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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