Transcript Diagnoses in 204 Patients with Non-AMI

ACUTE CHEST PAIN
NEW 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
Fairfax ED 2000 Cardiac Patients
3790
Number of
Patients
4000
3500
3000
2500
2000
1500
1000
500
0
1389
221
Myocardial
infarction
Total # of Patients - 5400
Chest pain Other cardiac
DX
Diagnosis
Breakdown of Chest Pain Patients
2769
3000
2500
2000
Number of
1500
Patients
1000
500
590
426
5
0
Intermediate
coronary
syndrome
Total # Chest Pains - 3790
Chest pain,
unspecified
Precordial
pain
Diagnosis
Other chest
pain
Chest Pain Patients
Discharged
Chest Pains
1484 (39%)
Total # of Patients - 3790
Admitted
Chest Pains
2306 (61%)
Discharged Chest Pains
1484 (39%)
• 5% missed MI rate = 74.2 Patients
• Missed MI malpractice payout = $500,000 to $1,000,000 per patient
• Potential liability Fairfax ED = $37 to $74 Million
Average hospital cost per patient = $1400/day
Average length of stay = 2 to 3 days
Total cost = $6.5 to $9.7 Million
Admitted Chest Pains
2306 (61%)
30% to 50% = 692 to 1153 Patients
Potential 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, MD
Associate Director, Acute Cardiac Care
Director, Nuclear Cardiology
Assistant Professor, Cardiology, Radiology and
Emergency Medicine
Medical 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
Sent home (40 %)
40,000 (MI)
5,000,000
Possible or actual MI (60 %)
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
7%
$155,000
Cardiology
Cardiac Markers
Development
• 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 Markers
Myoglobin
• 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
Stone
108 admission
Grenadier
15
3
Isakov
178 admission
Ohman
82
admission
Mair
126 2-4
Vrenna
60
6-8
Bakker
290 4
Tucker
110 6
De Winter
309 4
Montague
89
admission
Gornall
98
admission
Laurino
100 4-6
De Winter
309 5
SN
97
100
95
87
82
95
36
87
84
56
43
70
87
95
SP
95
NA
NA
82
91
97
87
95
96
81
98
81
97
86
(90 ug/L)
(50 ug/L)
Cardiac Markers
CK-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
Initial MB
Initial MB or Myo
0 or 3 hr MB
0 or 3 hr MB or Myo
0 or 3 hr MB or
doubling of MB
Sens
Spec
46%
64%
78%
94%
93%
99%
89%
99%
86%
98%
Kontos et al AJC 1999;83:155
Cardiac Markers
Marker Combinations
Initial MB
Initial MB or Myo
0 or 3 hr MB
0 or 3 hr MB or Myo
0 or 3 hr MB or
doubling of MB
Sens
Spec
# TP # FP
46%
64%
78%
94%
93%
99%
89%
99%
86%
98%
22
20
230
21
Kontos et al AJC 1999;83:155
MCV Critical Pathway
Chest Pain Marker Strategy
Level
Adm
3
1
Myo
CK-MB
cTnI
Myo
CK-MB
cTnI
Myo
CK-MB
cTnI
-
-
2
3
4
6
8
12
18
CK-MB
cTnI
-
CK-MB
cTnI
-
-
-
-
-
CK-MB
cTnI
CK-MB CK-MB CK-MB
cTnI
CK-MB CK-MB CK-MB
cTnI
-
Is <8 hours Sufficient for Diagnosis of MI?
Patient 1
Time
hours
CK-MB
ng/mL
TnI
ng/mL
<0.5
Patient 2
CK-MB
ng/mL
1.8
TnI
ng/mL
0 hr
1.5
<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, TnT
FRISC Substudy
20
Death
Death or MI
17.7
14.1
15
11.4
10
8.4
4.4
5
3.9
2.6
0
0
<0.06
0.06 to 0.18
>0.18
MI
Lindahl Circ 1996;93:1651
30 and 90 day Cardiac and All Cause
Mortality Based on Peak TnI Value
8
7
None (n=3215)
Low (n=269)
Inter (n=210)
High (n=421)
7.1
6.2
6
5
4
3.3
2.9
3
2.2
2
1.5
1
1
0.6
0
30 Day Cardiac Mortality
90 Day Cardiac Mortality
Outcomes Based on Peak TnI Value
Excluding Patients with MI
60
None (n=3209)
Low (n=266)
Inter (n=181)
High (n=120)
50
54
53
38
40
35
34
30
27
25
20
17
16
23
22
17
10
10
5.8
0.6 1.5
2.2
5.5
1.4
3
0
Death
Death/MI
Death/MI
Revasc
Death/MI Death/MI
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
25
Heparin
GP IIb/IIIa+Heparin
19.6
20
15
19
13
11
10
5.8
5
4.3
0
Prism
Capture
Paragon B
14 Day Outcomes, TnI (+) and (-)
Enoxaparin vs UFH
40
Troponin (+)
Enox
UFH
40
30
Troponin (-)
21
20
17
10
9
10
6
4
0
0
D/MI
Morrow JACC 2000;36:1812
D/MI/UR
D/MI
D/MI/UR
Cardiac Markers
Comparison 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 I
Assay Variations
20
16.8 ng/mL
15
13.7 ng/mL
10
5
9.2 ng/mL
5.3 ng/mL
2.5 ng/mL
0
10 ng/mL
AxSym
Opus
ACS:180
Stratus
Access
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
100
Optimal
90
LLD
Opt 1.0 ng/ml
Sn 96 % Sp 93 %
MUL
80
LLD 0.5 ng/ml
Sn 97 % Sp 86 %
URL 2.5 ng/ml
Sn 87 % Sp 97 %
70
60
0
5
10
15
1- Specificity (False Positive)
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
Troponin
False Negatives
• Sample Timing
• Imperfect gold standard
• Choice of diagnostic value
• Inability to detect ischemia alone
Frequency of Elevated TnT in U/A
11 Studies, 1731 patients
70
65
Overall 33 %
TnT (+)
60
52
50
48
42
40
39
38
35
33
30
21
21
20
10
0
Rottbauer et al Eur Heart J 1996;17 (Supp);17:1
19
21
Sensitivity of TnI For Cardiac Events
100
96
92
75
50
43
25
20
14
0
MI
Kontos JACC 2000;36:1818
MI/D
M/D/S
Sig Dz
Comp
The Acute Coronary Syndrome
Risk
perfusion imaging
Myocardial Ischemia
ECG
Myocardial Necrosis
CK-MB, TnI
Diagnostic Focus
Myocardial Infarction
Reduced Blood Flow
Unstable Angina
Intracoronary Thrombus
Asymptomatic
Plaque Rupture
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 ED
Information Obtained
• Myocardial perfusion
• Wall motion
• Wall thickening
• Ejection fraction
%
Cardiac Events, (+) and (-) Mibi
60
(+) Mibi
50
53
(-) Mibi
42
40
31
30
20
15
10
3.9
4.4
6.4
0.6
0
MI
Rev
M I/Rev
M I/Sig
Kontos JACC 1997;30:976
Sensitivity for Cardiac Events
Sestamibi and TnI
%
100
(+) Mibi
(+) Serial TnI
97
92
Initial (+) TnI
82
81
75
75
52
50
30
29
29
21
25
10
10
Rev
Sig
0
MI
Kontos Circ 1999;99:2073
M+S
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 Imaging
Sensitivity
• 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 3
Probable 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:
• 7 am markers:
normal
CK 150 U/L
MB 1.3 ng/ml
TnI <.1 ng/ml
• 9 am stress test:
• 12 pm discharge home
normal
LEVEL 4
Possible 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 Imaging
Cocaine Chest Pain
• 216 pts with acute
imaging
• 5 patients (+) (2 %)
– 2 MIs
• 211 patients (-)
– no MIs
– 2 with significant
coronary disease
250
211
No MIs
200
150
100
2 MIs
50
5
0
Kontos Ann Emer Med 1999;33:639
(-) MPI
(+) MPI
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/ml
MB 1.8 ng/ml
CK 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:
Acute Sestamibi
Short Axis
Vertical Long Axis
Horizontal Long Axis
Case 6492345
Markers
Time
CK
CK-MB
5 pm
8 pm
1 am
3 am
7 am
4 pm
107 U/L
99 U/L
127 U/L
120 U/L
108 U/L
78 U/L
1.6 ng/ml
2.4 ng/ml
5.2 ng/ml
5.2 ng/ml
4.4 ng/ml
1.8 ng/ml
TnI
<0.5 ng/ml
0.6 ng/ml
2.2 ng/ml
1.7 ng/ml
1.8 ng/ml
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 Comparison
Control Vs ACT
Level 1
Level 2
Level 3
Level 4
Overall
* p=0.02
Control
19,408
10,425
5,051
1,794
ACT
15,604
9,435
4,958
1,529
Difference
-20 %
- 9.5 %
- 1.8 %
-15 %
6,044
5,030
-17 % *
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