Eisenmenger Syndrome: A Rare Condition in Pregnancy

As you may know, there are a variety of medical conditions that can make pregnancy dangerous, or that become dangerous on account of pregnancy. In some cases, the conditions can be severe enough to warrant recommendations that a women avoid ever getting pregnant. Of many categories of diseases, adult congenital heart disease (ACHD) in particular often warrants a discussion of the risks of ever being pregnant, because, though many cases of ACHD are mild and/or were corrected with great success during childhood, a significant number of such cases can indeed make pregnancy life-threatening. In all cases, the severity of the condition matters a lot. Recently, we discussed what happens when there is a connection that is not supposed to be there between the right and left atria of the heart, and how most commonly this connection is a patent foramen ovale (PFO), where the effects increase in pregnancy but usually are mild. In that same article, we also noted that another type of connection between the two atria, which is generally worse to have than a PFO, is an atrial septal defect (ASD). While an ASD is equivalent to having a hole in the wall between two rooms in your home, a PFO is like having a swinging door between the two rooms, a swinging door that doesn’t click closed. Rather than being a condition that is with you when you are born, Eisenmenger syndrome is something that can develop as a consequence of having some structural thing wrong between the right and left side of the circulation. We’re going to discuss it today, not because it’s likely to affect you —as noted above, Eisenmenger syndrome is rare— but rather because it is a very good way to explain the physiology of the heart, how it can change from abnormalities in the heart, the great blood vessels, and lungs, and how these changes work in the context of pregnancy.

Now, an ASD that is big enough to enable large amounts of blood to move between the right and left atria is one situation that can in some cases lead to Eisenmenger syndrome. Two other congenital structural abnormalities that also can lead to Eisenmenger syndrome are a ventricular septal defect (VSD, a hole between the left and right ventricles of the heart) and a patent ductus arteriosus (PDA). If you know that the ventricles are the two large chambers that pump blood out of the heart, then you are probably thinking that a VSD is worse than an ASD, and generally you are correct, but let’s keep in mind that the size of the defect also matters. A very large ASD can be worse than a small VSD. The problem in either case is that blood can move, or shunt, from one side of the heart to the other.

To discuss what a PDA is, we need to review the circulation of blood in the fetus and how it changes when you are born. In fetal life, it is normal for blood to move directly between the right and left side of the heart. Consequently, the septum that divides the two atria and the two ventricles forms little by little and even once it is all formed, the swinging door that we discussed, the foramen ovale, stays open up to the point of birth. Additionally, during fetal life, there is a blood vessel called the ductus arteriosus, which transmits blood between the pulmonary artery (which receives blood from the right ventricle) and the aorta (which receives blood from the left ventricle). In other words, for blood entering the right atrium of the fetal heart, there are two pathways to the body tissues. One pathway takes blood from the right atrium through the foramen ovale to the left atrium, from there to the left ventricle, into the aorta, which supplies all the body. For blood that doesn’t pass through the foramen ovale but moves instead from the right atrium into the right ventricle, it then moves into the pulmonary artery and from there most of it goes through the ductus arteriosus into the aorta to join with the blood that entered the other way, beginning its journey through the body. There is also another way blood can go from the pulmonary artery, which is through the lungs and from there to the left atrium, but not much blood does this, because the fetal lungs are collapsed, so the pressure in the pulmonary artery is very high beyond the branching point with the ductus arteriosus.

All of this is perfectly healthy in the fetus, because oxygen is supplied from the placenta, meaning ultimately from the mother’s lungs. Similarly, the carbon dioxide from the fetus gets out through the placenta, but it all changes at birth, when the newborn lungs inflate. This causes pressure in the pulmonary artery to drop dramatically, while the pressure in the left ventricle and also in the left atrium rises. As a result, the foramen ovale closes like a swing door being pushed by the wind, and in most people (but not all) locks shut over the course of the first year of life. Meanwhile, usually within a few days after birth, the ductus arteriosus closes off and turns into a ligament. In cases when it stays open, allowing blood to continue moving between the pulmonary artery and aorta, that’s what we mean by a PDA, a patent ductus arteriosus, which can have a variety of causes, one being that the mother became infected with  rubella virus during pregnancy (which is one reason why it is so important for women be vaccinated against rubella before getting pregnant).

So let’s say that a woman has a congenital PDA, a VSD, or an ASD and then she gets pregnant. The magnitude of the consequences can depend on how badly or how mildly she was affected before pregnancy. When blood can move between the right and left sides of the heart without going through the body or lungs, this is called a shunt and there are two broad categories of shunt: left-to-right and right-to-left, depending on whether blood is shunted from the left side of the heart to the right, or the other way around. Of the two shunt types, right-to-left is worse. It’s called a cyanotic heart condition, because blood that is depleted of oxygen, because it has not passed through the lungs, gets mixed into the oxygenated blood that is leaving the heart bound for body tissues. The more deoxygenated blood from the right that mixes in, the more cyanotic the condition.

As for the other kind of shunt, left-to-right, initially, or if the shunt is small, it’s not as bad as a right-to-left shunt, because left-to-right just means that already-oxygenated blood goes back to the right side of the circulation and makes an unnecessary second pass through the lungs. The problem comes in if the left-to-right shunt is big, for instance if more than 1.5 times as much blood is going through the lungs from the right ventricle as goes through the body from the left atrium. Recall that the pressure on the left side of the heart is much higher than on the right side and what can happen with a left-to-right shunt is that the increasing volume that the right ventricle must handle and the connection with the high pressure system of the left side of the heart causes the pressure in the right ventricle to rise. This pressure rise also transmits to the blood vessels of the lungs, which also adapt, leading to pulmonary hypertension, meaning high blood pressure in the lungs.

Now, just as during fetal life when the collapsed state of the lungs meant high pressure in the fetal pulmonary artery, discouraging blood from moving from the right ventricle through the lungs, the high pressure in the lungs during adulthood as a consequence of the left-to-right shunt, once again discourages blood flow through the pulmonary artery. The pressure in the right ventricle continues to rise, while less blood moves through the lungs, causing pressure in the left ventricle to drop. This situation can become so extreme that the direction of the shunt reverses from left-to-right to right-to-left. This is Eisenmenger syndrome and it can worsen with any situation that causes the pressure on the left of the circulation to decrease.

One such situation that drops the pressure in the left ventricle is a decrease in what’s called the systemic vascular resistance (SVR), which is something that happens during pregnancy. Essentially, SVR is how much resistance the blood vessels through the body put up against the blood that is trying to move through. To accommodate the increased blood volume of pregnancy, SVR decreases, thereby reducing the pressure that the left ventricle must exert to pump the blood. Usually, this is a good thing in pregnancy, but not in someone with structural heart disease so severe that it has led to Eisenmenger syndrome.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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