In the Journals

High-sensitivity cardiac troponin I assay may help identify or rule out MI

Results from two studies published in JAMA Cardiology indicate that a high-sensitivity cardiac troponin I assay may help identify or rule out MI in patients who arrive at the ED with chest pain.

High-sensitivity cardiac troponin I assays are not currently available in the United States, but could ultimately enable acute MI to be excluded as a diagnosis faster than it is now, according to the findings.

1-hour algorithm

In an analysis of three cohorts (BACC, ADAPT and APACE), Johannes Tobias Neumann, MD, of the department of general and interventional cardiology at the University Heart Center Hamburg, University Hospital Hamburg–Eppendorf, Germany, and colleagues identified an optimal cutoff for diagnosing non-STEMI using troponin I levels and then developed and validated an algorithm for more accurate diagnosis and exclusion of acute MI.

First, data from 1,040 patients from the BACC cohort, aged 18 years and older, who had presented with chest pain or other symptoms suggestive of MI between July 19, 2013, and Dec. 31, 2014, at the ED of the University Medical Center Hamburg–Eppendorf, were used to identify the optimal cutoff of 6 ng/L and to develop an algorithm for rapid exclusion and diagnosis of acute MI after 1 hour. European Society of Cardiology guidelines advise ED doctors to use the high-sensitivity troponin assays on admission and after 3 hours.

According to the results, applying the troponin I cutoff value of 6 ng/L to the rule-out algorithm resulted in a negative predictive value (NPV) of 99.8% (95% CI, 98.6-100) with only one false-negative finding for non-STEMI type 1. The NPV was 99% (95% CI, 97.5-99.7) with four false-negative findings for all patients with non-STEMI. According to the researchers, this is higher than the 10% coefficient of variation of 5.2 ng/L.

When measuring troponin I levels based on the 1-hour algorithm, the NPV for non-STEMI type I after 1 hour was 99.8% (95% CI, 98.6-100); after 3 hours, it was 100% (95% CI, 98.5-100). Of all non-STEMI patients, 406 (39%) could be discharged. Four of these patients had a false negative (NPV = 99%; 95% CI, 97.5-99.7).

The positive predictive value when using the troponin I cutoff level to diagnose MI was 82.8% (95% CI, 73.2-90) using the 1-hour algorithm and 78.6% (95% CI, 69.8-85.8) after 3 hours for patients with non-STEMI type I. For all patients with non-STEMI, the positive predictive value was 87.1% (95% CI, 79.6-92.6) after 1 hour and 84.6% (95% CI, 78-89.9) after 3 hours.

The algorithm was then validated in the ADAPT and APACE cohorts. In ADAPT, a 2-hour algorithm was used on 1,748 patients and 249 non-STEMIs were recorded. The NPV was 99.6% (95% CI, 99.1-99.9) right after admission and 99.7% (95% CI, 99.2-99.4) after 2 hours. Based on the rule-in algorithm, the positive predictive value was 81.5% (95% CI, 75.3-86.3). The APACE cohort used a similar 1- and 3-hour algorithm when assessing 2,261 patients, of whom 429 had non-STEMIs. In this cohort, the NPV was 98.6% (95% CI, 98.6-99.2) directly after admission and 99.2% (95% CI, 98.4-99.2) after 1 hour and 99.1% (95% CI, 97.1-99.8) after 3 hours. The positive predictive value was 80.4% (95% CI, 75.1-84.9) after 1 hour and 68.8% (95% CI, 59.2-77.3) after 3 hours.

“The primary finding of this study is that a rapid 1-hour algorithm with a troponin I level cutoff lower than the routinely used 99th percentile enables safe diagnosis of [acute] MI,” the researchers wrote. “This cutoff enables a rapid triage that excludes [acute] MI and a faster initiation of evidence-based treatment for patients diagnosed as having [acute] MI.”

Lower concentrations

Another study by Edward Carlton, PhD, of the North Bristol National Health Service Trust in Bristol, England, and colleagues also evaluated the performance of low concentrations of high-sensitivity cardiac troponin I in patients with symptoms suggestive of MI. This analysis included 3,155 patients from five international observational cohort studies. The primary endpoint was acute MI occurring within 30 days of hospital attendance. Secondary endpoints included the proportion of patients suitable for early discharge at each cutoff concentration.

According to the researchers, 291 patients developed acute MI within 30 days of index visit. Of these, 277 patients received diagnosis during index presentation and 14 during the following 30 days. Troponin concentrations of less than 1.2 ng/L were found in 18.8% (n = 594) of the 3,155 patients. By using this cutoff along with a nonischemic ECG, 18.8% of patients could be discharged with a sensitivity of 99% (95% CI, 96.8-99.7) and a NPV of 99.5% (95% CI, 98.4-99.9).

“To place these results in the context of absolute numbers of presenting patients, a number-needed-to-diagnose approach shows that, for the 1.2-ng/L cutoff level, for every 10,630 patients assessed, 1,990 would be correctly reassured that they are not having an [acute] MI, 10 would be falsely reassured, and 8,630 would undergo further investigation, of whom 990 would ultimately receive a diagnosis of [acute] MI,” the researchers wrote.

Carlton and colleagues also wrote that, “Physicians should be aware that, at low concentrations, test results are less reliable than at the 99th percentile; therefore, any clinical implementation should be a multidisciplinary decision between ED physicians, cardiologists and laboratory staff.”

More research needed

In a related editorial, David A. Morrow, MD, MPH, of the TIMI Study Group, cardiovascular division, Brigham and Women’s Hospital and Harvard Medical School, wrote: “Taken together with prior studies, the findings from the studies of Neumann et al and Carlton et al lend strong support to the notion that accelerated diagnostic protocols that incorporate [a high-sensitivity cardiac troponin I assay] can facilitate earlier triage while maintaining an acceptable NPV. These studies illustrate key concepts that will continue to shape emerging accelerated diagnostic protocols. Better-performing assays enable a shift to more rapid exclusion strategies.”

David A. Morrow

Morrow also emphasized the need for additional studies to “add to the robustness of the estimated NPV across a variety of populations.” – by Tracey Romero

References:

Carlton F, et al. JAMA Cardiol. 2016;doi:10.1001/jamacardio.2016.1309.

Morrow DA. JAMA Cardiol. 2016;doi:10.1001/jamacardio.2016.1205.

Neumann JT, et al. JAMA Cardiol. 2016;doi:10.1001/jamacardio.2016.0695.

Disclosure: The BACC study received funding from Abbott Diagnostics. Carlton reports receiving funding from Abbott and Randox Laboratories. Morrow reports receiving funding from Abbott Laboratories, Amgen, AstraZeneca, Daiichi Sankyo/Eli Lilly, diaDexus, Eisai, Gilead, GlaxoSmithKline, Merck, Novartis and Roche Diagnostics; and personal fees from Abbott Laboratories. Neumann reports no relevant financial disclosures. Please see the full studies for the other researchers’ relevant financial disclosures.

Results from two studies published in JAMA Cardiology indicate that a high-sensitivity cardiac troponin I assay may help identify or rule out MI in patients who arrive at the ED with chest pain.

High-sensitivity cardiac troponin I assays are not currently available in the United States, but could ultimately enable acute MI to be excluded as a diagnosis faster than it is now, according to the findings.

1-hour algorithm

In an analysis of three cohorts (BACC, ADAPT and APACE), Johannes Tobias Neumann, MD, of the department of general and interventional cardiology at the University Heart Center Hamburg, University Hospital Hamburg–Eppendorf, Germany, and colleagues identified an optimal cutoff for diagnosing non-STEMI using troponin I levels and then developed and validated an algorithm for more accurate diagnosis and exclusion of acute MI.

First, data from 1,040 patients from the BACC cohort, aged 18 years and older, who had presented with chest pain or other symptoms suggestive of MI between July 19, 2013, and Dec. 31, 2014, at the ED of the University Medical Center Hamburg–Eppendorf, were used to identify the optimal cutoff of 6 ng/L and to develop an algorithm for rapid exclusion and diagnosis of acute MI after 1 hour. European Society of Cardiology guidelines advise ED doctors to use the high-sensitivity troponin assays on admission and after 3 hours.

According to the results, applying the troponin I cutoff value of 6 ng/L to the rule-out algorithm resulted in a negative predictive value (NPV) of 99.8% (95% CI, 98.6-100) with only one false-negative finding for non-STEMI type 1. The NPV was 99% (95% CI, 97.5-99.7) with four false-negative findings for all patients with non-STEMI. According to the researchers, this is higher than the 10% coefficient of variation of 5.2 ng/L.

When measuring troponin I levels based on the 1-hour algorithm, the NPV for non-STEMI type I after 1 hour was 99.8% (95% CI, 98.6-100); after 3 hours, it was 100% (95% CI, 98.5-100). Of all non-STEMI patients, 406 (39%) could be discharged. Four of these patients had a false negative (NPV = 99%; 95% CI, 97.5-99.7).

The positive predictive value when using the troponin I cutoff level to diagnose MI was 82.8% (95% CI, 73.2-90) using the 1-hour algorithm and 78.6% (95% CI, 69.8-85.8) after 3 hours for patients with non-STEMI type I. For all patients with non-STEMI, the positive predictive value was 87.1% (95% CI, 79.6-92.6) after 1 hour and 84.6% (95% CI, 78-89.9) after 3 hours.

The algorithm was then validated in the ADAPT and APACE cohorts. In ADAPT, a 2-hour algorithm was used on 1,748 patients and 249 non-STEMIs were recorded. The NPV was 99.6% (95% CI, 99.1-99.9) right after admission and 99.7% (95% CI, 99.2-99.4) after 2 hours. Based on the rule-in algorithm, the positive predictive value was 81.5% (95% CI, 75.3-86.3). The APACE cohort used a similar 1- and 3-hour algorithm when assessing 2,261 patients, of whom 429 had non-STEMIs. In this cohort, the NPV was 98.6% (95% CI, 98.6-99.2) directly after admission and 99.2% (95% CI, 98.4-99.2) after 1 hour and 99.1% (95% CI, 97.1-99.8) after 3 hours. The positive predictive value was 80.4% (95% CI, 75.1-84.9) after 1 hour and 68.8% (95% CI, 59.2-77.3) after 3 hours.

“The primary finding of this study is that a rapid 1-hour algorithm with a troponin I level cutoff lower than the routinely used 99th percentile enables safe diagnosis of [acute] MI,” the researchers wrote. “This cutoff enables a rapid triage that excludes [acute] MI and a faster initiation of evidence-based treatment for patients diagnosed as having [acute] MI.”

Lower concentrations

Another study by Edward Carlton, PhD, of the North Bristol National Health Service Trust in Bristol, England, and colleagues also evaluated the performance of low concentrations of high-sensitivity cardiac troponin I in patients with symptoms suggestive of MI. This analysis included 3,155 patients from five international observational cohort studies. The primary endpoint was acute MI occurring within 30 days of hospital attendance. Secondary endpoints included the proportion of patients suitable for early discharge at each cutoff concentration.

According to the researchers, 291 patients developed acute MI within 30 days of index visit. Of these, 277 patients received diagnosis during index presentation and 14 during the following 30 days. Troponin concentrations of less than 1.2 ng/L were found in 18.8% (n = 594) of the 3,155 patients. By using this cutoff along with a nonischemic ECG, 18.8% of patients could be discharged with a sensitivity of 99% (95% CI, 96.8-99.7) and a NPV of 99.5% (95% CI, 98.4-99.9).

“To place these results in the context of absolute numbers of presenting patients, a number-needed-to-diagnose approach shows that, for the 1.2-ng/L cutoff level, for every 10,630 patients assessed, 1,990 would be correctly reassured that they are not having an [acute] MI, 10 would be falsely reassured, and 8,630 would undergo further investigation, of whom 990 would ultimately receive a diagnosis of [acute] MI,” the researchers wrote.

Carlton and colleagues also wrote that, “Physicians should be aware that, at low concentrations, test results are less reliable than at the 99th percentile; therefore, any clinical implementation should be a multidisciplinary decision between ED physicians, cardiologists and laboratory staff.”

More research needed

In a related editorial, David A. Morrow, MD, MPH, of the TIMI Study Group, cardiovascular division, Brigham and Women’s Hospital and Harvard Medical School, wrote: “Taken together with prior studies, the findings from the studies of Neumann et al and Carlton et al lend strong support to the notion that accelerated diagnostic protocols that incorporate [a high-sensitivity cardiac troponin I assay] can facilitate earlier triage while maintaining an acceptable NPV. These studies illustrate key concepts that will continue to shape emerging accelerated diagnostic protocols. Better-performing assays enable a shift to more rapid exclusion strategies.”

David A. Morrow

Morrow also emphasized the need for additional studies to “add to the robustness of the estimated NPV across a variety of populations.” – by Tracey Romero

References:

Carlton F, et al. JAMA Cardiol. 2016;doi:10.1001/jamacardio.2016.1309.

Morrow DA. JAMA Cardiol. 2016;doi:10.1001/jamacardio.2016.1205.

Neumann JT, et al. JAMA Cardiol. 2016;doi:10.1001/jamacardio.2016.0695.

Disclosure: The BACC study received funding from Abbott Diagnostics. Carlton reports receiving funding from Abbott and Randox Laboratories. Morrow reports receiving funding from Abbott Laboratories, Amgen, AstraZeneca, Daiichi Sankyo/Eli Lilly, diaDexus, Eisai, Gilead, GlaxoSmithKline, Merck, Novartis and Roche Diagnostics; and personal fees from Abbott Laboratories. Neumann reports no relevant financial disclosures. Please see the full studies for the other researchers’ relevant financial disclosures.

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