In the JournalsPerspective

High-sensitivity troponin T levels detect low-risk patients

W. Frank Peacock IV

High-sensitivity troponin T measurements identified patients with suspected ACS who were at low risk for acute MI and 30-day adverse cardiac events, according to a study published in JAMA Cardiology.

W. Frank Peacock IV, MD, FACEP, associate chief of emergency medicine research and professor of emergency medicine at Baylor College of Medicine in Houston, and colleagues analyzed data from 1,679 patients (median age, 55 years; 48% women) who presented to 15 EDs with suspected ACS from 2011 to 2015. Patients were excluded for criteria such as an acute MI within the past 3 months, surgery including PCI or hospitalization within the past 3 months and recent defibrillation or cardioversion.

High sensitivity troponin T measurements

Blood samples were collected after patients presented with symptoms at the ED, 3 hours, 6 to 9 hours and 12 to 24 hours later. Follow-up was conducted through telephone contact and medical record review for 30 days for acute cardiac events.

The reference range for the high-sensitivity troponin T assay was determined by evaluating blood samples of 1,301 healthy volunteers (median age, 48 years; 50% women) who did not have a history of chronic disease or a current cancer diagnosis. The 99th percentile high-sensitivity troponin T concentration was 19 ng/L, which was then used as an upper reference level to evaluate diagnostic performance.

Patients with a single high-sensitivity troponin T level of less than 6 ng/L had a negative predictive value of 99.4% for acute MI (95% CI, 98.6-99.8).

Those with serial high-sensitivity troponin T measurements that was less than the upper reference level (77.1%) had a negative predictive value of 99.3% for 30-day adverse cardiac events (95% CI, 99.1-99.6).

Minimal differences were seen in the C-statistic for acute MI between men (0.962) and women (0.952).

Multilevel benefits

“Identifying a low-risk cohort may permit early ED discharge and avoid unnecessary hospitalization,” Peacock and colleagues wrote. “Rapid turnaround of low-risk patients could translate into a reduction in ED volumes, which would benefit patients (shorter waiting times, increased satisfaction, improved outcomes and saved costs), clinicians (decreased diagnostic ambiguity and medicolegal burden) and hospitals (by providing cost-saving benefits).”

“The long-awaited FDA approval of [single high-sensitivity troponin] assays is now here,” Frederick K. Korley, MD, PhD, assistant professor of emergency medicine at University of Michigan Medical School in Ann Arbor, wrote in a related editorial. “There are numerous potential benefits to clinical use of [single high-sensitivity troponin] tests. However, we need to proceed cautiously. To reap the potential rewards of clinical use of [single high-sensitivity troponin] assays, we need (1) a better understanding of the safety of accelerated rule-out strategies in early presenters; (2) a game plan for managing patients without ACS who have elevated high-sensitivity troponin test results; (3) guidelines for distinguishing between type 1 and type 1 non-ST elevation MI and new recommendations for how they ought to be treated; and (4) additional evidence on the optimal cutoff level to rule MI in or out.” – by Darlene Dobkowski

Disclosures: Peacock reports he received grants from Alere and Roche and personal fees from Abbott, Alere, Beckman, Prevencio and Roche. Korley reports he has consulted for Abbott Laboratories and Roche Diagnostics. Please see the study for all other authors’ relevant financial disclosures.

W. Frank Peacock IV

High-sensitivity troponin T measurements identified patients with suspected ACS who were at low risk for acute MI and 30-day adverse cardiac events, according to a study published in JAMA Cardiology.

W. Frank Peacock IV, MD, FACEP, associate chief of emergency medicine research and professor of emergency medicine at Baylor College of Medicine in Houston, and colleagues analyzed data from 1,679 patients (median age, 55 years; 48% women) who presented to 15 EDs with suspected ACS from 2011 to 2015. Patients were excluded for criteria such as an acute MI within the past 3 months, surgery including PCI or hospitalization within the past 3 months and recent defibrillation or cardioversion.

High sensitivity troponin T measurements

Blood samples were collected after patients presented with symptoms at the ED, 3 hours, 6 to 9 hours and 12 to 24 hours later. Follow-up was conducted through telephone contact and medical record review for 30 days for acute cardiac events.

The reference range for the high-sensitivity troponin T assay was determined by evaluating blood samples of 1,301 healthy volunteers (median age, 48 years; 50% women) who did not have a history of chronic disease or a current cancer diagnosis. The 99th percentile high-sensitivity troponin T concentration was 19 ng/L, which was then used as an upper reference level to evaluate diagnostic performance.

Patients with a single high-sensitivity troponin T level of less than 6 ng/L had a negative predictive value of 99.4% for acute MI (95% CI, 98.6-99.8).

Those with serial high-sensitivity troponin T measurements that was less than the upper reference level (77.1%) had a negative predictive value of 99.3% for 30-day adverse cardiac events (95% CI, 99.1-99.6).

Minimal differences were seen in the C-statistic for acute MI between men (0.962) and women (0.952).

Multilevel benefits

“Identifying a low-risk cohort may permit early ED discharge and avoid unnecessary hospitalization,” Peacock and colleagues wrote. “Rapid turnaround of low-risk patients could translate into a reduction in ED volumes, which would benefit patients (shorter waiting times, increased satisfaction, improved outcomes and saved costs), clinicians (decreased diagnostic ambiguity and medicolegal burden) and hospitals (by providing cost-saving benefits).”

“The long-awaited FDA approval of [single high-sensitivity troponin] assays is now here,” Frederick K. Korley, MD, PhD, assistant professor of emergency medicine at University of Michigan Medical School in Ann Arbor, wrote in a related editorial. “There are numerous potential benefits to clinical use of [single high-sensitivity troponin] tests. However, we need to proceed cautiously. To reap the potential rewards of clinical use of [single high-sensitivity troponin] assays, we need (1) a better understanding of the safety of accelerated rule-out strategies in early presenters; (2) a game plan for managing patients without ACS who have elevated high-sensitivity troponin test results; (3) guidelines for distinguishing between type 1 and type 1 non-ST elevation MI and new recommendations for how they ought to be treated; and (4) additional evidence on the optimal cutoff level to rule MI in or out.” – by Darlene Dobkowski

Disclosures: Peacock reports he received grants from Alere and Roche and personal fees from Abbott, Alere, Beckman, Prevencio and Roche. Korley reports he has consulted for Abbott Laboratories and Roche Diagnostics. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Arnold H. Seto

    Arnold H. Seto

    This study demonstrates the real-world utility of the new high-sensitivity troponin assay in excluding a diagnosis of acute MI. Using an exclusively U.S. population of 1,600 ED patients, the authors demonstrate that a low single baseline level of 6 ng/L was sufficient to exclude ACS with very high (99.4%) sensitivity. Similarly, so long as both the baseline and 3-hour high-sensitivity troponin level were < 19 ng/L (the upper reference level), there was similarly a very high sensitivity (99.3%).
    With U.S. approval of the first high-sensitivity troponin assay this year, this study is very timely in demonstrating how cardiologists and emergency room physicians can use high-sensitivity troponin to very effectively and efficiently rule out MI within 3 hours of presentation. In this study, 77.6% of patients presenting with suspected ACS could have been ruled out by their protocol and potentially discharged from the ED. This contemporary diagnostic pathway could help reduce inappropriate admissions for chest pain, and potentially keep patients in the emergency room during their relatively brief 3-hour observation period.
    Many practicing cardiologists have been concerned about the low specificity of abnormal troponin levels for the diagnosis of true ACS, let alone MI. In the current study, the majority of patients with abnormal troponin (> 19 ng/L) did not have an MI after adjudication. The introduction of high-sensitivity troponin will certainly increase the number of “false-positive” troponin findings that may require further investigation. However, the introduction of high-sensitivity troponin highlights both the strengths (high sensitivity) and weaknesses (even lower specificity for ACS) of troponins in general. High-sensitivity troponin is a nearly perfect initial screening test for MI, but a terrible confirmatory test for what we really need to treat: ACS.  
    For confirmation of ACS, we can turn to the clinical symptoms and ECG findings as suggested by the guidelines, but these are rarely sufficient. I teach my fellows to always check a creatine kinase-MB to confirm any troponin diagnosis of ACS, because it is not elevated or as elevated by the many conditions (congestive HF, myocarditis, pericarditis, strain, left ventricular hypertrophy, sepsis, demand) that affect troponin. The introduction of high-sensitivity troponin will make this dichotomy between troponin and CK-MB more clear, and hopefully bring our practice and guidelines to use the best qualities of both tests.

    • Arnold H. Seto, MD, FSCAI, FACC
    • Chief of Cardiology, Long Beach VA Medical Center Associate Clinical Professor Director, Interventional Cardiology Research University of California, Irvine

    Disclosures: Seto reports no relevant financial disclosures.