High-Sensitivity Troponin I Assay May Rule Out MI in Large Number of Patients
About 60% of patients presenting with suspected ACS have cardiac troponin I levels, as measured by a high-sensitivity assay, that are low enough to indicate a minimal risk of cardiac events, according to a study published online October 8, 2015, ahead of print in The Lancet.
Those low-risk patients could be eligible for immediate discharge rather than hospitalization, Anoop S.V. Shah, MD, of the University of Edinburgh (Edinburgh, Scotland), and colleagues say, adding that “implementation of this approach could substantially reduce hospital admissions and have major benefits for both patients and healthcare providers.
In the High-STEACS study, the researchers examined data on 6,304 consecutive patients presenting with suspected ACS at the emergency departments of 3 Scottish hospitals and 1 US center between June 2013 and January 2014. A total of 4,870 patients were included in the derivation cohort and 1,434 in 2 validation cohorts.
Plasma cardiac troponin I levels were measured at presentation by a sensitive assay (ARCHITECTSTAT) for the purpose of clinical decision making and by a high-sensitivity assay (ARCHITECTSTAT high-sensitive troponin I assay; both Abbott Laboratories) for the study. The high-sensitivity results were not available to clinicians. Troponin testing was repeated at 6 and 12 hours at the discretion of attending physicians.
In the derivation cohort, median time from hospital arrival to blood sampling for troponin testing was 54 minutes. Repeat testing was performed in 42% of patients with troponin levels below the 99th percentile at presentation. Overall, 16% of patients had an index MI, defined as a type 1 MI arising during the first clinical episode, and 1% and 2% of patients returned to the hospital with MI and died of cardiac causes, respectively, within 30 days.
Identifies Low-Risk Population
Troponin concentrations using the high-sensitivity assay were below 5 ng/L in 61% of derivation-cohort patients who did not have MI at presentation. Levels below that threshold had a negative predictive value of 99.6% for the composite of index MI or type 1 MI or cardiac death at 30 days (primary endpoint), exceeding the goal of at least 99.5% that was prespecified by the trial’s steering committee.
The 5 ng/L threshold’s negative predictive value was consistent across subgroups defined by age, sex, risk factors, prior cardiovascular disease, GRACE score, and presence of myocardial ischemia on presenting electrocardiography. The value was slightly lower, however, for patients tested for troponin within 2 hours of chest pain onset compared with after longer intervals (97.6% vs 99.8%).
At 1 year, patients with troponin levels below 5 ng/L had a lower risk of MI or cardiac death compared with patients with higher levels (0.6% vs 3.3%; adjusted HR 0.41; 95% CI 0.21-0.80).
Results were similar in 2 independent validation cohorts, in which 56% of patients had troponin concentrations less than 5 ng/L and the negative predictive value of low levels was 99.4%.
Across the derivation and validation cohorts, 12 patients (0.4%) with troponin concentrations less than 5 ng/L at presentation met the primary endpoint—10 had an index MI, including 5 who had clear evidence of myocardial ischemia at presentation. The other 2 were in cardiac arrest when they arrived and later died.
Questions Remain About Clinical Impact
The findings complement those of prior studies looking at how troponin assays can be used to triage patients with suspected ACS, although the study authors say this study is the first to test troponin I instead of T.
The troponin I assay “has greater precision and reproducibility at low concentrations and at the proposed threshold. This will ensure the application of this approach is consistent across sites, analyzers, and reagent batches: a prerequisite for use in clinical practice,” Dr. Shah and colleagues write. “Furthermore, use of cardiac troponin I at our threshold identifies 2-to-3 times more low-risk patients than do previous approaches, which would avoid the need for repeat testing in most patients, or the incorporation of clinical risk scores used in accelerated diagnostic pathways.”
The main limitation of the study, however, is that the results of the high-sensitivity assay were not used for clinical decision making, they say. “Although we determined the number of patients who could be safely discharged, whether clinicians can effectively implement this threshold in clinical practice and whether this will substantially improve rates of discharge is unknown,” they write.
They stress that “this threshold should not be implemented in isolation and without regard to appropriate clinical assessment. One in 200 patients still had an index or 30-day event and many had other evidence of myocardial ischemia.”
And lastly, they point out, “we had no data about later investigations and treatments. Implementation of this threshold is expected to reduce healthcare costs but these benefits might be lost if recurrent presentations or additional outpatient consultations increase.”
‘Highly Promising’ Results
In an accompanying editorial, Louise Cullen, MBBS, of Royal Brisbane and Women’s Hospital (Brisbane, Australia), and colleagues call the findings “highly promising.” But they note that the low number of patients with serial troponin testing could have led to missed events and that the 54-minute median time to initial blood sampling could have influenced negative predictive value.
In addition, they write, use of a single troponin test did not meet the predefined negative predictive value of 99.5% in early presenters. As such, the editorialists advise, “serial testing should continue in such patients.” Moreover, each high-sensitivity assay is different, so these results do not apply to other tests, they say.
“When considering local implementation of this diagnostic strategy, the assay’s precision should be discussed by the laboratory and clinicians (eg, specialists in emergency medicine, cardiology, and internal medicine) with an assessment made about the ability to maintain acceptable precision,” the editorialists write.
“Reassuringly, in this study, the interlaboratory precision across 33 instruments at 3.5 ng/L was good, suggesting that the accuracy of this assay in clinical practice might be reliable,” they continue. “The ultimate validation for the safety and efficacy of discharging patients with cardiac troponin concentrations less than 5 ng/L will be the report of clinical outcomes after this threshold is implemented in routine clinical practice.”
1. Shah ASV, Anand A, Sandoval Y, et al. High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome. Lancet. 2015;Epub ahead of print.
2. Cullen L, Parsonage W, Than M. Myocardial infarction: rapid ruling out in the emergency room [editorial]. Lancet. 2015;Epub ahead of print.
- The study was funded by the British Heart Foundation and by an NHS Scotland Health Informatics Challenge Grant from the Chief Scientist Office. Abbott Laboratories provided the troponin I assay reagents, calibrators, and controls for free.
- Dr. Shah reports serving as a consultant for Abbott Laboratories.
- Dr. Cullen reports receiving grants, personal fees, and nonfinancial support from Abbott Diagnostics; grants from Roche; grants and personal fees from Alere; and personal fees and nonfinancial support from Siemens.