Heart procedure saves young kids’ lives but over time blood circulation weakens. Research at Cincinnati Children’s could help improve and extend their lives.

by Tom O’Neill

David Munro is a fairly unlikely first-time patient at Cincinnati Children’s. For one thing, he’s 23. For another, he lives in Nebraska. 

However, his recent arrival illustrates our emerging prominence as a national leader in pediatric and adult congenital heart care. It also reflects the innovative research that is fueling better evaluation strategies for long-term patients like Munro who have been treated with Fontan procedures. 

The Fontan procedure is an ingenuous yet imperfect treatment that helps children born with only one heart ventricle. This complex form of bypass surgery redirects pulmonary arteries so that blood can flow directly to the lungs without being driven by heart contractions, thus relieving strain on the single ventricle. 

fontan before after heartpedia illustrations.

Patients typically undergo Fontan surgery between the ages of 2 and 5 as part of a three-stage series of operations. The procedure is life-saving but by adolescence, weak functional cardiac capacity begins to betray the patient’s organs. The declining function can occur so gradually that it frequently escapes early detection. 

“The average 11-year-old with Fontan looks pretty close to their peers,” says Bryan Goldstein, MD, of the Heart Institute. “The average 18-year-old with Fontan, you could pick them out of a lineup if they all ran around a track.”

But by then, many have aged out of pediatric care. Approximately 20 to 30 percent of Fontan patients eventually receive a heart transplant. However, many die on the waiting list due to lack of available organs.

Innovative evaluations shed new light on organ function

Our Fontan team has transitioned its focus from excitement about survival to long-term chronic management. This requires a broad-er approach to the impact of Fontan circulation. Cincinnati Children’s new evaluation methods are a national model. 

“The key is idealizing the circulation, anatomically and physiologically, and screening for problems with the kidneys, liver, neurodevelopmental function, bone growth, endocrine, all these things,” Goldstein explains.

From his bed in the Cardiac Intensive Care Unit, Munro’s body is extremely frail but his words are not. “My hope, long-term,” he says, “is to get things fixed, essentially.”

Mother, Susan Keisler-Munro: “Path forward, right?”

Son: “Yeah.”

Mother with slight laugh: “He looks better in person than he does on paper.”

The journey to Cincinnati Children’s

The family spent two years trying to find the best experts in long-term Fontan care. Their cardiologists in Omaha ultimately referred them to Cincinnati Children’s. 

“There are things being done here that, you know, potentially aren’t being done elsewhere,” Keisler-Munro says. “There’s a serious concentration of brainpower here.”

That brainpower is driving first-of-its-kind research into earlier interventions and far more extensive assessments for Fontan management. The goal: faster identification of when and how declining circulation affects physical activity and organ function. Then, employ better medications and care methods to slow the rate of deterioration.

In trying to improve Munro’s health to the point where he might be eligible for a transplant, Goldstein implanted covered stents into the Fontan circulation, where thrombus had formed, in an effort to improve blood flow. 

He also dilated the shrunken Fontan conduit back to its original diameter. It had narrowed significantly over time, contributing to Munro’s poor organ function.

If Munro becomes eligible for a transplant, the procedure would be considered high-risk, a risk Munro and his mother say they are willing to take.

Losing patients to adult care, and getting them back

Cincinnati Children’s has greatly expanded its reach through our Adult Congenital Heart Disease program, directed by Gruschen Veldtman, MD

“One surprising thing is that anyone with a serious heart condition can get lost to care. It’s not uncommon,” he says. “But increasingly, we’re reaching out to cardiologists to ensure that doesn’t happen.”

Behind every advancement in Fontan care, is research. 

In a study published in September 2016 in the Journal of the American Heart Association, researchers examined 60 adolescent and young-adult Fontan patients to tease out the relationship between vascular function and clinical outcomes. 

This had not been established previously. One key difference: instead of measuring blood flow while subjects are lying down, they measured it during cardiopulmonary exercise. Teen Fontan patients often face a Catch-22: the poorer their circulation, the less they exercise, and the weaker the heart structure becomes. 

The team included first-author Goldstein and six colleagues at Cincinnati Children’s, including Andrew Redington, MD, Executive Co-Director of the Heart Institute. They found that the poorest vascular measures were associated with the poorest functional measures, potentially identifying new avenues of treatment. Also, other organs were impacted.

“You can look at the brain, lungs, kidneys, liver, musculature, and see changes,” Veldtman says.

Squeezing and relaxing, the two-way street of cardiac function

The Fontan procedure fails over time in a number of different ways. One way is that the heart does not squeeze well, so it introduces less blood circulation through the lungs. The lungs too are implicated, commonly with abnormalities in pulmonary artery resistance. Often though, the single ventricle has trouble refilling during the relaxation phase of the heartbeat. This results in decreased output.

“Diastolic dysfunction cannot be identified well non-invasively,” says Goldstein, Associate Director of the Cardiac Catheterization Laboratory. “The right ventricle wasn’t designed to pump against high pressure and resistance.”

fontan angiograms.

In a paper published in the June 2016 issue of Heart, senior author Goldstein and four Cincinnati Children’s colleagues revealed that rapid-volume expansion was an important method of identifying “occult” diastolic dysfunction in Fontan patients.

Researchers were able to identify a large cohort of Fontan patients with high end diastolic pressure (diastolic dysfunction) that was only present with ventricular stress testing. This suggests that the longer duration of Fontan circulation, the worse the diastolic function.

In Munro’s case, “we found substantial obstruction in his Fontan conduit due to thrombosis,” says Goldstein, who often collaborates—both clinically and academically—with Veldtman.

Veldtman Goldstein.

Drs. Gruschen Veldtman, left, and Bryan Goldstein, are key physician/researchers in the Adolescent and Adult Congenital Heart Disease program, which was recently accredited by the Adult Congenital Heart Association. Veldtman directs the program.

“Collaboration is utterly vital to our success,” Veldtman says. Much like their teamwork in research, Goldstein and Veldtman applied their shared expertise to Munro’s evaluation and care.

That reputation for collaboration was not lost on Keisler-Munro. Or her son. 

“They’re certainly encouraging. They wanted to see me in-person,” he says. “So I don’t look like the walking wounded, you know.”

A heart transplant, even if a donor were available, is a tenuous option. 

“In the past, people who have seen David were a bit gun-shy about considering him for a transplant,” she says, “or even other major interventions. As we’ve gone down this journey, a transplant has been presented as the best alternative for an extended lifespan, but it’s been so difficult.”

In a systematic review of 28 studies, involving 6,707 patients, senior author Veldtman noted that assessing mortality rates is a challenge because outcome measures vary greatly. The findings were published in January, 2017, in Heart

Of 697 late deaths, the five most common causes were heart/Fontan failure (22 percent), arrhythmia (16 percent), respiratory failure (15 percent), renal disease (12 percent) and thrombosis/bleeding (10 percent). 

Long-term cancer care a template for Fontan patients

Researchers know far more now than they did just a decade or so ago. In 2005, scientists saw what Veldtman calls a “startling” increase in rates of liver cancer in Fontan patients. “That started a revolution of thinking differently,” he says. “That it was about more than just the heart.” 

Whether patients like Munro ever become eligible for heart transplants, Goldstein and Veldtman emphasize that their long-term care should look more like the care of a cancer survivor, where active organ surveillance is the norm, and not the exception.

“Every Fontan patient deserves that,” Goldstein says.

Munro and his mother agree.