Nguyen et al report an evaluation of the safety, effectiveness, and resource use associated with conventional biomarker reporting (before) vs high-sensitivity cardiac troponin (hs-cTn) reporting to the lowest limit of quantification (after) among adults aged 18 years or older who had at least 1 troponin blood test performed in the emergency department (ED) at all public hospitals in South Australia, Australia. Included were 20 715 patients in the before group (conventional troponin reporting) and 20 206 in the after group (unmasked hs-cTnT reporting). The authors found that unmasked hs-cTnT reporting was associated with greater ED discharge rates (45.2% vs 39.0% with conventional troponin reporting; P < .001) and a briefer median hospital length of stay (7.68 [IQR, 4.32-46.80] hours vs 7.92 [IQR, 4.56-49.92] hours; P < .001). There was no significant difference in rates of subsequent myocardial infarction (MI) (3.5% vs 3.4%), coronary angiography (4.4% vs 4.6%), percutaneous coronary intervention (2.3% vs 2.1%), or coronary artery bypass graft (0.4% vs 0.5%). Thus, use of hs-cTn testing was associated with decreased resource use but not increased adverse events.
Overcrowding of EDs is common and associated with poor patient outcomes and increased resource use. Chest pain is the second most common concern for patients presenting to the ED in the US. Only 14% of such visits result in a hospital admission. As much as $3 billion could be avoided annually by reducing variation in ED hospitalizations for chest pain. Approximately 2% of patients discharged from the ED after assessment for chest pain have a missed acute coronary occlusion (ACO). Thus, there is a need to improve the efficiency of care of patients with chest pain in the ED setting by reducing the time to diagnosis of acute coronary syndrome (ACS) vs not ACS.
Troponin is a protein involved in myocardial contraction that is released as soon as 30 seconds after the onset of ACO and is, therefore, an early, accurate biomarker for myocardial injury. High-sensitivity diagnostic tests using troponin I or troponin T were first introduced more than 15 years ago and are now widely available.
Strengths of the Nguyen et al study include its broad community-based implementation, unselected population, and large sample size. Each of these increase the generalizability of the results to other settings. A limitation of this study is the lack of use of a specific protocol for the number and timing of hs-cTnT testing in each patient. Another limitation is the use of machine learning rather than expert adjudication to classify the presence or absence of MI.
High-sensitivity cardiac troponin testing is accurate across a broad range of pretest probabilities for ACO. Clinical prediction rules, such as the HEART (history, electrocardiogram [ECG], age, risk factors, initial troponin) score, that incorporate troponin results are more accurate than patient history, physical examination, and ECG results alone. In a study of patients who presented at least 3 hours after symptom onset in Scotland, a single-sample rule-out hs-cTnI test with a cutoff of 5 ng/dL reported a reduced ED length of stay, increased rate of ED discharge, and low incidence of MI or death compared with standard care using serial sampling. In another study of patients who presented with chest pain in Australia, clinicians were masked (ie, not informed if hs-cTnT concentrations were very low) or unmasked (hs-cTnT results were shared, and a single-sample rule-out was allowed) to assay results. Readmission was less common in the masked group vs the unmasked group (2.7% vs 4.0%, P < .001). During long-term follow-up, increased mortality was observed in patients who had elevated hs-cTnT levels in the unmasked group.
Another trial enrolled low-risk patients with suspected ACO in the UK. Participants were allocated to a single-sample rule-out group using hs-cTnI or hs-cTnT assay (intervention) or a standard care (control) group. No participant who had a single-sample rule-out had an adverse cardiac event within 30 days, but there was no significant reduction in the proportion of patients who were discharged from the ED.
Other diagnostic strategies can differentiate ACS from no ACS. A 64-slice computed tomography angiography has high sensitivity for detection of ACO in patients who have non-ST-segment elevation ACS. As well, computed tomography angiography may reveal alternative diagnoses, such aortic dissection or pulmonary embolism. ECG interpretation augmented by graphical decision support or artificial intelligence may in the future outperform traditional ST-segment elevation MI criteria for the diagnosis of ACO. Overall, a combination of clinical assessment, biomarkers, ECG, and imaging techniques appears to offer the most comprehensive approach to diagnosis in patients with chest pain.
Use of hs-cTn has increased over time in the US but lags behind that in Europe. Slower adoption of hs-cTn in the US may reflect, in part, differences in regulation of diagnostic tests, as well as differences in diagnostic cutoff values used, patient prognosis, individual physician decision making, and perceptions about medicolegal liability associated with a missed diagnosis of ACO. Application of 0/1-hour hs-cTn-based pathways that were originally derived and validated in Europe have sometimes yielded mixed results when implemented in the US. In a Scottish multicenter trial enrolling patients with suspected ACS, use of hs-cTn testing was not associated with subsequent mortality or recurrence of ACS at 1 year. The diagnostic accuracy of hs-cTn was decreased among patients tested within 2 hours of symptom onset compared with those who presented after more than 2 hours. Use of hs-cTn testing was associated with a reduced risk of MI or death at 5 years, particularly in patients with initial myocardial injury. A recent multicenter trial that enrolled patients with chest pain in the US demonstrated that use of a 0/1-hour hs-cTn protocol compared with standard care with a 0/3-hour protocol did not significantly increase rates of discharge from the ED or worsen subsequent clinical outcomes.
Where do we go from here? Implementation of a single-sample rule-out hs-cTn test should use validated cutoff values. By convention, broad adoption of existing or future diagnostic strategies for ACS requires demonstration that the risk of missed major adverse cardiac events in patients with ACO ruled out is less than 1% at 30 days. Challenges remain in distinguishing between acute and chronic elevations of hs-cTn. Consensus is required on whether it is better to use hs-cTn reporting at the limit of detection or at higher concentrations to classify a greater proportion of patients as being at low risk for ACS. Different cutoff values could be warranted for older patients, women, and patients with underlying cardiac or kidney diseases. Broader adoption of existing hs-cTn testing into clinical algorithms may reduce resource use without worsening clinical outcomes when EDs in most settings have insufficient resources to adequately serve patient needs in a timely manner. Adoption of point-of-care hs-cTn testing may reduce the time required for diagnostic workup of chest pain, as testing in a central laboratory requires sample transportation, specimen preparation, processing, and reporting of results. Moreover, an hs-cTn-based risk score may be used in the out-of-hospital setting to rapidly diagnosis ACS and unburden receiving EDs. Accurate point-of-care devices for hs-cTn testing are now available in Europe. At least 1 such device has been approved for use by the US Food and Drug Administration (Pathfast; Polymedco LLC). Others are developing bloodless infrared sensors of acute myocardial injury (eg, RCE Technologies, Inc). If these newer technologies have adequate diagnostic performance and are not associated with deleterious clinical outcomes, their dissemination to and implementation within ED and home settings may decrease health care resource use by individuals unlikely to have ACO and reduce the time to definitive care for those likely to require emergent percutaneous coronary intervention.
Corresponding Author: Graham Nichol, MD, MPH, Harborview Center for Prehospital Emergency Care, University of Washington, 325 Ninth Ave, PO Box 359727, Seattle, WA 98040 ([email protected]).
Conflict of Interest Disclosures: Dr Nichol reported receiving salary support from Medic One Foundation; grants from the Patient Centered Outcomes Research Institute; research contracts from Johnson & Johnson MedTech, ZOLL Medical Corp; consultant fees from Celecor Inc, Invero Health LLC, and Orixha Inc; an equipment loan from RCE Technologies Inc outside the submitted work; and a patent for measurement of blood flow during cardiopulmonary resuscitation issued to the University of Washington and a patent pending for a combination drug-device to reduce reperfusion injury issued to the University of Washington. No other disclosures were reported.