High-sensitivity Troponin-T

As of November 12, 2019, the cardiac troponin assay utilized by the Yukon-Kuskokwim Delta Regional Hospital (YKDHR) is the Roche Diagnostics Elecsys® Troponin T Gen 5 STAT. This is a high-sensitivity fifth-generation cardiac troponin assay.

Cardiac troponin assays measure the concentration of either troponin-T or troponin-I. Both high-sensitivity and traditional troponin assays measure the exact same molecule, but high-sensitivity assays measure much more precisely and at much lower concentrations. The high-sensitivity and traditional assays can be distinguished by the units in which they are reported: high-sensitivity assays are reported in ng/L whereas the traditional assays are reported in ng/mL.

Conversion between the results can be done by moving the decimal point three places: a traditional concentration of 0.4 ng/mL is equivalent to a high-sensitivity concentration of 400 mg/mL, and a high-sensitivity concentration of 14 ng/L is equivalent to a traditional concentration of 0.014 ng/L. This latter conversion illustrates that the high-sensitivity assays accurately measure concentrations which are two orders of magnitude lower than the assay we were previously using.

Though high-sensitivity troponin assays have been used in Europe and Canada since approximately 2009, the first U.S. FDA approval occurred in 2017.

NOTE: The information below is not a guideline, but rather excerpts and links intended to augment and/or help develop clinical judgement.

Definition

To qualify as high-sensitivity (or highly-sensitive), a cardiac troponin assay must be able to detect a level of cardiac troponin in >50% of normal individuals. This means that the majority of patients without cardiac ischemia will have a detectable level of cardiac troponin. This has substantial implications for how clinician conceptualize and interpret cardiac troponin levels.

High-sensitivity troponin Myths versus Reality

Myths:

• more patients will undergo catheterization
• ED stays will be longer
• there will be fewer ED discharges
• there will be more stress tests

FACT: the APACE trial showed that adoption of a high-sensitivity troponin assay was associated with no change in the number of catheterizations, decreased "normal cath" results, shorter ED stays, more ED discharges, and fewer stress tests.

FACT: Across numerous trials, increasing troponin sensitivity has shown a dose-response relationship with increased ED discharges.

Level versus Delta (Δ)

With traditional troponin assays, a troponin level was not detectable in most patients who lack cardiac ischemia. Therefore the level of the troponin was the focus while the subsequent delta (Δ) (i.e. a change) was a secondary consideration.

Due to the high-sensitivity assays' ability to detect a troponin level in most patients who lack cardiac ischemia, many experts recommend a reversal in diagnostic thinking: for most patients the delta (Δ) should be the focus while the level is a secondary consideration.

However, there are initial levels below and above which a delta is not required:

• If >= 3 hours since onset of symptoms and a normal EKG, then an initial troponin level < 6 ng/L can rule-out ACS.
• In the context of new symptoms consistent with ACS, an initial troponin level >100 ng/L rules-in ACS.

Troponin Delta

Relative versus Absolute Delta (Δ)

With traditional troponin assays, a delta of 20% was often used to rule-in ACS.

However, common situations arise with high-sensitivity troponin assays where relative deltas can lead to both over- and underdiagnosis. For example, if the initial troponin level is 5 ng/L, then a delta of 1 ng/L is a 20% rise, despite the change being within the expected margin of error of the assay. Alternately, the 20% relative change can miss ACS in patients with chronically elevated troponin levels.

Therefore many experts recommend using an absolute delta to rule-out or rule-in ACS.

Delta Cutoffs

The YKDHR Laboratory recommends that a Δ1h > 3 ng/L be used to rule-in ACS.

Troponin Level

Level Cutoffs

Hs-cTnT is considered "positive" when above the gender-specific 99th percentile URL (upper reference range). Per eMail from Scott Cox (YKDHR Director of Diagnostic Services) on 11/10/2019, the following cutoff are recommended for our assay:

Positive Values

Women	>= 14 ng/L
Men	>= 22 ng/L

Δ1h >= 3 ng/L is considered positive for acute myocardial injury (AMI).

Per the ACC white paper (see below):

• A single Hs-cTnT >= 100 ng/L is diagnostic of AMI (in the appropriate clinical context).
  
• When chest pain has been present for >= 2 hours, a single Hs-cTnT < 6 ng/L has been reported to rule out AMI with essentially 100% negative predictive value.

Diagnostic Algorithms

The following diagnostic algorithm has been proposed for high-sensitivity cardiac troponin-T by the ACC (American College of Cardiology), though they caution that "The safety of this approach is currently unclear":



The internet contains several somewhat similar algorithms on reputable medical sites. In particular, the ACEP Webinar (see below, page 16) displays the following diagnostic algorithm:



Note that this algorithm does not include risk stratification, such as with the HEART score. Yet the same Webinar contains other algorithms which separate out Hs-cTnT and call the risk stratification a HEAR score (or "modified-HEART" score) and guide diagnosis/management based upon different combinations of Hs-cTnT and HEAR values. Yet other algorithms in the same Webinar recommend skipping risk stratification in those who have low- or high-risk EKG/Hs-cTnT results and only risk stratifying those with intermediate-risk EKG/Hs-cTnT results.

Helpful Links

ACC (American College of Cardiology)

High-Sensitivity Cardiac Troponin in the Evaluation of Possible AMI (July 16, 2018)

SUMMARY: Fourth Universal Definition of Myocardial Infarction (Aug 25, 2018)

ACEP

Webinar: Incorporating High-Sensitivity Troponin into Your ED

Critical Issues in the Evaluation and Management of Emergency Department Patients with Suspected Non–ST-Elevation Acute Coronary Syndromes (Jun 2018)

MD Calc

HEART Score for Major Cardiac Events

ACEPNow Articles

03-19-2019: High Sensitivity Cardiac Troponin Tests for Acute Myocardial Infarction May be Flawed

09-18-2019: Chest-Pain Patients and High-Sensitivity Troponin Tests: the New Frontier

Definitions

• Myocardial injury

Elevated cardiac troponin values (cTn) with at least one value above the 99th percentile upper reference limit (URL).

• Acute myocardial injury

Myocardial injury with a rise and/or fall of cTn values.

• Acute myocardial infarction (types 1, 2 and 3 MI)

Acute myocardial injury and at least one of the following:

- Symptoms of myocardial ischaemia;

- New ischaemic ECG changes;

- Development of pathological Q waves;

- Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischaemic aetiology;

- Identification of a coronary thrombus by angiography or autopsy (not for type 2 or 3 MIs).