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Friday, December 19, 2008
When the clinical team gathered in the cardiac catheterization lab at Massachusetts General Hospital on a recent Tuesday morning, its objective was to treat the patient for a heart condition that was causing her shortness of breath, dizziness and chest pain. To alleviate these symptoms the patient was about to undergo a procedure that is – in essence – a planned heart attack.
This unique procedure is also allowing researchers a chance to see metabolic activity that occurs in the blood after the onset of a heart attack. Researchers hope that the changes they have identified will lead to a blood test that would confirm within minutes, instead of hours, if a patient is having a heart attack, allowing a more rapid treatment that could limit damage to heart muscle.
"The blood test that is in current clinical use for heart attacks can not confirm if a person has had one for nearly four to six hours. Because our treatments for heart attacks are most effective in the first hours after symptoms occur, these newly identified markers could help patients sooner," says Robert Gerszten, MD, a cardiologist with the Massachusetts General Hospital Heart Center and the study's senior author.
The "Planned" Heart Attack
Dr. Gerszten, was considering the possibilities of a new advanced mass spectrometry technology to analyze the metabolic changes in blood after a heart attack. However, he had not figured out what the research model would look like given the unpredictable nature of heart attacks. "One day, I was talking with Dr. Michael Fifer in the cardiac ICU, and he was telling me about a patient who was coming in for a planned heart attack. It was then that the idea sort of clicked for us both," said Gerszten.
Michael Fifer, MD, director of the cardiac catheterization laboratory, was referring to alcohol septal ablation, an innovative therapy for the treatment of hypertrophic obstructive cardiomyopathy (HCM). HCM occurs when a segment of thickened heart muscle blocks the flow of blood out of the left ventricle to the body. When the patient's symptoms can not be controlled with medication, alcohol septal ablation can be an option.
Introduced in London 13 years ago, Dr. Fifer brought the technique to MGH in 1999. During the procedure, a catheter is threaded through the patient's femoral artery into the aorta. An interventional cardiologist then injects a small amount of alcohol into the thickened heart muscle at the location of the blocked blood flow. The process destroys the excess tissue in a scenario that mimics the damage that occurs during a heart attack.
Thanks to the possibilities offered by septal alcohol ablation, Gerszten and his team were able to take blood samples before and after patients received this procedure, enabling study participants to act as their own experimental controls.
The researchers analyzed blood samples from 36 patients taken before and at several points after the ablation. Using the advanced mass spectrometry system that can assess hundred of metabolites in as a little as 10 minutes, researchers were able to identify several metabolites that significantly changed directly following the ablation process. Some of the changes occurred within 10 minutes of the procedure, in great contrast to the currently available blood markers for heart attack that take several hours to change.
"We are very excited by these findings and hope this new technology will lead to innovations in the diagnosis of heart attacks," said Gerszten, who is also a senior associate member of the Broad Institute of Harvard and MIT.
In addition, the team studied the metabolites' effects on cultured animal heart cells to see if they were harmful of beneficial to the cells. One of the metabolites increased cell death, with two others had a protective quality.
"We think this could open the road for new therapies in the future," said Gerszten. "Someday we may be able to reverse the damage caused by a heart attack using a 'cocktail' made up of these protective metabolites."
The research was published this fall in the Journal of Clinical Investigation and was funded by grants from the National Institutes of Health, the Donald W. Reynolds Foundation, and the Leducq Foundation. The study's lead author is Gregory Lewis, MD, of the Mass General Hospital Heart Center.
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