Laboratory

Tests
in the diagnosis and management of

Acute Chest Pain

Phuong Loc Nguyen

phuongloc04@gmail.com

H C M C , J a n . 1 5 t h , 2 0 1 8
HCMC, Jan. 15th, 2018
◉ Acute Chest Pain

◉ Roles of Laboratory Tests

◉ Cardiac Biomarkers

◉ High-sensitivity Cardiac Troponin

>>> hs-cTn Criteria
>>> hs-cTnI vs. hs-cTnT
>>> Test Interpretation

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 Acute Chest Pain
Burden Challenges

100 M
ER
6 M Chest pain
5 – 10% STEMI
15 – 20% NSTEMI
10% UAP

15% Other cardiac

50% Non-cardiac

NCHS, Hospital Discharge Data, 2002 Pope et al, NEJM, 2000 Marco Roffi, Carlo Patrono et al, 2015 ESC NSTE-ACS Guideline,
European Heart Journal (2016) 37, 267–315 3
 Acute Chest Pain

Marco Roffi, Carlo Patrono et al, 2015 ESC NSTE-ACS Guideline, European Heart Journal (2016) 37, 267–315
4
 Acute Chest Pain

Clinical Life-threatening/treatable
assessment Acute Aortic Dissection (AAD)
Acute Pulmonary Embolism (APE)
Tension pneumothorax

Serial Cardiac arrest/hemodynamic

Imaging
ECG
instability of CV origin
12-lead ECG >>> TTE

Cardiac
Biomarkers AAD, APE
D-Dimer & MSCT
Multidisciplinary approach to acute chest pain

. Marco Roffi, Carlo Patrono et al, 2015 ESC NSTE-ACS Guideline, European Heart Journal (2016) 37, 267–315
5
Amsterdam et al, 2014 AHA/ACC NSTE-ACS Guideline, Circulation. 2014;130:e344-e426
 Laboratory Tests

◉ Diagnosis
❄ Clinical presentation, EKG, cTn, TTE, CXR
❄ CK-MB: Class III

◉ Risk Stratification
❄ TIMI, GRACE
❄ Treatment strategy & timing according to initial risk stratification

◉ Prognosis

Marco Roffi, Carlo Patrono et al, 2015 ESC NSTE-ACS Guideline, European Heart Journal (2016) 37, 267–315
6
Amsterdam et al, 2014 AHA/ACC NSTE-ACS Guideline, Circulation. 2014;130:e344-e426
 Cardiac Biomarkers

Amsterdam et al, 2014 AHA/ACC NSTE-ACS Guideline, Circulation. 2014;130:e344-e426

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 Cardiac Biomarkers

Kinetic profiles of cardiac markers following STEMI

John K French and Harvey D White, Clinical implications of the new definition of myocardial infarction, Heart. 2004 Jan; 90(1): 99–106.
 Cardiac biomarkers

Properties of cardiac marker proteins

Protein Molecular mass (kD) First detection* Duration of detection Sensitivity Specificity

FABP 12 1.5–2 hours 8–12 hours +++ ++

Myoglobin 16 1.5–2 hours 8–12 hours +++ +
CK-MB 83 2–3 hours 1–2 days +++ +++
Troponin I 33 3–4 hours 7–10 days ++++ ++++

CK 96 4–6 hours 2–3 days ++ ++

AST ~103 6–10 hours 3–5 days ++ +
LDH 135 6–10 hours 5–7 days ++ +

*Hours after symptom onset.

CK, creatine kinase; LDH, lactate dehydrogenase; FABP, Fatty acid binding protein

John K French and Harvey D White, Clinical implications of the new definition of myocardial infarction, Heart. 2004 Jan; 90(1): 99–106 9
Cytoplasm’s cTn >>> Early release

Filaments’ cTn >>> Late, prolonged release

Sylvia Archan, M.D.; Lee A. Fleisher, M.D, From Creatine Kinase-MB to Troponin: The Adoption of a New Standard, Anesthesiology 4 2010, Vol.112, 1005-1012 10
High-sensitivity Cardiac Troponin
(hs-cTn)

hs-cTn Criteria

hs-cTnI vs. hs-cTnT

>>> Gender-specific cutoff
>>> eGFR inducing hs-cTn elevation

Test Interpretation

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 High-sensitivity Cardiac Troponin
(hs-cTn)

Hochholzer, W, et al,, Am Heart J, 2010, 160(4): 583-594 12

 hs-cTn Criteria – IFCC

CV ≤ 10% at 99
Measurable concentrations
th percentile
LoD è 99th percentile

≥ 50% healthy individuals

(ideally > 95%)

CV, Coefficient of Variation

LoD, Limit of Detection

Apple FS, Collinson PO, IFCC Task Force on Clinical Applications of Cardiac Biomarkers. Analytical characteristics of high-sensitivity
cardiac troponin assays. Clin Chem 2012;58:54–61.
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 hs-cTnI vs. hs-cTnT
IFCC Criteria

Tan JWC, Lam CSP, Kasim SS, et al. Asia-Pacific consensus statement on the optimal use of high-sensitivity troponin assays in acute coronary syndromes diagnosis:
focus on hs-TnI, Heart Asia 2017;9:81–87. 14
 hs-cTnI vs. hs-cTnT
Gender-specific cutoff

Tan JWC, Lam CSP, Kasim SS, et al. Asia-Pacific consensus statement on the optimal use of high-sensitivity troponin assays in acute coronary syndromes diagnosis:
focus on hs-TnI, Heart Asia 2017;9:81–87. 15
Shah AS V, Griffiths M, Lee KK, et al. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study.
BMJ 2015;350:g7873. 16
 hs-cTnI vs. hs-cTnT
Gender-specific cutoff
hs-cTnI
S e x - S p e c i f i c C u t o f f

♀ ↑↑ △MI
11% >>> 22%; p < 0.001

♂ minimal effect
19% >>> 21%, p = 0.002

Shah AS V, Griffiths M, Lee KK, et al. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study.
BMJ 2015;350:g7873. 17
 hs-cTnI vs. hs-cTnT
Impaired renal function

Slide courtesy of Prof. Aw Tar Choon, Changi General Hospital, Singapore TSIC symposium 2014, Ho Chi Minh city, Vietnam 18
 hs-cTnI vs. hs-cTnT
Impaired renal function
Elevated cTn & no AMI Optimal
Tests Impaired Normal Cutoff levels
Renal Function Renal Function GFR < 60

Abbott hs-TnI 17% 6% 1.1 x

Roche hs-TnT 71% 15% 2.1 x
Siemens hs-TnI 46% 23% 3.6 x
Beckman hs-TnI 54% 21% 2.8 x
Abbott cTnI 12% 7% 1.0 x
Siemens Ultra-s-TnI 20% 7% 1.2 x
Beckman Accu s-TnI 12% 7% 0.9 x
Raphael Twerenbold et al, Optimal Cutoff Levels of More Sensitive Cardiac Troponin Assays for the Early Diagnosis of Myocardial Infarction in Patients With Renal
Dysfunction, Circulation. 2015;131:2041-2050
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 hs-cTnI vs. hs-cTnT
Impaired renal function

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 hs-cTn Interpretation

3 main caveats in cTn Interpretation

Multidisciplinary approach Very early presenting High clinical suspicion

Algorithm of cTn Presenting very early High clinical suspicion

+ Chest pain characteristics (< 1 h of chest pain onset) Recurrent chest pain
+ ECG >>> 2nd cTn at 3 h >>> serial cTn

Marco Roffi, Carlo Patrono et al, 2015 ESC NSTE-ACS Guideline, European Heart Journal (2016) 37, 267–315
21
0 h/3 h rule-out algorithm of NSTE-ACS using hs-cTn assays

Marco Roffi, Carlo Patrono et al, 2015 ESC NSTE-ACS Guideline, European Heart Journal (2016) 37, 267–315
22
>>> ULN (ng/L)
16 (F) & 36 (M)

>>> Rule-in
10 x ULN

>>> Suspected AMI

△ 0h-3h >50%

ACS, acute coronary syndrome

ULN, upper limit of normal.
Consensus-based algorithm for hs-TnI levels in Asia Pacific

Tan JWC, Lam CSP, Kasim SS, et al. Asia-Pacific consensus statement on the optimal use of high-sensitivity troponin assays in acute coronary syndromes diagnosis:
23
focus on hs-TnI, Heart Asia 2017;9:81–87. doi:10.1136/heartasia-2016- 010818
 Risk Stratification

TIMI

GRACE

2015 ESC

2014 ACC/AHA

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 Risk Stratification

T I M I R i s k S c o r e Điểm
Age ≥ 65 1
≥ 3 risk factors for CAD (*) 1
Prior coronary stenosis ≥ 50% 1
ST deviation on ECG ≥ 0.5 mm 1
≥ 2 anginal events in prior 24 hours 1
Use of aspirin in prior 7 days 1
Elevated cardiac biomarkers (**) 1
(*)Family history of premature CAD; HTN; T2DM; Hypercholesterolemia; Smoking
(**) CKMB or Troponin

Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication
and therapeutic decision making. JAMA. 2000;284:835-42 25
 Risk Stratification
G R A C E R i s k M o d e l
Age SBP Heart rate Creatinine
Killip class Other risk factors
years mmHg beats/minute mg/dL
< 30 0 < 80 58 < 50 0 I 0 0-0.39 1 Cardiac arrest at admission 39
30-39 8 80-99 53 50-69 3 II 20 0.4-0.79 4 ST deviation 28
40-49 25 100-119 43 70-89 9 III 29 0.8-1.19 7 Elevated cardiac enzyme level 14
50-59 41 120-139 34 90-109 15 IV 59 1.2-1.59 10
60-69 58 140-159 24 110-149 24 1.6-1.99 13
70-79 75 160-199 10 150-199 38 2-3.99 21
80-89 91 ≥ 200 0 ≥ 200 46 ≥ 4 28
≥ 90 100

Granger CB, Goldberg RJ, Dabbous O, et al. Predictors of hospital mortality in the
Global Registry of Acute Coronary Events. Arch Intern Med. 2003;163:2345-53 26
http://www.gracescore.org
Marco Roffi, Carlo Patrono et al, 2015 ESC NSTE-ACS Guideline, European Heart Journal (2016) 37, 267–315
27
Amsterdam et al, 2014 AHA/ACC NSTE-ACS Guideline, Circulation. 2014;130:e344-e426
 Prognosis

Kaplan–Meier estimated rates of CV

death/MI through 30 days

Erin A. Bohula May, Marc P. Bonaca; Prognostic Performance of a High-Sensitivity Cardiac Troponin I Assay in Patients with Non–ST-Elevation Acute Coronary Syndrome,
Clinical Chemistry 60:1 (2014) 28
 Prognosis

Graded relationship between hs-cTnI

and CV death/MI at 30 days

Testing for a trend across all

categories of hs-cTnI was significant
(p-trend < 0.001)

Erin A. Bohula May, Marc P. Bonaca; Prognostic Performance of a High-Sensitivity Cardiac Troponin I Assay in Patients with Non–ST-Elevation Acute Coronary Syndrome,
Clinical Chemistry 60:1 (2014) 29
 Prognosis

Risk for CV Death/Heart Failure by

Baseline hs-TnI Level

Erin A. Bohula May, Marc P. Bonaca; Prognostic Performance of a High-Sensitivity Cardiac Troponin I Assay in Patients with Non–ST-Elevation Acute Coronary Syndrome,
Clinical Chemistry 60:1 (2014) 30
 T a k e – h o m e messages
Multidisciplinary approach to acute chest pain
hs-cTn è Cornerstone è AMI è 0 h/3 h algorithm (ESC, AHA, Asian-Pacific)

>> >>> >>> >>> >>> >>> >>> >>> >>> >>> Abbott hs-cTn I

>>> IFCC Criteria

~
>>> Less vulnerable to eGFR impairment
>>> Gender-specific cut-off values: 16/F & 36/M (ng/L)
>>> Important roles in diagnosis, risk assessment, prognosis
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T h a n k y o u
f o r y o u r
attention!

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