Biomarkers in Forensic Diagnosis of Sudden Cardiac Death (SCD)

Saikat Das, Soumeek Chowdhuri, Ritwik Ghosh

Abstract


Abstract
Diagnosis of sudden cardiac death (SCD) is challenging for
medical professionals. For this reason, to make diagnosis easier for
forensic pathologists, there is a pressing need for the use of biomarkers.
This article highlights biomarkers that can be used in the
postmortem diagnosis of SCD.
Cardiac troponins, high-sensitivity C-reactive protein, and creatine
kinase-MB have proven to be very useful for this purpose.
Lactate dehydrogenase, myoglobin and tumor necrosis factor α, although
useful, are not efficient enough to be included in the list of
biomarkers for the diagnosis of SCD.
Previous studies have shown both positive and negative results
for natriuretic peptides as a biomarker, and further studies are required
to confirm its use as a biomarker for diagnosis of SCD in autopsy
cases. In living subjects, a multi-marker strategy is useful in
predicting risk of cardiovascular deaths. It is suggested that for the
diagnosis of SCD, a multi-marker strategy may be more efficient.
However, more studies are required to confirm this.


Keywords


Forensic Science, Sudden Cardiac Death, Biomarkers, Forensic Diagnosis.

Full Text:

PDF

References


Mehra R. Global public health problem of sudden

cardiac death. J Electrocardiol. 2007;40(6):S118-22.

https://doi.org/10.1016/j.jelectrocard.2007.06.023

World Health Organization. 1992. International Classification

of Diseases, 10th Revision (ICD-10). http://

www.who.int/classifications/icd/en/.

Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul

C, Blom N, Brugada J, Chiang CE, Huikuri H, Kannankeril

P. HRS/EHRA/APHRS expert consensus

statement on the diagnosis and management of patients

with inherited primary arrhythmia syndromes: document

endorsed by HRS, EHRA, and APHRS in May

and by ACCF, AHA, PACES, and AEPC in June

Heart rhythm. 2013;10(12):1932-63. https://doi.

org/10.1016/j.hrthm.2013.05.014

Schoen FJ. Ischemic heart disease. In: Cotran RS, Kumar

V, Robbins SL, editors. Robbins pathologic basis

of disease. 5th ed. Phiadelphia: Saunders; 1994. p.

–41.

Knight B. In: The pathology of sudden death. Forensic

pathology. London: Edward Arnold; 1991. p. 444–72.

Zhu BL, Ishikawa T, Michiue T, Li DR, Zhao D, Oritani

S, Kamikodai Y, Tsuda K, Okazaki S, Maeda H.

Postmortem cardiac troponin T levels in the blood and

pericardial fluid. Part 1. Analysis with special regard to

traumatic causes of death. Leg Med. 2006;8(2):86-93.

https://doi.org/10.1016/j.legalmed.2005.10.004

Mohan H. Textbook of Pathology. 7th ed. The Health

Science Publishers; 1992. 414 p.

Jaffe, A. S., & Ordonez-Llanos, J. (2010). High sensitivity

troponin in chest pain and acute coronary

syndromes. A step forward?. Revista espanola de cardiologia,

(07), 763-769. https://doi.org/10.1016/

S0300-8932(10)70178-0

Reichlin T, Hochholzer W, Bassetti S, Steuer S, Stelzig

C, Hartwiger S, Biedert S, Schaub N, Buerge C, Potocki

M, Noveanu M. Early diagnosis of myocardial infarction

with sensitive cardiac troponin assays. N Engl

J Med. 2009;361(9):858-67. https://doi.org/10.1056/

NEJMoa0900428

Zhu BL, Ishikawa T, Michiue T, Li DR, Zhao D, Kamikodai

Y, Tsuda K, Okazaki S, Maeda H. Postmortem

cardiac troponin T levels in the blood and pericardial

fluid. Part 2: analysis for application in the diagnosis

of sudden cardiac death with regard to pathology. Leg

Med. 2006;8(2):94-101. https://doi.org/10.1016/j.legalmed.

10.003

Reichlin T, Twerenbold R, Reiter M, Steuer S, Bassetti

S, Balmelli C, Winkler K, Kurz S, Stelzig C, Freese

M, Drexler B. Introduction of high-sensitivity troponin

assays: impact on myocardial infarction incidence and

prognosis. Am J Med. 2012;125(12):1205-13. https://

doi.org/10.1016/j.amjmed.2012.07.015

González-Herrera L, Valenzuela A, Ramos V, Blázquez

A, Villanueva E. Cardiac troponin T determination by

a highly sensitive assay in postmortem serum and pericardial

fluid. Forensic Sci Med Pathol. 2016;12(2):181-

doi:10.1007/s12024-016-9749-1. https://doi.

org/10.1007/s12024-016-9749-1

Kumar S, Ali W, Singh US, Kumar A, Bhattacharya

S, Verma AK, Rupani R. Temperature-Dependent

Postmortem Changes in Human Cardiac Troponin-

T (cTnT): An Approach in Estimation of Time Since

Death. J Forensic Sci. 2016;61:S241-5. https://doi.

org/10.1111/1556-4029.12928

Carvajal-Zarrabal O, Hayward-Jones PM, Nolasco-

Hipolito C, Barradas-Dermitz DM, Calderón-Garcidueñas

AL, López-Amador N. Use of cardiac injury

markers in the postmortem diagnosis of sudden cardiac

death. J Forensic Sci. 2017;62(5):1332-5. https://doi.

org/10.1111/1556-4029.13397

Brush JE, Kaul S, Krumholz HM. Troponin Testing for

Clinicians. J Am Coll Cardiol. 2016;68(21):2365-2375.

https://doi.org/10.1016/j.jacc.2016.08.066

Barberi C, van den Hondel KE. The use of cardiac troponin

T (cTnT) in the postmortem diagnosis of acute

myocardial infarction and sudden cardiac death: A

systematic review. Forensic sci int. 2018. https://doi.

org/10.1016/j.forsciint.2018.09.002

Du Clos TW. Function of C-reactive protein.

Ann med. 2000;32(4):274-8. https://doi.

org/10.3109/07853890009011772

Young B, Gleeson M, Cripps AW. C-reactive protein: a

critical review. Pathol. 1991;23(2):118-24. https://doi.

org/10.3109/00313029109060809

Kushner I. C-reactive protein and the acute-phase response.

Hospital practice (Office ed.). 1990;25(3A):13-6.

Peltola H, Jaakkola M. C-reactive protein in early

detection of bacteremic versus viral infections in immunocompetent

and compromised children. J pediatr.

;113(4):641-6. https://doi.org/10.1016/S0022-

(88)80372-X

Benjamin DR, Siebert JR. C-Reactive protein and

prealbumin in suspected sudden infant death syndrome.

Pediatr pathol. 1990;10(4):503-7. https://doi.

org/10.3109/15513819009067139

Rambaud C, Guibert M, Briand E, Grangeot-Keros

L, Coulomb-L’Herminé A, Dehan M. Microbiology

in sudden infant death syndrome (SIDS) and other

childhood deaths. FEMS Immunol Med Microbiol.

;25(1-2):59-66. https://doi.org/10.1111/j.1574-

X.1999.tb01327.x

Quan L, Fujita MQ, Zhu BL, Ishida K, Maeda H. Immunohistochemical

distribution of C-reactive protein

in the hepatic tissue in forensic autopsy. Forensic sci

int. 2000;113(1-3):177-82. https://doi.org/10.1016/

S0379-0738(00)00259-0

Uhlin-Hansen L. C-reactive protein (CRP), a comparison

of pre-and post-mortem blood levels. Forensic sci

int. 2001;124(1):32-5. https://doi.org/10.1016/S0379-

(01)00558-8

Kentaro S, Kimiharu I, Sari M, Shojiro T, Yuko K.

Exploration of Predictive Biomarkers for Sudden Unexplained

Cardiac Death in Nonelderly People: A

Case-Control Study With Biochemical Parameters

Related to Heart Failure. Am J Forensic Med Pathol.

Biomarkers in Forensic Diagnosis of Sudden Cardiac Death (SCD)

;39(1):41-5.

Ghormade PS, Kumar NB, Tingne CV, Keoliya AN.

Distribution & diagnostic efficacy of cardiac markers

CK-MB & LDH in pericardial fluid for postmortem

diagnosis of ischemic heart disease. J Forensic

Leg Med. 2014;28:42-6. https://doi.org/10.1016/j.

jflm.2014.09.011

Antman E, Bassand JP, Klein W, Ohman M, Sendon

JL, Rydén L, Simoons M, Tendera M. Myocardial infarction

redefined—a consensus document of the Joint

European Society of Cardiology/American College of

Cardiology committee for the redefinition of myocardial

infarction: the Joint European Society of Cardiology/

American College of Cardiology Committee. J Am Coll

Cardiol. 2000;36(3):959-69. https://doi.org/10.1016/

S0735-1097(00)00804-4

Lewandrowski K, Chen A, Januzzi J. Cardiac markers

for myocardial infarction: a brief review. Pathol Patterns

Reviews. 2002;118(suppl_1):S93-9.

Henderson AR, Moss DW. Enzymes. In: Burtis CA,

Ashwood ER, editors. Tietz textbook of clinical chemistry.

th ed. Philadelphia: Saunders Co.; 1986. p.

e66.

Osuna E, Pérez-Cárceles MD, Vieira DN, Luna A.

Distribution of biochemical markers in biologic fluids:

application to the postmortem diagnosis of myocardial

infarction. The Am J Forensic Med Pathol.

;19(2):123-8. https://doi.org/10.1097/00000433-

-00005

Carceles-Perez DM, Noeguera J, Jimenez JL, Martinez

P, Luna A, Osuna E. Diagnostic efficacy of biochemical

markers in diagnosis post-mortem of ischemic heart

disease. Forensic Sci Int. 2004;142(1):1-7. https://doi.

org/10.1016/j.forsciint.2004.02.007

Luna A, Villanueva E, Castellano MA, Jimenez G.

The determination of CK, LDH and its isoenzymes in

pericardial fluid and its application to the post-mortem

diagnosis of myocardial infarction. Forensic Sci

Int. 1982;19(1):85-91. https://doi.org/10.1016/0379-

(82)90154-2

Luna A, Carmona A, Villanueva E. The postmortem determination

of CK isozymes in the pericardial fluid in

various causes of death. Forensic Sci Int. 1983;22(1):23-

https://doi.org/10.1016/0379-0738(83)90116-0

Stewart RV, Zumwalt RE, Hirsch CS, Kaplan L.

Postmortem diagnosis of myocardial disease by

enzyme analysis of pericardial fluid. Am J Clin

Pathol. 1984;82(4):411-7. https://doi.org/10.1093/

ajcp/82.4.411

Osuna E, Perez MC, Jakobsson SW, Luna A. Biochemical

and morphological markers in the post mortem diagnosis

of ischemic heart distress. Acta Med Leg Soc

(Liege). 1990;40:275-83.

Burns J, Milroy CM, Hulewicz B, West CR, Walkley

SM, Roberts NB. Necropsy study of association

between sudden death and cardiac enzymes. J Clin

Pathol. 1992;45(3):217-20. https://doi.org/10.1136/

jcp.45.3.217

Perez-Carceles MD, Osuna E, Vieira DN, Martinez A,

Luna A. Biochemical assessment of acute myocardial

ischaemia. J Clin Pathol. 1995;48(2):124-8. https://doi.

org/10.1136/jcp.48.2.124

Batalis NI, Marcus BJ, Papadea CN, Collins KA.

The role of postmortem cardiac markers in the diagnosis

of acute myocardial infarction. J Forensic Sci.

;55(4):1088-91. https://doi.org/10.1111/j.1556-

2010.01368.x

Barabas B. CK-MB study in myocardial infarction and

sudden cardiac death. Rom J Leg Med. 2009;17(2):156-

https://doi.org/10.4323/rjlm.2009.156

Chen JH, Michiue T, Ishikawa T, Maeda H. Pathophysiology

of sudden cardiac death as demonstrated by

molecular pathology of natriuretic peptides in the myocardium.

Forensic Sci Int. 2012;223(1-3):342-8. https://

doi.org/10.1016/j.forsciint.2012.10.018

Hashimoto M, Nakajima M, Kuroda R, Yamaguchi R,

Maeda H, Nagai H, Ikegaya H, Yoshida KI. Sudden

unexpected death in a patient with epilepsy presenting

with high N-terminal probrain natriuretic peptide

level, cardiac lesions, and pulmonary edema. Int J cardiol.

;172(2):e265-7. https://doi.org/10.1016/j.ijcard.

12.069

Rae N, Finch S, Chalmers JD. Cardiovascular disease

as a complication of community-acquired pneumonia.

Curr Opin Pulm Med. 2016;22(3):212-8. https://doi.

org/10.1097/MCP.0000000000000261

Brown AO, Millett ER, Quint JK, Orihuela CJ. Cardiotoxicity

during invasive pneumococcal disease. Am J

Respir Crit Care Med. 2015;191(7):739-45. https://doi.

org/10.1164/rccm.201411-1951PP

Morris JA, Harrison LM, Biswas J, Telford DR. Transient

bacteraemia: a possible cause of sudden life

threatening events. Med hypotheses. 2007;69(5):1032-

https://doi.org/10.1016/j.mehy.2007.02.039

López-Amador N, Alfonso-Bravo JA, Ortíz-Valdez K,

Carvajal-Zarrabal O. Postmortem Blood Culture Profile

in Sudden Cardiac Death: An Exploratory Study. J Forensic

Sci. 2017; 5(2).

Palmiere C, Tettamanti C, Bonsignore A, De Stefano

F, Vanhaebost J, Rousseau G, Scarpelli MP, Bardy D.

Cardiac troponins and NT-proBNP in the forensic setting:

Overview of sampling site, postmortem interval,

cardiopulmonary resuscitation, and review of the literature.

Forensic Sci Int. 2018;282:211-8. https://doi.

org/10.1016/j.forsciint.2017.11.034

Chen JH, Inamori-Kawamoto O, Michiue T, Ikeda S,

Ishikawa T, Maeda H. Cardiac biomarkers in blood, and

pericardial and cerebrospinal fluids of forensic autopsy

cases: A reassessment with special regard to postmortem

interval. Leg med. 2015;17(5):343-50. https://doi.

org/10.1016/j.legalmed.2015.03.007

Luna A. Is postmortem biochemistry really useful?

Why is it not widely used in forensic pathology?. Leg

Med. 2009;11:S27-30. https://doi.org/10.1016/j.legalmed.

02.040

Vanhaebost J, Ducrot K, de Froidmont S, Scarpelli MP,

Egger C, Baumann P, Schmit G, Grabherr S, Palmiere

C. Diagnosis of myocardial ischemia combining

multiphase postmortem CT-angiography, histology,

and postmortem biochemistry. La radiol medica.

;122(2):95-105. https://doi.org/10.1007/s11547-

-0698-2

Palmiere C, Tettamanti C, Bonsignore A, De Stefano

F, Vanhaebost J, Rousseau G, Scarpelli MP, Bardy D.

Cardiac troponins and NT-proBNP in the forensic setting:

Overview of sampling site, postmortem interval,

cardiopulmonary resuscitation, and review of the literature.

Forensic Sci Int. 2018;282:211-8. https://doi.

org/10.1016/j.forsciint.2017.11.034

St-Pierre AC, Cantin B, Bergeron J, Pirro M, Dagenais

GR, Després JP, Lamarche B. Inflammatory markers

and long-term risk of ischemic heart disease in men:

a 13-year follow-up of the Quebec Cardiovascular

Study. Atherosclerosis. 2005;182(2):315-21. https://

doi.org/10.1016/j.atherosclerosis.2005.02.009

Wang TJ, Gona P, Larson MG, Tofler GH, Levy D,

Newton-Cheh C, Jacques PF, Rifai N, Selhub J, Robins

SJ, Benjamin EJ. Multiple biomarkers for the prediction

of first major cardiovascular events and death. N Engl

J Med. 2006;355(25):2631-9. https://doi.org/10.1056/

NEJMoa055373

Kim HC, Greenland P, Rossouw JE, Manson JE, Cochrane

BB, Lasser NL, Limacher MC, Lloyd-Jones

DM, Margolis KL, Robinson JG. Multimarker prediction

of coronary heart disease risk: the Women’s Health

Initiative. J Am Coll Cardiol. 2010;55(19):2080-91.

https://doi.org/10.1016/j.jacc.2009.12.047

Sabatasso S, Mangin P, Fracasso T, Moretti M, Docquier

M, Djonov V. Early markers for myocardial

ischemia and sudden cardiac death. Int J Legal Med.

;130(5):1265-80. https://doi.org/10.1007/s00414-

-1401-9




DOI: http://dx.doi.org/10.26735/16586794.2019.011

Refbacks

  • There are currently no refbacks.




Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.