proof of concept #1: occluded arteries cause acute mi proof of concept #1: occluded arteries cause...

Proof of Concept #1:Occluded Arteries

Cause Acute MI

Proof of Concept #1:Occluded Arteries

Cause Acute MI

Proof of Concept #2:Drugs (in this case IC SK)

Recanalize Occluded Arteries

Proof of Concept #2:Drugs (in this case IC SK)

Recanalize Occluded Arteries

The “Code White” Team of Dr. William Ganz: 1979The “Code White” Team of Dr. William Ganz: 1979

Results of the NIH Sponsored TIMI 1 TrialResults of the NIH Sponsored TIMI 1 Trial

6270

31

43

0

10

20

30

40

50

60

70

80

Recanalization Patency

tPA

SK

6270

31

43

0

10

20

30

40

50

60

70

80

Recanalization Patency

tPA

SK

% Arteries Opened Documented to be Closed

% Arteries Opened Documented to be Closed

% All Arteries Open at 90 Min.

% All Arteries Open at 90 Min.

% o

f Pa

tien

ts%

of P

atie

nts

Cheesboro et al, Circulation 1987;76: 142-154 Cheesboro et al, Circulation 1987;76: 142-154

DSMB stopped trial early; felt that greater rate of patency would necessarily translate into improved outcomesDSMB stopped trial early; felt that greater rate of patency would necessarily translate into improved outcomes

The Dark Days of the Open Artery Hypothesis: Results of Early Megatrials

The Dark Days of the Open Artery Hypothesis: Results of Early Megatrials

Despite the fact that TIMI 1 showed superior patency for tPA over SK, early megatrials showed no difference in mortality

Early megatrials used 3 hour dosing of tPA (not front-loaded) and late SQ heparin (not early IV heparin)

Despite the fact that TIMI 1 showed superior patency for tPA over SK, early megatrials showed no difference in mortality

Early megatrials used 3 hour dosing of tPA (not front-loaded) and late SQ heparin (not early IV heparin)

GUSTO-I

GUSTO Investigators: NEJM 1993;329:673-82. NEJM 1993;329:1615-22

No. Pts 9796 10377 10344 10328

30 day mortality

7.2 7.4 6.3* 7 0.005

24 hr mortality

2.8 2.9 2.3* 2.8 0.005

ICH 0.5 0.5 0.7* 0.9 0.03Net clinical

benefit7.7 7.9 6.9* 7.6 0.006

CHF 17.5 16.8 15.2* 16.8 <0.001

Card. Shock 6.9 6.3 5.1* 6.1 <0.001

TIMI 2/3 Flow 54 60 81* 73 <0.001

TIMI 3 Flow 29 32 54* 38 <0.001

Main Results

SK (SQ) SK (IV) t-PA t-PA+SK p value

OcclusionOcclusion PenetrationPenetration Slow FlowSlow Flow Normal FlowNormal Flow

TIMI 0TIMI 0 TIMI 1TIMI 1 TIMI 2TIMI 2 TIMI 3TIMI 3

% M

ort

alit

y%

Mo

rtal

ity

9.3%9.3%

6.1%6.1%

3.7%3.7%

p<0.0001 vs TIMI 0/1p<0.0001 vs TIMI 2

p<0.0001 vs TIMI 0/1p<0.0001 vs TIMI 2

P=0.003 vs TIMI 0/1P=0.003 vs TIMI 0/1

Tea

m 2

Tea

m 2

Tea

m 2

Tea

m 2

Tea

m 2

Tea

m 2

Ger

ma

nG

erm

an

Ger

ma

nG

erm

an

Ger

ma

nG

erm

an

GU

ST

O 1

GU

ST

O 1

GU

ST

O 1

GU

ST

O 1

GU

ST

O 1

GU

ST

O 1

TA

M I

1-7

TA

M I

1-7

TA

M I

1-7

TA

M I

1-7

TA

M I

1-7

TA

M I

1-7

TIM

I 1

,45,

10B

TIM

I 1

,45,

10B

TIM

I 1

,45,

10B

TIM

I 1

,45,

10B

TIM

I 1

,45,

10B

TIM

I 1

,45,

10B

CM Gibson 1998 in Acute Coronary SyndromesCM Gibson 1998 in Acute Coronary SyndromesSample Size of Pooled Analysis: 5,498Sample Size of Pooled Analysis: 5,498

0

2

4

6

8

10

12

0

2

4

6

8

10

12

10 16 33 34 44 2784 13 19 9 15 18 29 34

Restoration of “Normal” Epicardial Flow Yields Better OutcomesRestoration of “Normal” Epicardial Flow Yields Better Outcomes

Unfortunately rate of agreement only 71%Unfortunately rate of agreement only 71%

GUSTO I

7872

62 63 62 60 57 54

46 4539

1312

19 19 1824

22 27

25 2831

TIMI 4 RAPID II

n=146n=292

RAAMITAPS

n=128n=199

Neuhaus

n=74

TIMI 3 Flow TIMI 2 Flow

TIMI 10B

n=133n=312

60

21

AllTrials

n=1,758

In Time1

n=124

TIMI 5

n=84

Gibson, American Heart Journal,1999

TIMI 14

n=214 n=55

IMPACTAMI

IMPACT AMI Phase 2

Core Lab: 77%

IMPACT AMI Phase 2

Core Lab: 77%

IMPACT AMI Phase 1

Core Lab: 26%

IMPACT AMI Phase 1

Core Lab: 26%

IMPACT AMI Phase 2

Site Reading: 62% (n=13)

IMPACT AMI Phase 2

Site Reading: 62% (n=13)

IMPACT AMI Phase 1

Site Reading: 52%

IMPACT AMI Phase 1

Site Reading: 52%

LAD

Frame 1: Frame 1: Dye Dye Touches Both Touches Both

Borders & Borders & Moves Moves

ForwardForward

Frame 0: Frame 0: Dye Dye Touches One Touches One or No Bordersor No Borders

Last Frame Definition

Frame 21: Frame 21: Dye Dye firstfirst

enters enters landmark landmark

First Frame Definition

RCA

LCX

DistalLandmark

Normal Flow in the Normal Flow in the Absence of MI :Absence of MI :

21.0 21.0 ++ 3.1 frames 3.1 frames

1st branch off posterolateral

Last branch offmost distal OM

“Whale’s tail” or “pitchfork”or most distalbranch LAD atapex

Gibson, Circulation 1996; 93: 879-888Gibson, Circulation 1996; 93: 879-888

Even Faster Epicardial Coronary Blood Flow is Better

Even Faster Epicardial Coronary Blood Flow is Better

0

1

2

3

4

5

6

7

CTFC < 14CTFC < 14 CTFC > 40CTFC > 40

0.0%0.0%(n=41)(n=41) (n = 18/640)(n = 18/640) (n =35/563)(n =35/563)

2.8%2.8%

p= 0.003p= 0.003

“TIMI 4” Flow“TIMI 4” Flow TIMI 3 FlowTIMI 3 Flow14 < CTFC < 4014 < CTFC < 40

6.2%6.2%

% R

isk

of

In H

osp

ital

Mo

rtal

ity

% R

isk

of

In H

osp

ital

Mo

rtal

ity

Gibson, Circulation 1999; 99: 1945-1950Gibson, Circulation 1999; 99: 1945-1950

Hyperemic FlowHyperemic FlowReproducibility:

r = 0.97 between readersAccuracy:

r=0.88 vs Doppler velocity

Reproducibility: r = 0.97 between readers

Accuracy:r=0.88 vs Doppler velocity

2121

00

1010

1515

55

Percent Stenosis 67.8%

Percent Stenosis 67.8%

Percent Stenosis69.5%




Distal to Stenosis: 11.8 cm or 76.6%Distal to Stenosis: 11.8 cm or 76.6%



Diameter: 2.97 mmDiameter: 2.97 mm

Diameter: 3.10 mmDiameter: 3.10 mm

Diameter: 3.23 mmDiameter: 3.23 mmSBP

120.2 mmHg

SBP120.2 mmHg

SBP120.6 mmHg

SBP120.6 mmHg

SBP121.7 mmHg

SBP121.7 mmHg

Wedge Pressure: 18.0 mm HgWedge Pressure: 18.0 mm Hg



N = 1,044N = 1,044

N = 264N = 264

N = 778N = 778

RCA:90 Min. TIMI 3 Flow: 64.2%Composes 2/3 rds of TIMI 3 flow

90 Min. CTFC: 33.4Post PTCA CTFC 25.5

Thin walled RVLow filling pressures

RCA:90 Min. TIMI 3 Flow: 64.2%Composes 2/3 rds of TIMI 3 flow


Thin walled RVLow filling pressures

LCX:90 Min. TIMI 3 Flow: 56.4%


Thick walled LVHigh filling pressures

LCX:90 Min. TIMI 3 Flow: 56.4%



LAD:90 Min. TIMI 3 Flow: 46.0%Composes 2/3rds of TIMI 2 flow



LAD:90 Min. TIMI 3 Flow: 46.0%Composes 2/3rds of TIMI 2 flow



Differences Among the Three Epicardial Arteries Following Thrombolytic Administration in 2,068 TIMI Patients

Differences Among the Three Epicardial Arteries Following Thrombolytic Administration in 2,068 TIMI Patients

CM Gibson J Am Coll Cardiol 1999; 34: 1403-12CM Gibson J Am Coll Cardiol 1999; 34: 1403-12

proof of concept #1: occluded arteries cause acute mi proof of concept #1: occluded arteries cause...

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