c. michael gibson, m.s., m.d

Clinical Trial Results . orgClinical Trial Results . org

C. Michael Gibson, M.S., M.D.

Director TIMI Data Coordinating Center

Invasive Cardiologist Beth Israel Deaconess Medical Center& Chief of Clinical Research

Associate Professor of Medicine, Harvard Medical School

The Pathophysiology of Myocardial PerfusionThe Pathophysiology of Myocardial PerfusionThe Pathophysiology of Myocardial PerfusionThe Pathophysiology of Myocardial Perfusion


Closed Muscle on Closed Muscle on Angiogram During LifeAngiogram During Life

Closed Muscle on Closed Muscle on Angiogram After DeathAngiogram After Death

Erling Falk et al. Circulation 1985; 71: 699-708Erling Falk et al. Circulation 1985; 71: 699-708

Closed Muscle in Life and DeathClosed Muscle in Life and Death

Gibson CM, 2006Gibson CM, 2006


Pathophysiology of Downstream Microvascular Obstruction

Pathophysiology of Downstream Microvascular Obstruction

• Platelet / fibrin aggregates (micro embolii)Platelet / fibrin aggregates (micro embolii)

• Swelling and edema of endothelial and myocardial Swelling and edema of endothelial and myocardial cellscells

• Neutrophil pluggingNeutrophil plugging

• Capillary leakCapillary leak


TIMI Myocardial Perfusion (TMP) Grades TIMI Myocardial Perfusion (TMP) Grades

0

1

2

3

4

5

6

7

8

0

1

2

3

4

5

6

7

8

6.2%6.2%

4.4%4.4%

2.0%2.0%n = 203n = 203 n = 46n = 46 n = 434n = 434

TMP Grade 3 TMP Grade 3

p = 0.05p = 0.05

Mo

r ta l

ity

( %)

Mo

r ta l

ity

( %)

n = 79n = 79

5.1%5.1%

Gibson et al, Circulation 2000Gibson et al, Circulation 2000

Normal ground glassappearance of blushDye mildly persistent

at end of washout

Normal ground glassappearance of blushDye mildly persistent

at end of washout

Dye strongly persistentat end of washout

Gone by next injection

Dye strongly persistentat end of washout

Gone by next injection

Stain presentBlush persists

on next injection

Stain presentBlush persists

on next injection

No or minimal blushNo or minimal blush

TMP Grade 2 TMP Grade 2 TMP Grade 1 TMP Grade 1 TMP Grade 0 TMP Grade 0


0

1

2

3

4

5

6

7

8

9

0

1

2

3

4

5

6

7

8

9

The Goal is to Restore Both Normal Epicardial & Normal Myocardial Blood Flow

0

1

2

3

4

5

6

7

8

9

0

1

2

3

4

5

6

7

8

9

3.7%3.7%

n = 487n = 487 n = 328 n = 328

Epicardial TIMI Grade 3 FlowEpicardial TIMI Grade 3 Flow Epicardial TIMI Grade 2 / 1 / 0 FlowEpicardial TIMI Grade 2 / 1 / 0 Flow

Myocardial Perfusion Grade 3


p = 0.05p = 0.05

2.9%2.9%

n = 136n = 136

5.4%5.4%

n = 279n = 279

7.5%7.5%

n = 64n = 64

4.7%4.7%

n = 226n = 226

5 way p = 0.007 5 way p = 0.007

Mo

rta

lit y

(%

)M

ort

ali

t y (

%)

Mo

rta

lit y

(%

)M

ort

ali

t y (

%)

n = 34n = 34

0.7%0.7%



Myocardial Perfusion Grades 0/1

Myocardial Perfusion Grades 0/1



Myocardial Perfusion

Grades 2/1/0

Myocardial Perfusion

Grades 2/1/0

7.0%7.0%

Gibson et al, Circulation 2000Gibson et al, Circulation 2000


Myocardial Perfusion & Mortality: 8 Years of Follow-UpMyocardial Perfusion & Mortality: 8 Years of Follow-Up

9090 360360 900900 14401440 22502250 27902790

0/10/1n=236n=236

22n=393n=393

33n=148n=148

Time (days)Time (days)

van ‘t Hof AWJet al. Circulation 1998; 97:2302-6.van ‘t Hof AWJet al. Circulation 1998; 97:2302-6.

Sur

viva

lS

urvi

val

Majority of patients have TIMI Grade 3 flow in epicardial artery after primary PCI

However

2 of 3 pts have a

cosed muscle after0

primary PCI

Majority of patients have TIMI Grade 3 flow in epicardial artery after primary PCI

However

2 of 3 pts have a

cosed muscle after0

primary PCI


Two Chamber ViewTwo Chamber View

Abn TMPGAbn TMPG

= 8 X = 8 X RiskRisk

Of HEOf HE

(p = 0.02)(p = 0.02)

Circulation. 2006;114:662-669.Circulation. 2006;114:662-669.


MRI Hyperenhancement and Troponin Release After PCIMRI Hyperenhancement and Troponin Release After PCI

• 37% of patients had tn elevation after PCI, all 37% of patients had tn elevation after PCI, all had hyperenhancement on MRIhad hyperenhancement on MRI

• 63% had no tn elevation and none of these 63% had no tn elevation and none of these pts had hyperenhancement on MRIpts had hyperenhancement on MRI

• Tn elevation was proportional to grams of Tn elevation was proportional to grams of MRI enhancementMRI enhancement

• Loss of myocardium was 5% of muscle massLoss of myocardium was 5% of muscle mass

Selvanayagam, Circulation. 2005;111:1027-1032.Selvanayagam, Circulation. 2005;111:1027-1032.


Early Impaired Myocardial Perfusion is Associated with Larger SPECT Infarct Size & Poorer Salvage

Early Impaired Myocardial Perfusion is Associated with Larger SPECT Infarct Size & Poorer Salvage

0

2

4

6

8

10

12

14

0

2

4

6

8

10

12

14

Median = 7Median = 7

p=0.004p=0.004

TMPG 2/3TMPG 2/3 TMPG 0/1TMPG 0/1

n=108n=108n=113n=113

Median = 13Median = 13

% S

PE

CT

In

farc

t S

ize

% S

PE

CT

In

farc

t S

ize

Angeja et al; Circulation 2002Angeja et al; Circulation 2002

In a multivariate model, TMPG 2/3 remained independently associated with a higher salvage index (p=0.001)

In a multivariate model, TMPG 2/3 remained independently associated with a higher salvage index (p=0.001)

Dibra et al, JACC 2003:41: 925-929 Dibra et al, JACC 2003:41: 925-929


Poorer TMPG is Associated with Higher Coronary Wedge Pressure (Pressure Distal to Stenosis) and Higher Pulmonary Capillary Wedge Pressure

Poorer TMPG is Associated with Higher Coronary Wedge Pressure (Pressure Distal to Stenosis) and Higher Pulmonary Capillary Wedge Pressure

0

5

10

15

20

25

30

0

5

10

15

20

25

30

Cor

onar

y W

edge

Pre

ssur

eC

oron

ary

Wed

ge P

ress

ure

Closed

TMPG 0/1

Closed

TMPG 0/1

Open

TMPG 2/3

Open

TMPG 2/3

28 mm Hg28 mm Hg

9 mm Hg9 mm Hg

K P Balachandran et al; Heart. 2004;90: 1450-1454.K P Balachandran et al; Heart. 2004;90: 1450-1454.

p=0.001p=0.001

30

35

40

45

50

55

60

30

35

40

45

50

55

60

Closed

TMPG 0/1

Closed

TMPG 0/1

Open

TMPG 2/3

Open

TMPG 2/3

p=0.02

% w

ith

PA

wed

ge

> 1

8 m

m

Hg

% w

ith

PA

wed

ge

> 1

8 m

m

Hg

56%56%

44%44%

Kirtane AJ et al; J Thromb Thrombolysis.2004;17:177-84


Wire Passage in STEMI Can Be Associated with Staining

(TMPG 1)

Wire Passage in STEMI Can Be Associated with Staining

(TMPG 1)

Gibson 2004Gibson 2004

c. michael gibson, m.s., m.d

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