Troponins at Admission and at Three Hours Allow MI Diagnosis

Marlene Busko

December 29, 2011

December 28, 2011 (Hamburg, Germany) — Among patients with suspected acute coronary syndrome (ACS), troponin measurement at three hours after admission--measured using a highly sensitive troponin I (hsTnI) assay or a sensitive contemporary troponin I (cTnI) assay--may help rule out MI, according to a new study. The study also suggests that change in troponin levels from admission to three hours may help establish an MI diagnosis [1].

"In my opinion there are only two very clear, but simple and extremely relevant, messages for the clinician," senior author Dr Stefan Blankenberg (University Heart Center, Hamburg, Germany) told heartwire . "The first is, after three hours you can [almost] 100% exclude myocardial infarction if the sensitive troponin is not above the 99th percentile, [while troponins at] six hours and 12 hours don't provide any additional information."

"The second simple and clear message is if you have an increase of 200% [in three hours], in particular in individuals having very minor, very little troponin elevation at baseline, then you are 96% sure that this is due to acute myocardial infarction and not any other reason . . . such as renal insufficiency or heart failure."

The possible introduction of highly sensitive troponin tests in the US is the subject of "hot debate" because of concerns about potential over-diagnosis of MI, according to Blankenberg. But, he noted, the tests are part of European guidelines, which clearly say the three-hour value is enough. "It is very important that we observe [for] the increase . . . within three hours."

The study is published in the December 28, 2011 issue of the Journal of the American Medical Association.

Is the Acute Chest Pain Due to an MI?

The group enrolled 1818 consecutive patients who presented with acute chest pain in the emergency departments of three German hospitals from 2007 to 2008. Blood was drawn at admission, and three and six hours later, to determine troponin levels plus levels of 10 other biomarkers, including classic necrosis markers, such as creatinine kinase, and newer markers, such as heart-type fatty-acid-binding protein and copeptin.

Troponin was measured using a sensitive, contemporary assay (Architect STAT cTnI assay, Abbott Diagnostics, Libertyville, IL) and a highly sensitive assay (Architect STAT hsTnI assay, Abbott Diagnostics). A total of 413 patients (22.7%) had a final discharge diagnosis of acute MI.

The sensitivity and negative predictive value of the hsTnI assay were higher than the cTnI assay at admission; however, the negative predictive value of both assays was 99.4% at three hours. For patients with detectable troponin on admission and a 250% increase in troponin at three hours, the probability of acute MI was 95.8%.

Ability of Troponin to Diagnose or Exclude Acute MI (at a Diagnostic Cut-Off >99th Percentile)

End point Sensitivity, % NPV, % PPV, %
hsTnI on admission 82.3 94.7 75.1
hsTnI at 3 h 98.2 99.4 95.8*
cTnI on admission 79.4 94.0 80.9
cTnI at 3 h 98.2 99.4 96.1*

*Troponin >99th percentile at admission plus relative change in troponin >250% from zero to three hours. cTnI=contemporary troponin I assay hsTnI=highly sensitive troponin I assay NPV=negative predictive value PPV=positive predictive value

Compared with the other evaluated biomarkers, troponin measured using either assay was superior in ruling in or ruling out acute MI.

What Does This Mean? Other Voices

"First and foremost, this study tells us that, like other high-sensitivity troponin assays, the Abbott Architect STAT hsTnI will identify more patients who are having acute MI at the time of presentation than a standard assay would," Dr Richard Body (University of Manchester, UK), who wasn't involved in the study, told heartwire in an email. However, he added, using the conventional cut-off, the assay cannot be used to rule out a diagnosis of acute MI at presentation, so serial testing remains necessary. "Even at three hours, the sensitivity of 98.2% means that 1.8% of infarctions (and possibly up to 4.1%, given the lower bound of the 95% confidence interval) would be missed, a risk that is likely to be unacceptable given the important medical and medicolegal implications," he noted.

The negative predictive value was 100% among 26% of patients who had no detectable troponin at admission measured using the hsTnI assay, Body added, which means that clinicians could potentially immediately rule out acute MI in a quarter of presenting patients, but this needs to be confirmed in further research.

Dr Marc Sabatine (Harvard Medical School, Boston, MA), who was not involved with the study, told heartwire in an interview that there are three major take-home points. "First, the combination of the troponin measurement at admission and just three hours later actually provides an excellent amount of information. Second, if you detect the values going up in time, then that is a pretty strong indication that the person is in fact having a myocardial infarction. Third, the more sensitive assay is going to be especially good in people who present very soon after symptom onset."

In an email to heartwire, Dr James Januzzi (Harvard Medical School), who was also not involved in the study, commented that the findings "further solidify the primacy of troponin--and particularly the hsTns--for the diagnostic evaluation of patients with symptoms suggestive of ACS, and suggests that most patients can be rapidly evaluated in a confident fashion within three hours."

The study's implications, he added, include:

  • Immeasurably low hsTn concentrations at presentation can rule out acute MI in one blood draw.

  • Measurable troponin concentrations <99th percentile meant that a three-hour blood draw was all they needed to rule in or rule out MI.

  • Elevated troponin at first blood draw but no change by three hours indicates it's probably not an MI, but is worth following up on, as the patient still is at increased risk.

  • Elevated troponin at first blood draw that rises rapidly indicates an acute MI.

"The bottom line is that while hsTn detects more MIs earlier and with more confidence than cTn, when low--even with hsTn--you still haven't excluded unstable angina, so you can know an MI isn't present but the patient may still merit relatively aggressive care," Januzzi noted. "It is important to recognize that these assays are not tests for myocardial infarction . . . they are exceptionally sensitive tests for myocardial necrosis."

Blankenberg reports receiving lecture fees from and consulting for Brahms Thermo Fisher and receiving lecture fees from Abbott Diagnostics and Siemens. Other author disclosures are listed in the article. Body reports conducting research under collaborative agreements with Roche, Siemens, Randox, and Alere; receiving travel and accommodation reimbursement in relation to conference presentations from Roche and Randox; and accepting honoraria for speaking from Bristol-Myers Squibb. Januzzi discloses receiving research grants from and consulting for Roche Diagnostics, Siemens Diagnostics, and Critical Diagnostics; and receiving fees for speaking from Roche Diagnostics and Siemens Diagnostics. Sabatine is chair of the TIMI Study Group, which has received research grant support from Abbott, Beckman Coulter, Nanosphere, Ortho Clinical Diagnostics, Roche, Siemens, and Singulex.

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