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 expert for Sony 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 and sometimes fatal disease that affects the heart muscle.
"They said everything was fine -- young kids don't get cardiomyopathy," said Yue, now 47 and living in Tenafly, N.J. "A month later he was dead."
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 -- just weeks away from his first birthday.
Searching for answers, Yue founded theChildren'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, it started out as a tribute to my two sons. Every parent, when they lose a child, wants to justify their 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 of sudden cardiac arrest. 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 found them donor hearts sooner.
The study also provides a risk calculator that cardiologists can use to evaluate which children should be considered for heart transplant immediately after diagnosis.
These guidelines for risk "can really make a difference," said lead researcher Dr. Stephen E. Lipschultz, professor of pediatrics and director of the Batchelor Children's Research Center at the University of Miami. "This has the potential to save lives." http://pediatrics.med.miami.edu/batchelor
Lipschultz, who founded the 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 on the list early and a better chance of getting" a heart transplant, he said.
Each year, an estimated 2,000 Americans under the age of 25 die of hypertrophic cardiomyopathy, one of four forms of the disease, according to the U.S. Centers for Disease Control and Prevention.
HCM is a leading cause of death in young people, damaging 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.
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," Lipschultz 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 [doctors] didn't know anything about that. This might have helped change the course of things."
Riley found resources from Yue's foundation to cope with her son's illness and later, after her son's death, turned to them for support. Each year she holds a fundraiser, "Casen's Crew," and donates $10,000 to $15,000 to CCF. She and her husband 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 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 this was so much bigger than just for Bryan and Kevin. These other families need an organization like CCF to work together to solve problems and save more lives and get better outcome for kids who have the disease."
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 convention in 2014.
"It's a testament to her strength," researcher Lipschultz 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."