'Big' Hearts Offer Hope for Marfan Syndrome
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Eleven-year-old Haley Dostalik has a big heart – in more ways than one.
More specifically, she has a larger-than-normal aortic root because she suffers from Marfan syndrome, a rare condition that could take her life.
Marfan syndrome is a genetic disorder that affects connective tissue, which is the kind of tissue found in the heart’s aorta.
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It often causes abnormal swelling of the aorta, which can eventually lead to an aneurysm, and sometimes, sudden death.
Experts estimate that about 90 percent of Marfan patients will require life-saving surgery to repair an aneurysm at some point in their lifetime. But Hayley’s parents don’t want her to be part of that startling statistic.
So, twice a year for the past three years, Haley, her parents and her brother have piled into the family car to make the six-hour drive from their home in Urbandale, Iowa, to the St. Louis Children’s Hospital in Missouri -- one of 27 sites involved in a clinical trial to test a promising new drug for the treatment of aortic growth in Marfan patients, called losartan.
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The trial aims to compare the effects of losartan to another drug that is frequently prescribed called atenolol.
Atenolol is a beta blocker used to treat patients with high blood pressure, but doctors also prescribe it for Marfan patients because lowering blood pressure can help slow the growth of the aorta. But this typically only delays the inevitable and most patients still require surgery later in life.
Losartan, on the other hand, lowers the activity of a protein transforming growth factor beta, which researchers believe may be the cause behind the physical effects of Marfan. This may mean that losartan not only has the potential to delay the onset of an aneurysm, but prevent it completely.
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“This would be very important, because it would eliminate the need for risky heart surgery,” said Dr. Josephine Grima, vice president of research for the National Marfan Foundation.
“Many lives could be saved,” agreed Dr. Ronald Lacro, assistant professor of pediatrics at Harvard Medical School and one of the principal investigators of the trial.
Haley’s parents decided to enroll her in the trial after attending a national Marfan conference three years ago and hearing about the successful effects losartan had had on Marfan mice.
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“The excitement in the room was amazing,” Haley’s mother, Kari Dostalik, said. “We just knew right away that if Haley qualified, this was something we wanted to be a part of to help the Marfan community.”
Haley, then age 7, had no objections and more importantly, neither did her doctors.
“Haley didn’t even bat an eyelash,” Dosalik said. “She’s grown up knowing all about Marfan and being an advocate for herself. Our cardiologist had no qualms either. He wanted to see the results of the trial as well.”
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In experiments with mice that had Marfan, losartan actually caused the size their aortas to normalize.
“The experiments with mice showed remarkable improvement,” said Dr. Ronald Lacro, assistant professor of pediatrics at Harvard Medical School and one of the principal investigators of the trial. “We’re hoping the results in mice can be translated to humans.”
The trial is being conducted by the Pediatric Heart Network and funded by the Heart Lung and Blood Institute and with support from the National Marfan Foundation. Recruitment for the trial began in 2007 and will end in January 2011. So far, 580 patients have been enrolled, but researchers hope to recruit 24 more in the coming months to add up to a total of 604 participants.
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Over the course of the trial, Haley’s aortic measurements remained stable, besides one small spike at the end, which doctors believe was brought on by 4 inch growth spurt.
Other characteristics of Marfan patients can include:
- a protruding or concave chest;
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- dislocation of one or both eye lenses;
- curvature of the spine;
- stretch marks, even without weight gain;
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- restrictive lung disease.
Some patients are mildly affected and have only a few of these characteristics, according to the Foundation's website; while others are severely affected.
However, just because you have one or any of these symptoms doesn't necessarily mean you have the disease. The only way to accurately diagnose Marfan's is with a multi-system clinical exam.
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The Dostaliks’ participation in the trial ended in June of this year. Now, with the trial only three years away from completion, they are eagerly awaiting to see the results, which will be published in 2014. In the meantime, Haley continues to take atenolol, rather than losartan.
“We’re waiting for the results,” Dostalik explained. “She’s doing well on atenolol. We decided to see what the trial does show and go from there.”
According to Lacro, this is the right course of action.
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“Because we have many years of experience using atenolol, and many studies have shown it can be beneficial, and because we don’t know if losartan is effective yet in humans, I recommend children stay on beta blockers,” he said.
However, losartan is FDA-approved, and therefore available to people who want to take the drug, but do not want to participate the trial. It has been used for years to lower blood pressure and is generally safe and well-tolerated by most people.
Potential side effects include effects on liver and kidney function, but this is rare, according to Lacro. Still, he said, the trial is necessary to determine how safe and effective losartan actually is for young people with Marfan.
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“We hope through this trial we can find better treatment and prolong lives,” Lacro said. “The main goal is to improve the lives of people living with Marfan.”
For those who are interested in participating in the trial, Grima recommends visiting one of the enrollment sites, or getting information from the National Marfan Foundation website or the Pediatric Heart Network. The National Marfan
Foundation is helping provide financial assistance for patients who cannot afford some of the expenses involved in participating in the trial.