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Detecting Acute Coronary Syndrome in the Emergency Department with Cardiac Magnetic Resonance Imaging
Raymond Y. Kwong MDCo-Director, Cardiac Magnetic Resonance Imaging
Brigham and Women’s Hospital
Cardiology Grand RoundBeth Israel Deaconess Hospital
April 11th, 2003
Acknowledgments
NHLBI• Andrew E. Arai, MD• Robert S. Balaban, PhD• Anthony Aletras, PhD• Adam Schussheim, MD• Suresh Rekhraj, MD• W. Patricia Ingkanisorn, MD• Kenneth Rhoads, MD
Clinical Center• Janice Davis, RN• Grace Graninger, RN
Suburban Hospital• Cardiology
Eugene Passamani, MD
• Emergency RoomBob Rothstein, MD
• RadiologyWayne Olan, MDSusan O’Flahavan, RTPaul LeBlanc, RTGian Serafini, RTChris Mancini, RTSarah Pirie, RT
Myocardial Infarction and Chest Pain in the Emergency Room
• 1,100,000 MI per year in the USAbout 1/3 will die from their MI *
• 6,200,000 people in the United States suffer from angina
• 5,000,000 patients are evaluated in ER for chest pain each year
American Heart Association. 1999 Heart and Stroke Statistical Update.
* Atherosclerosis Risk in Communities (ARIC) study, NHLBI
The Spectrum of Chest Pain in the ER
Chest Pain
STEMI
NSTEMI
UnstableAngina
ACSTroponin
Non-cardiacChest Pain
StableAngina
Mortality of ER patients with chest pain
Pope et al. NEJM 2000; 342: 1163
Chest Pain in Emergency Department
LCE/NHLBI/NIH
ST ElevationAcute MI
PTCA orThrombolytics
IntermediateLikelihood CAD
CardiacRx
Non-STEMI
UnstableAngina
Low LikelihoodCAD
CardiacEnzymes
Regional Wall Motion: SSFP
Dobutamine Stress MRI Sensitivity 83-86% Specificity 83-86%Nagel Circ 1999; 99: 763Hundley Circ 1999; 100: 1697
Interobserver Variability for Qualitative Regional Wall Thickening by MRI
VersusConsensu
s
Observer1
Observer2
Observer3
Observer4
Correlation 0.95 0.96 0.93 0.95
Avg Dif -0.02 -0.03 0.01 -0.02
SD of Dif 1.3 1.6 2.0 1.3
Sierra-Galan et al. JCMR in press
First PassPerfusion RV
LV
Myo
LCE/NHLBI/NIH
Comparison of Endocardial Microsphere Blood Flow and Endocardial MRI Contrast Enhancement Ratio
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9
y = 0.04 + 0.85x r = 0.92
Endocardial Microsphere Flow (ml/min/g)
MR
I End
ocar
dial
CER
NHLBI/NIH
Dipyridamole Stress MRI vs PET and QCA
Schwitter et al. Circ 2001; 103:2230
Dipyridamole Stress MRI vs PET and QCA
Schwitter et al. Circ 2001; 103:2230
MRI Vs PETSensitivity 91%Specificity 94%
MRI Vs QCASensitivity 87%Specificity 85%
Dipyridamole Stress First Pass Perfusion Myocardial Perfusion Reserve Index
Al-Saadi et al Circ 2000; 101:1379
MPR +
54
7
MPR -
6
35
Sensitivity 90%Specificity 83%
CAD+
CAD -
0
50
100
150
200
0 5 10 15 20
Time (s)
Sign
al In
tens
ity
Width = 0
Fermi Function
Decay rate =
Flow
0
500
1000
1500
2000
2500
3000
0 5 10 15 20
Time (s)
Sign
al In
tens
ity
Fermi Function Deconvolution
Estimates Absolute Myocardial Perfusion(ml/min/g)
InputFunction
MyocardialEnhancement
MathematicalModel
Endocardial and Epicardial AnalysisR = 0.92, P< 0.0001 R = 0.95, P < 0.0001
Infarct Size: TTC vs MRI
Kim R. et al. Circulation. 1999;100:1992-2002
Correlation between MRI Infarct Size and TTC Staining
Kim R. et al. Circulation. 1999;100:1992-2002
Kim RJ et al. NEJM 2000;343:1445
Irreversible LV Dysfunction: Pre-intervention
After revascularizationDiastole Systole
Diastole Systole
Transmural Hyper
0
20
40
60
80
100
0 1-25 26-50 51-75 76-100
0
20
40
60
80
100
0 1-25 26-50 51-75 76-100
Transmural Extent of Hyperenhancement Predicts Recovery of Function
Transmural Extent of Hyperenhancement (%)
Con
tract
ile R
ecov
ery
(%)
Con
tract
ile R
ecov
ery
(%)
Kim RJ et al. NEJM 2000;343:1445
All segments Akinetic or Dyskinetic
PET vs MRI Viability
Klein et al. Circulation 2002; 105: 162
Microinfarction after PCI associated withMinor Side Branch Occlusion
Ricciardi. Circulation 2001;103:2780-3
Patient 7: stent in the proximal LAD and minor side-branch
occlusion
Patient 2: stent in the mid-PDA and minor side-branch
occlusionMI size = 0.7 to 12 g
Comparison of MRI and SPECT for Detecting Myocardial Infarction
Wagner et al. Lancet 2003; 361: 374
Method: Acute Chest Pain Protocol
Localize Perfusion Function Viability
Time (min)0 10 20 30
Pilot phase
• To determine safety, feasibility, and logistic issues:• 37 patients presenting with chest pain to the ER were studied.
– Patients were either from the ER or within 72 hours of admission to the hospital.
» Well tolerated (1 failure to acquire any image due to clasutophobia)
» 13 cases of AMI with a wide range of troponins all have abnormal MRI
» Can perform MRI while receiving concurrent IV meds.
Case 1: 60 yo male Day 2 post acute MITroponin 2X ULN
Case 2: 80 yo female No prior CAD Chest pain with non-diagnostic EKG admitted 12 hours ago, small NQMI by troponin
Case 2: 70 yo male No prior CAD Chest pain with non-diagnostic EKG admitted 12 hours ago, small NQMI by troponin
Hypothesis
• We hypothesized that MRI could effectively triage patients presenting with possible acute coronary syndromes in the Emergency Room
Entry Criteria
• 30 minutes of chest pain compatible with myocardial ischemia
• ECG not diagnostic of ST-elevation MI
Exclusions• Pacemaker• Defibrillator• Other implanted active devices• Brain aneurysm clips
Method
Prospective observational trial.• Enrollment from 01/10/2000 to 09/27/2001
• Inclusion criteria: • Chest pain > 30 minutes without obvious non-cardiac cause
• Exclusion criteria: any of the following• ECG diagnostic of ST elevation acute myocardial infarction• Ongoing active chest pain• Hemodynamic instability• Contraindications to MRI scanning• > 12 hours since onset of last chest pain
.
Symptoms Suggestive of ACSNoncardiacdiagnosis
StableAngina
PossibleACS
DefiniteACS
ACC/AHA Practice GuidelinesUnstable Angina And NSTEMICirc 2000;102:1193
ST ElevationMI
Confirmed ACS
ECG NotDiagnostic
Troponin (-)
SerialStudies? Image
StressTest
- +
+- + -
+
UnstableAngina
ST or Tand/or
Troponin (+)
+Non-ST
ElevationMI
-
Method: Prospectively Defined Clinical Endpoints
Acute coronary syndrome (ACS): Possible or definite ACS according to ACC/AHA guidelines
Method: Prospectively Defined Clinical Endpoints
Acute coronary syndrome (ACS): Possible or definite ACS according to ACC/AHA guidelines as indicated by chest pain > 30 minutes (an entry criteria) AND either angiographically significant CAD AND/OR significantly abnormal stress testing performed during index hospitalization or the subsequent 6- 8 week follow-up period.
Non-ST elevation acute myocardial infarction (NSTEMI): Abnormal troponin-I with a temporal pattern consistent with acute MI and clinical evidence of coronary artery disease (Coronary angiography, echo, or noninvasive imaging).
Method: Definitions
Angiographically significant CAD =
1) > 50% left main lesionor 2) > 70% epicardial coronary artery stenosis
Method: Prospectively Defined Abnormal MRI
Abnormal defined by either:• Regional wall motion abnormality (RWMA), or• Myocardial hyperenhancement (Hyper).
Reading included perfusion images:• Although independent diagnoses were not made using
perfusion alone, the perfusion images helped identify abnormal regions.
TIMI risk score
Antman et al. JAMA 2000; v284;7:835
Results: Study population
• 193 consecutive patients • 11 refused to participate• 21 excluded:
– 6 hemodynamically unstable– 2 metallic implants– 3 large body size– 10 claustrophobia
• Remaining 161 formed the study cohort.• All patients underwent conventional cardiac
workup as determined by the admitting cardiologists or ER physician
161 enrolled•92 Male : 69 Female
•Age: 59 + 15 years old
•Average # of risk factors: 3.4
•History of prior MI: 25/161
•Median time since ER arrival:2.7 hours (off hours cases excluded)6.0 hours (off hours cases included)
•Average MRI scan duration: 38 + 12 minutes
Results: Study population
Patient Follow-up at 6 –8 weeks
161 patients• 158 (98%) were successfully contacted at 6-8 week follow-up
• 3 were lost to follow-up: all troponin negative, 2 clinical low risk with normal MRI and 1 high risk with abnormal MRI
Results: Demographic summary ACS
(n = 25) No ACS (n = 136)
p value
Age (yr) 68 + 13 57 + 14 p = 0.0006 Men (%) 60 57 NS CAD risk factors Advanced Age (M>45, W>55) (%) 92 68 p = 0.03 Hypertension (%) 56 43 NS Diabetes (%) 28 10 p < 0.001 Hypercholesterolemia (%) 64 47 NS CAD in family (%) 32 42 NS Hx. of smoking (%) 48 39 NS Total number of CAD risk factors 4.2 3.2 p = 0.003 Characteristics of Chest Pain Location Substernal (%) 32 31 NS Precordial (%) 24 18 NS Quality Crushing, heaviness, pressure or tightness (%) 56 54 NS Radiation to neck/arm (%) 32 31 NS Dyspnea, diaphoresis, or nausea (%) 32 40 NS Previous angina (%) 40 12 p = 0.001 Average Chest Pain Score 8.4 7.5 NS ( p= 0.06) TIMI risk score P < 0.00011.6 + 0.82.5 + 1.2
Table 1. Demographic Summary
ACS
n = 25
68 + 13
28%
40%
8.4
2.5 + 1.2
No ACS
n = 136
57 + 14
10%
12%
7.5
1.6 + 0.8
p value
0.0006
0.001
0.001
0.06
0.0001
Age
Diabetes
HTN
CP Score
TIMI Risk Score
Kwong et al. Circulation 2003; 107:531-7
11620No ACS
421
+ MRI
ACS
- MRI
Results: Qualitative MRI assessment compared with clinical evaluation ( N = 161)
MRI Historyof MI ECG
StrictECG
Initial Troponin-
I
Peak Troponin-
I
TIMIRisk Score
ACS
Sensitivity (%)
84 28 80 19 16 40 76
Specificity (%)
85 87 61 95 97 97 52
NonSTEMI
Sensitivity (%)
100 30 70 20 44 NA 80
Specificity (%)
79 85 56 94 97 97 50
IHD
Sensitivity (%)
91 51 79 14 10 24 81
Specificity (%)
98 97 67 96 97 97 58
Sensitivity and Specificity for ACS
0
10
20
30
40
50
60
70
80
90
100
MRI ECG ECGstrict
Trop Troppeak
TIMI
Sens
itivi
ty o
r Spe
cific
ity (%
)
NS
0.00
1
0.00
1 0.00
4
NS
0.00
1
0.00
1
0.01
1
0.00
1
0.00
1
Sensitivity
Specificity
Kwong et al. Circulation 2003; 107:531-7
Multivariate Logistic Regression Analysis: Predict Acute Coronary Syndrome
0
20
40
60
80
100
0 20 40 60 80 100False Positive Portion
(1 - specificty, %)
True
Pos
itive
Por
tion
(Sen
sitiv
ity, %
)
TIMI Risk Score
NIH with MRI
NIH without MRI
Kwong et al. Circulation 2003; 107:531-7
Detecting CAD by presence of Regional Wall Motion Abnormality (RWMA)
1231No IHD
864IHD
No RWMARWMADetect IHD
Sensitivity: 89% Specificity: 99%
Regional wall motion images were interpretable in 196/197 patients (99%)
Detecting CAD by Delayed Hyperenhancement (HYPER)
1121No IHD
2448IHD
HYPERDetect IHD
Sensitivity: 67% Specificity: 99%
No HYPER
Delayed hyperenhancement images were acquired and interpretable in 185/197 patients (94%)
Methods
Anterior Septum
Lateral wall
RWMA
Inferior Septum
D S
End-systolic thickness (S) in mm
End-diastolic thickness (D) in mm
Absolute wall thickening in mm = S - D
Systolic diastolic ratio = S/D
Percent change in wall thickening (%) = (S-D)/D x 100%
Methods
0
20
40
60
80
100
0 20 40 60 80 100False Positive Portion
(1 – specificity, %)
True
Pos
itive
Por
tion
(Sen
sitiv
ity, %
)
0
20
40
60
80
100
0
20
40
60
80
100
0 20 40 60 80 100False Positive Portion
(1 – specificity, %)
0 20 40 60 80 100False Positive Portion
(1 – specificity, %)
ACS Non-STE MI IHD
Receiver Operator Characteristic Analysis: Quantitative Wall Thickening
3220 Kwong et al. Circulation 2003; 107:531-7
84 year old female with Acute Non-ST Elevation MI
-20
0
20
40
60
80
100
120
140
160
0 10 20 30
Time (image number)
Sign
al In
tens
ity-50
050
100150
200250
300350
400450
500
0 10 20 30
Time (image number)SI
Inte
gral
33%
68 year old female, with 2 hours CP, no risk factors, nonspecific ECG, and normal troponin
68 year old female, with 2 hours CP, no risk factors, nonspecific ECG, and normal troponin
A 53 year old female with 3 days of intermittent rest chest pain
A 53 year old female with 3 days of intermittent rest chest pain
A 53 year old female with 3 days of intermittent rest chest pain
Adenosine Stress
Rest SSFP Adenosine Perfusion Gd Hyperenhancement
67 year old female with no prior CAD+ DM, FMH, Tob, HTNTroponin (-)Cath: RCA 99%, Cx 99%, LAD 75%
Cardiac MRI UnitThe General Infirmary at Leeds
Diastolic Systolic
Perfusion
LAD/LCX RCA
Delayed image
MRI conclusion: significant mid RCA lesion
X-ray angiogram
Comprehensive Approach to Chest Pain:MRI: Does It Have Any Role?
• ST Elevation MI• Post-MI risk stratification
• Detection of residual ischemia
• Viability
• Non-ST elevation MI• Same as ST elevation MI
• Also potential for more rapid diagnosis
• Unstable angina• Early rest scan to detect evidence of recent ischemia
• Alternatively, scan after excluding MI with a stress test
Conclusions
• Use of cardiac MRI in the ER in assessment of patients presenting with chest pain and a non-diagnostic ECG is feasibility and safe.
• Cardiac MRI has high sensitivity and specificity for detecting ACS, NSTEMI, and IHD in patients with chest pain, and could provide useful diagnostic information beyond clinical assessment.
• MRI parameters could be interpreted both qualitatively and quantitatively with high accuracy in prediction of clinical endpoints
• Further work is needed to differentiate acute from chronic myocardial infarction and to improve scan efficiency.
Conclusions
• Add a slide:
The additional benefit of adenosine stress testing
Cost effectiveness of early patient triage translating into savings in health care cost dollars
12 months prognostic data
Clinical Cases
50 yo male lawyer, atypical chest painFirst troponin negative
60 yo female presenting with an episode of prolonged chest pain 24 hours ago, then another episode for several minutes.
60 yo female presenting with “good story” of unstable angina. EKG: NSST changesFirst troponin 3X ULN
Cath during index hospitalization: NS stenosis Uneventful at 6 weeks on no medications
Recommended