Chest Pains: The Case For (and Against) High-Sensitivity Troponin Testing.

Troponin is a crucial biomarker in the diagnosis and management of acute coronary syndrome (ACS) and other heart-related conditions. Traditionally, regular troponin tests have been used to detect elevated levels of troponin in the blood, indicating heart muscle damage. In recent years, however, high-sensitivity troponin (hs-cTn) tests have been developed and increasingly adopted in clinical practice. These newer tests offer the ability to detect much lower concentrations of troponin, potentially allowing for earlier and more accurate diagnosis of cardiac events. As troponin assays get more sensitive, they do not lose specificity heart muscle damage, but they may lose specificity to the cause, as we’ll see below.

A total eclipse of the heart.

Advantages of High-Sensitivity Troponin Testing

Earlier Detection of Myocardial Infarction (MI): One of the most significant advantages of high-sensitivity troponin testing is its ability to detect very low levels of troponin, which can lead to earlier diagnosis of myocardial infarction (MI). Traditional troponin tests typically require a certain threshold of troponin to be present in the blood before a diagnosis can be made, which can delay treatment. In contrast, high-sensitivity troponin assays can detect troponin at levels that are ten to one hundred times lower than those detectable by regular troponin tests. This increased sensitivity means that clinicians can identify myocardial injury within hours of its occurrence, potentially leading to quicker intervention and improved outcomes for patients.

Improved Risk Stratification: High-sensitivity troponin testing allows for more accurate risk stratification of patients presenting with chest pain or other symptoms suggestive of ACS. By measuring troponin levels more precisely, clinicians can better categorize patients into low, intermediate, or high-risk groups. This stratification is crucial for determining the appropriate level of care and intervention. For example, patients with very low levels of troponin might be safely discharged from the emergency department, while those with higher levels may require admission and more aggressive treatment. This improved stratification can reduce unnecessary hospitalizations and focus resources on patients who are at genuine risk of adverse cardiac events.

Detection of Subclinical Cardiac Injury: High-sensitivity troponin tests can detect cardiac injury even in the absence of symptoms or significant ECG changes. This capability is particularly valuable in identifying patients with chronic conditions such as chronic kidney disease, heart failure, or diabetes, who may experience subclinical myocardial injury over time. Early detection of such injury can prompt closer monitoring, lifestyle modifications, or therapeutic interventions aimed at preventing the progression to more severe cardiac events. Moreover, high-sensitivity troponin levels have been shown to correlate with long-term cardiovascular risk, providing a valuable tool for ongoing patient management.

Reduced Time to Rule Out MI: High-sensitivity troponin testing can expedite the rule-out process for myocardial infarction, which is beneficial both for patient care and hospital efficiency. With traditional troponin tests, it often takes six to twelve hours of serial testing to confidently rule out an MI. High-sensitivity troponin assays, on the other hand, can sometimes allow clinicians to rule out an MI within just one to three hours. This faster rule-out process can lead to earlier discharge of patients who do not have an MI, freeing up emergency department resources and reducing patient anxiety.

Possibility for evaluating non-AMI events: Elevated troponin levels detected by high-sensitivity assays can also be found in non-ischemic conditions such as myocarditis, pulmonary embolism, or renal failure. This broadens the clinical utility of the test but also requires careful interpretation by healthcare providers. This is not a common use of this test, as it is generally used to rule in/out AMI.

Disadvantages of High-Sensitivity Troponin Testing

Increased False Positives: One of the primary drawbacks of high-sensitivity troponin testing is the potential for increased false positives. Because these tests can detect very low levels of troponin, they may identify troponin elevations in individuals without clinically significant myocardial injury. For example, troponin can be elevated in patients with conditions such as sepsis, pulmonary embolism, heart failure, or even strenuous exercise. This increased sensitivity can lead to confusion and unnecessary diagnostic workups, which may result in patient anxiety, additional healthcare costs, and exposure to unnecessary treatments.

Difficulty in Interpreting Results: The interpretation of high-sensitivity troponin results can be challenging, particularly in the absence of clear clinical guidelines. While traditional troponin tests have well-established cut-off values for diagnosing MI, the interpretation of high-sensitivity troponin levels is more complex. Small elevations in troponin may not always indicate an acute coronary event, and clinicians must carefully consider the clinical context, patient history, and other diagnostic findings when interpreting results. This complexity can lead to diagnostic uncertainty and potentially inappropriate management decisions.

Overdiagnosis and Overtreatment: The increased sensitivity of high-sensitivity troponin tests raises concerns about overdiagnosis and overtreatment. In some cases, patients with mild troponin elevations may be diagnosed with myocardial injury or acute coronary syndrome, even if they are not at immediate risk of a cardiac event. This can lead to unnecessary interventions, such as invasive coronary angiography or aggressive pharmacotherapy, which carry their own risks and costs. Additionally, the psychological impact of being labeled with a cardiac condition should not be underestimated, as it may lead to increased stress and a reduced quality of life for some patients.

Increased Healthcare Costs: The widespread adoption of high-sensitivity troponin testing has the potential to increase healthcare costs, both directly and indirectly. The tests themselves may be more expensive than traditional troponin assays, and the increased sensitivity can lead to more follow-up testing, imaging studies, and hospital admissions. Furthermore, the potential for overdiagnosis and overtreatment could drive up costs by increasing the use of medical resources for patients who may not benefit from such interventions. In a healthcare system already burdened by rising costs, the economic impact of high-sensitivity troponin testing is a significant consideration.

As we can see, the high-sensitivity troponin tests are not an unalloyed benefit, and in fact some medical facilities have chosen to forgo the upgrade. At the very least, they must be accompanied by a change in treatment guidelines to account for the [now detected] smaller elevations. The strategy of resisting the switch may not be a long-term solution, as most test systems are moving toward high-sensitivity troponin assays.

Comparative Time Course:

Initial Rise: With an AMI, troponin levels measured by both assays begin to rise shortly after the onset of symptoms. However, hs-Tn assays will detect this rise much earlier—often within 1-2 hours—whereas traditional assays might only detect the rise after 3-6 hours.

Peak Levels: Both assays will detect peak troponin levels, but hs-Tn assays will provide a more accurate peak due to their higher sensitivity. This peak typically occurs 12-24 hours after the onset of symptoms.

Resolution Phase: Traditional assays continue to show elevated troponin levels for a longer period, often making it difficult to distinguish between recent and past cardiac events. In contrast, hs-Tn assays can track the decline of troponin more precisely, providing better insight into the resolution of the myocardial injury.

Clinical Interpretation: The more sensitive nature of hs-Tn assays allows for earlier and more accurate diagnosis, which is particularly useful in emergency settings where rapid decision-making is required. The patterns observed with hs-Tn assays—such as an initial rise followed by a decrease—can help differentiate between ongoing myocardial injury and a past event.

Practical Implications:

Early Rule-In or Rule-Out: The ability of hs-Tn assays to detect troponin at very low levels and observe changes in levels over a short time frame allows for the rapid rule-in or rule-out of AMI. This can significantly reduce the time to diagnosis and treatment (or discharge!).

Serial Measurements: In clinical practice, serial measurements using hs-Tn assays (e.g., at 1, 3, and 6 hours) are often employed to observe the rise or fall of troponin levels. This helps to confirm or exclude AMI and also assists in assessing the severity and progression of myocardial injury.

How to incorporate high-sensitivity troponin assays into an AMI workup? (an example)

Correlate Clinical, ECG, and Troponin Data:

• STEMI: If ECG shows STEMI, confirm with troponin, but prioritize immediate intervention.

• NSTEMI: Rising troponin without ST-elevation on ECG confirms NSTEMI.

• Unstable Angina: Normal troponin but with suggestive symptoms and ECG changes may indicate unstable angina.

Consider Alternative Diagnoses:

• Non-Cardiac Causes: Evaluate for conditions like pulmonary embolism, aortic dissection, or gastrointestinal issues if troponin is stable and ECG findings are nonspecific.

• Chronic Troponin Elevation: Consider chronic conditions like heart failure, renal failure, or chronic myocardial injury if troponin is elevated without acute change.