Abraham Rudolph, MD, who recently turned 93, has watched his chosen corner of the medical profession — pediatric cardiology — grow from rudimentary beginnings into a robust, multivariate discipline. Yet while his name is known worldwide in pediatric cardiology circles, he entered cardiology more than 50 years ago only by happenstance.
Born in South Africa in 1924, Rudolph came to the United States in 1951 to train in cardiology by invitation of Charles Janeway, MD, then Physician-in-Chief at Boston Children’s Hospital. Concerned about providing for his wife and newborn daughter, he chose cardiology over hematology or neurology because it offered a salary; many other physician-training opportunities at the time were unpaid. That first year, as the hospital’s first cardiology fellow, he made $3,000 — thanks to a family donation.
He stayed on for nine years, becoming director of the cardiac catheterization laboratory. There he found his focus.
“I became more and more interested in the physiology of the circulation, particularly the problems surrounding infancy,” he said in a 1996 interview with the American Academy of Pediatrics. “At that time, there were relatively few places that were doing anything about infants with heart disease. Most of the emphasis was on older children.”
Troubled to see that most of the children were dying in early infancy, he was the first person to perform cardiac catheterizations on small babies in 1956. Following in the footsteps of another pioneer and maverick at Boston Children’s Hospital, Robert Gross, MD, he took this opportunity while the cardiology chief, Alexander Nadas, MD, was on sabbatical. “When he got back and saw that it could be done, he was terribly enthusiastic,” Rudolph recounted. “So we then really started to push for trying to understand more about infants.”
Foundational studies of the heart
In 1960, Rudolph moved to New York’s Albert Einstein College of Medicine, where he had an opportunity to build his own program, further his teaching skills and explore the physiology of congenital heart disease. In 1966, he moved to the University of California San Francisco to head up the pediatric cardiology program. The opportunity to be part of UCSF’s Cardiovascular Research Institute was a major lure.
“People were working together and very interested in helping one another. It was a marvelous environment in which to do research. And this is where I began to work actively, really actively, in fetal research.”
Working with live sheep models, he sought to uncover the mysterious workings of the human heart as it develops in utero and soon after birth. The abrupt change in heart physiology when babies take their first breath, called “transitional circulation,” was not well understood at the time.
Rudolph spearheaded studies to document this transition and was early to recognize its importance in congenital heart conditions. “He was one of the pioneers in mapping out normal perinatal physiology, and laid the groundwork for trying to understand much of congenital heart disease,” says cardiologist Wayne Tworetzky, MD, who decades later would arrive at USCF to train in Rudolph’s departments of pediatrics and pediatric cardiology.
Before fetal ultrasound became available, researchers would study fetal physiology by putting catheters in the uterus of pregnant sheep and performing a series of measurements under different clinical conditions. Rudolph and his team perfected a new technique to measure fetal blood flow.
As the story goes, Rudolph got the idea in a dentist’s waiting room, looking at a magazine ad for radioactive plastic microspheres. The 3M Corporation originally developed the microspheres to treat tumors, but this application had been abandoned for safety reasons.
Rudolph saw the microspheres’ potential to measure blood flow in fetal organs. Injected into the bloodstream, the effect was like pouring ink into a river and watching it disperse. This rapidly advanced knowledge about the fetal circulation, and the technique is still used today.
Another breakthrough was using prostaglandin and prostaglandin inhibitors to open and close the ductus arteriosus, a blood vessel connecting the pulmonary artery and aorta in utero. The blood vessel normally closes after birth, but remains patent (open) in many types of congenital heart disease, causing problems with blood flow. At the time, there was an epidemic of patent ductus arteriosus caused by outbreaks of rubella, prompting Rudolph to delve into studies of ductus physiology and pharmacology in fetal lambs. In other types of heart disease, the ductus needs to stay open to help the baby survive.
“Dr. Rudolph’s work is very important to our patients to this day,” says Tworetzky, now director of the Fetal Cardiology Program at Boston Children’s Hospital. “We’re still using the same medications.”
Rudolph was early to foresee the logical extension of his work: the use of interventions before birth to correct cardiac anatomy.
The birth of fetal cardiology
Tworetzky, who had also begun his medical training in South Africa, was fascinated with Rudolph’s foundational studies. When he started his residency at UCSF in 1993, Rudolph was still chief of cardiology.
“A lot of my research interests were sparked by what was going on there,” Tworetzky says. “I spent some time in the sheep lab, watching and participating in fetal surgical and interventional procedures, and then took it over to the human field.”
Tworetzky came to Boston Children’s in July 1999. In 2001, he was part of a team from Boston Children’s and Brigham and Women’s Hospital that performed the first successful fetal intervention for aortic stenosis to prevent hypoplastic left heart syndrome (HLHS). The team used a catheter-based procedure to open the baby’s blocked aortic heart valve in utero. This allowed the boy’s left ventricle to develop properly, and to date he has had few complications.
“When I started training, most babies were not diagnosed before birth,” Tworetzky says. “Today, we can plan the delivery of high risk patients to help preserve the health of the brain and heart prior to surgery. The next frontier is in the field of genetics: trying to understand why congenital heart disease develops in the first place and trying to solve those problems.”
Today, babies with congenital heart disease are surviving well into adulthood, thanks to work by Rudolph and other pioneers.
“We started off being able to offer almost nothing, and now are able to offer phenomenal success in treating these babies,” Rudolph has said. “So it’s been a wonderful time to see all this develop.”
Explore bostonchildrens.org/fetalheart for more information and resources for expectant parents.