Research and Clinical Trials

Sacubitril/valsartan (Entresto) combines 2 medicines that help control sodium and fluid levels in the body and relax and open the blood vessels. Doctors have used it to treat heart failure in adults for several years. Seattle Children’s took part in a multicenter study testing Entresto for pediatric heart failure. Results of this study led the U.S. Food and Drug Administration (FDA) to fast-track approval of the drug for use in children.

A biomarker is a molecule found in the body that is a sign of a process or condition. When the heart begins to fail, it makes more of the biomarker B-type natriuretic peptides (BNPs). For years, doctors have used a test to measure BNPs in adults with heart problems. This is a quick, inexpensive way to find out if a person’s heart is failing. Our research showed that this test also works in children. Now we are studying if a patient’s BNP levels can predict how they will respond to heart failure treatments.

Many children with heart problems also have obstructive sleep apnea, iron and vitamin deficiencies and other health problems. Dr. Yuk Law and his colleagues are studying if these conditions play a part in heart failure or worsen it — and if treatment for them can improve results for children with heart failure.

Heart surgery can injure the heart, kidneys and other organs by stopping blood from flowing to them for a short time. Law and his colleagues are studying if a method called remote ischemic preconditioning can reduce this injury. It involves restricting blood flow to a leg or other body part right before surgery. This sends the organs a signal that blood flow is about to stop and gives them a chance to prepare. The investigators have seen some degree of kidney protection and are considering the next step.

In children who have a heart transplant, organ rejection is fairly common. It happens if the child’s immune system attacks and injures their new heart. It’s important to detect rejection early because this helps us treat it. Our researchers are studying ways to improve early detection. These include using unique echocardiography measurements, biomarkers and an app to track heart-rate changes that could signal rejection.

We are also working with immunologists to better understand why some transplant patients never have organ rejection while other patients do.

The Fontan procedure is surgery to send blue (oxygen-poor) blood from the body to the lungs without going through the right ventricle of the heart. This may be done for children whose heart valves or ventricles did not form normally. Our researchers are creating a registry and collecting tissue samples to study so we can learn how and why heart failure happens in some patients who had this surgery.

Dr. Jack Salerno is working to prevent deaths from sudden, unexpected cardiac arrest. Salerno partners with the Nick of Time Foundation to do heart screenings in high schools. These tests help doctors and families know if a child might have a heart problem and needs to see a heart doctor.

Salerno also uses the screenings to gather details about children’s hearts. The details will help him understand more about factors that put children at risk of sudden cardiac death and find ways to prevent cardiac arrest. Cardiomyopathy is 1 of several heart conditions that increases risk for sudden cardiac arrest and death. It can also lead to heart failure.

We are part of a nationwide effort to develop safer, more effective ventricular assist devices (VADs). VADs are mechanical pumps that help patients’ hearts while they wait for transplant. They are also used with patients whose hearts need to rest.

Seattle Children’s is 1 of a small number of hospitals selected to participate in the Pumps for Kids, Infants and Neonates (PumpKIN) trial. It tests smaller VADs that may be more efficient than current devices.

The use of VADs to support children with severe heart disease has increased greatly over the past 10 years. But there are no agreed-upon guidelines about the right time to implant a VAD in a child. Dr. Joshua Friedland-Little is working to better understand when the benefits of VAD support outweigh the risks. He led a group of national experts that surveyed children’s hospitals in the Advanced Cardiac Therapies Improving Outcomes Network. The goal was to understand differences in how doctors select VAD patients. The researchers also reviewed data that could guide doctors in choosing the right time for a VAD.

At Seattle Children’s, we are committed to making careful, individualized decisions about when patients will benefit from VAD support. This is key to making sure each child with advanced heart failure has the best chance at either recovering heart function or staying safe through a heart transplant.

When a child’s heart or lungs fail, doctors may use mechanical support called extracorporeal membrane oxygenation (ECMO) to help them survive. But putting patients on ECMO is tricky. The machine must quickly be connected to veins in a patient’s neck to keep blood flowing during heart failure or cardiac arrest. Dr. Michael McMullan’s team developed an easy, inexpensive way for surgery teams to practice this procedure.

McMullan and his colleagues used synthetic skin — the same kind used for special effects in movies — and plastic tubes to create a simulated “neck.” The tubes are filled with pressurized liquid to make it seem like blood is flowing through them. Users can change the pressure to mimic cardiac arrest and other complications. The system is easy to build and costs just a few dollars. It helps teams measure how long it takes them to set up ECMO and how well they handle complications.

Seattle Children’s has some of the nation’s best outcomes for patients on ECMO. The simulation systems developed here are being used around the world to help keep patients safe.

Dr. Michael Portman is studying why many children have learning delays and other neurological issues after being on life support or heart bypass machines. Portman’s research group is investigating solutions to prevent these effects, such as changing heart surgeries, testing hormone and nutrition supplements and improving support machines.

An atrial septal defect (ASD) is a congenital hole between the top 2 chambers of the heart (atria). Often, children with ASD need the hole closed with a device placed through a small catheter. Seattle Children’s is studying a new device called the reSept ASD Occluder. This is the first ASD closure device designed to dissolve in the body over 20 to 24 months. It leaves behind 2 cloth patches that close the hole in the heart without leaving any metal. Seattle Children’s is 1 of 15 hospitals around the country that can offer this device as part of the ASCENT ASD research study.

In patent ductus arteriosus (PDA), a blood vessel near the heart stays open instead of closing within a few days after birth, like it typically does. As part of the landmark trial called the PIVOTAL trial, we are studying the use of transcatheter devices to close PDAs in babies born early and how this treatment affects their health and development. PIVOTAL stands for Percutaneous Intervention Versus Observational Trial of Arterial Ductus in Low-Weight Infants. The study is funded by the National Institutes of Health. Seattle Children’s is 1 of 25 study sites around the country.

There are currently no stents designed or approved for use in children who need a narrow blood vessel opened up. The new Minima stent is designed specifically to treat blood vessel narrowing in children. It is small enough to fit a child’s vessels. Then, as the child grows, doctors can expand the stent up to adult sizes. Seattle Children’s is 1 of 7 hospitals around the country participating in an important study, called the Growth Trial, to research this approach.

The Alterra adaptive prestent lets doctors implant a new pulmonary valve in the heart without the need for open-heart surgery. It was designed and approved for use in both children and adults. Seattle Children’s took part in the early clinical trial that led to full approval of the device by the U.S. Food and Drug Administration (FDA). Now, we are participating in a follow-up trial to keep studying the results of the Alterra prestent in children who’ve received it.

Led by Dr. Brian Soriano, the Heart Center’s Core Lab works with and supports researchers, helping them understand how new treatments can affect heart health. The Core Lab is one of a handful of labs with the technology and expertise to analyze large numbers of images such as ultrasounds and cardiac MRI (magnetic resonance imaging) scans. The lab collects and analyzes these images for studies led by Seattle Children’s and by many other hospitals and institutions.

For example, the lab supports studies by Dr. Michael Portman on inflammatory diseases that can damage the heart, like Kawasaki disease and multisystem inflammatory syndrome in children (MIS-C). The Core Lab checks these images to see if the diseases cause any heart changes.

The Core Lab also does echocardiograms as part of large national studies. Some examples include studies looking at:

• Organ rejection in children who have had a heart transplant
• Safety and efficacy of cardiac catheterization devices
• Heart muscle disease in patients with Duchenne muscular dystrophy or Pompe disease

Our heart doctors (cardiologists) use an ultrasound process called strain imaging. It gives doctors a clearer, more detailed view of subtle changes in heart function. This technology helps us understand how heart problems and treatments affect the heart muscle. Our researchers are using strain imaging to help monitor cardiac function in children receiving treatment for cancer.

Babies born with complex heart disease need early diagnosis and timely treatment. But in our region (Washington, Alaska, Idaho, Montana and Wyoming), many babies are born at hospitals that do not have direct access to pediatric cardiology services. Led by Dr. Matthew Studer, our team is helping to make sure these babies receive high-quality echocardiograms like they would get at a specialized children’s hospital. We have created and are studying a safety-net system so babies across the region can get the echocardiograms they need from providers who usually scan adult hearts.

Dr. Christina Greene is a surgeon-scientist who studies what makes tissues of the heart grow or not grow. She established a cardiac tissue bank at Seattle Children’s and uses leading-edge techniques to study the underlying genetic reasons why some babies develop congenital heart disease. By understanding the genetic and protein pathways, she hopes to one day help treat congenital heart conditions without the need for surgery.

Researchers in Dr. Vishal Nigam’s lab work across disciplines to improve outcomes for infants and children who need cardiac surgery. These efforts involve people from a range of fields, including engineers, molecular biologists and immunologists. Their topics of study include protecting the brain from injury due to cardiac surgery, reducing inflammation that happens after surgery and developing better devices.

Dr. Michael Portman and others in his research group are working on several projects related to children’s heart health. A main focus is Kawasaki disease. Funded by the National Institutes of Health (NIH), the team is studying genetic factors that affect or predict who is susceptible to Kawasaki disease and how patients will respond to treatment. They are also working to develop a specific blood test to diagnose the condition.

In the area of COVID-19, Dr. Portman’s lab is collaborating with the Pediatric Heart Network on the COVID MUSIC study to collect data from patients with multisystem inflammatory syndrome in children (MIS-C) and another study with the NIH Pediatric Heart Network looking at outcomes for patients with myocarditis linked to COVID-19.

Their other work includes research to protect children’s brains by learning how brain injury happens with heart-lung bypass during heart surgery and a project to develop a surgical heart valve that expands as a child grows.

Dr. Mark Majesky studies how stem cells in the arterial adventitia turn into special cells that rebuild the heart and blood vessels after injury. Researchers in Majesky's lab also study how to replace or restore (regenerate) complex organs without fibrotic scars. Their work uses lessons learned from the African spiny mouse, a mammal that can regrow tissue, like skin and skeletal muscle. This could lead to new therapies that repair or regenerate children’s hearts without surgery or a heart transplant. 

Several years ago, researchers discovered that the drug propranolol can shrink hemangiomas in babies, the most common childhood tumors. It blocks the blood vessels that feed tumors. Dr. Mark Majesky teamed up with Dr. Jonathan Perkins to study how propranolol works. This taught the researchers key lessons about the growth of infantile hemangiomas. They followed this with research that showed lymph vessels play an important role in congenital heart disease.

Dr. Lisa Maves studies zebrafish for clues to improve how we diagnose and treat heart defects. DNA mutations in genes important for heart development often cause heart defects. But for many patients with heart defects, we are not able to pinpoint the genetic causes. Zebrafish are ideal research subjects for understanding heart defects because they carry many of the same genes as humans. Also, scientists can easily observe how their heart develops because they have transparent embryos that grow outside the mother.

The Maves Lab is using CRISPR genome editing to engineer genetic mutations in zebrafish. They are testing the roles certain genes and mutations may play in developmental heart malformations. Recently, their efforts have found several new genes needed for heart development. This research, which uses Seattle Children’s Research Institute’s Zebrafish Aquatics Facility, could be a step toward better genetic testing for heart problems.

Congenital heart disease and other cardiac problems change how the heart produces energy (metabolism). This can weaken the heart, leading to heart failure. Dr. Aaron Olson is trying to pinpoint the causes of these energy changes. The team in his lab is pursuing strategies to overcome this problem with the goal of developing new heart failure therapies.