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Issue 12013

When Little Hearts Fail

Surgical staff members examine a Berlin Heart before inserting it into a patient.

Eden McCleskey

Photos by Paul Vincent Kuntz

Leanny Rodriguez was born seemingly healthy on July 1, 2008. Within three months, however, her heart was failing. She was on the list to receive a heart transplant, but she was rapidly running out of time.

Texas Children’s Heart Center specialists recommended that Leanny have a Berlin Heart implanted. This device — a ventricular assist device, or VAD — connects to the heart from outside the body and helps the patient’s heart circulate blood.

The Berlin Heart didn’t just buy Leanny more time, it improved her circulation and helped her grow stronger each day. She learned to crawl and stand up, and by the time she received a donor heart four months later, she was a better candidate for transplant surgery.

But the most remarkable part of Leanny’s story isn’t that she was able to thrive on a heart device. It’s that this option didn’t even exist a few years ago.

Elenterio Rodriguez and Suanny Vasquez proudly watch their daughter, Leanny, read a favorite book.

Elenterio Rodriguez and Suanny Vasquez proudly watch their daughter, Leanny, read a favorite book.

A pressing need for new expertise

When Charles D. Fraser, Jr., M.D., arrived at Texas Children’s Hospital in 1995 to take up his new position as chief of congenital heart surgery, he didn’t intend to become a leader in the use of pediatric VADs. He planned to build a surgical team that would provide the finest heart surgery for children with the best long-term outcomes.

“It’s a completely new day as compared to when I came to Texas Children’s,” said Fraser, now Texas Children’s surgeon-in-chief and chief of congenital heart surgery and Baylor College of Medicine professor of surgery.

“At that time, we did everything we could to avoid putting in a mechanical device, because with the only device option we had then, the patient had to be in the intensive care unit, oftentimes with the chest open, on a ventilator. It was a desperate operation to try and buy a few days, maybe on rare occasions a week or two.

“It was a terrible situation because everybody knew that once you started down this road of connecting the patient to a temporary machine, it was usually a matter of time before some fatal complication occurred. It felt like there was an anvil over your head the entire time.”

Fraser explained the frustration of knowing that mechanical support might be the only way to keep a child alive who was declining and in desperate need of a heart transplant, because even though pediatric heart transplantation is an effective and accepted management strategy for pediatric patients with end-stage heart failure, pediatric heart donations are rare. This means that many babies and children die while on the waiting list for a donor organ.

“The unfortunate truth is that some patients get to the point where we simply cannot repair their hearts,” Fraser said. “If you’re going to do transplants, you’re also going to face situations where a donor heart is unavailable for whatever reason, so an interest in VADs is essentially mandatory.”

Mechanical circulatory support — a brief history

The device that helped keep Leanny Rodriguez alive is just one of the latest iterations of the mechanical heart pump that scientists have been working to perfect since the middle of the 20th century.

In 1977, the National Heart, Lung and Blood Institute of the National Institutes of Health made funding available to companies who wanted to develop VADs, and by the mid-1990s four VADs were FDA-approved and successfully in use in selected adult centers. While this was a significant breakthrough for cardiac care in general, it had little impact on the pediatric population.

A key challenge was variability in physical size: pediatric patients range in size from 6-pound newborns to teenagers who are almost fully grown. Even so, a number of manufacturers of adult VADs were determined to make “spin-offs” for the smaller set. Just as they had done in the 1970s for the adult population, the National Heart, Lung and Blood Institute recognized that federally funded research support was needed. In 2004, they provided a multicenter award worth about $23 million to develop VADs for children.

“It doesn’t sound like a lot of money, and it’s really not if you think about how much has been expended in adult cardiac care, but it’s better than nothing,” Fraser said. “It’s a start.”

Mechanical hearts at Texas Children’s

Texas Children’s Heart Center’s experience with VADs began soon after Fraser arrived. Instead of waiting for device manufacturers to develop scaled-down versions for children, Fraser and his team began experimenting with existing technology. The early experiments made some significant headway, and several patients were successfully bridged to transplant, but still they lacked options with long-term durability.

“We were doing what we could, but there were many years where it didn’t seem like very much progress was being made,” Fraser said. “Thankfully Dr. Michael DeBakey maintained his interest. He was working with his longtime colleague Dr. George Noon and with NASA to develop what came to be known as the DeBakey Noon VAD, a small device that could be implanted inside the patient. In 2004, they developed a children’s version of that, and we had the chance to put the first one in.”

The device was implanted into a 6-year-old girl, who was supported for 11 days before she died.

“With our first patient, we were all just heartbroken when she didn’t survive,” said Texas Children’s Heart Center study coordinator and case manager Karol Arrington. “It was scary. You think, ‘Well, that can’t be the right thing to do’ if we lost this patient.”

“But you have to have courage as a surgeon, as someone who wants to make things better for patients. Thankfully, this little girl’s family had the courage to allow us to try it, and we learned so very much and advanced so much as a program.” As it turned out, the next big breakthrough for the program — and the start of a new era — was actually just months away.

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The Berlin Heart breakthrough

In Germany, engineers at the Berlin Heart Institute had developed an experimental pediatric ventricular assist device for older children, which they first used in 1990. By 1994, they offered a scaled-down version for infants. Over the years, the pump was used successfully in Germany and other parts of Europe but was not FDA-approved for use in the United States.

Early evidence suggested the Berlin Heart VAD could provide stable circulatory support for up to 421 days in children as small as 3 kilograms (6.6 pounds). Furthermore, the experience indicated that many subjects could be weaned from mechanical ventilation, discontinue sedation/paralysis and even become ambulatory — clinical benefits that help improve suitability for transplantation, but were generally considered unfeasible with other mechanical devices in children.

Between 2000 and 2004, two U.S. hospitals used the scaled-down heart pump in infants under the FDA’s Humanitarian Device Exemption (HDE) program for a “compassionate use.” The news of these uses piqued interest among pediatric heart surgeons around the country.

The Berlin Heart comes to Texas Children’s Hospital

In 2005, Fraser implanted the Berlin Heart into a 3-month-old baby who had been born with a failing heart. The baby did well after the surgery and soon went on to receive a donor heart. Encouraged by the successful implantation, Fraser accompanied Berlin Heart representatives to Washington, D.C., requesting that the FDA allow an investigational device exemption (IDE) study.

In January 2008, Texas Children’s Heart Center announced that Texas Children’s had been chosen to serve as the national lead center of a first-ever, prospective multicenter North American clinical trial on what is officially known as the Berlin Heart EXCOR® Pediatric Ventricular Assist Device. Fraser was chosen as the National Principal Investigator who would coordinate the multicenter IDE study on the safety and efficacy of the Berlin Heart VAD as a bridge to cardiac transplantation. Once the study began, investigators around the country were able to enroll patients, implant the device and keep children alive while they waited for heart transplantation.

At the end of the clinical trial, Fraser and his study colleagues took the Berlin Heart results before a 22-member FDA advisory panel comprising pediatric and adult cardiovascular experts. At the end of a challenging round of questions about the study evidence, the panel members voted unanimously to recommend to the FDA that they grant approval. On December 16, 2011, the EXCOR® device received FDA approval for use in U.S. children as a bridge to heart transplantation.

“One of the most exciting things to come out of the trial — other than, of course, the approval of the only device that can help infants and small children — is that device companies have taken notice of our work, and there will definitely be other big clinical trials in our future,” said Arrington, who acted as study coordinator for the Berlin Heart trial.

For Arrington and her colleagues at the Heart Center, it’s not about making a big name for themselves, it’s about contributing to a growing body of knowledge.

“I always say we’ve learned so much, and we’re so much better than we were when we started out,” she said. “We’ve made a difference by doing what we’ve done here because we can share that information with other centers. So they’re starting out where we are now, not where we were 10 years ago.”

Six devices, one common goal

Today, Texas Children’s Heart Center leads the country in the use of VADs with pediatric patients whose hearts are failing. The Heart Center uses six different devices — more than any other pediatric hospital in the country.

This breadth of activity is helping make Texas Children’s a center for the use and investigation of new artificial heart technologies. And this critical mass of experience, insight and scientific rigor will help Texas Children’s advance the science of mechanical circulatory support in pediatric patients.

In the meantime, however, the success stories are adding up, as Leanny Rodriguez and her family can attest. Today, Leanny is a healthy, energetic 4-year-old with a strong heart and an encouraging future.

See Leanny’s progress at texaschildrens.org/LeannyStory.

Six Circulatory Support Devices in Use at Texas Children’s Hospital

Figure-6c_Total

1. Syncardia Total Artificial Heart

Long-term usage: bridge to transplant

Used in cases in which both sides of the heart are failing, this internal device completely replaces the patient’s heart while the patient awaits a donor heart. In March 2012, the FDA approved a Humanitarian Use Device designation allowing the Total Artificial Heart to be used on a permanent basis for patients who are not eligible for transplant. The device can only be used on patients who are approximately normal adult size.

HeartMateII

2. Thoratec HeartMate II

Long-term usage: bridge to transplant; destination therapy (permanent)

The HeartMate II is an internal device used for temporary support in patients awaiting transplant and as a permanent device in transplant-ineligible patients. The HeartMate II is a ventricular assist device (VAD) supporting the left ventricle’s work as the “power stroke” that sends blood throughout the body. It is suitable for use on patients 13 to 14 years and older.

EXCOR-pump-30ml-side-view

3. Berlin Heart EXCOR

Long-term usage: bridge to transplant

The Berlin Heart EXCOR® is an external VAD specifically designed for use in pediatric patients — with different sizes available for patients ranging from infants weighing at least 6 pounds to adolescents. While patients must remain in the hospital, they have considerable mobility with the device. Results of a highly successful national study on its effectiveness were published August 9, 2012, in the New England Journal of Medicine; Texas Children’s Hospital, Surgeon-in-Chief Charles D. Fraser, Jr., M.D., was the principal investigator.

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4. Maquet RotaFlow

Short-term usage: bridge to recovery; bridge to decision

This paired console and centrifugal pump is used for cardiac bypass support. As an external device, it is easier to install and remove than a conventional VAD. It requires the patient to remain intubated and sedated, so it is only for short-term use — as when a patient is suffering from a temporary condition or when the diagnosis is unclear. There are no age/size requirements.

TandemHeart-Pump-MEDIUM

5. Cardiac Assist Tandem Heart

Short-term usage: bridge to recovery; bridge to decision

This external VAD can be connected to the patient via cannulae to the left atrium, or for a less invasive option with less risk of infection, it can be connected via the patient’s femoral artery. It is suitable for use in patients with a body weight of approximately 110 pounds — generally 14 to 15 years of age.

PVAD_LVAD

6. Thoratec Paracorporeal VAD

Long-term usage: bridge to transplant; bridge to recovery

The external Paracorporeal VAD is the only device approved by the FDA for right ventricle support — that is, helping the heart pump blood to the lungs for oxygenation. In some cases, Texas Children’s surgeons pair the Paracorporeal VAD with the HeartMate II to provide extra support for patients whose hearts are failing on both sides. It is suitable for use in patients 7 to 8 years and older.