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Is There a Role for Nonivasive Imaging Strategies For Risk Stratification in ACS?. George A. Beller MD No Disclosures. Clinical History. - PowerPoint PPT PresentationTRANSCRIPT
George A. Beller MDGeorge A. Beller MD
No DisclosuresNo Disclosures
Is There a Role for Nonivasive Imaging StrategiesIs There a Role for Nonivasive Imaging Strategies
For Risk Stratification in ACS?For Risk Stratification in ACS?
Clinical History• Mr. H is a 63 year-old male with a past history of
hypertension, hyperlipidemia, and uncontrolled Type 2 diabetes mellitus who presented with a 3-day history of progressive shortness of breath and lower extremity edema.
• He recalled having some vague substernal chest discomfort lasting approximately 2-3 hours associated with the onset of his SOB three days previously.
• PMH:– Newly-diagnosed CHF– Type 2 DM– Hypertension– Dyslipidemia
• Meds:– Verapamil, Lisinopril, Lasix,
Pravastatin, Indomethacin, Metformin
• Social Hx:– Lives with his wife– No known ETOH, tobacco, or
drugs
• PE:– 114/65, 82, 18– Increased JVP to 3cm above
clavicle– Lungs- bibasilar crackles– RRR, no MRG– 2+ LE edema, 2+ pulses
• Labs:– K 4.1, Cr 1.5, Gluc 379– BNP 1429– Troponins 2.4, 1.8, 1.2– Hct 51.3
• CXR: – Mild pulmonary venous
congestion
EKG
Hospital Admission• He was diagnosed with CHF secondary to
an MI which occurred 3 days previously.• LVEF was 15-20% by echo.
Admission• He was successfully diuresed, the verapamil
discontinued and started on metoprolol• He then underwent cardiac cath showing the
following:proximal LAD: 100%
mid LCx: 70% PDA: 80%
Question
Which of the following would be the next step in management?
1. Refer directly to cardiac cath for PCI of the total LAD occlusion
2. Refer the patient directly for CABG.3. Perform a noninvasive imaging study of
ischemia/viability. 4. Continue with medical therapy without
revascularization
Subsequent Evaluation
• He underwent adenosine stress/rest SPECT sestamibi myocardial perfusion imaging to assess for viability and ischemia.
Sestamibi Stress/ Rest Images
Quantitative Perfusion
Sestamibi Rest Gated Images .
Quantitative Function
QuestionWhich of the following would be the next
step in management?1. The patient has poor viability and should
be treated medically.
2. The patient should have a cardiac MRI study to assess extent of scar.
3. The patient has preserved viability and would have a better long term outcome with revascularization.
Subsequent Management
• It was decided to proceed with coronary revascularization based on the finding of moderately preserved viability in the distribution of all 3 coronary territories.
• Four weeks later he returned for a follow-up adenosine stress sestamibi perfusion imaging study
Sestamibi Stress / Rest Images G.A.
Quantitative Perfusion- post revascularization
Sestamibi Stress / Rest Images G.A.
Quantitative Function- post revascularization
The Message• The patient appeared too late after his MI for
primary PCI of his totally occluded LAD to attain myocardial salvage with RP
• He had multivessel CAD with severe LV dysfunction but had preserved viability in all 3 coronary territories.
• Such patients with multivessel CAD and severe LV dysfunction benefit from a viability study prior to considering revascularization.
Myocardial Imaging in ACS1. Detection of CAD in low-intermediate risk
patient presenting with chest pain in ED
2. Noninvasive assessment of LV function and infarct size for prediction of remodeling
3. Stress imaging for risk stratification
4. Determination of functional significance of intermediate stenosis (50%-70%)
5. Assessment of viability in infarct zone to determine value of late reperfusion
Immediate Evaluation for Possible ACS
(ACC/AHA UA/NSTEMI Guideline Revision, Circ 2007;116:803-877)
Class I In pts with suspected ACS in whom IHD is present or suspected, if the follow-up ECG and cardiac biomarker levels are normal, a stress test (exercise or pharmacogic) to provoke ischemia should be performed in the ED, in a CPU, or on an outpatient basis in a timely fashion (within 72hr) as an alternative to inpatient admission. Low risk patients with a negative diagnostic test can be managed as outpatients (Level of Evidence: C)
Class IPatients with possible ACS and negative biomarkers who are unable to exercise or who have an abnormal resting ECG should undergo a pharmacologic stress test (Level of Evidence: B).
Immediate Evaluation for Possible ACS -2
(ACC/AHA UA/NSTEMI Guideline Revision, Circ 2007;116:803-877)
Class IIa In pts with suspected ACS with a low or intermediate probability of CAD, in whom the follow-up 12-lead ECG and cardiac biomarker measurements are normal, performance of a non-invasive coronary imaging test (i.e. coronary CT angiography) is reasonable as an alternative to stress testing. (Level of Evidence: B)
Class IPatients discharged from the ED or CPU should be given specific instructions for activity, medications, additional testing and follow-up with a personal physician. (Level of Evidence: C)
Stat ECG, rest MPI orEchocardiogram
Troponin I; Serial ECGs; Observation
Negative Findings
Recurrent Pain
Positive
Positive
Negative
ECG Stress Testing, Stress Imaging or CTA
Admit
8-10 hrs
Chest Pain And Possible Acute Coronary Syndrome
Admit Home
Resting Sestamibi Scan in Patient With Chest Pain And Normal Initial ECG
(Udelson, Heart 2004; 90: v16-v25)
SA
VLA
HLA
Negative Predictive Value of Resting MPI For Acute MI in The ED
Author Year N (Total) N (Normal)Rest MPI
NPV
Varetto et al. 1993 64 34 100%
Hilton et al. 1994 102 70 99%
Tatum et al. 1997 438 338 100%
Kontos et al. 1997 532 361 99%
Heller et al. 1998 357 204 99%Kontos et al. 1999 620 379 99%
64-Multidetector Row CTA in Patients Without Known CAD (ACCURACY Trial)
(Budoff, JACC 2008; 52: 1724-32)
0
50
100
Sens Spec PPV NVP Sens Spec PPV NVPPatients (≥ 50% Stenosis) Patients (≥ 70% Stenosis)
%
95 9483
48
9999
83
64
CTA vs Standard of Care (SOC) in Chest Pain
(Goldstein JACC 2007; 49: 863-71)(Goldstein JACC 2007; 49: 863-71)
CT Characteristics of Culprit Plaques in 2 Pts.
(Cyrus, J Nucl Cardiol 2009; 16: 466-73)
ACS- Free Survival vs. Positive Vessel Remodeling and Low Attenuation Plaques on CTA
(Motoyama, JACC 2009: 54: 19-57)
SPECT Imaging After Acute ST Segment Elevation MI
1. Quantitation of infarct size
2. Assessment of infarct zone viability
3. Identify myocardial stunning after reperfusion
4. Residual infarct zone ischemia in patients not undergoing angiography (stress imaging)
5. Determination of functional significance of non-infarct stenoses (stress imaging)
Diagnosis, Risk Assessment, Prognosis and Assessment of Therapy After Acute STEMI
Indication Test Class
1. Detection of ischemia and myocardium at risk in thrombolytic pts. without cath.
2. Infarct size and residual viable myocardium in acute STEMI
(ACC/AHA Guidelines, 2003)
Stress/ Rest MPI
Rest/ Stress MPI
1 B
1 B
Correlation Between Defect Size by Sestamibi SPECT And Myocardial Scar Pathology
(Medrano, Circ 1996; 1010-17)
Def
ect b
y SP
ECT
(%)
Scar by Pathology (%)0 10 20 30 40 50 60 70
70
60
50
40
30
20
10
0
Y = 6.60 + 1.03 x r = 0.89, P< 0.001
SPECT Infarct Size vs 6 Months Mortality
(Alamanni, Heart 2004; 90: 1291-98)
Infarct Size LV (%)
6 M
onth
Mor
talit
y (%
)
<12 12-19 20-35 36-50 >500
2
4
6 P= 0.006
N= 424
N= 137
N= 129
N= 251
N= 181
99mTc-Sestamibi Infarct Size at Hospital Discharge vs LVESV at One Year
(Chareonthaitawee, JACC 1995; 25: 567)
Delayed Hyperenhancement MRI in Delayed Hyperenhancement MRI in Acute Transmural MI With No-ReflowAcute Transmural MI With No-Reflow
(Shan, Circ 2004; 109: 1328-34)(Shan, Circ 2004; 109: 1328-34)
Viability Assessment Predicts Future Ventricular Remodeling After Acute MI And Treatment With
Primary Angioplasty
End-diastolic Volume 53 14 76 18End-systolic Volume 22 11 42 176 mo. patency rate (%) 98 96Baseline EF (%) 45 11 44 10
(Bolognese, Circ 1997; 96: 3353-3359)
Infarct-Zone Viability Yes NoVariables
(Hochman, NEJM 2006; 355: 2395)
PCI vs Medical Therapy in OAT Trial
Total Events Nonfatal Myocardial Infarction
Risk Stratification Before Discharge: UA/NSTEMI
(ACC/AHA UA/NSTEMI Guideline Revision, Circ 2007;116:803-877)
Class I Nononvasive stress testing is recommened in low-risk patients who have been free of ischemia at rest or with low-level activity and of HF for a minimum of 12 to 24 hrs (Level of Evidence:C)
Class INoninvasive stress testing is recommended in patients at intermediate risk who have been free of ischemia at rest or with low-level activity and of HF for a minimum of 12 – 24 h) (Level of Evidence:C)Choice of stress test is based on the resting ECG, ability to perform exercise, local expertise and technologies available; treadmill exercise is useful in patients able to exercise in whom the resting ECG is free of abnormalities (e.g. LVH, BBB, ST ↓)
Risk Stratification Before Discharge (Cont’d)
(ACC/AHA UA/NSTEMI Guideline Revision, Circ 2007;116:803-877)
Class I An imaging modality should be added in patients with resting ST depression, LVH, BBB, intraventricular conduction defect,preexcitation, or digoxin who are able to exercise. In patients undergoing a low-level exercise test, an imaging modality can add sensitivity (Level of Evidence: B)
Class IPharmacologic stress testing with imaging is recommended when physical limitations (e.g. arthritis, amputation, severe peripheral vascular disease, severe COPD, orgeneral debility) preclude adequate exercise stress. (Level of Evidence: B
Cardiac Death (CD) or Nonfatal MI (MI) in Non-ST Elevation ACS Based on NI Testing
(Udelson, Heart 2004; 90: v16-v25)
Stress ECG Stress Myocardial Perfusion Imaging
0
5
10
15
20
25%
CD
/ MNegative Positive
Events Related to METS in Post-MI Patients
(Valuer, Eur Heart J 2005;26:119-27)Years
< 6 METS
6 -8 METS
> 8 METS
0 1 2 3
0.20
0.15
0.10
0.05
0.00
Proportion of Death or re-MI
0
2
4
6
8
10
12
14
16
18
Ann
ual C
ardi
ac D
eath
or
MI R
ate
(%)
(Brown, Circulation,1999)
Event Rate in Acute Uncomplicated First MIPatients vs DP Sestamibi Findings
SSS = Summed Stress Score
Low SSSSSS
Intermed High SSS
Summed Difference Score used for Ischemia Extent
Intermed
Low
High
Extent of Reversibility
Follow-up - 1 year
Stable pts following Acute MI
Adenosine Sestamibi SPECT #1 (N=728)
PDS <20%(N=242)
PDS >20%, IPDS <10%(N=213)
PDS >20%, IPDS >10%(N=273)
LVEF <35%(N=68)
Coronary Angiography
LVEF >35%(N=205)
Adenosine Sestamibi SPECT #2 - Blinded Analysis
Strategy 1 Strategy 2
Intensive Medical Rx
PTCA/CABG + Medical Rx
Revascularization and/or Medical Rx
INSPIRE Study Design
Perfusion Defect Size vs Events After AMI
(Mahmarian, JACC 2006; 48: 2448-57)(Mahmarian, JACC 2006; 48: 2448-57)
Car
diac
Eve
nts
(%Pa
tient
s)
Perfusion Defects Size (%LV)
0.00 0.20 0.40 0.60 0.80 1.00
Time to Follow-up (Year)
0.7
0.8
0.9
1.0
0 (n=167)
1-6 (n=345), RR=1.78, p=0.11
7-14 (n=127), RR=2.80, p=0.008
15-20 (n=35), RR=4.75, p=0.001
>20 (n=54), RR=6.15, p<0.0001
Even
t-Fre
e Su
rviv
al
Risk Based on Ischemic Defect Size Overall Event-Free Survival
Outcome vs Therapy in INSPIRE Trial of Acute MI
(Mahmarian, JACC 2006; 48: 2458-67)(Mahmarian, JACC 2006; 48: 2458-67)
Initial Conservative vs Initial Invasive Strategy
(ACC/AHA UA/NSTEMI Guideline Revision, Circ 2007;116:803-877)
Class I An early invasive strategy (diagnostic angiography with intent to perform revascularization) is indicated in initially stabilized UA/NSTEMI patients (without serious comorbidities or contraindications to such procedures) who have an elevated risk for clinical events (Level of Evidence A)
Class IIbIn initially stabilized patients, an initially conservative strategy (i.e. selective invasive) may be considered as a treatment strategy for UA/NSTEMI patients who have an elevated risk for clinical events including those who are troponin positive. The decision to implement an initial conservative strategy may be made by considering physician and patient preference (LOE: C)
Initial Conservative vs Initial Invasive Strategy
(ACC/AHA UA/NSTEMI Guideline Revision, Circ 2007;116:803-877)
Class III An early invasive strategy (i.e. diagnostic angiography with intent to perform revascularization) is not recommended in patients with acute chest pain and a low liklihood of an ACS (Level of Evidence: C)
Class IIIAn early invasive strategy is not recommended in patients with extensive comorbidities (e.g. liver or pulmonary failure, cancer), in whom the risks of revascularization and comorbid conditions are likely to outweigh the benefits of revascularization (Level of Evidence: C)
Long-Term Outcome of Routine Invasive (RI) vs. Selective Invasive (SI) Strategy In
Patients With Non-STEMI ACS
(Fox, JACC 2010; 55:2435-45)
a. Pooled analysis from FRISC-II, RITA-3 and ICTUS
b. Over 5 years 14.7% of patients randomized to an RI strategy experienced CV death or MI vs 17.9% in the SI strategy (P=0.002)
c. Differences in CV death not significant (P=0.068)
Long-Term Outcome of Routine Invasive (RI) vs Selective Invasive (SI) Strategy In
Patients With Non-STEMI ACS (con’t)
(Fox, JACC 2010; 55:2435-45)
d. There were 2.0% to 3.8% absolute reductions in CV death or MI in the low- and intermediate-risk groups and an 11.1% absolute risk reduction in the highest-risk patients.
e. During 5 years of observation, the majority of patients RI and SI ultimately underwent PCI or CABG (81% vs 60%).
Meta-Analysis for CV Death or MI (FRISC-II, RITA-3, ICTUS) Selective Invasive vs. Routine Invasive.
(Fox KAA et al JACC 2010; 55: 2435-45)
Hazard Ratio
Favors Selective InvasiveFavors Routine Invasive0.5 0.75 1 1.33 2
Study
FRISC-II
RITA-3
ICTUS
Overall
Cumulative Risk of CV Death or MI Comparing Routine Invasive vs. Selective Invasive Strategies for ACS
(Fox, JACC 2010; 55: 2435-45)
Conclusions
1. Noninvasive imaging for detection of ACS or CAD useful in evaluation of chest pain in the ED for patients with nondiagnostic ECGs and negative biomarkers.
2. Rest imaging after acute MI can estimate infarct size and determine extent of infarct zone viability which have prognostic value.
Conclusions (cont’d)
3. Exercise or pharmacologic gated myocardial perfusion imaging can be used to separate high-and low-risk stable post-MI patients, particularly in patients not undergoing acute angiography or who have intermediate stenoses on angiography
4. A meta-analysis of long-term outcomes in
FRISC-2, RITA-3 and ICTUS trials favors routine invasive over selective invasive strategies with best outcome in the highest risk patients.
Conclusions (cont’d)
5. Viability imaging in STEMI patients is useful in identifying which patients may develop LV remodeling and an increased risk of an adverse outcome; infarct size accurately determined
6. Stress imaging provides good prognostic information when performed in STEMI patients who have undergone thrombolytic therapy
Recommendations in Emergency Department for Suspected ACS
Indication Test Class Rest MPI 1 A
Stress/ 1 B Rest MPI
1. Assessment of myocardial risk in possible ACS pts. with non diagnostic ECG and negative serum markers or enzymes, if available
2. CAD diagnosis in possible ACS pts with chest pain and non diagnostic ECG and negative serum markers
(ACC/AHA Guidelines, 2003)
Outcome of Patients Post MI With (Group A) and Without (Group B) Viability in The Infarct
Zone
Surv
ival
RVS (Group A1)
Med (Group A2)
(Zhang, JNM 2001; 42: 1166-73)
Log RankX2 = 10.86 P= 0.001 Log Rank P> 0.05
RVS (Group B1)
Med (Group B2)
Surv
ival
Follow-up (months) Follow-up (months)
1.0
0.8
0.6
0.4
0.2
00 8 16 24 32 40 0 8 16 24 32 40
1.0
0.8
0.6
0.4
0.2
0A B
CV Death or MI: Routine Invasive vs. Selective Invasive Strategies After ACS (Meta-Analysis)
(Fox, JACC 2010; 55: 2435-45)
Selective Invasive
Routine Invasive
The Incremental Prognostic Value of Scintigraphic Variables Compared with TIMI Risk Score
(Mahmarian, JACC 2006; 48: 2448-57)(Mahmarian, JACC 2006; 48: 2448-57)
Strategy 1 Strategy 2 Medical Therapy Revascularization p (N=86) (N=83) Value
Total PDS (Δ change) -16.2±10 -17.8±12 0.36Ischemic PDS (Δ change) -15.0±9 -16.2±9 0.44Scar PDS (Δ change) -1.2±8 -1.6±7 0.73
% Patients >9% decrease Total PDS 75 79 0.50 Ischemic PDS 80 81 0.76
LVEF (Δ change) 4.7±7 4.6±8 0.93
Objective 2: Randomized Patients Gated SPECT Results: Medical vs
Revascularization Strategy
Risk Assessment / Prognosis in Pts. with Non STEMI
Indication Test Class1. Identification of inducible ischemia
in the distribution of the “culprit lesion” or in remote areas in pts. with intermediate to low risk for major adverse cardiac events
2. Identification of the severity/ extent of inducible ischemia in pts whose angina is satisfactorily stabilized with medical therapy or in whom diagnosis is uncertain
3. Hemodynamic significance of intermediate stenosis
(ACC/AHA Guidelines, 2003)
1 B
1 AStress/ MPI
Stress/ MPI
1 B
Stress/ MPI
Prior CABGHigh-risk findings on noninvasive stress testing
PCI within 6 monthsRecurrent angina/ischemia with CHF, S3, PE, rales, etc.
Sustained VTST-segment depression
Hemodynamic instabilityElevated TnT or Tnl
Ejection fraction <.40Recurrent angina/ischemia
Class IAn early invasive strategy in patients with UA/NSTEMI and any of the following high-risk indicators (Level of Evidence: A)
Braunwald E, et al. J Am Coll Cardiol. 2002;40:1366-1374.
ACC/AHA Guidelines for UA/NSTEMI:Early Invasive Strategy
Sestamibi Stress / Rest Images F.P.
Quantitative Function
Likelihood of ACS Secondary to CAD“CONFIDENCE OF DIAGNOSIS”
Adapted from Braunwald E, et al. Available at: http://www.acc.org/clinical/guidelines/unstable/unstable.pdf
High Intermediate LowHistory Chest or left arm pain Chest or left arm Sx w/o intermediate
Sx as in prior angina pain; age >70 yr likelihood character-Known history of CAD Male sex; DM istics; recent cocaine
Exam Transient MR, Extracardiac Chest pain hypotension, vascular reproduced
diaphoresis, disease by palpation pulmonary edema, or
rales
ECG New transient Fixed Q waves T-wave flattening orST-segment deviation Abnormal ST-seg inversion in leads
or T-wave inversion or T-waves not w/dominant R waveswith symptoms documented as new Normal ECG
Cardiac Elevated Normal NormalMarkers
Early and 6-Month outcome in CTA vs Standard of Care (SPECT MPI) in Patients With Chest Pain
(Goldstein JACC 2007; 49: 863-71)(Goldstein JACC 2007; 49: 863-71)
Variable CTA SOC p-Value
In-hospital cath. 11.1% 3.1% 0.03 Cath. cumulative 12 % 7.1% 0.24 Death- 6 mo 0% 0%NA MI- 6 mo 0% 0%NA Clinically correct Dx 97% 98%1.00 PCI cumulative 4.0% 1.0%0.37 CABG cumulative 2.0% 0%
0.50