The Shifting Landscape of Cardiac Biomarkers
For decades, cardiac troponins have served as the cornerstone for diagnosing myocardial infarction (MI). The advent of high-sensitivity cardiac troponin (hs-cTn) assays revolutionized the field by allowing for earlier detection and more rapid rule-out protocols. However, a prevailing assumption in clinical practice is that high-sensitivity troponin I (hs-cTnI) and troponin T (hs-cTnT) are clinically interchangeable. Recent evidence challenges this notion, suggesting that the choice of assay—and the transition between them—can have profound implications for hospital resources, diagnostic labeling, and patient management without necessarily translating into better clinical outcomes.
Highlights of Recent Evidence
1. Transitioning from hs-cTnI to hs-cTnT was associated with a near doubling of myocardial injury diagnoses (21% to 38%).
2. The shift to hs-cTnT led to a significant increase in hospital admissions (OR 2.24) and a six-fold increase in serial testing requirements.
3. Despite increased diagnostic intensity and resource utilization, one-year cardiovascular outcomes (MI, heart failure, or death) remained unchanged.
4. In contrast, a low-threshold hs-cTnI strategy (<5 ng/L) remains a highly effective and safe tool for identifying low-risk patients at presentation.
Background: The Clinical Dilemma of Interchangeability
In the emergency department (ED) setting, the primary goal of troponin testing is to safely and efficiently distinguish between acute coronary syndrome (ACS) and other causes of chest pain. International guidelines recommend high-sensitivity assays but do not explicitly favor troponin I over T. While both proteins are components of the cardiac troponin complex, they are encoded by different genes and have different clearance kinetics and baseline distributions in the general population. As hospitals consolidate laboratory services or switch vendors, clinical teams often face assay transitions without a clear understanding of how these changes affect the real-world diagnostic threshold and patient flow.
Study Design: Evaluating the Impact of Assay Switching
The TWITCH-ED study (Boeddinghaus et al., 2025) was a prospective, multicenter, interrupted time-series study conducted across three acute care centers. The study included 25,849 consecutive patients presenting with suspected ACS. In October 2021, all sites transitioned from an hs-cTnI assay to an hs-cTnT assay. The researchers sought to measure the impact of this change on the primary outcome of hospital admission, as well as secondary outcomes including myocardial injury identification, serial testing frequency, and 1-year major adverse cardiovascular events (MACE).
Separately, to understand the safety of low-threshold strategies, a meta-analysis by Chapman et al. (2017) evaluated 22,457 patients across 19 cohorts to determine the performance of an hs-cTnI threshold of 5 ng/L for risk stratification at the time of presentation.
Key Findings: The Impact of Transitioning to hs-cTnT
Increased Identification of Myocardial Injury
The transition from hs-cTnI to hs-cTnT resulted in a dramatic increase in the proportion of patients identified with myocardial injury (defined as at least one troponin concentration above the 99th percentile). The rate rose from 21% (2,800 of 13,146 patients) during the hs-cTnI period to 38% (4,781 of 12,703 patients) after the switch to hs-cTnT. This represents a significant broadening of the patient population flagged for further cardiac investigation.
Hospital Admissions and Serial Testing
Clinical decision-making was heavily influenced by the assay switch. Patients were significantly more likely to be admitted to the hospital after the transition to hs-cTnT (OR 2.24; 95% CI, 1.81-2.77). Furthermore, the requirement for serial testing—often needed to distinguish acute MI from chronic injury—increased six-fold (OR 6.03; 95% CI, 4.85-7.49). This surge in testing and admission places substantial strain on ED throughput and hospital bed capacity.
Long-term Clinical Outcomes
Critically, the increased sensitivity and subsequent clinical interventions did not result in improved patient safety or prognosis. The composite outcome of subsequent MI, heart failure, or cardiovascular death at one year was comparable between the two periods (OR 0.83; 95% CI, 0.48-1.41; P = .49). These findings suggest that the additional patients identified by hs-cTnT may represent a population with chronic myocardial injury or non-ischemic pathology rather than undiagnosed ACS that benefits from aggressive admission.
Key Findings: The Safety of Low-Threshold hs-cTnI
While the transition between assays causes friction, the use of specific thresholds remains highly effective for rule-out. The meta-analysis by Chapman et al. demonstrated that an hs-cTnI concentration of <5 ng/L at presentation identifies nearly 50% of the population as low risk. In this group, the negative predictive value (NPV) for MI or cardiac death at 30 days was 99.5%. At one year, the NPV for cardiac death remained remarkably high at 99.9%. This underscores the utility of hs-cTnI in rapidly identifying patients who can be safely discharged from the ED.
Expert Commentary: Mechanistic Insights and Clinical Strategy
The discrepancy between hs-cTnI and hs-cTnT performance is often attributed to the biological characteristics of the biomarkers. hs-cTnT is known to be more frequently elevated in patients with chronic kidney disease, skeletal muscle disorders, and older age, even in the absence of acute coronary ischemia. This “baseline noise” can lead to diagnostic uncertainty when using hs-cTnT, as clinicians must determine whether a positive result reflects an acute event or a chronic elevation.
From a health policy perspective, the TWITCH-ED study highlights the unintended consequences of laboratory changes. Hospital administrators and laboratory directors must recognize that assay transitions are not merely technical updates; they are clinical interventions that can alter the diagnostic threshold of a whole health system. The lack of improved outcomes at one year despite increased admissions suggests that many of these additional hospitalizations may have been unnecessary.
Study Limitations
The TWITCH-ED study was an interrupted time-series design, which, while robust, cannot account for all temporal changes in clinical practice. Additionally, the study was conducted in a specific geographic context, and the results may vary based on local admission thresholds and population demographics.
Conclusion
The transition from hs-cTnI to hs-cTnT assays leads to a significant increase in the detection of myocardial injury and hospital resource utilization without providing a measurable benefit in cardiovascular outcomes at one year. Conversely, hs-cTnI remains a powerful tool for rapid rule-out when using low-concentration thresholds. Clinicians and health systems should approach assay transitions with caution, ensuring that diagnostic protocols are adjusted to account for the unique performance characteristics of each biomarker to avoid unnecessary hospitalizations and patient anxiety.
Funding and Registration
The TWITCH-ED study is registered at ClinicalTrials.gov (NCT05748691). The research was supported by various grants detailed in the primary publications, focusing on improving the diagnosis of myocardial infarction in emergency settings.