proof of concept #1: occluded arteries cause acute mi
DESCRIPTION
The “Code White” Team of Dr. William Ganz: 1979. Proof of Concept #1: Occluded Arteries Cause Acute MI. Proof of Concept #2: Drugs (in this case IC SK) Recanalize Occluded Arteries. Results of the NIH Sponsored TIMI 1 Trial. % of Patients. % Arteries Opened Documented to be Closed. - PowerPoint PPT PresentationTRANSCRIPT
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%
Percent Stenosis69.5%
Percent Stenosis67.1%
Percent Stenosis67.1%
Distal to Stenosis: 11.8 cm or 76.6%Distal to Stenosis: 11.8 cm or 76.6%
Distal to Stenosis: 9.2 cm or 70.1%Distal to Stenosis: 9.2 cm or 70.1%
Distal to Stenosis: 7.8 cm or 59.8%Distal to Stenosis: 7.8 cm or 59.8%
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
Wedge Pressure: 16.4 mm HgWedge Pressure: 16.4 mm Hg
Wedge Pressure: 19.7 mm HgWedge Pressure: 19.7 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
90 Min. CTFC: 33.4Post PTCA CTFC 25.5
Thin walled RVLow filling pressures
LCX:90 Min. TIMI 3 Flow: 56.4%
90 Min. CTFC: 40.4Post PTCA CTFC 36.5
Thick walled LVHigh filling pressures
LCX:90 Min. TIMI 3 Flow: 56.4%
90 Min. CTFC: 40.4Post PTCA CTFC 36.5
Thick walled LVHigh filling pressures
LAD:90 Min. TIMI 3 Flow: 46.0%Composes 2/3rds of TIMI 2 flow
90 Min. CTFC: 39.1Post PTCA CTFC 30.0
Thick walled LVHigh filling pressures
LAD:90 Min. TIMI 3 Flow: 46.0%Composes 2/3rds of TIMI 2 flow
90 Min. CTFC: 39.1Post PTCA CTFC 30.0
Thick walled LVHigh filling pressures
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