Boston, MA - In an analysis of serial blood samples from 36 patients undergoing alcohol septal ablation for hypertrophic obstructive cardiomyopathy (HOCM), which causes necrosis that mimics an MI, elevated levels of an array of infarction-related metabolites could be detected within 10 minutes of myocardial injury [1]. The finding provides proof of principle for the future development of assays that could distinguish patients with evolving MI from those with noncardiac chest pain far earlier than managed by available blood tests, according to the authors of a study published online September 2, 2008 in the Journal of Clinical Investigation.

"We're hoping that ultimately we will have a biomarker signature within four to six minutes after the onset of the infarction," principal author Dr Robert E Gerszten (Massachusetts General Hospital, Boston) told heartwire. It may even be possible to obtain such a signature for reversible ischemia in patients with unstable angina, he added, "something that's far more subtle than we believe can be measured with troponins."

The report, with first author Dr Gregory D Lewis (Massachusetts General Hospital), is scheduled for the journal's October issue.

Based on prior reports suggesting that the necrosis induced by alcohol septal ablation in HOCM "faithfully reproduces spontaneous myocardial infarction," the group screened serial blood samples from 36 patients undergoing that procedure for 210 metabolites considered possible markers of myocardial injury. The blood had been obtained from the circulation through femoral venous catheters.

Do we see the same changes in the spontaneous heart attack that we see in the planned heart attack? The answer is yes, but there are many other clinical hurdles.

They also confirmed in this group that the induced infarctions actually resembled spontaneous MI in terms of the time course and degree of associated creatine kinase (CK), CK-MB, and troponin elevations.

Using mass spectrometry, the group identified significant increases in seven metabolites in peripheral blood sampled 10 minutes after induced infarction in 20 of the HOCM patients, the "derivation cohort." In the remaining 16 patients, the "validation cohort," they observed similar and temporally consistent elevations in six of the same seven metabolites.

"Metabolic changes included products of purine and pyrimidine catabolism . . . as well as several amino acids," the group writes. "Of note, the alterations in these metabolites were seen when no significant rises in the clinically available biomarkers, CK-MB and troponin T, were detectable in the plasma."

The process was repeated at 60 minutes, at which time the derivation cohort showed elevations in 13 metabolites, including the seven observed before and of which 10 were similarly elevated in the validation cohort.

Diagnostic cath in a control cohort of 16 patients without acute myocardial ischemia was associated with rises in three of the metabolites that had been elevated in the HOCM patients at either 10 or 60 minutes; the three molecules were then excluded from further analysis.

In 13 of the HOCM patients, serial samples of blood obtained from the coronary sinus showed the same metabolite elevations found in peripheral blood, and in some cases elevations in the coronary sinus blood occurred earlier. "The pattern of early enrichment in the coronary sinus with later detection in the periphery supports the cardiac origin of these observed metabolic changes," the group writes.

Four of the metabolites—hypoxanthine, aconitic acid, trimethylamine N-oxide, and threonine—had been significantly elevated at 60, 120, and 240 minutes after alcohol-induced infarction. Those four metabolites showed similar patterns of concentrations in a cohort of 12 patients undergoing emergency cardiac catheterization for acute ST-segment-elevation MI.

But the group didn't see the same patterns in a control cohort of nine patients undergoing elective, diagnostic cardiac cath for CV disease who did not have acute myocardial ischemia.

"Do we see the same changes in the spontaneous heart attack that we see in the planned heart attack? The answer is yes, but there are many other clinical hurdles as we begin to get our mind around how these could be used clinically," according to Gerszten. "How specific are they is the first one that comes to mind. . . . We will see how they validate in large cohorts of patients."