title: Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury.
abstract: Emerging metabolomic tools have created the opportunity to establish metabolic signatures of myocardial injury. We 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 myocardial infarction (PMI). Serial blood samples were obtained before and at various intervals after PMI, with patients undergoing elective diagnostic coronary angiography and patients with spontaneous myocardial infarction (SMI) serving as negative and positive controls, respectively. We identified changes in circulating levels of metabolites participating in pyrimidine metabolism, the tricarboxylic acid cycle and its upstream contributors, and the pentose phosphate pathway. Alterations in levels of multiple metabolites were detected as early as 10 minutes after PMI in an initial derivation group and were validated in a second, independent group of PMI patients. A PMI-derived metabolic signature consisting of aconitic acid, hypoxanthine, trimethylamine N-oxide, and threonine differentiated patients with SMI from those undergoing diagnostic coronary angiography with high accuracy, and coronary sinus sampling distinguished cardiac-derived from peripheral metabolic changes. Our results identify a role for metabolic profiling in the early detection of myocardial injury and suggest that similar approaches may be used for detection or prediction of other disease states.
authors.affiliation: Cardiology Division and Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Lewis
authors.forename: Ru
authors.initials: R
authors.lastname: Wei
authors.forename: Emerson
authors.initials: E
authors.lastname: Liu
authors.forename: Elaine
authors.initials: E
authors.lastname: Yang
authors.forename: Xu
authors.initials: X
authors.lastname: Shi
authors.forename: Maryann
authors.initials: M
authors.lastname: Martinovic
authors.forename: Laurie
authors.initials: L
authors.lastname: Farrell
authors.forename: Aarti
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authors.lastname: Asnani
authors.forename: Marcoli
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authors.lastname: Cyrille
authors.forename: Arvind
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authors.forename: Oded
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authors.lastname: Shaham
authors.forename: Gabriel
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authors.lastname: Berriz
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Lowry
authors.forename: Igor F
authors.initials: IF
authors.lastname: Palacios
authors.forename: Murat
authors.initials: M
authors.lastname: Taşan
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Roth
authors.forename: Jiangyong
authors.initials: J
authors.lastname: Min
authors.forename: Christian
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authors.lastname: Baumgartner
authors.forename: Hasmik
authors.initials: H
authors.lastname: Keshishian
authors.forename: Terri
authors.initials: T
authors.lastname: Addona
authors.forename: Vamsi K
authors.initials: VK
authors.lastname: Mootha
authors.forename: Anthony
authors.initials: A
authors.lastname: Rosenzweig
authors.forename: Steven A
authors.initials: SA
authors.lastname: Carr
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fifer
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.forename: Robert E
authors.initials: RE
authors.lastname: Gerszten