Lisa Yue had a "mother's instinct" that something was wrong when her seemingly healthy 11-month-old, Bryan, just didn't get better after catching a cold in 1999.
"He wouldn't eat and he was lethargic -- he was like a rag doll," said Yue, a marketing director for Sony Pictures who was living in Hong Kong at the time.
But Yue's doctors dismissed her concerns and never recommended screening on Bryan, despite a family history. Her husband, Eddie Yu, had hypertrophic cardiomyopathy (HCM), a rare disease that affects the heart muscle.
"The pediatrician said everything was fine -- young kids don't get cardiomyopathy," said Yue, now 47 and living in Cresskill, N.J. "A month later Bryan was dead -- just weeks from his first birthday."
Bryan died in her arms en route to the hospital. Then, in 2001, tragedy struck again when the couple returned to the United States. Their son Kevin also died of cardiac arrest from cardiomyopathy waiting for a heart transplant at just 9 months old.
Searching for answers, Yue founded the Children's Cardiomyopathy Foundation (CCF), which over the last decade has contributed more than $2.1 million to research and treatment initiatives.
"I became obsessed, trying to find out what happened," said Yue. "At first, CCF started out as a tribute to my two sons. Every parent, when they lose a child, wants to justify their child's existence. But I was also hoping I could help other families with the knowledge gained."
And now, a North American population-based study, inspired by Yue's loss, has identified risk factors that explain why some children do well on medication while others die. Researchers analyzed more than 1,000 children with the disease from 98 medical centers in Canada and the United States from 1990 to 2009.
The study, published today in the medical journal Lancet, found that the worst outcomes for those diagnosed with HCM, were children less than a year old or those with metabolic disorders, malformation syndromes or a mixed form of the disease in combination with dilated or restrictive cardiomyopathy.
The risk of death jumped when two or more of these risk factors were present: decreased weight, congestive heart failure and abnormal electrocardiograms.
Such information might have saved Bryan or Kevin Yu, had cardiologists been able to identify their risk factors earlier in the course of the disease and listed them for a heart transplant sooner.
“”It gives us greater lead time if we can identify right at diagnosis who will be dead in the first two years and get them listed earlier so they have a better chance of getting a heart transplant. -- Dr. Steven E. Lipshultz, University of Miami
The study provides a risk calculator that cardiologists can use to evaluate which children should be considered for heart transplant after diagnosis.
These guidelines for risk "can really make a difference," said lead researcher Dr. Steven E. Lipshultz, professor of pediatrics and director of the Batchelor Children's Research Center at the University of Miami. "This has the potential to save lives."
Lipshultz, who founded the Pediatric Cardiomyopathy Registry, sits on the CFF's medical advisory board. The study was funded by the National Heart, Lung, and Blood Institute and a grant from CCF.
"It gives us greater lead time if we can identify right at diagnosis who will be dead in the first two years and get them listed earlier so they have a better chance of getting a heart transplant," he said.
HCM damages the muscles of the heart and its ability to pump effectively. It can be inherited, as in the Yu family, or acquired through a viral infection or cancer chemotherapy in children.
For doctors, predicting the outcomes of children with HCM is challenging because its presentation is so variable.
The success rate for early childhood heart transplants is "quite good," Lipshultz said. "On average, they can live 15 years or more before they need another one. And of those, 90 percent or more go home alive."
Heather Riley of Abilene, Texas, wonders if her son Casen might have been saved when he was diagnosed with HCM in 2009 and put on medications.
Born 10 weeks premature, Casen was diagnosed with Noonan syndrome and HCM. He died at 6 months old.
"He had two of the risk factors," said Riley, 31. "He was underweight and had a malformation syndrome. As parents, we were clueless and didn't know anything about cardiomyopathy. This study might have helped change the course of things."
Riley and her husband Casey, who runs a home improvement business, found resources from Yue's foundation to cope with their son's illness and later, after the baby's death, turned to CCF for support.
Each year they hold a fundraiser, "Casen's Crew," and donate $10,000 to $15,000 to CCF. They have since had another boy, Carter Casen.
"People live every day with cardiomyopathy and do fine," she said. "But some children, like Casen, are so much worse. I think the study will help others."
As for Yue, she now juggles her full-time foundation work with being a mother. She now has four children, aged 5 to 13, two of them adopted (the oldest from China and the youngest from Korea). Her two biological daughters are healthy, but continue to be medically screened, she said.
Doctors could never find a genetic mutation in their father, who takes medication, so genetic testing on the children has been impossible.
Yue's Tenafly-based foundation has grown from a one-woman operation to a staff of five.
"It's my personality. I just don't give up," said Yue.
"I realized CCF was so much bigger than just about Bryan and Kevin," she said. "It's about the kids who are diagnosed today and those who will be diagnosed tomorrow. CCF is their advocate, and together with other families, we will save more lives and improve outcomes for children living with cardiomyopathy."
In addition to advocating for families and legislation, CCF founded the first-ever tissue and blood sample repository and is also holding its third scientific conference in 2014.
"It's a testament to her strength," researcher Lipshultz said of Yue's success. "Most families want to do something, but their interest wanes. She is impatient and driven and she wants a cure yesterday."