JCI: New process could shorten biomarker wait time for MI diagnosis
A heart attack can be detected within 10 minutes of its occurrence using a new panel of biomarkers, according to study published Sept. 2 online in the Journal of Clinical Investigation.
Robert Gerszten, MD, and colleagues from the Massachusetts General Hospital in Charlestown, Mass., said that they have discovered several small molecules, detected in blood samples, which can reliably differentiate an MI from other cardiac events.
Researchers applied a mass spectrometry–based metabolite profiling platform to 36 patients undergoing alcohol septal ablation treatment for hypertrophic obstructive cardiomyopathy, a human model of planned MI.
The process, if it is validated in larger studies, will markedly shorten the time before biomarkers can be used to confirm a MI, which is currently about four hours, according to investigators.
Because blood was available before and after the procedure, the researchers said that the patients were their own controls, and the researchers looked for molecules that differed significantly from baseline at various times after the procedure.
In the initial group of patients, they found seven metabolites that were significantly changed (with a notional significance of P<0.005), the authors wrote.
To validate the finding, the researchers turned to a second group of 16 patients undergoing the procedure and found significant changes for six of the seven metabolites.
The magnitude and direction of the changes were highly correlated, they wrote. However, the investigators said that three of the seven metabolites also changed significantly during cardiac catheterization and were excluded from further analysis.
The remaining four compounds—hypoxanthine, aconitic acid, trimethylamine N-oxide and threonine—were then tested against patients presenting with a spontaneous MI.
The panel distinguished MI patients from the controls undergoing cardiac catheterization and the area under the receiver operating characteristic curve (AUC) was 0.88, demonstrating both sensitivity and specificity.
The researchers noted that hypoxanthine may not always originate in cardiac muscle, but even with it removed, the AUC for the remaining three compounds was 0.83.
The changes in the four compounds could be detected as quickly as 10 minutes after the planned MI procedure, and remained significant at 60, 120 and 240 minutes, Gerszten and colleagues said.
The authors cautioned that the work needs further testing in larger cohorts for confirmation, to see how the panel performs in the presence of co-morbid conditions and to see what happens in different subgroups based on sex and race.
The four-compound panel will also need to be evaluated in MI patients presenting soon after onset to evaluate its clinical performance, according to researchers.
According to Gerszten and colleagues, the finding makes use of new ‘metabolomic’ techniques that allow researchers to take “snapshots of a whole organism's metabolic status.” Such ‘metabolic signatures’ may aid in diagnosis, or have a range of other uses, they said, including predicting disease, acting as a reference for return to normality, or aiding in development of new therapeutics.
Robert Gerszten, MD, and colleagues from the Massachusetts General Hospital in Charlestown, Mass., said that they have discovered several small molecules, detected in blood samples, which can reliably differentiate an MI from other cardiac events.
Researchers applied a mass spectrometry–based metabolite profiling platform to 36 patients undergoing alcohol septal ablation treatment for hypertrophic obstructive cardiomyopathy, a human model of planned MI.
The process, if it is validated in larger studies, will markedly shorten the time before biomarkers can be used to confirm a MI, which is currently about four hours, according to investigators.
Because blood was available before and after the procedure, the researchers said that the patients were their own controls, and the researchers looked for molecules that differed significantly from baseline at various times after the procedure.
In the initial group of patients, they found seven metabolites that were significantly changed (with a notional significance of P<0.005), the authors wrote.
To validate the finding, the researchers turned to a second group of 16 patients undergoing the procedure and found significant changes for six of the seven metabolites.
The magnitude and direction of the changes were highly correlated, they wrote. However, the investigators said that three of the seven metabolites also changed significantly during cardiac catheterization and were excluded from further analysis.
The remaining four compounds—hypoxanthine, aconitic acid, trimethylamine N-oxide and threonine—were then tested against patients presenting with a spontaneous MI.
The panel distinguished MI patients from the controls undergoing cardiac catheterization and the area under the receiver operating characteristic curve (AUC) was 0.88, demonstrating both sensitivity and specificity.
The researchers noted that hypoxanthine may not always originate in cardiac muscle, but even with it removed, the AUC for the remaining three compounds was 0.83.
The changes in the four compounds could be detected as quickly as 10 minutes after the planned MI procedure, and remained significant at 60, 120 and 240 minutes, Gerszten and colleagues said.
The authors cautioned that the work needs further testing in larger cohorts for confirmation, to see how the panel performs in the presence of co-morbid conditions and to see what happens in different subgroups based on sex and race.
The four-compound panel will also need to be evaluated in MI patients presenting soon after onset to evaluate its clinical performance, according to researchers.
According to Gerszten and colleagues, the finding makes use of new ‘metabolomic’ techniques that allow researchers to take “snapshots of a whole organism's metabolic status.” Such ‘metabolic signatures’ may aid in diagnosis, or have a range of other uses, they said, including predicting disease, acting as a reference for return to normality, or aiding in development of new therapeutics.