Circulation

RESEARCH LETTER

Evaluation of a Novel Rule-Out Myocardial

Infarction Protocol Incorporating High-
Sensitivity Troponin T in a US Hospital

T
he US Food and Drug Administration recently approved a high-sensitivity (hs) Rebecca Vigen, MD,
troponin T (cTnT) assay that has greater sensitivity and precision than the con- MSCS
ventional fourth-generation cTnT assay currently in use in the United States.1 Patricia Kutscher, MT,
Using this assay, European Society of Cardiology (ESC) guidelines endorse a 0/1- ASCP
hour “rule-out” of myocardial infarction (MI) in low-risk individuals,2 as well as a Fernabelle Fernandez,
more traditional 3-hour algorithm.3 However, the safety and effectiveness of rapid MLS, ASCP
MI rule-out algorithms using hs-cTnT in US practice have not been established. Amy Yu, MLS, ASCP
A multidisciplinary team at Parkland Health and Hospital System developed a nov- Bryan Bertulfo, MLS, ASCP
el hs-cTnT protocol modified from published data.2–4 An important difference from Ibrahim A. Hashim, MSc,
previous protocols was the addition of a 3-hour hs-cTnT measurement for patients PhD
classified into the indeterminate zone at 1 hour (Figure [A]). An observational study Kyle Molberg, MD
of unselected patients undergoing MI rule-out was performed to evaluate the safety Deborah B. Diercks, MD,
of the protocol and its potential impact on patient disposition. The proportion of MPH
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patients who would have been eligible for early rule-out with the new protocol in- Jeffery C. Metzger, MD,
corporating hs-cTnT was compared with existing practice in which the conventional MBA
fourth-generation cTnT assay was tested at baseline and ≥3 hours after presentation. Jose Soto, MD
The negative predictive value was calculated to assess safety. Both cTnT and hs-cTnT Dergham Alzubaidy, MD
were measured at 0, 1, and 3 hours after presentation to the Parkland Health and Lorie Thibodeaux, MHA
Hospital System emergency department in 536 patients with symptoms warranting Jose A. Joglar, MD
MI rule-out (60% chest pain, 16% shortness of breath, 24% other complaints), but James A. de Lemos, MD
no ST elevations on ECG, between August and October of 2017. Individuals were Sandeep R. Das, MD, MPH
classified into 2 mutually exclusive categories, “ruled out” or “abnormal,” based on
hs-cTnT levels and change values (Figure [A]). Individuals were classified as ruled out
with the conventional assay if cTnT was <0.01 ng/mL at all time points and abnormal
if any value was ≥ 0.01 ng/mL. The final diagnosis was adjudicated by 3 cardiologists
based on all available clinical information, including the conventional cTnT assay,
using the Third Universal Definition of MI. A second adjudication was performed
as a sensitivity analysis using the hs-cTnT assay instead of the conventional assay.2,5
Finally, we compared our new hs-cTnT algorithm with the 0/1 hour ESC algorithm.3
The University of Texas Southwestern institutional review board approved this quality
improvement study with a waiver of informed consent.
In this cohort (N=536, mean age 55 years, 44% women), the final adjudicated
diagnosis was MI in 2.1%, unstable angina in 0.4%, and nonischemic myocar-
dial injury in 17.0%. With the conventional assay, 80.4% of patients ruled out
for MI at 3 hours. With the new hs-cTnT protocol, 83.8% ruled out by 3 hours,
including 30.0% at baseline, 24.8% at 1 hour, and 28.9% at 3 hours. Compared
Key Words:  myocardial infarction
with 19.6% of patients considered abnormal by the conventional assay, 16.2% of ◼ sensitivity ◼ specificity ◼ troponin
patients were abnormal under the new protocol (P=0.03; McNemar’s test; Figure
© 2018 American Heart Association, Inc.
[B]). The new protocol had a sensitivity and negative predictive value of 100%,
specificity of 86%, and positive predictive value of 13% for a final adjudicated di- https://www.ahajournals.org/journal/circ

Circulation. 2018;138:00–00. DOI: 10.1161/CIRCULATIONAHA.118.033861 xxx xxx, 2018 1

 Vigen et al High-Sensitivity Troponin in the United States

agnosis of MI. After readjudication using hs-cTnT as the assay, and did so sooner, with more than half of all pa-
gold standard, operating characteristics were identical tients ruled out by 1 hour after presentation. This proto-
CORRESPONDENCE

except for a slightly lower positive predictive value of
12%. Of the patients who ruled out, no recurrent MI
events were detected over 30 days of follow-up. When
compared with the ESC 0/1 hour algorithm, a higher
proportion ruled out with our new algorithm (83.8 ver-
sus 55.4%, P<0.0001), resulting from movement of
152/154 patients assigned to observation status with
the ESC 0/1 hour algorithm to the rule-out group with
the new protocol (Figure [C]).
In summary, a new protocol for rapid rule-out of MI
using the hs-cTnT assay, applied to a contemporary US
emergency department population, ruled out more pa-
tients than the existing protocol using the conventional
col also appropriately ruled out a much higher propor-
tion than the ESC 0/1 hour algorithm. This early rule-out
protocol appears safe, with a sensitivity and negative
predictive value of 100%. The positive predictive value
of an abnormal hs-cTnT value was notably lower in
this population than in prior studies,1 reflecting similar
specificity applied to a population with much lower MI
prevalence. Thus, clinical judgment remains essential in
the interpretation of abnormal troponin values as the hs-
cTnT assay becomes adopted in the United States, where
troponin is measured more indiscriminately than in many
other countries. A subtle but important distinction of our
protocol from the ESC 0/1 protocol is the classification

A
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Figure. High-sensitivity (hs) troponin T (cTnT) algorithm and comparisons with conventional cTnT algorithm and European Society of Cardiology
(ESC) 0/1 algorithm.
A, Parkland Hospital/UT Southwestern protocol for rapid myocardial infarction rule-out using the hs-cTnT assay. B, Proportions of patients ruled out for acute
myocardial infarction based on the conventional cTnT algorithm and new hs-cTnT algorithm. (Continued )

2 xxx xxx, 2018 Circulation. 2018;138:00–00. DOI: 10.1161/CIRCULATIONAHA.118.033861

 Vigen et al
Figure Continued. C, Comparison of ESC 0/1 algorithm and new hs-cTnT algorithm. NPV indicates negative predictive value; and PPV, positive predictive value.
of individuals as “abnormal” rather than “rule-in.” We
recommend a similar approach in other centers with an
anticipated low MI prevalence among those undergoing
troponin measurement. This study is limited by its small
size and lack of external validation; thus, future studies
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are needed to externally validate this novel algorithm
and determine its resource implications.
ARTICLE INFORMATION
Data sharing: The data and study materials will not be made available to other
researchers.
Guest Editor for this article was Evangelos Giannitsis, MD.
Correspondence
Rebecca Vigen, MD, MSCS, 5323 Harry Hines Blvd, Dallas, TX 75390–8830.
Email Rebecca.vigen@utsouthwestern.edu
Affiliations
Department of Internal Medicine, Division of Cardiology (R.V., J.A.J., J.A.d.L.,
S.R.D), Department of Pathology (I.A.H., K.M.), Department of Emergency Medi-
cine (D.B.D., J.C.M.), and Department of Internal Medicine, Division of Hospitalist
Medicine (J.S., D.A.), University of Texas Southwestern Medical Center, Dallas.
Rapid Response Lab (P.K., F.F., A.Y., B.B.), Performance Improvement Department,
Quality Safety Division (L.T.), and Parkland Center for Healthcare Innovation and
Clinical Outcomes (S.R.D.), Parkland Health and Hospital System, Dallas, TX.
Sources of Funding
Dr Vigen was supported by the National Center for Advancing Translational
Sciences of the National Institutes of Health under award UL1TR001105. The
content is solely the responsibility of the authors and does not necessarily rep-
resent the official views of the National Institutes of Health.
Disclosures
Dr Diercks reports consulting income from Roche Diagnostics, and consulting
income and research support from Siemens Diagnostics. Dr de Lemos reports
Circulation. 2018;138:00–00. DOI: 10.1161/CIRCULATIONAHA.118.033861
High-Sensitivity Troponin in the United States
CORRESPONDENCE
grant support from Roche Diagnostics and Abbott Diagnostics and consulting
income from Roche Diagnostics, Abbott Diagnostics, Ortho Clinical Diagnos-
tics, and Endpoint Committees for Radiometer and Siemen’s Health Care Diag-
nostics. Dr Das reports consulting income from Roche Diagnostics. The other
authors report no conflicts.
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