Testing Both Troponin Types at Once May Sharpen Early MI Rule-Out

May 02, 2018

Performing high-sensitivity assays for both cardiac troponin types (hs-TnI and hs-TnT) from a single early blood draw may allow "very early and safe" rule-out of acute myocardial infarction (MI) better than can conventional single-troponin tests, conclude researchers from a new study.

But such combined-troponin testing didn't improve MI diagnosis in the analysis, based on a primary cohort of 2225 patients suspected of having MI and a similar 2537-patient validation cohort, both drawn from other studies.

The group explored several different decision strategies for pairing the two early biomarker concentrations in conjunction with the clinical assessment, achieving about the same results each way.

"The major benefit of combining cardiac troponin T and I is the increase in number of patients eligible for safe rule-out after one single blood draw at presentation, from approximately 10% to 40% of patients," several authors of the study wrote to theheart.org | Medscape Cardiology in response to emailed questions.

"This will cause a decrease in the number of patients who need consecutive blood draws for cardiac troponin tests," which "may have profound consequences for clinical practice, since it could help overcome unnecessary resource use, overcrowding of the emergency department, and anxiety among patients."

The respondents were lead authors Noreen van der Linden, MD, PhD, Maastricht University Medical Center, the Netherlands, and Karin S. Wildi, MD, University Hospital Basel, Switzerland, and The Prince Charles Hospital, Brisbane, Australia, along with senior author, Christian Mueller, MD, University Hospital Basel. Their report was published April 24 in Circulation.

They pointed out that patients in the two cohorts entered their international studies consecutively and so are likely "representative of the overall patient population presenting to an emergency department with symptoms suggestive of chest pain."

Potential Challenges

Used individually, the high-sensitivity troponin assays have shown great safety in MI rule-out algorithms, "but few patients can be ruled out within an hour," observed James A. de Lemos, MD, University of Texas Southwestern Medical Center, Dallas, in an interview. Many more can safely go home within 3 hours after serial testing.

The dual-troponin strategy of the current analysis, he said, "is conceptually interesting, like much of what this group does," he said, agreeing that it has potential for expanding the proportion of patients in whom MI can be safely ruled out very early.

The strategy could potentially be considered in Europe, which is "about 6 or 7 years ahead of the US with high-sensitivity troponin," noted de Lemos, who was not involved in the study. But here in the United States, "We have to get our heads around one high-sensitivity troponin before we start thinking about using two of them in the same patient."

He pointed to some issues that will arise wherever the dual-troponin strategy is adopted.

For example, what if the two troponin levels are discordant? "It's easy if they're both low," he said. "But how do we interpret it when it looks like it might be a heart attack with troponin T and might not be with troponin I?"

Also, "What to do with for patients you don't think have an MI but have abnormal values? That's a difficult situation with a regular troponin assay, it's worse with a high-sensitivity troponin, and it would probably be worse with two high-sensitivity assays," de Lemos said.

"Those sorts of things would have to be worked out because you can't just ignore that information."

Two Cohorts, Two Troponins

The primary cohort consisted of 398 patients with a final diagnosis of acute MI and 1827 without an acute MI; the corresponding numbers in the validation cohort were 408 and 2129, respectively.

The hs-TnI (Architect, Abbott) and hs-TnT (Elecsys, Roche) assays were performed from a single blood draw at presentation.

Treatment of each patient was at the discretion of attending physicians, and as the group noted, "The adjudicated final diagnosis in both cohorts was made according to the most recent guidelines."

Combining the two assays wasn't consistently better at diagnosing MI than was either troponin alone, but it performed much better for MI rule-out, the authors concluded.

Up to 24% of the patients met criteria for MI rule-out based on the guidelines, depending on the assay and other criteria. But 34% to 41% were ruled out by pairing hs-TnI and hs-TnT, depending on the method for combining the concentration numbers, which included adding them, multiplying them, and an algorithm using cutoff values for both markers.

Table. Negative and Positive Predictive Values for Early MI Rule-Out and Rule-In Combining hs-TnI and hs-TnT

Combination Method Original Cohort, n = 2225 (%) Validation Cohort, n = 2537 (%)
NPV    
  Sum 100 99.6
  Product 100 99.4
  Algorithm 99.9 99.5
PPV    
  Sum 76.9 87.5
  Product 76.8 87.2
  Algorithm 74.4 84.0
NPV = negative predictive value (hs-TnI and hs-TnT level sum, rule out at < 9 ng/L; product, rule out at < 18 ng2/L2; algorithm, rule out at hs-TnI < 4 ng/L and hs-TnT < 9 ng/L); PPV = positive predictive value (hs-TnI and hs-TnT level sum, rule in at > 99 ng/L; product, rule in at > 1608 ng2/L2; algorithm, rule in at hs-TnI ≥ 54 ng/L or hs-TnT ≥ 57 ng/L).

 

"It is quite practical to implement this dual testing in the emergency department," as laboratories generally have both kinds of assay, said van der Linden, Wildi, and Mueller.

Still, "that high-sensitivity cardiac troponin T and high-sensitivity cardiac troponin I assays do not currently run on the same platform, and most laboratories have only one platform running 24/7 for routine measurements, is an important obstacle for the introduction of this strategy in clinical practice.

"Development of devices suitable for combined measurement, a challenge for diagnostic companies, laboratories and physicians, is therefore crucial," they said.

Van der Linden had no disclosures. Wildi discloses receiving grants from the Gottfried & Julia Bangerter-Rhyner-Stiftung and FAG Basel. Mueller discloses receiving research grants from the Swiss National Science Foundation and the Swiss Heart Foundation, the European Union, the Cardiovascular Research Foundation Basel, 8sense, Abbott, ALERE, Brahms, Critical Diagnostics, Nanosphere, Roche, Siemens, and the University Hospital Basel; and speaking or consulting for Abbott, ALERE, Brahms, Cardiorentis, Novartis, Roche, and Siemens. Disclosures for the other authors are in the report. De Lemos discloses that within the last  year he has received grant support from Abbott Diagnostics and has consulted for Abbott, Roche Diagnostics, and Ortho Clinical Diagnostics.

Circulation. Published online April 24, 2018. Abstract

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