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Evaluation of Ischemia in the Cath Lab

Morton J. Kern, MDProfessor of Medicine

Chief of Cardiology, LBVAAssociate Chief Cardiology, UCI

University California IrvineOrange, California

Disclosure:

Morton J. Kern, MD

Within the past 12 months, the presenter or their

spouse/partner have had a financial

interest/arrangement or affiliation with the organization

listed below.

Company Name Relationship

St. Jude Medical Inc. Speakers’ Bureau

Volcano Therapeutics Speakers’ Bureau

Merrit Medical Inc. Consultant

Opsens Consultant

To treat or not to treat?

Ischemia is the question

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R1

R2

R3

The Disconnect: Anatomy (angio or IVUS) = Ischemia, i.e., not every coronary plaque needs a stent.

- Ischemia guides decision for revascularization.- The angiogram cannot always tell us.

How severe is this stenosis?

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PET 1ml/gram flow, Radionuclide perfusion imaging,

Coronary blood flow velocity

Biomarkers, Troponin

Wall motion abnormalities, thickening

and shortening

Transmyocardial Lactate

Exercise ECG

What is Gold Standard of Ischemia in Man in or out of

the Cath Lab?

Pa

Pd

Entrance effects Separation losses

Friction loss

Flow

P

1

2

3

4,5,6

7

ischemic

Not ischemic

Pressure

Coronary flow

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1. CFR = max flow/basal flow and decreases with increasing stenosis (R1) severity.

2. CFR may also be reduced with abnormal microvasculature

The Failing of both Angiography and CFR to predict lesion

significant is major rationale for FFR

The limitation of CFR:

Because there are 2 components, CFR cannot distinguish between

an epicardial stenosis and an impaired microcirculation.

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Stress Testing and Coronary Vasodilatory Reserve

Author (n) Ischemic Test CVR Sens Spec AccuracyCVRMiller 33 Ad/Dipy MIBI <2.0 82 100 89

Joye 30 Ex thall <2.0 94 95 94

Deychak 17 Ex thall <1.8 94 94 96

Heller 100 Ex thall <1.7 89 92 92

Danzi 30 Dipy echo <2.0 91 84 87

Schulman 35 Ex ECG <2.0 95 71 86

Akasaka 59 Ex thall <2.0 92 88 92

Chamuleau 127 Spec MIBI <2.0 - - 85

rCVR

El Shafei 48 Ex Thall/Mibi <0.80 63 88 87

Verberne 37 Spect Mibi <0.65 - - 85

Chamuleau 127 Spec MIBI <0.65 - - 85

The resting gradient is not nearly enough

but it’s all I have now.

Aortic Pressure, PA

Coronary wire pressure, Pd

Aortic Pressure, PA

Coronary wire pressure, Pd

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Functional Assessment

FFR detects ischemia

Pressure

5

4

3

2

1

FFR=

Qs

QN

max

max

Qs

QN

Q base

Qs

Q base

max

CFR=

Differences between FFR and CFR

ETT

Thallium

Stress

Echo

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Fractional Flow ReserveThresholds for Reversible Myocardial Ischemia

FFR as a Surrogate for Non-Invasive Stress Testing

NO INDUCIBLE ISCHEMIA

INDUCIBLE ISCHEMIA

ISCHEMIA AT REST OR NECROSIS

Positive Noninvasive

Stress Testing

Negative Noninvasive

Stress Testing

FFR

0.75

0.80

0.20

1.0

FFR Gray Zone ?

Limitations of Non-Invasive Stress Testing for detecting ischemia

1. Intermediate lesion

2. During and after acute coronary syndromes

3. Valvular Disease

4. Left main stenosis

5. Multivessel disease

6. Bundle branch blocks, LVH, LV asynchrony, Poor LV function...

7. General problems: obesity, orthopedic problems, elderly...

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Ref Diam (mm)

% Stenosis for an Cross Sectional Area of 4 mm²

< 4 mm² = significant stenosis ?

025502

3

4

5

Q: Why can we not use IVUS/OCT for functional assessment?A: A single cross-sectional area does not mean the same thing everywhere.

Title(Year) N=

Study Design Question Outcome Journal

FAME

(2009)

750 Prospective

Multicenter

Registry

FFR guide PCI vs. Angio

guided for MVD

Less MACE*,

lower cost

w FFR

FAME II

(2012)

1,220 Prospective

Multicenter

Randomized

Abn FFR treated with

PCI+OMT vs OMT alone

Less MACE

with FFR

DEFER

(2007)

325 Prospective

Multicenter

Randomized

Is it safe to defer FFR

normal intermediate

lesions?

Less MACE

in FFR normal

when rx’d

medically

Mayo

(2013)

7,358 Retrospective

Registry

FFR guide PCI vs Angio

guided for MVD in routine

practice

Less MACE

when using

FFR

Ischemia-Guided PC bests Angio-

Guided PCI

There is considerable uncertainty in various

Angiographic presentations.

Q: Shouldn’t Interventions be ischemia driven?

• Intermediate Stenosis, no evidence

ischemia

• Left Main Stenosis

• Multivessel CAD

• Serial Lesions

• Ostial and Branch Disease

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71 yo Man with typical angina, pos stress, CAD risk factors

What’s your best approach?

FFR CFX

FFR CFX=0.88

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After Stent, remaining LAD narrowing? All done?

?

FFR = 0.68

FFR summary:

1. Appropriate need

for Stents

2. Objective info re

ischemia

3. Eliminates operator

uncertainty

Without FFR, this patient would have had one

unnecessary stent (CFX) and would not have

had one necessary stent, (LAD2)

PCI of Functionally Non-

significant Stenosis 5y FU in

the DEFER Study

Pijls NHJ et al J Am Coll Cardiol 2007;49:2105–11

Does Stenosis Severity of Native

Vessels Influence Bypass Graft

Patency? A Prospective FFR–

Guided Study

Botman CJ et al Ann Thorac Surg

2007;83:2093–7

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FAME I

PCI for MVD Guided by FFR or Angio

10

0

5

2 year

12.7

8.4

%

FFR-guided

Angio-guided

P= 0.03

9.5

6.1

P= 0.03

2 year(exclusion of small

periprocedural infarction)

Tonino et al, NEJM 2009, Pijls et al, JACC 2010

Death or MI MI

Incremental QALY

FFR Guidance Improves Outcomes

FFR GuidanceSaves

Resources

Inc

rem

en

tal

Co

st

[$]

DES

CABG

ROTO

BMS

Balloon

Economic Evaluation of FAME pts with MVD.

Fearon WF et al. Circ 2010;122:25450-2550

Nam, C.-W. et al. J Am Coll Cardiol 2011;58:1211-1218

Reducing the ischemic Burden by Functional (FFR+) Syntax Score

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FAME II – Ischemia directed PCI+OMT vs OMT alone

Stable patients scheduled for 1, 2 or 3 vessel DES stenting

FFR in all target lesions

When all FFR >0.80

OMT

At least 1 stenosiswith FFR ≤ 0.80

Randomisation 1:1

PCI + OMT OMT

Follow-up after 1, 6 months, 1, 2, 3, 4, and 5 years

Randomised Trial Registry

34

50% randomly assigned to FU

De Bruyne B et al. N Engl J Med 2012.

FAME II

Is Optimal medical therapy better than PCI + OMT for patient with

abnormal FFR (i.e. ischemia)?

Angiogram

Angiogram

Distal LAD Guide catheter

Distal LAD Guide catheter

Focal Stenosis

Diffuse disease

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DeBruyne et al, Circulation 2001 104: 2401 - 2406.

Diffuse CAD and Ischemia in the absence of significant

focal epicardial stenosis

FFR

J Am Coll Cardiol Intv. 2012;5(10):1013-1018.

Serial lesions?

Pre FFR (1+2) with

pullback

Lesion 1 large dP,

Stent

Recheck FFR

Treat lesion 2,

Final FFR

Assessment of the LM63 yo M w recent CP, 2y of fatigue. Cath 2005 100% RCA, 50% LAD,

50% CFX with collaterals to RCA. Normal LV function. LM now

significant?

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FFR across LAD

FFR across CFX

FFR=0.92

Hamilos, M. et al. Circulation 2009;120:1505-1512

LM FFR Assessment and 5 year outcomes

Survival MACE free survival

No CABG

CABG

FFR and Acute MI

• Culprit vessel – not for >5 days [De Bruyne et al,

Circulation 2001]

Pijls and Sels, JACC 2012;59:1045

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Class IIa Guidelines - ACC/ AHA/ SCAI

Class IA Guidelines - ESC

Physiologic (ischemia) Guidance is supported by

guidelines

Chest pain, No evidence ischemia

FFR

FFR FFR

FFR FFR FFR

FFR

FFR

FFR FFR FFR

FFR FFR

Asymptomatic Patients

FFR facilitates appropriate Interventions

Ischemia-Driven PCI Decisions

• Improves Outcomes and Appropriateness

• FFR is in-lab marker of specific ischemic

lesion.

• FFR Reduces Uncertainty

• If you’re not using FFR…

“Retool or Retire”