A novel strategy to discover markers of heart attacks
Heart attacks are currently diagnosed based on blood tests that detect proteins that leak from injured heart muscle cells. These blood tests do not become positive until 4 to 6 hours after the onset of the heart attack. Since treatments for heart attacks are more effective the sooner they are given, a test that would diagnose a heart attack within minutes of its onset would be of great clinical value. However, given the unpredictable nature of heart attacks, it is logistically difficult to study patients in the very early stages of a heart attack.
As reported in the October 2008 issue of the Journal of Clinical Investigation, Fondation Leducq-supported researchers Drs. Robert Gerszten and Anthony Rosenzweig and their team decided to tackle this problem by studying a group of patients who have “planned” heart attacks. These patients have hypertrophic obstructive cardiomyopathy, a condition in which excess heart muscle tissue blocks the normal flow of blood out of the heart to the body, causing symptoms such as shortness of breath. One treatment available for this condition is alcohol septal ablation, a catheterization procedure in which a small amount of alcohol is injected into the artery supplying the excess tissue, thereby destroying it. This treatment reproduces what happens during a “spontaneous,” heart attack, with the corresponding symptoms of chest pain and electrocardiographic changes. In alcohol septal ablation, however, the precise timing of the onset of injury is known and blood samples could be available before and after the procedure.
The investigators hypothesized that blood levels of small molecules like biochemical metabolites might change sooner in a heart attack than large proteins from heart muscle. Using advanced mass spectrometry technology, the investigators were able to compare metabolic profiles in the blood before and after alcohol septal ablation. Sure enough, they were able to show that some metabolite levels change as early as10 minutes after the “planned” heart attack. They also studied patients undergoing routine catheterization without alcohol septal ablation or evidence of heart attack to eliminate the markers that were not specific for heart attacks. Finally, the metabolic markers were validated in patients presenting to the hospital with spontaneous heart attacks.
The investigators also tested the effects of these metabolites on rat cardiac muscle cells. They found that some metabolites improved how these cells adapted to hypoxia, or insufficient oxygen, while others worsened the response. Consequently, in addition to achieving the initial goal of discovering new markers to diagnose heart attacks, this research might lead to new treatments for heart attacks as well.
Dr. Anthony Rosenzweig is the American coordinator and Dr. Robert Gerszten is an associated member of Integrative Networks Regulating Cardiomyocyte Metabolism and Survival in Heart Failure and Insulin Resistance network. This research was also supported by the National Institutes of Health, Donald W. Reynolds Foundation, Heart Failure Society of America, and American Heart Assocation.
Click on the title to access the article in JCI: Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury