In our series on congenital heart disease (CHD) here on the Pulse, we have discussed different types of CHD. Examples include transposition of the great arteries and Tetralogy of Fallot, both of which are cyanotic CHD, meaning that deoxygenated blood from the right side of the heart can get into the the left circulation, causing body tissues to be deprived of oxygen. Today’s topic is one of the acyanotic congenital heart conditions. The one that we’re covering is patent ductus arteriosus (PDA), but let’s begin with a story about one of the infectious diseases that can cause a PDA, rubella, one of the childhood viruses against which we have been vaccinating for more than a half century.
In the past, rubella has been called “German measles” and also “3-day measles”. It causes fever, rash, joint swelling, and lymph node swelling. The virus actually played a role in Apollo 13, a 1970 NASA mission, in which an explosion aboard the spacecraft’s service module prevented the astronauts from landing on the Moon and turned the mission into a struggle just to get the three men home alive. A few days before the mission launched in April, 1970, astronaut Charlie Duke –who later would fly to the Moon on Apollo 16– developed rubella, because there had been no vaccine during his childhood. Because Duke had been in contact with the Apollo 13 crew, and because Apollo 13 command module pilot (CMP), Ken Mattingly, had never had rubella, the backup CMP Jack Swigert, was swapped in to replace Mattingly just a couple of days before the launch. This was necessary, because, had he developed rubella, Mattingly would have been become ill in space, just when his two crewmates were exploring the surface of the Moon, ill enough to pose a danger to himself and crewmates, because he would not have been able to concentrate on his work.
Of course, NASA was worried about rubella developing in the crew of Apollo 13, because it would have increased the danger of the mission considerably. Astronauts would have been developing terrible fevers and other symptoms right around the time that two of them were making their way from lunar orbit down to the surface of the Moon. But health authorities in general were especially worried about women of reproductive age catching rubella virus. That’s because rubella is one of the TORCH infections, which stands for Toxoplasmosis, Others (such as syphilis, listeriosis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes simplex virus (HSV).
Rubella infections in the mother can lead to congenital rubella syndrome (CRS) in the newborn. CRS is a constellation of effects that we have discussed in other posts, but for today’s discussion the particular aspect of CRS to remember is that it includes a PDA, a parent ductus arteriosus. Recall that the ductus arteriosus is a blood vessel present in the fetus that connects the pulmonary artery with the aorta. This allows fetal blood to move from the high pressure pulmonary artery to the lower pressure aorta. The blood has received oxygen in the placenta and the fetal lungs are collapsed, so the blood doesn’t need to go through the lungs in fetal life, except for a tiny amount of blood to nourish the lungs themselves. Consequently, it’s greatly important for the ductus arteriosus to remain open —patent— up until the point of birth, channeling blood from the pulmonary artery directly into the aorta
In a normal term infant, the ductus arteriosus closes after birth, usually within a couple of days, sometimes sooner. It then transforms into a ligament. But there are situations that can cause the ductus arteriosus to remain patent, meaning that they cause a patent ductus arteriosus, a PDA. One such situation is maternal rubella. This can be prevented with vaccination prior to pregnancy. The rubella vaccine is a live attenuated vaccine that is given in combination with live attenuated vaccines for other viruses. Since these vaccines are live, they are not given during pregnancy, so make sure that your rubella vaccination is up to date before you get pregnant. Most women will have completed this vaccination series as young children.
Another cause of a PDA is preterm birth, which makes sense, since the ductus arteriosus knows what time it is, in a sense. It didn’t think it was time to close, because it wasn’t time for birth. Female babies are more likely than males to have a PDA and there are various genetic conditions running in families that are associated with PDA. A chromosomal abnormality called Turner syndrome also is associated with PDA. This is a syndrome in which the baby has one X chromosome and no other sex chromosome, meaning that it is genetically an XO female, rather than an XX female or an XY male. Also high altitude living increases the incidence of PDA.
PDA furthermore is associated with another blood vessel anomaly called coarctation of the aorta. This is a narrow area of the aorta, the big artery that carries blood from the left ventricle. The coarctation can be located, either upstream of the ductus arteriosus, or downstream from it, but in babies it tends to be upstream of the ductus, meaning upstream of the PDA. This means that less blood reaches the PDA than would reach it otherwise. Blood pressure is high in the arms, because the coarctation is downstream from where the arteries that supply the arms branch of the aorta, but the blood pressure is low in the legs.
Another thing that happens with PDA and coarctation of the aorta is that each deformity causes a murmur —a funny sound— that can be heard with a stethoscope placed over a particular spot. The murmur of a PDA is a very unusual kind of murmur, because you can hear it through both phases of the heartbeat cycle. You hear it stronger when the ventricles contract and then it gets softer when the ventricles relax, so it’s kind of like those annoying leaf blowers that the users rev up and down. This happens because blood is always moving through the PDA, since pressure in the aorta is higher than pressure in the pulmonary artery, not only when the ventricles contract (systole), but even when they relax (diastole).
If a PDA is allowed to persist, it can cause problems. High pressure on the aortic side of the circulation sends extra blood through the pulmonary artery and through the blood vessels of the lungs. This denies the systemic circulation of blood that was oxygenated anyway and didn’t need to go through the lungs again, but the extra volume in the lung vessels is bad in itself. It causes high blood pressure in the lungs (pulmonary hypertension). Over time, this changes the blood vessels of the lungs. They narrow and harden, increasing the pulmonary blood pressure still more. This higher pressure transmits to the pulmonary artery and the heart’s right atrium and when the pressure in those sites reaches a certain point, the shunting of blood between the right and left sides reverses direction. This happens especially if there’s another heart defect called an atrial septal defect, but it also can happen through the PDA. Known as Eisenmenger syndrome, it causes deoxygenated blood that has returned from body tissues to the right side of the heart to get into the aorta and mix with oxygenated blood. Thus blood traveling to the body tissues is low in oxygen.
As for treatment of PDA, if the newborn is preterm, it generally closes easily with medicines called NSAIDs, but this may not work for a term infant with a PDA, in which case the child will need a catheter procedure. This means that cardiologists extend a tube through a big vein in the leg, through the right side of the heart and into the pulmonary artery to the PDA. Using a camera and instruments passed through the tube, they then close the ductus arteriosus and withdraw the instruments.