High-sensitivity Troponin-T - Revision history

AndyS: /* Definitions */

2022-01-20T22:15:25Z

Definitions

← Older revision		Revision as of 22:15, 20 January 2022
Line 227:		Line 227:
	== Definitions ==		== Definitions ==
	*'''Myocardial injury'''		*'''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>		::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> ''NOTE: "myocardial injury" is NOT synonymous with ischemia, as injury can be due to <u>non-ischemic</u> conditions such as infiltrative diseases, trauma, inflammation, heart failure, etc.''
	*'''Acute myocardial injury'''		*'''Acute myocardial injury'''
	::<u>Myocardial injury</u> with a rise and/or fall of cTn values.<ref name="FUDoMI"/>		::<u>Myocardial injury</u> with a diagnostic rise and/or fall of cTn values.<ref name="FUDoMI"/>
	*'''Acute myocardial infarction''' (types 1, 2 and 3 MI)		*'''Acute myocardial infarction''' (types 1, 2 and 3 MI)
	::<u>Acute myocardial injury</u> '''and''' at least one of the following:<ref name="FUDoMI"/>		::<u>Acute myocardial injury</u> '''and''' at least one of the following:<ref name="FUDoMI"/>
	::::::- Symptoms consistent with acute coronary occlusion;		::::- Symptoms consistent with acute coronary occlusion;
	::::::- New ~~ischaemic~~ ECG changes;		::::- New ischemic ECG changes;
	::::::- Development of pathological Q waves;		::::- 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~~;		::::- Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology;
	::::::- Identification of a coronary thrombus by angiography or autopsy (not for type 2 or 3 MIs).		::::::- Identification of a coronary thrombus by angiography or autopsy (not for type 2 or 3 MIs).
	<br>		<br>

AndyS: /* Troponin Delta */

2022-01-20T22:07:37Z

Troponin Delta

← Older revision		Revision as of 22:07, 20 January 2022
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	== Troponin Delta ==		== Troponin Delta ==
			=== Terminology ===
			:For verbal communiction, delta's are most easily understood with the phrase Δ1h ("delta-1-h"). Starting the phrase with "delta" signals the listener that which is coming (i.e. a duration and magnitude).<ref>Personal opinion of Andrew W. Swartz, MD</ref>
			<br>

			=== 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-out ACS.

			:However, the ACC's (American College of Cardiology) whitepaper specifically recommends against this Δ1h cutoff due to being too similar to the Roche assay's margin of error; they explicitly suggest a cutoff of Δ2h < 4 ng/L.<ref name="ACC_whitepaper_2018"/>
			<br>

	== Troponin Level ==		== Troponin Level ==

AndyS: /* Delta (Δ) versus Level */

2022-01-20T22:07:06Z

Delta (Δ) versus Level

← Older revision		Revision as of 22:07, 20 January 2022
Line 75:		Line 75:

	== Delta (Δ) versus Level ==		== Delta (Δ) versus Level ==
			With traditional troponin assays, a troponin level was not detectable in most patients who lack cardiac ischemia. Emergency departments typically performed serial measurements to see if the troponin ''level'' became detectable over time. Therefore the ''level'' of the troponin was the focus while quantifying the magnitude of the ''delta (Δ)'' (i.e. the change of the level over time) 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 with regard to ACS/AMI: 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>

			However, there are initial levels below 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.
			<br>
			<br>

	== Troponin Delta ==		== Troponin Delta ==

AndyS: /* Statistical/Epidemiological Properties */

2022-01-20T22:05:51Z

Statistical/Epidemiological Properties

← Older revision		Revision as of 22:05, 20 January 2022
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	== Statistical/Epidemiological Properties ==		== Statistical/Epidemiological Properties ==
			=== Diagnostic Performance ===
			:High-sensitivity troponin assays have a much higher sensitivity for ACS than conventional assays, which yields a much higher '''negative predictive value''' ('''NPV'''). This allows clinicians to more quickly and accurately identify those chest pain patients who do not have ACS and who are at very low risk of 30-day MACE (major adverse cardiac events).

			:Yet the increased sensitivity comes at the cost of decreased specificity, yielding a lower '''positive predictive value''' ('''PPV'''). The clinical consequence of this is summed up well by Dr. Rebecca Vigen of UTSWMS (University of Texas Southwestern Medical Center) grand rounds transcript:
			::::''As the MI probability goes down, the additional positive test results with the hs-cTnT assay vs. the standard assay increases (false positives). Therefore, the proportion of positive tests with the high-sensitivity assay who do not have myocardial infarction will increase''.<ref>Vigen R. Providing High Value Care to Patients with Acute Chest Pain. Grand Rounds Presentation presented at the: Grand Rounds; June 14, 2019; University of Texas Southwestern Medical Center. https://cme.utsouthwestern.edu/sites/default/files/em1906g_061419_protocol_vigen.pdf. Accessed December 5, 2019.</ref>
			<br>
			:The following data reported by de Lemos et al. (2011)<ref>de Lemos JA, Morrow DA, deFilippi CR. Highly sensitive troponin assays and the cardiology community: a love/hate relationship? Clin Chem. 2011;57(6):826-829. doi:[https://doi.org/10.1373/clinchem.2011.163758 10.1373/clinchem.2011.163758]</ref> illustrates the effect:
			<br>
			{\| class="wikitable" style="width: 85%;margin: auto;"
			\|+ style="caption-side:bottom;text-align:left;" \|Additional cTnT values above the MI-detection threshold with a highly sensitive (hs) cTnT assay,
			compared with a standard cTnT assay, across differing MI probabilities in the target population.
			\|-
			! scope="col"\| MI probability
			! scope="col"\| Positive tests with standard assay, /1000 patients
			! scope="col"\| Positive tests with hs assay, /1000 patients
			! scope="col"\| Additional positive tests with hs assay vs standard assay meeting MI definition, /1000 patients
			! scope="col"\| Additional positive tests with hs assay vs standard assay not meeting MI definition, /1000 patients
			\|-
			\| style="text-align:center;"\| 17%
			\| style="text-align:center;" \| 199
			\| style="text-align:center;" \| 328
			\| style="text-align:center;" \| 21
			\| style="text-align:center;" \| 108
			\|-
			\| style="text-align:center;"\| 10%
			\| style="text-align:center;" \| 146
			\| style="text-align:center;" \| 275
			\| style="text-align:center;" \| 12
			\| style="text-align:center;" \| 117
			\|-
			\| style="text-align:center;"\| 5%
			\| style="text-align:center;" \| 108
			\| style="text-align:center;" \| 237
			\| style="text-align:center;" \| 8
			\| style="text-align:center;" \| 121
			\|-
			\| style="text-align:center;"\| 3%
			\| style="text-align:center;" \| 93
			\| style="text-align:center;" \| 222
			\| style="text-align:center;" \| 3
			\| style="text-align:center;" \| 126
			\|}
			<br>
			:de Lemos derived these outcomes from calculations using the limit of detection for the conventional troponin assay and with the 99th percentile for the high-sensitivity troponin assay. However, clinicians must recognize that these calculations to not include the delta troponin (discussed below), but rather single values.
			<br>
			=== Population Distribution ===
			:The manufacturer recommended rule-out cutoffs (99% ULN) are based upon the following distribution:
			<br>
			<br>
			[[File:Hs-Tnt 4G histogram Giannitsis 2009.jpg\|thumb\|700px\|center\|Troponin-T distribution in healthy individuals.<ref>Giannitsis E, Kurz K, Hallermayer K, Jarausch J, Jaffe AS, Katus HA. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem. 2010;56(2):254-261. doi:[https://doi.org/10.1373/clinchem.2009.132654 10.1373/clinchem.2009.132654]</ref>]]
			<br>
			<br>

	== Delta (Δ) versus Level ==		== Delta (Δ) versus Level ==

AndyS: /* Definition */

2022-01-20T22:05:14Z

Definition

← Older revision		Revision as of 22:05, 20 January 2022
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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 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 clinicians conceptualize and interpret cardiac troponin levels.
			<br>
			<br>

	== Statistical/Epidemiological Properties ==		== Statistical/Epidemiological Properties ==

AndyS at 22:04, 20 January 2022

2022-01-20T22:04:18Z

@@ Line 4: / Line 4: @@
 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/L, 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.
+:::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 ng/L, and a high-sensitivity concentration of 14 ng/L is equivalent to a traditional concentration of 0.014 ng/mL. 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.
@@ Line 15: / Line 16: @@
 <br>
 == 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 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 clinicians conceptualize and interpret cardiac troponin levels.
 == Statistical/Epidemiological Properties ==
 == Delta (Δ) versus Level ==
 == Troponin Delta ==
 == Troponin Level ==

AndyS: /* Troponin Delta */

2022-01-20T21:55:37Z

Troponin Delta

← Older revision		Revision as of 21:55, 20 January 2022
Line 83:		Line 83:

	== Troponin Delta ==		== Troponin Delta ==
			=== Terminology ===
			:For verbal communiction, delta's are most easily understood with the phrase Δ1h ("delta-1-h"). Starting the phrase with "delta" signals the listener that which is coming (i.e. a duration and magnitude).<ref>Personal opinion of Andrew W. Swartz, MD</ref>
			<br>

			=== 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-out ACS.

			:However, the ACC's (American College of Cardiology) whitepaper specifically recommends against this Δ1h cutoff due to being too similar to the Roche assay's margin of error; they explicitly suggest a cutoff of Δ2h < 4 ng/L.<ref name="ACC_whitepaper_2018"/>
			<br>

	== Troponin Level ==		== Troponin Level ==

AndyS: /* Delta (Δ) versus Level */

2022-01-20T21:54:38Z

Delta (Δ) versus Level

← Older revision		Revision as of 21:54, 20 January 2022
Line 73:		Line 73:

	== Delta (Δ) versus Level ==		== Delta (Δ) versus Level ==
			With traditional troponin assays, a troponin level was not detectable in most patients who lack cardiac ischemia. Emergency departments typically performed serial measurements to see if the troponin ''level'' became detectable over time. Therefore the ''level'' of the troponin was the focus while quantifying the magnitude of the ''delta (Δ)'' (i.e. the change of the level over time) 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 with regard to ACS/AMI: 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>

			However, there are initial levels below 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.
			<br>
			<br>

	== Troponin Delta ==		== Troponin Delta ==

AndyS: /* Statistical/Epidemiological Properties */

2022-01-20T21:53:52Z

Statistical/Epidemiological Properties

@@ Line 19: / Line 19: @@
 <br>
 == Statistical/Epidemiological Properties ==
 == Delta (Δ) versus Level ==

AndyS at 21:52, 20 January 2022

2022-01-20T21:52:44Z

@@ Line 4: / Line 4: @@
 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.
+:::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/L, 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.
@@ Line 19: / Line 19: @@
 <br>
 == Statistical/Epidemiological Properties ==
 == Delta (Δ) versus Level ==
 == Troponin Delta ==
 == Troponin Level ==