clinical trial results. org c. michael gibson, m.s., m.d. director timi data coordinating center...
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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
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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
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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
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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
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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
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 Grade 2
Myocardial Perfusion Grade 2
Myocardial Perfusion Grades 0/1
Myocardial Perfusion Grades 0/1
Myocardial Perfusion Grade 3
Myocardial Perfusion Grade 3
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
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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
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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.
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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.
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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
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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
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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