While engineered heart tissues can replicate muscle contraction and electrical activity in a dish, many aspects of heart disease can only adequately be captured in 3D. In a report published online yesterday by Nature Biomedical Engineering, researchers describe a scale model of a heart ventricle, built to replicate the chamber’s architecture, physiology and contractions. Cardiac researchers at Boston Children’s Hospital think it could help them find treatments for congenital heart diseases. …
New tools and technologies fueled biomedicine to great heights in 2017. Here are just a few of our top picks. All are great examples of research informing better care for children (and adults).
1. Gene therapy arrives
In 2017, gene therapy solidly shed the stigma of Jesse Gelsinger’s 1999 death with the development of safer protocols and delivery vectors. Though each disease must navigate its own technical and regulatory path to gene therapy, the number of clinical trials is mounting worldwide, with seven gene therapy trials now recruiting at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. In August, the first gene therapy won FDA approval: CAR T-cell therapy for pediatric acute lymphoblastic leukemia. …
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.” …
Tertiary care centers such as the Boston Children’s Hospital Heart Center have led the way in groundbreaking surgical innovations for years, pushing boundaries and correcting ever more complex abnormalities.
But innovation is also making a difference when it comes to more “common” procedures.
“We’re always trying to make the less complex procedures shorter and less invasive,” says Sitaram Emani, MD, director of the Complex Biventricular Repair Program at the Heart Center. “Making surgery and recovery less painful and disruptive for all of our patients is a priority.”
Emani and his fellow cardiac surgeons have pioneered a minimally-invasive “scope” approach, repairing a host of common problems normally requiring open-heart surgery — including ventricular septal defects, atrial septal defects, tetralogy of fallot, aortic valve defects, vascular rings and patent ductus arteriosis (PDA) — through small incisions.
The new method not only decreases pain discomfort, and scarring, but also gets patients in and out of the hospital in half the time. …
Jason Ayres, a family doctor in Alabama, was speechless as he held his adopted son Patrick’s heart in his hands. Well, a replica of his son’s heart — an exact replica, 3-D printed before the 3-year-old boy had lifesaving open-heart surgery.
Patrick was one of the first beneficiaries of 3-D printing technology at Boston Children’s Hospital, which last year helped open a new frontier in pediatric cardiac surgery. Patrick was born with numerous cardiac problems; in addition to double outlet right ventricle and a complete atrioventricular canal defect, his heart lay backwards in his chest.
“We knew early on that he’d need complex surgery to survive,” says Jason.
Finely detailed models of Patrick’s heart created by the Simulator Program at Boston Children’s gave surgeon Sitaram Emani, MD, at the Boston Children’s Heart Center an up-close-and-personal look at his complex cardiac anatomy. …
As survival has improved dramatically for children with even the most serious forms of heart disease, neurodevelopmental disabilities have been increasingly recognized. These can affect not only school performance, but also future employment, quality of life and social relationships.
“We’ve known for a while that children with congenital heart disease (CHD) have a higher risk of developmental delays,” says Amy Roberts, MD, a genetic cardiologist at the Boston Children’s Hospital Heart Center. “There are multiple hypotheses as to why that might be, and they’re not mutually exclusive.”
The side effects of surgery, such as oxygen deprivation during bypass, are commonly thought to be to blame. Others suspect problems with the in utero environment. But these factors are not the whole story.
“Even in studies that have measured every known risk factor, only one third of neurodevelopmental disabilities in children with CHD can be explained by factors related to the child’s heart disease, medical history or family factors,” notes Jane Newburger, MD, MPH, director of the Cardiac Neurodevelopment Program at Boston Children’s.
Perhaps there is a genetic component?
In a recent study published in Science, a team of researchers from seven hospitals (Boston Children’s, Brigham and Women’s Hospital, Children’s Hospital of Philadelphia, Columbia, Mount Sinai, Yale and University of California Los Angeles), examined the whole genomes of 1,213 patients with complex CHD, looking for genetic indicators that a child will have developmental delays alongside his or her CHD. …
Developing a child-centric approach to treating heart failure is no easy task. For one thing, the underlying causes of decreased cardiac function in children vastly differ from those in adults. While most adults with heart failure have suffered a heart attack, heart failure in children is more likely the result of congenital heart disease (CHD), or a structural defect present at birth that impairs heart function. And most therapies designed for adults haven’t proven equally effective in children.
Stimulating heart muscle cells to regenerate is one way cardiac researchers at Boston Children’s Hospital’s Translational Research Center hope to restore function to children’s ailing hearts. In this area, children actually have an advantage over adults: their young heart cells are better suited for regrowth.
Reporting in the April 1 Science Translational Medicine, Brian Polizzotti, PhD, and Bernhard Kuhn, MD, demonstrate that not only does the drug neuregulin trigger heart cell regeneration and improve overall heart function in newborn mice, but its effects are most potent for humans within the first six months of life. …
Advances in medical care sometimes present challenges on the flipside. Case in point: Over the past three decades, progressive developments in pediatric cardiac care have allowed many babies born with congenital heart disease (CHD) to survive. And longevity continues to improve. This progress, however, has brought hospitals a burgeoning patient population with tremendously complex and varied disease states.
About 90 percent of children born with heart defects now survive to adulthood, thanks to diagnostic, interventional and critical care improvements. Specifically, one-year survival has improved from 67.4 percent from 1979 to 1993, to 82.5 percent from 1994 to 2005.
“The number of pediatric hospital admissions for congenital heart disease is increasing relatively slowly, but as the patients live longer and develop common adult medical issues, adult patient admissions are increasing much more rapidly,” says Alexander Opotowsky, MD, MPH, cardiologist at the Boston Adult Congenital Heart (BACH) and Pulmonary Hypertension services at Boston Children’s Hospital. …
When the first fetal cardiac surgery was performed at Children’s Hospital Boston in 2001 – entering Jack Miller’s heart through his mother’s abdomen and opening blood flow – the world was stunned. But more than 60 years earlier, another operation was equally game-changing.
It was 1938, a time before heart-lung bypass, when ether and chloroform were only starting to be supplanted by more controllable anesthetics, when tinkering with the heart or even opening the chest were seen as dangerous and taboo.
Tinkering was what Robert E. Gross, chief surgical resident at The Children’s Hospital, liked to do. He was interested in a congenital heart condition known as patent ductus arteriosus, a passageway between the pulmonary artery and the aorta that’s supposed to close after birth — but doesn’t. …