ACUTE CHEST PAINNEW APPROACHES

TO AN OLD PROBLEM

Peter J. Paganussi MD, FACEP Assistant Clinical Professor

Georgetown University School of Medicine Staff Physician / Department of Emergency Medicine INOVA Fairfax Hospital

221

3790

1389

0500

1000150020002500300035004000

Number of Patients

Myocardialinfarction

Chest pain Other cardiacDX

Diagnosis

Fairfax ED 2000 Cardiac Patients

Total # of Patients - 5400Total # of Patients - 5400

426

2769

5

590

0

500

1000

1500

2000

2500

3000

Number of Patients

Intermediatecoronarysyndrome

Chest pain,unspecif ied

Precordialpain

Other chestpain

Diagnosis

Breakdown of Chest Pain Patients

Total # Chest Pains - 3790Total # Chest Pains - 3790

Chest Pain Patients

Admitted Chest Pains2306 (61%)

Discharged Chest Pains

1484 (39%)

Total # of Patients - 3790Total # of Patients - 3790

Discharged Chest Pains

1484 (39%)

• Missed MI malpractice payout = $500,000 to $1,000,000 per patient• Potential liability Fairfax ED = $37 to $74 Million

• 5% missed MI rate = 74.2 Patients

Admitted Chest Pains

2306 (61%)

Average hospital cost per patient = $1400/dayAverage length of stay = 2 to 3 daysTotal cost = $6.5 to $9.7 Million

30% to 50% = 692 to 1153 PatientsPotential cost savings = $1.9 to $4.8 Million

Myocardial Markers and Perfusion Imaging in the Evaluation of the

Emergency Department Chest Pain Patient

Michael C. Kontos, MDAssociate Director, Acute Cardiac Care

Director, Nuclear CardiologyAssistant Professor, Cardiology, Radiology and

Emergency MedicineMedical College of Virginia

Richmond, Virginia

Emergency Department Visits-US

95,000,000 ED Visits annually

8,000,000 Chest pain (8.4%)

3,000,000 5,000,000Sent home (40 %) Possible or actual MI (60 %)

40,000 (MI) 2,900,000 1,000,000 800,000 Non-cardiac AMI UA

(60 %) (20 %) (20 %)

Physician Insurers Association of America

AMI Study 1996 Malpractice Claims By Specialty

Group % All Claims Mean Payment

Family Practice 32 % $162,000

Internal Medicine 22 % $252, 000

Emergency Medicine 15 % $181,000

Cardiology 7 % $155,000

Cardiac MarkersDevelopment

• AST 1954

• LDH 1955

• CK 1960

• CK-MB isoenzymes 1970

• CK-MB mass 1985

• Myoglobin 1975

• TnT 1988

• TnI 1992

Current Myocardial Markers

• Myoglobin

• CK-MB

• Troponin

Timing of Marker Appearance

JACC 2000;36:970

Cardiac MarkersMyoglobin

• Advantages– Rapid release

– High early sensitivity

– Most useful for excluding MI

• Disadvantages– Not cardiac specific; false positives with:

• skeletal muscle damage

• renal failure

– specificities of 77-97%

– false negative if the patient presents very early

Myoglobin- -Diagnostic Accuracy

Study # Patients Time SN SPStone 108 admission 97 95Grenadier 15 3 100 NAIsakov 178 admission 95 NAOhman 82 admission 87 82Mair 126 2-4 82 91Vrenna 60 6-8 95 97Bakker 290 4 36 87Tucker 110 6 87 95De Winter 309 4 84 96Montague 89 admission 56 81Gornall 98 admission 43 98Laurino 100 4-6 70 81De Winter 309 5 87 97 (90 ug/L)

95 86 (50 ug/L)

Cardiac MarkersCK-MB

• Advantages

– Newer immunassays are rapid and cost effective

– Diagnostic standard for MI

– High specificity

• Disadvantages

– Not completely cardiac specific

– Early sensitivity low

Improving Sensitivity: Marker Combinations

• No marker has optimal diagnostic accuracy at all time points

• Sensitivity can be improved by combining two markers

– Early rising marker (eg, myoglobin)

– Later rising, more specific marker (eg, troponin)

• Caveats for interpreting study results:

– Number of samples and sample timing

– Number of patients with MI

– Overall MI prevalence

Improving Sensitivity Marker Combinations

Sens Spec

Initial MB 46% 99%

Initial MB or Myo 64% 89%

0 or 3 hr MB 78% 99%

0 or 3 hr MB or Myo 94% 86%

0 or 3 hr MB or 93% 98%

doubling of MBKontos et al AJC 1999;83:155

Cardiac Markers Marker Combinations

Sens Spec # TP # FP

Initial MB 46% 99%

Initial MB or Myo 64% 89%

0 or 3 hr MB 78% 99%

0 or 3 hr MB or Myo 94% 86% 22 230

0 or 3 hr MB or 93% 98% 20 21

doubling of MBKontos et al AJC 1999;83:155

MCV Critical Pathway Chest Pain Marker Strategy

Level Adm 3 6 8 12 18

1 Myo CK-MB

cTnI

- CK-MB

cTnI

- CK-MB

cTnI

CK-MB

cTnI

2 Myo CK-MB

cTnI

CK-MB

CK-MB

CK-MB

cTnI

- -

3 Myo CK-MB

cTnI

CK-MB

CK-MB

CK-MB

cTnI

- -

4 - - - - - -

Is <8 hours Sufficient for Diagnosis of MI?

Patient 1 Patient 2

Time CK-MB TnI CK-MB TnIhours ng/mL ng/mL ng/mL ng/mL

0 hr 1.5 <0.5 1.8 <0.5

3 hr 1.9 3.1

6 hr 2.6 8.0

8 hr 14.6 <0.5 14.3 <0.5

13 hr 23.2 4.6 22.3 3.0

Cardiac Markers

Troponin

• Structural Proteins

– TnT-binds to tropomyosin– TnI-inhibits A/M coupling

– TnC-binds calcium

• Cardiac specific

• Highly sensitive

• Prolonged elevations post MI

Cardiac Events, TnTFRISC Substudy

0

2.63.9

8.4

4.4

11.4

14.1

17.7

0

5

10

15

20

<0.06 0.06 to 0.18 >0.18 MI

Death Death or MI

Lindahl Circ 1996;93:1651

30 and 90 day Cardiac and All Cause Mortality Based on Peak TnI Value

0.61

1.5

2.2

2.93.3

6.2

7.1

0

1

2

3

4

5

6

7

8None (n=3215)Low (n=269)Inter (n=210)High (n=421)

30 Day Cardiac Mortality 90 Day Cardiac Mortality

Outcomes Based on Peak TnI ValueExcluding Patients with MI

0.6 1.4

10

17

22

1.5 3

17

23

27

2.25.5

25

34 35

5.8

16

38

53 54

0

10

20

30

40

50

60None (n=3209)Low (n=266)Inter (n=181)High (n=120)

Death Death/MI Death/MI Death/MI Death/MI Revasc Sig Dis Sig Dis/+Stress

Why do Troponin Elevations Predict Adverse Outcomes?

• More objective marker of an ACS

• Down stream thrombus/platelet embolization

• Increased prevalence of:

– Significant coronary disease

– Multi-vessel coronary disease

– Visible thrombus

– Suboptimal coronary flow

– Reduced systolic function

Benefit of GP IIb/IIIa and Troponin (+)30 Day MI/Death

13

19.6 19

4.35.8

11

0

5

10

15

20

25

Prism Capture Paragon B

HeparinGP IIb/IIIa+Heparin

14 Day Outcomes, TnI (+) and (-)Enoxaparin vs UFH

4

9 10

21

0

6

17

40

0

10

20

30

40

D/MI D/MI/UR D/MI D/MI/UR

EnoxUFH

Troponin (-)

Morrow JACC 2000;36:1812

Troponin (+)

Cardiac MarkersComparison Between TnI and TnT

• Troponin T

– only one assay available

• Troponin I

– multiple assays available

– different values for similar TnI concentrations

• Overall diagnostic sensitivity similar between TnT and TnI

Troponin IAssay Variations

0

5

10

15

20

10 ng/mL

AxSymOpusACS:180StratusAccess

16.8 ng/mL

13.7 ng/mL

9.2 ng/mL

5.3 ng/mL

2.5 ng/mL

Troponin

Choice of Diagnostic Value

• Upper Reference Level (Manufacturers’ Cut-off value; URL)

– higher specificity, decreased sensitivity

• Lower Limit of Detectability (LLD)

– higher sensitivity

– results in more FPs related to assay variability

• Optimal diagnostic value

– chosen by ROC curve analysis

Troponin ROC Curve

60

70

80

90

100

0 5 10 15

Sens

itivi

ty

(Tru

e Po

sitiv

e)

1- Specificity (False Positive)

LLD 0.5 ng/mlSn 97 % Sp 86 %

Opt 1.0 ng/mlSn 96 % Sp 93 %

URL 2.5 ng/mlSn 87 % Sp 97 %

Optimal LLD

MUL

Troponin False Positives

• Analytical False Positives

– hemolysis, clotting

– heterophile antibodies, Rheumatoid factor

• Non-Perfect Gold Standard

– Comparison with CK and CK-MB

• Biological False Positives

– Myocarditis

– Cardiac contusion

– Radio Frequency Ablation

– Transplant rejection

– Pulmonary embolism

TroponinFalse Negatives

• Sample Timing

• Imperfect gold standard

• Choice of diagnostic value

• Inability to detect ischemia alone

Frequency of Elevated TnT in U/A11 Studies, 1731 patients

48

39

65

35

21

52

2119

21

3842

33

0

10

20

30

40

50

60

70

Rottbauer et al Eur Heart J 1996;17 (Supp);17:1

Overall 33 % TnT (+)

Sensitivity of TnI For Cardiac Events96

92

43

1420

0

25

50

75

100

MI MI/D M/D/S Sig Dz Comp

Kontos JACC 2000;36:1818

The Acute Coronary Syndrome

Plaque Rupture

Intracoronary Thrombus

Reduced Blood Flow

Myocardial Ischemia

Myocardial NecrosisA

sym

ptom

atic

Uns

tabl

e A

ngin

a

Myo

card

ial I

nfar

ctio

n

Risk

Diagnostic Focus

perfusion imaging

ECG

CK-MB, TnI

Acute Perfusion Imaging in the ED

• Technetium-99m sestamibi and tetrofosmin are radioisotopes that do not redistribute

• Patients can be injected during symptoms and imaged after stabilization

• Images will provide a “snapshot” of the blood flow at the time of injection

Acute Perfusion Imaging in the EDInformation Obtained

• Myocardial perfusion

• Wall motion

• Wall thickening

• Ejection fraction

Cardiac Events, (+) and (-) Mibi

15

31

42

53

0.63.9 4.4

6.4

0

10

20

30

40

50

60

M I Rev M I/Rev M I/Sig

(+) Mibi

(-) Mibi

%

Kontos JACC 1997;30:976

Sensitivity for Cardiac EventsSestamibi and TnI

92

8175

82

30

10 10

21

97

29 29

52

0

25

50

75

100

MI Rev Sig M+S

(+) Mibi Initial (+) TnI(+) Serial TnI

Kontos Circ 1999;99:2073

%

Limitations of Acute Imaging

• Can’t tell the difference between

– acute ischemia

– acute infarction

– old infarction

• Requires 24 hour imaging capability

• Imperfect sensitivity

Myocardial Perfusion ImagingSensitivity

• Overall Sensitivity: 92 % (175/191)

• Mean risk area: 16 + 10 % of LV

• 16 patients had MI but (-) MPI

– Median peak CK: 235 U/L

– Median peak CK-MB: 12 ng/ml

– Mean EF: 58 %

• Cath in 12 patients:– 0 V in 5

– 1 V in 3

– 2 V in 4

Role of Perfusion Imaging

• Level 3--Probable Unstable Angina

– Rule in ACS---early intervention

– Rule out ACS--early stress testing and discharge

• Level 4--Possible Unstable Angina

– Rule in unsuspected ACS--prevent “missed MI”

LEVEL 3Probable Unstable Angina

• Moderate probability of MI or ischemia• Diagnostic criteria:

– ECG-non-ischemic– Symptoms--prolonged (>30 min)

• typical symptoms w/o known CAD• atypical symptoms in pt with known CAD

• Disposition– Observe in CCU-Fast track protocol

• Diagnostic strategy– Early markers– MPI

Case 2003146

• 50 yo female with 2 hr substernal CP

• 11 pm ECG: NSST

• Triaged as Level 3

• Rest mibi: normal• 7 am markers: CK 150 U/L

MB 1.3 ng/ml TnI <.1 ng/ml

• 9 am stress test: normal

• 12 pm discharge home

LEVEL 4Possible Unstable Angina

• Low probability of MI and low-moderate Probability of unstable angina

• Diagnostic criteria:– ECG-non-ischemic– Symptoms

• Suggestive symptoms <30 min• Prolonged atypical symptoms• Cocaine-associated chest pain

• Disposition– ED evaluation

• Diagnostic strategy– MPI

ED Perfusion ImagingCocaine Chest Pain

• 216 pts with acute imaging

• 5 patients (+) (2 %)– 2 MIs

• 211 patients (-)– no MIs– 2 with significant

coronary disease

211

50

50

100

150

200

250

2 MIs

No MIs

(-) MPI (+) MPIKontos Ann Emer Med 1999;33:639

Case 5906303

• 54 yo male presented at 00:19 with two day history of intermittent chest discomfort

– described as burping sensation

– no radiation

• Now continuous for 1 1/2 hrs

• Risk factors--tob, HTN

• ECG:

Case 5906303

• Initial triage level 4

• Mibi shows high grade inferior defect, absent WM

• ECG repeated at 4:30 am

Case 5906303

• Treated with tPA

• Initial markers 6 am: myo 68 ng/mlMB 1.8 ng/mlCK 81 U/L

• PTCA to RCA next day

• Follow up stress test 1 month later: normal

Case 6492345

• 40 year old male had substernal chest burning and aching for 4 days

• Evaluated at another hospital 3 days previously and d/c’d with ranitidine

• Symptoms continued with increased frequency

• Evaluated at MCV

• ECG:

Short Axis

Vertical Long Axis

Horizontal Long Axis

Acute Sestamibi

Case 6492345Markers

5 pm 107 U/L 1.6 ng/ml <0.5 ng/ml

8 pm 99 U/L 2.4 ng/ml 0.6 ng/ml

1 am 127 U/L 5.2 ng/ml 2.2 ng/ml

3 am 120 U/L 5.2 ng/ml

7 am 108 U/L 4.4 ng/ml 1.7 ng/ml

4 pm 78 U/L 1.8 ng/ml 1.8 ng/ml

Time CK CK-MB TnI

Initial Diagnostic Cath Post PTCA

Case 6492345

• Coronary angiography performed next

day--LAD 90-95%

• Successful angioplasty

• Repeat sestamibi 2 days later

Acute

Post PTCA

Acute

Post PTCA

Cost ComparisonControl Vs ACT

Control ACT Difference

Level 1 19,408 15,604 -20 %

Level 2 10,425 9,435 - 9.5 %

Level 3 5,051 4,958 - 1.8 %

Level 4 1,794 1,529 -15 %

Overall 6,044 5,030 -17 % *

* p=0.02 Kontos et al AHA 1999

Etiology of Cost Savings

• Reduced admissions in low risk (level 4) patients– 26 % vs 14 %

• Shorter LOS of intermediate risk (level 3) patients– 3.2 vs 2.6 days

• Decreased use of invasive procedures in intermediate and low risk (level 3 and 4) patients– 19 % vs 12.5 %

• Increased yield in patients having angio– Revascularization in 33 % vs 50 %

Conclusions

• Rapid diagnosis of MI can be made using individual or combinations of markers

• Troponin has both a higher sensitivity and additional prognostic value

• Acute imaging identifies patients with both infarction and ischemia

• No one method is sufficient for diagnosis; optimal accuracy requires a combination of tools and strategies