©2015 MFMER |

Coronary

Revascularization

and the Bad LV

Implications of the STICH

Trial Substudy

Is the concept of

viability testing still

viable ?

ACC New York 2016 3492638-7

Is s

©2015 MFMER |

Prognosis of PatientsWith LV Dysfunction and CAD

Results of revascularization – a paradox

Periproceduralrisk Late mortality

Severity of LV dysfunction

Severity of CAD/ischemia

Major determinants

Pt with LV dysfunctionPt with CAD

3411890-9

©2016 MFMER |

STICH Trial – 10-Year Outcomes1,212 Pts (EF 0.35)

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11

Velasquez: NEJM, 2013

Even

t ra

te (

%)

Death from Any Cause (Primary

Outcome)

Years since randomization

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11

Death from Cardiovascular

Causes

Years since randomization

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10

Death from Any Cause or

Cardiovascular Hospitalization

Years since randomization

Med

CABG

Hazard ratio, 0.84(95% CI, 0.73-0.97)

P=0.02 by log-rank test

Med

CABG

Hazard ratio, 0.79(95% CI, 0.66-0.93)

P=0.006 by log-rank test Med

CABG

Hazard ratio, 0.72(95% CI, 0.64-0.82)

P<0.001 by log-rank test

3587177-02

NNT –14

©2016 MFMER |

Mechanisms of Improved Prognosis Following Revascularization – ?

Prevention

of ventricular

arrhythmias

Inducible ischemia

and repetitive stunning

Ventricular remodeling

in resting LVEF

Recovery in regional function

Potential

benefits

Diastolic dysfunction

Symptoms of CHF

? Benefits independent of effects on ischemia & viability but prevention of recurrent events

3587177-01

©2015 MFMER |

Definition of Viable Myocardium

3432359-5

Myocardium that is dysfunctional at rest and not scarred and has the potential for

functional recovery

Shah: EHJ, 2013

“Hibernation’ should be used retrospectively

only to describe those segments which

actually improve following revascularization

Before Surgery – LVEF = 26%

After Surgery – LVEF = 45%

©2015 MFMER |

Viability and Prognosis in Patients with LV Dysfunction

3432775-9

Different Substrates

• Hibernation (resting ischemia)

• Repetitive stunning (inducible ischemia)• Extent of scar• Extent of remodeling• Duration of hibernation

“How much is enough – not an all or none issue”

Need for combined imaging approaches to

characterize substrates and reversibility

©2014 MFMER |

Quantity of Viable Myocardial Required to Improve Survival With Revascularization in

Patients With Ischemic Cardiomyopathy

• 29 studies

• 4,167 patients

• Meta-analysis

3362090-4

25.8

35.938.7

0

10

20

30

40

50

PET Stress Echo SPECT

% V

iable

/tota

l m

yocard

ium

Optimal Threshold for Presence of Viability

Inaba: J NuclCardiol, 2010

©2015 MFMER |

Clinical Indications for Viability Testing

• Subtotal occlusions

• Collaterals

Patients with CAD and severe

LV dysfunction (EF 0.35)

“Flash” pulmonary

edema with subsequent

improvement

Clinical EF?

Severe CAD and no history of MI

Absent Q waves on ECG

Significant angina or stress-induced ischemia

Angiography

3471328-3

©2013 MFMER |

STICH – Myocardial Viability and Survival

3309958-10

0.0

0.2

0.4

0.6

0.8

1.0

0 1 2 3 4 5 6

601 pt – viability

testing

SPECT

DSE

Years since randomization

Pro

bab

ilit

y o

f d

eath

Hazard ratio 0.64

95% CI 0.48-0.86

P=0.003

Without viability (114 pt)

With viability (487 pt)

Bonow: NEJM, 2011

©2016 MFMER |

Subgroup No. Deaths HR (95% CI) P

Without 114 58 0.70 (0.41-1.18) NSviability

With 487 178 0.86 (0.64-1.16) NSviability

STICH – Myocardial Viability and Survival

359768-1

0.25 0.50 1.0 2.0

CABG better

Medical therapy better

Bonow: NEJM, 2011

©2015 MFMER |

“If you are not confused

by this – you are not

thinking clearly.”

Pogo

3492638-8

©2016 MFMER |

STICH Viability StudyLimitations

• Study is underpowered

• Non-randomized – viability performed at physician discretion and unblinded

• Baseline differences between pt with/without viability testing – comorbidities

• Viability determined in a binary fashion – PET and CMRI – greater accuracy and provide additional information

• Does not distinguish between dysfunctioning potentially viable myocardiumand reversibility

• 3 VD only present in approximately one third

• 85% of patients in substudy – non-USA

• Generalizability to contemporary populationICD – 50%

CRT – 20%

3507142-12

©2016 MFMER |

Not Essential

• Significant angina

• Good distal vessels

• ECG

• Reasonable surgical risk

3507142-13

Role of Viability Testing in Clinical Decision Making in Patients With LV Dysfunction

No Q waves

Preserved voltage

Potentially Helpful

• Severe LV dysfunction

• Extensive LV remodeling

• Multiple comorbidities

• Incomplete revascularization is likely

• Angina – less severe

©2013 MFMER |

Inducible Myocardial Ischemia andOutcomes of Revascularization

Panza: JACC, 2012

• STICH Trial

• EF <0.35

Stress testing

• Inducible ischemia 64%

• % ischemic myocardium (18±11%)

No Ischemia

Years following randomization0 1 2 3 4 5 6

Ischemia

Years following randomization0 1 2 3 4 5 6

MED (56 events)

CABG (47 events)

1.0

0.8

0.6

0.4

0.2

0.0

Mortality

Mort

alit

y r

ate

MED (31 events)

CABG (22 events)

3267767-3

©2014 MFMER |

Impact of Ischemia and Scar on Therapeutic Benefit from Coronary Revascularization

Lo

g h

aza

rd r

atio

Hachamovich: EHJ, 2011

Total myocardium ischemic (%)

-0.5

0.0

0.5

1.0

1.5

0.0 12.5 25.0 37.5 50.0

Medical therapy

Early revascularization

• % ischemic myocardium = P=0.089

• Ischemia treatment interaction = P=0.489

Role of ischemia in pt with >10% fixed myocardial

defect

• 13,969 pt

• Adenosine orexercise SPECT

P<0.001

3357109-17

©2014 MFMER |

Impact of Ischemia and Scar on Therapeutic Benefit from Coronary Revascularization

Lo

g h

aza

rd r

atio

Hachamovich: EHJ, 2011

Total myocardium ischemic (%)

-0.5

0.0

0.5

1.0

1.5

0.0 12.5 25.0 37.5 50.0

Medical therapy

Early revascularization

Role of ischemia on benefit of revascularization was nullified by presence of extensive infarction/scar

• 13,969 pt

• Adenosine orexercise SPECT

P<0.001

3391078-6

©2015 MFMER | 3485852-8

But CABG does improve angina symptoms compared withmedical therapy alone”

“Presence of angina does not confer markedly worse prognosis or a greater benefit from revascularization by CABG

Jolicouer et al

©2015 MFMER |

• No effect of viability, inducible ischemia and angina on surgical outcomes

• remodeling with non-viability but no effect on surgical outcomes

Is There a Role for Viability and Ischemia Testing? Is the Concept Still Valid and Rational?

3485205-06

Bonow: NEJM, 2011; Panza: JACC, 2012

Jolicouer: JACC, 2015; Bonow: JACC, 2015

No Yes

STICH patientsOther patient

subgroups

©2015 MFMER | 3459251-4

In patients with LV dysfunction and CAD, are the presence of viability, inducible ischemia and angina still therapeutic targets?

YES

Considerations

Viability and Ischemia Extent of scar and

remodeling

What is the point of no return?

©2015 MFMER |

• May influence response to medical therapy

Role of Viability TestingConclusions

• May predict response to revascularization in selected pts with CAD and LV dysfunction

• Impact of viability and residual ischemia may be overwhelmed by extensive scar and remodeling.

• Marker of prognosis

3493400-10

• Should “not” be a routine determinant of decision to revascularize

©2015 MFMER |

“The reports of my

death are greatly

exaggerated.”

Text of a cable sent by Mark Twain

from London to the press in the U.S.

after his obituary had been

mistakenly published

3492638-7