MD, PhD, a scientist in the CardioVascular Institute at Beth Israel Deaconess Medical Center, recently published new research findings in the journal Nature that help explain why this extremely serious condition strikes otherwise healthy mothers-to-be and describes the role that blood vessels play in the onset of the disease. Here, he talks about these new findings.

Peripartum cardiomyopathy affects one in 3,000 pregnancies each year. What has been known about this condition?

Dr. Arany: It's been a real mystery, because the majority of new mothers who develop peripartum cardiomyopathy (PPCM) are otherwise healthy, even active. And, seemingly all of a sudden, they begin to exhibit symptoms of heart failure: swelling in the feet and legs, shortness of breath. In mild cases, these symptoms may go unnoticed because they are so similar to typical symptoms that occur in the third trimester of pregnancy. But in severe cases, new mothers experience a more dangerous situation in which their hearts' pumping abilities are significantly impaired. In these cases, women may never fully recover and could go on to have lifelong chronic heart failure, even to the point that they face a life-threatening situation and could require a heart transplant to survive.

Your discovery has focused on the role that blood vessels play in the disease. Can you explain?

Dr. Arany: Yes. To take a step back, angiogenesis is the term for the biological process in which new blood vessels grow and develop. My laboratory focuses on a particular gene called PGC1-alpha, and over the years, we have been able to demonstrate that this gene can activate the angiogenic process.

It was while we were studying this gene in the heart - which we can do by creating genetically engineered mice that are missing the PGC1-alpha gene - that we observed that these animals developed all of the symptoms of peripartum cardiomyopathy following pregnancy. In other words, the animals' normal blood vessel growth was being disrupted. We went on to conduct additional experiments that enabled us to say with certainty that PPCM is a vascular disease.

Why is this specific to pregnancy?

Dr. Arany: This is exactly what we wanted to determine. And through collaborations with Sarosh Rana, MD, and other BIDMC investigators from the Department of Obstetrics and Gynecology and from the Center for Vascular Biology [which specifically focuses on the study of blood vessels], we gained some important insights.

Near the end of a normal pregnancy, large quantities of antiangiogenic molecules are released. It is presumed that this occurs to halt blood vessel growth in order to prevent excessive bleeding when the mother's placenta is delivered following the baby's birth. In their previous studies, our BIDMC colleagues had found that when women had preeclampsia, which is characterized by high blood pressure and loss of protein in the urine during pregnancy, they had markedly increased levels of an antiangiogenic protein called sFLT1. It is this protein that causes the mother's blood vessels to become excessively constricted, which leads to the sharp rise in blood pressure and the onset of preeclampsia.

We thought that this same antiangiogenic overreaction might be affecting women's hearts and triggering PPCM. To test this theory, we performed echocardiographic studies in patients with preeclampsia and, sure enough, we discovered that their hearts were affected, even though they didn't show any symptoms. At the same time, in collaboration with a scientific team in Germany led by Dr. Hilfiker-Kleiner, we showed that a number of women with PPCM had elevated sFlt1 levels in their blood.

So do all PPCM patients also have preeclampsia?

Dr. Arany: Not necessarily. Preeclampsia is a risk factor for the development of PPCM, as are multiple births, but neither are absolutely necessary, much in the same way, for example, that smoking is a risk factor for lung cancer, but some non-smokers get lung cancer too.

You have referred to peripartum cardiomyopathy as a 'two-hit' disease. Can you explain what this means?

Dr. Arany: We think that two events have to take place before a new mother develops peripartum cardiomyopathy. The first is the excessive elevation of the signals that are released to halt blood vessel growth in late pregnancy. But in addition, normal "proangiogenic defenses" appear to be deficient in women who develop PPCM. This could be the result of an infection or a genetic predisposition or something else entirely, we don't know.

What will be the next steps in your research?

Dr. Arany: We want to find out why some women's hearts can handle the wave of antiangiogenic factors in late pregnancy and other women can't. We also want to determine if proangiogenic therapies can be used to treat PPCM.

Above content provided by the CardioVascular Institute at Beth Israel Deaconess Medical Center. For advice about your medical care, consult your doctor.

Posted June 2012

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CardioVascular Institute at
Beth Israel Deaconess Medical Center
330 Brookline Avenue
Boston, MA 02215
888-99-MYCVI
617-632-9777

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