george a. beller md no disclosures

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

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


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


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)


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


Initial Conservative vs Initial Invasive Strategy


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


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


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


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


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

george a. beller md no disclosures

Documents

viability study

preserved viability

myocardial imaging

assessment of viability

poor viability

lowintermediate risk

coronary revascularization

cardiac mri study