Cardiac Biomarkers in Pediatrics - Revision history

AndyS: /* hs-cTnT */

2022-02-12T08:36:41Z

hs-cTnT

← Older revision		Revision as of 08:36, 12 February 2022
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			:::*Figure-1 is an adaptation of Guo et al's figure illustrating the distribution of hs-cTnT versus age:
			[[File:Guo et al Fig-2.PNG\|frameless\|center\|526px]]
	=== Diagnostic Cutoff[s] ===		=== Diagnostic Cutoff[s] ===
	99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.		99th percentile for a healthy population. Since this is a definition (as discussed above), the term "diagnostic cut-off" does not clearly apply to this cut-off.
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	<br>		<br>
	<br>		<br>


	== N-Pro-BNP ==		== N-Pro-BNP ==

AndyS: /* Biochemistry */

2022-01-22T02:00:30Z

Biochemistry

← Older revision		Revision as of 02:00, 22 January 2022
Line 27:		Line 27:
	The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle.<br>		The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle.<br>

	Troponin ~~I and T~~ "~~leak~~" from cardiomyocytes when cell membrane permeability is increased; this condition is ~~referred to as~~ myocardial "injury," and can be caused by both ischemic and non-ischemic processes. Ischemic processes include acute coronary syndrome and chronic coronary ischemia (such as ischemic cardiomyopathy), while ~~a multitude of~~ non-ischemic processes ~~can yield myocardial cell "injury"~~ (~~including~~ inflammation, apoptosis, cytotoxicity, infiltrative diseases, hypoxemia, shock, ventricular strain, trauma, etc).<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (available on Sci-Hub)</ref> Clinical decisions regarding elevated troponin must incorporate an understanding <u>non-ischemic</u> myocardial injury. Indeed, while ischemic causes of myocardial injury predominate in older adults, non-ischemic causes vastly predominate in ~~the~~ pediatric age groups.<ref name=Wang2021/>		Troponin "leaks" from cardiomyocytes when cell membrane permeability is increased; this condition is termed myocardial "injury," and it can be caused by both ischemic and non-ischemic processes. Ischemic processes include acute coronary syndrome and chronic coronary ischemia (such as ischemic cardiomyopathy), while non-ischemic processes include a multitude of diverse conditions (such as inflammation, apoptosis, cytotoxicity, infiltrative diseases, hypoxemia, shock, ventricular strain, trauma, etc).<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (available on Sci-Hub)</ref> Clinical decisions regarding elevated troponin must incorporate an understanding <u>non-ischemic</u> myocardial injury. Indeed, while ischemic causes of myocardial injury predominate in older adults, <u>non-ischemic causes vastly predominate in all pediatric age groups</u>.<ref name=Wang2021/>
	<br>		<br>

AndyS at 01:41, 22 January 2022

2022-01-22T01:41:40Z

← Older revision		Revision as of 01:41, 22 January 2022
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	The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle.<br>		The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle.<br>

	Troponin I and T "leak" from cardiomyocytes when cell membrane permeability is increased; this condition is referred to as myocardial "injury," and can be caused by both ischemic and non-ischemic processes. Ischemic processes include acute coronary syndrome and chronic coronary ischemia (such as ischemic cardiomyopathy), while a multitude of non-ischemic processes can yield myocardial cell "injury" (including inflammation, apoptosis, cytotoxicity, infiltrative diseases, hypoxemia, shock, ventricular strain, trauma, etc).<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (available on Sci-Hub)</ref> Clinical decisions regarding elevated troponin must incorporate an understanding <u>non-ischemic</u> myocardial injury.		Troponin I and T "leak" from cardiomyocytes when cell membrane permeability is increased; this condition is referred to as myocardial "injury," and can be caused by both ischemic and non-ischemic processes. Ischemic processes include acute coronary syndrome and chronic coronary ischemia (such as ischemic cardiomyopathy), while a multitude of non-ischemic processes can yield myocardial cell "injury" (including inflammation, apoptosis, cytotoxicity, infiltrative diseases, hypoxemia, shock, ventricular strain, trauma, etc).<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (available on Sci-Hub)</ref> Clinical decisions regarding elevated troponin must incorporate an understanding <u>non-ischemic</u> myocardial injury. Indeed, while ischemic causes of myocardial injury predominate in older adults, non-ischemic causes vastly predominate in the pediatric age groups.<ref name=Wang2021/>
	<br>		<br>

	=== Normal Range[s] ===		=== Normal Range[s] in Pediatric Age Groups ===
	Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH). Search methods are documented in the ''Methods'' section (below).		Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH). Search methods are documented in the ''Methods'' section (below).
	<br>		<br>

AndyS: /* Biochemistry */

2022-01-22T01:35:08Z

Biochemistry

← Older revision		Revision as of 01:35, 22 January 2022
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	== hs-cTnT ==		== hs-cTnT ==
	=== Biochemistry ===		=== Biochemistry ===
	The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle. Troponin I and T ~~are released~~ from cardiomyocytes ~~due~~ to ~~multiple types of~~ myocardial ~~cell~~ "injury" ~~(including ischemia, necrosis, apoptosis, cytotoxicity, inflammation, etc). Clinical decision making must incorporate the understanding that troponin I~~ and T can ~~undergo <u>~~non-ischemic~~</u> release~~ (such as ~~during non-~~ischemic ~~heart failure~~, non-ischemic inflammation, ~~and other conditions which injure the cardiomyocites without associated ischemia~~.<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (available on Sci-Hub)</ref>		The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle.<br>

			Troponin I and T "leak" from cardiomyocytes when cell membrane permeability is increased; this condition is referred to as myocardial "injury," and can be caused by both ischemic and non-ischemic processes. Ischemic processes include acute coronary syndrome and chronic coronary ischemia (such as ischemic cardiomyopathy), while a multitude of non-ischemic processes can yield myocardial cell "injury" (including inflammation, apoptosis, cytotoxicity, infiltrative diseases, hypoxemia, shock, ventricular strain, trauma, etc).<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (available on Sci-Hub)</ref> Clinical decisions regarding elevated troponin must incorporate an understanding <u>non-ischemic</u> myocardial injury.
	<br>		<br>

	=== Normal Range[s] ===		=== Normal Range[s] ===
	Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH). Search methods are documented in the ''Methods'' section (below).		Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH). Search methods are documented in the ''Methods'' section (below).

AndyS at 21:04, 21 January 2022

2022-01-21T21:04:06Z

@@ Line 86: / Line 86: @@
 <br>
+:;Guo et al (2021)<ref>Guo Q, Yang D, Zhou Y, Zhang S, Zhu T, Wang A, Lei M, Yang X. Establishment of the reference interval for high-sensitivity cardiac troponin T in healthy children of Chongqing Nan'an district. Scand J Clin Lab Invest. 2021 Nov;81(7):579-584. doi:[https://doi.org/10.1080/00365513.2021.1979245 10.1080/00365513.2021.1979245]. Epub 2021 Sep 28. PMID:[https://pubmed.ncbi.nlm.nih.gov/34581638/ 34581638]. (obtained through the Alaska Medical Library)</ref>
 === Diagnostic Cutoff[s] ===

AndyS at 15:45, 21 January 2022

2022-01-21T15:45:42Z

← Older revision		Revision as of 15:45, 21 January 2022
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	== hs-cTnT ==		== hs-cTnT ==
	=== Biochemistry ===		=== Biochemistry ===
	The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle. Troponin I and T are released from cardiomyocytes due to multiple types of myocardial cell "injury" (including ischemia, necrosis, apoptosis, cytotoxicity, inflammation, etc). Clinical decision making must incorporate the understanding that troponin I and T can undergo <u>non-ischemic</u> release (such as during non-ischemic heart failure, non-ischemic inflammation, and other conditions which injure the cardiomyocites without associated ischemia.<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (~~[https://web.archive.org/web/20220121152936/https://jcp.bmj.com/content/jclinpath/57/10/1025.full.pdf Archived]~~)</ref>		The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle. Troponin I and T are released from cardiomyocytes due to multiple types of myocardial cell "injury" (including ischemia, necrosis, apoptosis, cytotoxicity, inflammation, etc). Clinical decision making must incorporate the understanding that troponin I and T can undergo <u>non-ischemic</u> release (such as during non-ischemic heart failure, non-ischemic inflammation, and other conditions which injure the cardiomyocites without associated ischemia.<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. (available on Sci-Hub)</ref>
	<br>		<br>
	=== Normal Range[s] ===		=== Normal Range[s] ===

AndyS at 15:35, 21 January 2022

2022-01-21T15:35:50Z

← Older revision		Revision as of 15:35, 21 January 2022
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	== hs-cTnT ==		== hs-cTnT ==
	=== Biochemistry ===		=== Biochemistry ===
	~~Released~~ due to multiple types of myocardial injury (ischemia, necrosis, apoptosis, cytotoxicity, inflammation). ~~Certain levels, ''in the proper context'', constitute~~ the ~~definition of myocardial infarction. However,~~ troponin can undergo ''non-ischemic'' release during heart failure, inflammation, and other conditions (~~such as infiltrative diseases~~).~~'''~~[~~REF~~]~~'''~~		The [https://en.wikipedia.org/wiki/Troponin troponin Wikipedia article] provides an excellent, succinct review of the biochemistry of troponin. In summary, the troponin complex is a molecule bound to myosin within muscle cells and involved in muscle contraction. Troponin-I and troponin-T are specific to cardiac muscle. Troponin I and T are released from cardiomyocytes due to multiple types of myocardial cell "injury" (including ischemia, necrosis, apoptosis, cytotoxicity, inflammation, etc). Clinical decision making must incorporate the understanding that troponin I and T can undergo <u>non-ischemic</u> release (such as during non-ischemic heart failure, non-ischemic inflammation, and other conditions which injure the cardiomyocites without associated ischemia.<ref name=Ammann2004>Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ. 2004 May 1;328(7447):1028-9. doi:[https://doi.org/10.1136/bmj.328.7447.1028 10.1136/bmj.328.7447.1028]. PMID:[https://pubmed.ncbi.nlm.nih.gov/15117768/ 15117768]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc403831/ PMC403831]. ([https://web.archive.org/web/20220121152936/https://jcp.bmj.com/content/jclinpath/57/10/1025.full.pdf Archived])</ref>
	<br>		<br>
	=== Normal Range[s] ===		=== Normal Range[s] ===
	Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH).		Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH). Search methods are documented in the ''Methods'' section (below).
	<br>		<br>
	<br>		<br>

AndyS at 15:12, 21 January 2022

2022-01-21T15:12:09Z

← Older revision		Revision as of 15:12, 21 January 2022
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	:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref>		:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref>
	::Prospective, single-cohort study of cord blood of 241 healthy, term ~~newborn~~ in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several findings ~~worthy of presenting~~:		::Prospective, single-cohort study of cord blood of 241 <u>healthy</u>, term <u>newborns</u> in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several notable findings:
	:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''		:::*''"The difference between hscTnT concentrations in boys and girls tended to be statistically significant (38.7 ng/l [33.0 to 52.8 ng/l] and 36.7 ng/l [29.2 to 47.1 ng/l], respectively, p=0.052)."''
	:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''		:::*''"The concentration of hscTnT was found to be significantly lower in newborns delivered via Cesarean section when compared with vaginal delivery (35.0 ng/l [28.5 to 43.4 ng/l] and 38.9 ng/l [32.6 to 48.4 ng/l], respectively, p=0.0084)."''

AndyS at 15:02, 21 January 2022

2022-01-21T15:02:07Z

← Older revision		Revision as of 15:02, 21 January 2022
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	<br>		<br>
	=== Normal Range[s] ===		=== Normal Range[s] ===
			Only studies reporting values for the Roche hs-cTnT Gen 5 STAT assay are presented here (because other assays and/or troponin types have different cut-offs and are thus not pertinent to clinical decision making at YKDRH).
	<br>		<br>
			<br>

	:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref>		:;Jehlicka et al (2018)<ref>Jehlicka P, Huml M, Rajdl D, Mockova A, Matas M, Dort J, Masopustova A. How to interpret elevated plasmatic level of high-sensitive troponin T in newborns and infants? Physiol Res. 2018 May 4;67(2):191-195. doi:10.33549/physiolres.933704. Epub 2018 Jan 5. PMID:29303610.</ref>
	::Prospective, single-cohort study of cord blood of 241 healthy, term newborn in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several findings worthy of presenting:		::Prospective, single-cohort study of cord blood of 241 healthy, term newborn in the Czech Republic. The authors report means and quartile values similar to other studies of hs-cTnT, but they report 97.5th percentiles rather than 99th percentiles. These results help understand the distribution newborn hs-cTnT levels, but without the 99th percentiles use of this data is limited and thus not presented here. However, the authors report several findings worthy of presenting:
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	:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''		:::*''"The hscTnT level correlated inversely with the base status (BE: rho=-0.14, p=0.03) and with the pH level of the umbilical cord blood (rho=-0.14, p=0.03)."''
	:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''		:::*''"Elevated plasma concentrations of hscTnT decreased to adult range within six months."''
			<br>
			:;Bohn et al (2019)<ref name=Bohn2019>Bohn MK, Higgins V, Kavsak P, Hoffman B, Adeli K. High-Sensitivity Generation 5 Cardiac Troponin T Sex- and Age-Specific 99th Percentiles in the CALIPER Cohort of Healthy Children and Adolescents. Clin Chem. 2019 Apr;65(4):589-591. doi:[https://doi.org/10.1373/clinchem.2018.299156 10.1373/clinchem.2018.299156]. Epub 2019 Feb 8. PMID:[https://pubmed.ncbi.nlm.nih.gov/30737206/ 30737206]. [http://web.archive.org/web/20220121142237/https://watermark.silverchair.com/clinchem0589.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAtgwggLUBgkqhkiG9w0BBwagggLFMIICwQIBADCCAroGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMl4zG0GFTLFsAxQlSAgEQgIICi9rtEHt0uQdmISjuSqNplYMUPPB2BYgbGVmyTaXZCCBLN7trLTiIoyta3WQgX29Or77tWs5ehXEXxDOcDbihDW-7vNziCRnzM_fs6hEbx7xOaWWy0YnGxX8gtsBgYTZMmHu2BD9gkV4ZJTO6Y26yR2pxB320Uq5aCNyvmrTl_gJx6XeVAUrAKQJ-qRgbPcxu8jC-BtUK3cxHW183n6k9-Sq0o1bjy1kJCUVZhGoLJasd6KuY9EhabfNvVrhnc5E3boLF-lNoof8pChLa-b9MHHg01m334zOpSyAdXSa8yUpEr3fyBoPk_A_EoshIfwEpu4nGGwhe8M8hwiOulBtlUp-oQt8neYVyqCobZcr2De8SHQoaeGSUXAK_Fv4XXACdl_C3NcyPJglzTvV67-Vfszd-4owWEuHDVUcv9UvtE21xJzuHGteyEbM67f1yjQ2uP0MJLNWtPNuEj-yj3S4PC8F4SeWUWV0y2bosDKsbU5KlYE5c65giuFvZQOLTtarmeXohElWPZHEe5GN2ekDEkvuUpQ57T8szWd7-LH1CG-jPrYSLEgf-8QI0MmV9zRm7rXYcpsVAvR0LHCm6DJU8ko-Ktjn9iAgp4Nq25ez3ZhrmlR-cZ78iTB3qi48imUEXDlitUEeo4nz1SoFMo0QokNrNc1D0sihRyoUcd4C_mkjU16tfLesK8Xr9gGgrdX2iYHGQVI7bsErMVjUVn-LdSctjFPWDCH67Yh3SRMFBQLsdGnzm9Uru5PXC_4mJg7WUirlQ_HQuY17dg3ImamMekHiRVxvkToTRtB9mbCMHiYsfc87iQm-QxYMcNYHj3YiD4EOVeBIUkEjx-al-r3jDMe_Qn3xF6nM4hPHEog Archived]</ref>
			::Unclear if retrospective or prospective; samples from "apparently" healthy infants (<1y) obtained from local maternity wards and outpatient clinics in Toronto, Canada; samples from >1 obtained from the "CALIPER biobank." Table-1 shows the reported 99th percentiles. Additionally, the authors report several notable observations:
			:::*''"hs-cTnT concentrations were markedly increased from 0 to <6 months and subsequently decreased and narrowed at 1 year."''
			:::*''"Although hs-cTnT concentrations from 0 to <1 year were normally distributed, hs-cTnT concentrations for both sexes of age 1 to <19 years were highly skewed."''
			:::*The authors comment about their 1y to 19y age group having 99th percentile cut-offs of 11 (F) and 14 (M) and this differing from the manufacturer package insert. They astutely note that the major cause for this difference is likely their use of a different reference population, and they highlight that neither reference population had imaging done (i.e. structural and coronary cardiac evaluations) to show that they were truly healthy with regard to establishing a distribution in "healthy" individuals.
			{\| class="wikitable" style="margin: auto;"
			\|+ Table-1.
			\|-
			! Age !! n !! 99th percentile
			\|-
			\| 0 – <6m \|\| style="text-align:center;" \| 55 \|\| style="text-align:center;" \| 93
			\|-
			\| 6m – <1y \|\| style="text-align:center;" \| 44 \|\| style="text-align:center;" \| 21
			\|-
			\| 1 – <19y F \|\| style="text-align:center;" \| 249 \|\| style="text-align:center;" \| 11
			\|-
			\| 1 – <19y M \|\| style="text-align:center;" \| 249 \|\| style="text-align:center;" \| 14
			\|}
	<br>		<br>
	:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref>		:;Karlen et al (2019)<ref name=Karlen2019>Karlén J, Karlsson M, Eliasson H, Bonamy AE, Halvorsen CP. Cardiac Troponin T in Healthy Full-Term Infants. Pediatr Cardiol. 2019 Dec;40(8):1645-1654. doi:[https://doi.org/10.1007/s00246-019-02199-9 10.1007/s00246-019-02199-9]. Epub 2019 Sep 5. PMID:[https://pubmed.ncbi.nlm.nih.gov/31489446/ 31489446]; PMCID:[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6848050/ PMC6848050].</ref>
	::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-1. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."		::Prospective, inpatient, single-cohort study of 158 [expected] <u>healthy</u>, term newborns, in Stockholm, Sweden. Summary results are shown in Table-2. The authors reported subgroup results for planned cesarean section versus vaginal delivery in their Table-3 (within the article). Regarding sex differences, the authors report "''When analyzing hs-cTnT in all infants (irrespective of mode of delivery), male infants had significantly higher values in cord blood than female infants (39[30–51] ng/L vs 28[24–39] ng/L, p = 0.001). However, in samples taken at 2–5 days of age the significant difference disappeared (96[62–157] ng/L vs 85[47–158] ng/L, p = 0.40)''."
	{\| class="wikitable" style="margin: auto;"		{\| class="wikitable" style="margin: auto;"
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	! Age !! n !! 99th percentile		! Age !! n !! 99th percentile
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	:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref>		:;Lam et al (2020)<ref name=Lam2020>Lam E, Higgins V, Zhang L, Chan MK, Bohn MK, Trajcevski K, Liu P, Adeli K, Nathan PC. Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort. J Appl Lab Med. 2021 Mar 1;6(2):344-353. doi:[https://doi.org/10.1093/jalm/jfaa090 10.1093/jalm/jfaa090]. PMID:[https://pubmed.ncbi.nlm.nih.gov/32995884/ 32995884]. (available on Sci-Hub)</ref>
	::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-2 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.		::Multi-center, outpatient study of 484 <u>healthy</u> outpatient pediatric patients in Toronto, Canada, aged 0 to 19 years. Both hs-cTnT and N-Pro-BNP were studied. Table-3 shows the study's reported age ranges and associated 99th percentile cut-offs for hs-cTnT. Within the article, Fig-1 shows the distribution of troponin versus age with different colors representing male and female values. The authors report finding no difference by sex, but the analysis was probably limited by sample size.
	{\| class="wikitable" style="margin: auto;"		{\| class="wikitable" style="margin: auto;"
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	! Age !! n !! 99th percentile		! Age !! n !! 99th percentile

AndyS at 05:50, 21 January 2022

2022-01-21T05:50:49Z

← Older revision		Revision as of 05:50, 21 January 2022
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	## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).		## As of January 2022, studies have only recently begun to quantify the distributions and normal ranges of troponin levels in healthy infants and children. At less than one year of age, the 99th percentile is markedly higher than in adults. At around one year the 99th percentiles are similar, and after one year the 99th percentiles are lower than in adults. Though sex-adjusting the 99th percentiles is not problematic, age-adjusting is: a hs-cTnT of 70 would be ''POSITIVE'' at 60 days old but ''NEGATIVE'' at 61 days old.<ref name=Jehlicka2021>Jehlicka P, Rajdl D, Sladkova E, Sykorova A, Sykora J. Dynamic changes of high-sensitivity troponin T concentration during infancy: Clinical implications. Physiol Res. 2021 Mar 17;70(1):27-32. doi:[https://doi.org/10.33549/physiolres.934453 10.33549/physiolres.934453]. Epub 2021 Jan 14. PMID:[https://pubmed.ncbi.nlm.nih.gov/33453718/ 33453718]. [http://web.archive.org/web/20220120164022/https://www.biomed.cas.cz/physiolres/pdf/2021/70_27.pdf Archived]</ref> In such a setting, decision making is less clear and the definition of "myocardial injury" starts seeming rather arbitrary (if not meaningless).
	## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref>		## ''Myocardial injury is NOT synonymous with ischemia''. Numerous non-ischemic causes of myocardial injury exist, such as infiltrative diseases, trauma, inflammation, etc. In fact, non-ischemic etiologies are greatly predominant in all pediatric age groups.<ref name=Wang2021>Wang AP, Homme JL, Qureshi MY, Sandoval Y, Jaffe AS. High-Sensitivity Troponin T Testing for Pediatric Patients in the Emergency Department. Pediatr Cardiol. 2021 Nov 17. doi:[https://doi.org/10.1007/s00246-021-02726-7 10.1007/s00246-021-02726-7]. Epub ahead of print. PMID:[https://pubmed.ncbi.nlm.nih.gov/34787696/ 34787696]. (available on Sci-Hub)</ref>
	#N-~~PRO~~-~~TERMINAL~~ BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.		#N-TERMINAL pro-BNP (N-Pro-BNP): Diagnostic cut-offs have been published for several disease conditions in some pediatric age groups, but few have been validated.
	#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.		#Indeed, considering the markedly higher normal ranges, and as argued by Assandro et al in 2013,<ref name=Assandro2013>Assandro P, Vidoni M, Starc M, Barbi E. Troponin T should not be considered as a screening test for pediatric myocarditis. Pediatr Emerg Care. 2013 Aug;29(8):955. doi:[https://doi.org/10.1097/pec.0b013e31829eca1d 10.1097/PEC.0b013e31829eca1d]. PMID:[https://pubmed.ncbi.nlm.nih.gov/23925259/ 23925259]. (available on Sci-Hub)</ref> these cardiac biomarkers ''may'' lack the ability to distinguish disease from non-disease in some (or all) pediatric age groups.
	#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without:		#No one should order a cardiac biomarker in a pediatric patient ''with the intent to rule-in or rule-out disease'' without: