Introduction: The Evolving Landscape of ACS Rule-Out
The assessment of suspected acute coronary syndrome (ACS) remains one of the most frequent and resource-intensive challenges in emergency medicine. For decades, clinicians relied on serial testing of conventional cardiac troponin, a process that often necessitated prolonged observation or hospital admission to ensure patient safety. However, the advent of high-sensitivity cardiac troponin (hs-cTn) assays has revolutionized this paradigm. By detecting much lower concentrations of troponin with high precision, these assays allow for earlier rule-out of myocardial infarction (MI) and more nuanced risk stratification.
While the utility of hs-cTn in identifying low-risk patients for immediate discharge is well-documented, questions have remained regarding the impact of these pathways on intermediate-risk cohorts and the long-term safety of increased discharge rates. The recent secondary analysis of the HiSTORIC (High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction) trial, published in the Journal of the American College of Cardiology, provides critical evidence addressing these uncertainties.
Study Design and Methodology: The HiSTORIC Trial Framework
The HiSTORIC trial was a stepped-wedge cluster-randomized controlled trial conducted across 7 secondary and tertiary care hospitals in Scotland. This secondary analysis specifically focused on 31,492 consecutive patients presenting with suspected ACS between 2014 and 2016. The study aimed to evaluate how the implementation of a high-sensitivity cardiac troponin I (hs-cTnI) pathway affected hospital efficiency and patient safety.
Patient Stratification
Patients were stratified into two primary groups based on their troponin levels at presentation:
- Low risk: hs-cTnI concentrations <5 ng/L.
- Intermediate risk: hs-cTnI concentrations between 5 ng/L and the sex-specific 99th percentile threshold.
Intervention and Comparison
The study compared the standard care period (validation phase) with the implementation period (implementation phase). During the implementation phase, clinicians were encouraged to use the hs-cTnI pathway to identify low-risk patients for early discharge and to use clinical risk scores to manage those in the intermediate-risk category. The primary effectiveness outcome was the length of hospital stay (LOS), while the primary safety outcome was the occurrence of subsequent myocardial infarction or cardiac death at one year.
Impact on Hospital Efficiency: Length of Stay and Discharge Patterns
The implementation of the hs-cTnI risk stratification pathway led to significant improvements in hospital efficiency across both risk categories. The data suggests that providing clinicians with precise, early biomarker data empowers more confident decision-making, thereby reducing unnecessary observation periods.
Reductions in Length of Stay
For low-risk patients, the mean length of stay decreased from 6.9 ± 3.2 hours to 4.7 ± 2.8 hours, representing a difference of 2.2 hours (95% CI: 0.7-3.7 hours). Even more striking was the impact on intermediate-risk patients, where the length of stay was reduced from 15.8 ± 4.7 hours to 11.0 ± 4.9 hours, a substantial difference of 4.8 hours (95% CI: 3.8-5.8 hours). Both findings reached high statistical significance (P < 0.001).
Increased Discharge Rates
The transition to the hs-cTnI pathway also resulted in a marked increase in the proportion of patients discharged directly from the emergency department. Among low-risk patients, discharge rates rose from 62% to 83% (adjusted OR: 3.31). For intermediate-risk patients, the discharge rate increased from 36% to 55% (adjusted OR: 2.06). These shifts indicate a fundamental change in clinical practice, where nearly half of the intermediate-risk population—previously often admitted for observation—could be safely managed as outpatients.
Safety First: Long-term Outcomes for Discharged Patients
A central concern in any protocol that increases discharge rates is the potential for missing subclinical or evolving cardiac events. However, this analysis provides reassuring safety data. Following the implementation of the pathway, patients who were discharged from the ED actually exhibited a lower risk of subsequent myocardial infarction or cardiac death at one year compared to those discharged during the validation phase.
Quantifying the Safety Margin
The overall 1-year rate of MI or cardiac death in discharged patients fell from 1.5% to 1.0% (adjusted HR: 0.65; 95% CI: 0.50-0.86). This safety benefit was consistent across strata:
- Low-risk patients: 1-year event rate fell from 0.6% to 0.3% (aHR: 0.46).
- Intermediate-risk patients: 1-year event rate fell from 3.4% to 2.4% (aHR: 0.74).
These findings suggest that the pathway does not merely discharge more patients, but it helps clinicians identify the *right* patients for discharge. By utilizing a lower threshold (<5 ng/L) to define low risk, the pathway effectively isolates a population with an extremely high negative predictive value for future events.
Expert Commentary and Clinical Implications
The results of the HiSTORIC secondary analysis have profound implications for emergency cardiology and hospital administration. The reduction in LOS, particularly the nearly 5-hour reduction for intermediate-risk patients, represents a major opportunity to alleviate ED crowding, a known driver of poor patient outcomes and clinician burnout.
Managing the Intermediate-Risk Group
The intermediate-risk group (5 ng/L to 99th percentile) has historically been a ‘grey zone’ for clinicians. This study demonstrates that many of these patients can be safely discharged if the hs-cTnI levels are interpreted within a structured risk-stratification framework. This shift likely reflects better integration of biomarker data with clinical risk scores (such as the HEART or GRACE scores), allowing for a more holistic assessment of patient risk rather than relying on binary troponin thresholds alone.
Mechanistic Insights
Why did safety outcomes improve despite higher discharge rates? Experts suggest that the high-sensitivity assay allows for the detection of minor myocardial injury that would have been missed by older assays. By identifying those with even slightly elevated troponin (the intermediate group), clinicians can better target outpatient follow-up and preventative therapies, such as statins or antiplatelet agents, which may contribute to the observed reduction in 1-year events.
Limitations and Generalizability
While the study is robust, it is a secondary analysis and was conducted within a single national healthcare system (Scotland). The specific hs-cTnI assay used and the thresholds applied may need to be validated in diverse populations with varying baseline cardiovascular risks. Furthermore, the study does not account for the impact of clinician experience or the specific outpatient follow-up protocols that may have been initiated post-discharge.
Conclusion: A New Standard for Emergency Cardiology
Risk stratification with high-sensitivity cardiac troponin is more than just a diagnostic tool; it is a powerful driver of health system efficiency and patient safety. By significantly reducing the length of stay for both low- and intermediate-risk patients and simultaneously improving 1-year cardiovascular outcomes, these pathways represent a rare ‘win-win’ in clinical medicine. As emergency departments continue to face unprecedented volumes, the adoption of evidence-based hs-cTn stratification protocols should be considered a priority for healthcare systems worldwide.
Funding and Trial Registration
The HiSTORIC trial was funded by the British Heart Foundation (SP/15/10/31598). ClinicalTrials.gov Identifier: NCT03005158.
References
Li Z, Doudesis D, Bularga A, Wereski R, Taggart C, Lowry MTH, Chapman AR, Tuck C, Ferry AV, Gray A, Newby DE, Anand A, Lee KK, Mills NL; HiSTORIC Trial Investigators. Safety of Using Risk Stratification Along With High-Sensitivity Cardiac Troponin in the Emergency Department: A Secondary Analysis. J Am Coll Cardiol. 2025 Nov 11;86(19):1738-1748. doi: 10.1016/j.jacc.2025.08.059. PMID: 41193094.
