Cardiac Troponin Testing

Cardiac Troponin Testing One Step Back, Two Steps Forward? James de Lemos, MD Disclosures • Grant Support from Roche Diagnostics, and Abbott Diagno...
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Cardiac Troponin Testing One Step Back, Two Steps Forward?

James de Lemos, MD

Disclosures • Grant Support from Roche Diagnostics, and Abbott Diagnostics

Diagnostic Criteria for MI

Detection of rise and/or fall of cardiac markers (preferably troponin) with at least one value >99th percentile of the URL together with evidence of myocardial ischemia

Circulation. 2012 Aug 24. Epub

Prognostic Value of Pos. Troponin Test in ACS ACC/AHA Guidelines for UA/NSTEMI JACC 36:970, 2000

RR 3.9 (2.9-5.3)

25 20

%

RR 3.8 (2.6-5.5) 20.8

Neg Pos (Trop I + T)

15 10 5 0

# Studies:

6.4

6.7

1849

737

1.9 3634

Death 13

322

Death/MI 6

Relation of cTnT to Epicardial and Microvasculature Perfusion in TACTICS 80

72

cTnT Pos 65

cTnT Neg

60 43

58 42

40 29 16

20

7

0

Thrombus

Stenosis Severity

Occluded Culprit

Impaired Microvascular Flow

Wong GC et al. Circulation 2002;106:202-7.

Troponins in Clinical Decision-Making 30

GPIIb/IIIa

Control

% 30-d Death/MI

25 20

LMWH

Invasive Rx Exper

19.6 17

15

10 10

5.8

10.7 5

5 0

CAPTURE

TIMI 11B

TACTICS

Heeschen NEJM 1999

Morrow JACC 2000

Morrow JAMA 2001

Non-ACS  of Cardiac Troponins • Pulmonary embolism

• Congestive Heart Failure • Sepsis • Renal Failure

• Chronic CAD/LVH/LVSD

Troponin Elevation in the General Population The Dallas Heart Study 0.7% prevalence of cTnT > 0.01 mg/L

Odds Ratio

Diabetes

4.6

LV Hypertrophy

5.4

Congestive Heart Failure

5.3

Chronic Kidney Disease

20.4

40

% with elevated cTnT

Risk Determinant

20 10

0 n

Wallace TW Circulation 2006; 113:1958-65

P3

2087

478

120

22

Number of Risk Determinants Present

Positive Predictive Value for the Diagnosis of ACS in Different Patient Profiles Troponin Levels

Patient Profile

Any Positive Result

0.1-1.0 ng/mL >1.0 ng/mL

All patients

56 (52-60)

48 (43-53)

76 (69-82)

Age < 70 y and creatinine < 1.13 mg/dL

78 (72-84)

73 (65-80)

89 (79-95)

Age < 70 y and creatinine ≥ 1.13 mg/dL

44 (35-55)

40 (29-52)

59 (36-79)

Age > 70 y and creatinine < 1.13 mg/dL

52 (42-63)

42 (31-54)

90 (68-99)

Age > 70 y and creatinine ≥ 1.13 mg/dL

37 (29-45)

27 (20-37)

59 (43-73)

Alcalai et al. Arch Intern Med. 2007;167:276-81.

Positive Predictive Value for the Diagnosis of ACS in Different Patient Profiles Troponin Levels

Patient Profile

Any Positive Result

0.1-1.0 ng/mL >1.0 ng/mL

All patients

56 (52-60)

48 (43-53)

76 (69-82)

Age < 70 y and creatinine < 1.13 mg/dL

78 (72-84)

73 (65-80)

89 (79-95)

Age < 70 y and creatinine ≥ 1.13 mg/dL

44 (35-55)

40 (29-52)

59 (36-79)

Age > 70 y and creatinine < 1.13 mg/dL

52 (42-63)

42 (31-54)

90 (68-99)

Age > 70 y and creatinine ≥ 1.13 mg/dL

37 (29-45)

27 (20-37)

59 (43-73)

Alcalai et al. Arch Intern Med. 2007;167:276-81.

Survival Curves According to Principal Diagnosis

Cumulative Survival ( %)

100

Diagnosis  ACS  Non-ACS

90

80

70

60 0

200

400

600

800

Survival Time (days) Alcalai et al. Arch Intern Med. 2007; 67:276-81.

What is an MI in 2016? Cardiac Injury?

Acute

Chronic

Rise and/or fall in cTn

Flat but elevated cTn

Ischemic Mechanism? History, ECG, echo, etc

yes Picture c/w plaque rupture?

Type I MI

no Precipitant? Anemia, HTN urgency, arrhythmia, etc

Type II MI

Think structural heart disease, renal disease

Non ischemic acute injury PE, CHF, myocarditis

Differentiating Type 1 vs. Type 2

Thygesen et al. EHJ 2012; 33: 2551-2567.

Discriminating Type 1 from Type 2 MI: Clinical Clues Rather than ‘Criteria’ Type 1 • Typical pattern of onset • Ischemic ECG abnormality at normal HR and BP • (Absence of a nonthrombotic cause)

Type 2 • Presence of identifiable cause • HR/BP plausibly consistent with increased demand • Situational symptom/signs

Diagnostic coronary imaging Morrow DA. ACC 2014

Next Generation Troponin Assays New Opportunities More Headaches?

hs-cTn Assays for MI Diagnosis Parameter Sens Spec NPV PPV

cTnT hs-cTnT 83 95 95 80 97 99 72 50

cTnT threshold=0.01 g/l hs-cTnT threshold=0.014 g/L

Reichlin, NEJM 2009; 361:858-867

Bayes’ Dirty Little Secret MI probability

Positive tests with standard assay (per 1000 patients)

Positive tests with Additional hs assay positive tests meeting MI definition

Additional positive tests not meeting MI definition

17%

199

328

21

108

10%

146

275

12

117

5%

108

237

8

121

3%

93

222

3

126

de Lemos JA, Morrow DA, deFilippi CR. Clin Chem 2011; 57:826-9

Can changes in troponin help to discriminate ischemic from non ischemic diagnoses?

Diagnostic Criteria for MI

Detection of rise and/or fall of cardiac markers (preferably troponin) with at least one value >99th percentile of the URL together with evidence of myocardial ischemia > 20% relative  suggested in NACB guideline

Circulation. 2012 Aug 24. Epub

Absolute vs Relative Change Serial measurement at 2 hours hs-cTnT

AUC

ROC cutpoint

Sens

Spec

PPV

NPV

Absolute 

0.95

7

89

93

64

98

Relative 

0.76

30%

64

84

35

94

Absolute 

0.98

5

100

95

22

100

Relative 

0.95

45%

100

86

10

100

Absolute 

0.91

8

90

87

76

95

Relative 

0.79

16%

75

80

64

88

0.014 at baseline**

Reichlin T et al. Circulation 2011;124:136-145

1 hr similar; 6 hr no added value

• n=703, 19% MI • 100% NPV for cTnT detection limit (0.001 μg/L) in 3594 patients (97.7%) 800

Frequency

600

400

200

0 0.025

CV Mortality Similar association with HF No association with MI

Omland T, et al. NEJM 2009; 361(26):2538-47

Hazard ratio (95% CI)

HS-cTnT in VAL-HEFT  Mortality  Hospitalization for HF

10



    

1

0

1

2

3

 





   

4

5

Deciles Latini, R. et al. Circulation 2007;116:1242-1249

6

7

8

9

10

Stability of hs-cTnT and BNP over 4 mos in Clinically Stable Patients

Latini, R. et al. Circulation 2007;116:1242-1249

hs-cTnT and Transplant Rejection

Dyer A. AHJ 2012;163:595-600

High(er) sensitivity troponins: advantages and disadvantages • ED rule out: – – – –

Major advantage is shortening of ROMI time Very low values may ROMI with single draw Absolute  more specific than relative  Get ready for an exponential increase in cTn consults

• Integrated algorithms like ADAPT will become standard of care • Increased sensitivity offers new opportunities – Disease screening – Chronic disease monitoring

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