3D models of infant hearts

Saving the Youngest of the Young

Advances in Congenital Heart Disease Research Are Helping Kids Thrive

In 1949 when the National Heart Institute—not yet the National Heart, Lung, and Blood Institute—began awarding research grants in pediatric cardiovascular disease, among the first was to a surgeon named Alfred Blalock, M.D. With his colleagues at Johns Hopkins University—Helen Taussig, a pediatric cardiologist, and Vivien Thomas, a talented laboratory technician—Blalock had invented a procedure that was saving the lives of so-called “blue babies.”  It used a shunt to bypass the obstructions that had restricted blood flow to the babies’ lungs—and for those who got it, life changed dramatically: for the first time, they could engage in normal, even fun, activities.      

The grant—for $11,000—helped Blalock continue his landmark research, and it was a big step, said Gail Pearson, M.D., Sc.D., associate director of NHLBI’s Division of Cardiovascular Sciences.

Back then congenital heart disease was still largely a mystery, and the grant was a recognition of how important it was to both understand it better—and help do something about it. “So from the beginning, we were supporting congenital heart disease research,” Pearson said.

Today NHLBI awards some $122 million annually in research grants to help learn more about these life-threatening diseases and how to treat them. The support has helped fuel a striking fivefold decline in congenital heart disease-related infant deaths since those first efforts and has inspired new discoveries. “Every week we’re gaining a more sophisticated understanding of the complex molecular and translational network by which a normal heart and an abnormal heart forms,” Pearson said. 

Vintage polaroid of a doctor in a white coat standing beside a young boy
Tom Kaminski, then 7, poses with one of the NIH doctors, Sherman Souther, M.D., who helped repair his heart in 1969. 

That funding has dovetailed with breathtaking advances not only in cardiovascular research and pediatric patient care—the advent of specialized intensive care units and antibiotic drugs, for example—but also in surgical and imaging techniques that are making it easier for surgeons to operate on these tiniest of humans.

In June, Pearson and other doctors gathered to talk about—and marvel at—some of these advances. The occasion was the return to NIH of a former patient, Tom Kaminski of New Jersey, who had had cardiac surgery for his own heart defect 50 years ago. Kaminski had tetralogy of Fallot, and the late Andrew “Glenn” Morrow, M.D., a cardiac surgeon who happened to train under Blalock, led the NIH team that repaired his defect.

Today NIH no longer does cardiac surgery—it ended the program in the early 1980s, mainly because so many other medical institutions were doing the very operations NIH had helped pioneer, explained David Henderson, M.D., the Clinical Center’s deputy director for Clinical Care. And because NIH “is all about scientific opportunity—looking at what’s coming,” he said, it shifted its focus.

What’s emerging now in the research it is supporting, said Richard Childs, clinical director of NHLBI’s Division of Intramural Research (DIR), is awe-inspiring. “It’s just phenomenal to see the advances and how quickly they are occurring,” he said.

Consider: It was in only in 1953 when the first heart-lung machine was invented, allowing surgeons to do open-heart operations while blood bypassed the heart and lung. But because those machines were too primitive to use on small babies, said Richard Jonas, chief of cardiac surgery at Children’s National Health System in Washington, D.C., researchers in the late 1970s developed a breakthrough procedure that cooled babies and stopped their circulation in order to operate. “But you needed to be a good surgeon to get a good outcome because you had to do the surgery in less than an hour,” he said. It wasn’t until the 1980s that the first heart-lung machines for infants were developed and being used on a wide scale.

A doctor in a white coat shakes hands with a man standing next to him.
Kaminski greeted Douglas Rosing, M.D., a cardiologist who was at NIH in 1969 when Kaminski had his surgery.

Now, not only can infants get highly complex surgeries, they can get them with the critical aid of imaging techniques that were not even a thought when Kaminski was a child. In 1969, for example, doctors were still diagnosing congenital heart defects mainly through the use of X-rays and catheterizations that involved cutting into a vein. “Now, they don’t even do cutdowns—they use needle sticks,” said Douglas Rosing, head of the Cardiology Consultation Service in the Cardiovascular Branch of DIR, who was at NHLBI when Kaminski had his surgery. Rosing co-authored a follow-up study of other tetralogy of Fallot patients who had repairs around that time.

But in an exciting shift, Pearson noted, many children don’t have to have these invasive catheterizations at all because of the panoply of noninvasive diagnostic techniques—primarily cardiac ultrasound and cardiac MRI—that now are available. Those techniques have even made it possible to diagnose congenital heart disease as early as the first trimester of a pregnancy.

And that’s just the start of the sea change going on in the field. Now, the researchers said, doctors are using 3-D representations of an infant or child’s heart to learn much of what they need to know before they even operate. Laura Olivieri, M.D., an NHLBI research grantee and practicing pediatric cardiologist specializing in imaging at Children’s National Health System in Washington, D.C., is one who’s leading the way.  She and her team are using programming to convert these 3-D images to digital, virtual, and printed models. And given the large spectrum of congenital heart disease, having access to those models is hugely helpful. They help guide the surgeon, she said, and also help in explaining to families what will happen and what the treatment plan will be for their particular child.

“Before, we’d walk into a room with parents and their new baby and use this little diagram to get our point across,” she said. “Now we’re at the point where we can actually show parents—and in some cases, children—exactly what we’re talking about with a personalized 3D heart model.” 

A woman holds up a model of a heart used to help doctors during surgery, while another woman looks on.
With NHLBI’s Gail Pearson looking on, Laura Olivieri, M.D., of Children’s National Health System, showed off a 3-D model of a heart now being used in cardiac imaging. She has developed models of infant and children’s hearts, too.

Even more exciting, she said, is the ongoing research, supported by NHLBI, to try to make personalized 3-D patient-specific grafts that can be implanted in the heart—then grow with the infants. This is the ultimate in personalized medicine, Olivieri said, and it could make it easier for surgeons to make repairs, and also “help make those repairs more durable and reduce the number of repeat surgeries.”      

While NHLBI is funding all kinds of fascinating studies like this, Pearson said, it is in learning more the genetic and genomic contributions to congenital heart disease that currently holds the greatest promise for helping people live successful normal lives. “We now know, for example, that there may be as many as 8 to 10 genetic mutations that give rise to tetralogy of Fallot—and they have implications for how people [with the condition] do.”

“There’s still a lot to learn, and it takes time and money,” she said.

The establishment in 2001 of the Pediatric Heart Network, which she led, has greatly helped in that process, Pearson noted. “There was not a nimble, sustainable infrastructure for multiple groups coming together on clinical trials.” Now that has changed—and researchers and doctors are sharing information that has had a powerful ripple effect. “We have trained hundreds of young researchers on how to do clinical trials in these fragile kids and have learned a great deal about therapies that work and don’t work.”

In the future, Pearson said, researchers will be looking at how social determinants of health may affect congenital heart disease and its outcomes—and also how to raise even more awareness about the disease.    

“People think of birth defects as something you can only see on the outside, and most children with congenital heart disease look like every other child,” Pearson said. But with more awareness about this important cause of birth defects, she added, more progress can be made.

Already, Richard Childs noted, advances in non-surgical methods like catheterizations are paving the way for procedures that one day could be especially beneficial for the youngest of the young. NHLBI researchers “are now doing things that could only be done through open heart surgery in the past,” he said. “When they tell you what they’re going to do, your jaw just falls open.

“It’s a really exciting time in cardiovascular research,” he went on, “and we’re really, really fortunate to have the talent we have here.”