Difference between revisions of "High-sensitivity Troponin-T"

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As of November 12, 2019, the cardiac troponin assay utilized by the Yukon-Kuskokwim Delta Regional Hospital (YKDHR) is the Roche Diagnostics  [https://diagnostics.roche.com/us/en/products/params/elecsys-troponin-t-high-sensitive-tnt-hs.html ''Elecsys® Troponin T Gen 5 STAT''].  This is a high-sensitivity fifth-generation cardiac troponin assay.
 
As of November 12, 2019, the cardiac troponin assay utilized by the Yukon-Kuskokwim Delta Regional Hospital (YKDHR) is the Roche Diagnostics  [https://diagnostics.roche.com/us/en/products/params/elecsys-troponin-t-high-sensitive-tnt-hs.html ''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 contemporary troponin assays measure the exact same molecule, but high-sensitivity assays measure ''much'' more precisely and at ''much'' lower concentrations.  The high-sensitivity and contemporary assays can be distinguished by the units in which they are reported:  high-sensitivity assays are reported in ng/'''L''' whereas the contemporary assays are reported in ng/'''mL'''.   
+
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 contemporary 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 contemporary 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.
+
:::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.   
 
Though high-sensitivity troponin assays have been used in Europe and Canada since approximately 2009, the first U.S. FDA approval occurred in 2017.   
  
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<br>
 
<br>
 
== Definition ==
 
== 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.<ref>High-Sensitivity Cardiac Troponin in the Evaluation of Possible AMI. American College of Cardiology. https://www.acc.org/latest-in-cardiology/articles/2018/07/16/09/17/high-sensitivity-cardiac-troponin-in-the-evaluation-of-possible-ami. Accessed December 3, 2019.</ref>  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.
+
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.<ref name="ACC_whitepaper_2018">High-Sensitivity Cardiac Troponin in the Evaluation of Possible AMI. American College of Cardiology. https://www.acc.org/latest-in-cardiology/articles/2018/07/16/09/17/high-sensitivity-cardiac-troponin-in-the-evaluation-of-possible-ami. Accessed December 3, 2019.</ref>  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.
 +
<br>
 +
<br>
 +
== 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''
 +
<br>
 +
 
 +
'''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.<ref>Twerenbold R, Jaeger C, Rubini Gimenez M, et al. Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction. Eur Heart J. 2016;37(44):3324-3332. doi:[https://doi.org/10.1093/eurheartj/ehw232 10.1093/eurheartj/ehw232]</ref>
 +
<br>
 +
 
 +
'''FACT''': Across numerous trials, increasing troponin sensitivity has shown a dose-response relationship with increased ED discharges.
 
<br>
 
<br>
 
<br>
 
<br>
 
== Level versus Delta (Δ) ==
 
== Level versus Delta (Δ) ==
With contemporary 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.
+
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.<ref>Helman, A. McRae, A. Lang, E. Low Risk Chest Pain and High Sensitivity Troponin – A Paradigm Shift. Emergency Medicine Cases. July, 2019. https://emergencymedicinecases.com/low-risk-chest-pain-high-sensitivity-troponin. Accessed December 2, 2019.</ref>
 
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.<ref>Helman, A. McRae, A. Lang, E. Low Risk Chest Pain and High Sensitivity Troponin – A Paradigm Shift. Emergency Medicine Cases. July, 2019. https://emergencymedicinecases.com/low-risk-chest-pain-high-sensitivity-troponin. Accessed December 2, 2019.</ref>
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<br>
 
<br>
 
<br>
 
<br>
== Relative versus Absolute Delta (Δ) ==
+
== Troponin Delta ==
With contemporary troponin assays, a delta of 20% was often used to rule-in ACS.
+
=== 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.
 
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.
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<br>
 
<br>
 
<br>
 
<br>
== Δh Terminology ==
+
<br>
::::* 0h: Troponin drawn at ED arrival
+
=== Delta Cutoffs ===
::::* Δ1h: Troponin drawn 1 hour after ED arrival
+
The YKDHR Laboratory recommends that a Δ1h > 3 ng/L be used to rule-in ACS.
::::* Δ2h: Troponin drawn 2 hours after ED arrival
 
::::* Δ3h: Troponin drawn 3 hours after ED arrival
 
 
 
 
<br>
 
<br>
 
<br>
 
<br>
== Cutoffs ==
+
 
 +
== 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:
 
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:
 
{| class="wikitable" style="margin: auto;"
 
{| class="wikitable" style="margin: auto;"
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|}
 
|}
 
<br>
 
<br>
A Δ1h (i.e. the change in Hs-cTnT from ED arrival to 1 hour later) >= '''3''' ng/L is considered positive for acute myocardial injury (AMI).<br>
+
Δ1h >= '''3''' ng/L is considered positive for acute myocardial injury (AMI).<br>
 
<br>
 
<br>
 
Per the ACC white paper (see below):<br>
 
Per the ACC white paper (see below):<br>
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<br>
 
<br>
== Diagnostic Algorithm ==
+
== 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''":<ref name="ACC_whitepaper_2018"/>
 +
<br>
 +
[[File:ACC Whitepaper Figure-1 2018-07-16.PNG]]
 +
<br>
 +
<br>
 +
<br>
 
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:
 
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:
 
<br><br>
 
<br><br>
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<br>
 
<br>
  
 +
''' ACEP''Now''''' Articles
 +
:03-19-2019:  [https://www.acepnow.com/article/high-sensitivity-cardiac-troponin-tests-for-acute-myocardial-infarction-may-be-flawed/ ''High Sensitivity Cardiac Troponin Tests for Acute Myocardial Infarction May be Flawed'']
 +
:09-18-2019: [https://www.acepnow.com/article/chest-pain-patients-high-sensitivity-troponin-tests-new-frontier/2/ ''Chest-Pain Patients and High-Sensitivity Troponin Tests: the New Frontier'']
 +
<br>
 +
<br>
 +
== Definitions ==
 +
*'''Myocardial injury'''
 +
::Elevated cardiac troponin values (cTn) with at least one value above the 99th percentile upper reference limit (URL).<ref name="FUDoMI">Thygesen K, Alpert JS, Jaffe AS, et al. Fourth Universal Definition of Myocardial Infarction (2018). Journal of the American College of Cardiology. 2018;72(18):2231-2264. doi:[https://doi.org/10.1016/j.jacc.2018.08.1038 DOI: 10.1016/j.jacc.2018.08.1038]</ref>
 +
*'''Acute myocardial injury'''
 +
::<u>Myocardial injury</u> with a rise and/or fall of cTn values.<ref name="FUDoMI"/>
 +
*'''Acute myocardial infarction''' (types 1, 2 and 3 MI)
 +
::<u>Acute myocardial injury</u> '''and''' at least one of the following:<ref name="FUDoMI"/>
 +
::::::- 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).
 +
<br>
 +
<br>
 +
<br>
 
== References ==
 
== References ==

Revision as of 13:36, 3 December 2019

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.[1] 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.[2]

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.[3]

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":[1]
ACC Whitepaper Figure-1 2018-07-16.PNG


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:

UTSW-Parkland hs-cTnT pathway.PNG

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).[4]
  • Acute myocardial injury
Myocardial injury with a rise and/or fall of cTn values.[4]
  • Acute myocardial infarction (types 1, 2 and 3 MI)
Acute myocardial injury and at least one of the following:[4]
- 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).




References

  1. 1.0 1.1 High-Sensitivity Cardiac Troponin in the Evaluation of Possible AMI. American College of Cardiology. https://www.acc.org/latest-in-cardiology/articles/2018/07/16/09/17/high-sensitivity-cardiac-troponin-in-the-evaluation-of-possible-ami. Accessed December 3, 2019.
  2. Twerenbold R, Jaeger C, Rubini Gimenez M, et al. Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction. Eur Heart J. 2016;37(44):3324-3332. doi:10.1093/eurheartj/ehw232
  3. Helman, A. McRae, A. Lang, E. Low Risk Chest Pain and High Sensitivity Troponin – A Paradigm Shift. Emergency Medicine Cases. July, 2019. https://emergencymedicinecases.com/low-risk-chest-pain-high-sensitivity-troponin. Accessed December 2, 2019.
  4. 4.0 4.1 4.2 Thygesen K, Alpert JS, Jaffe AS, et al. Fourth Universal Definition of Myocardial Infarction (2018). Journal of the American College of Cardiology. 2018;72(18):2231-2264. doi:DOI: 10.1016/j.jacc.2018.08.1038