Slayt 1

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The Code White Team of Dr. William Ganz 1979
Goal of IC SK Before PCI Get the artery open
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Acute MI Treated with Distal Protection and IC
tPA (8 mg)
Pre PCI
After Percusurge / Angiojet
Clot
Clot
After 8 mg IC tPA
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Intracoronary Streptokinase after Primary
Percutaneous Coronary Intervention Murat Sezer,
Hüseyin Oflaz, Taner Gören, Irem Okcular, Berrin
Umman, Yilmaz Nisanci, Ahmet Kaya Bilge, Yasemin
Sanli, Mehmet Meriç, Sabahattin Umman Istanbul
University, Istanbul Faculty of Medicine,
Department of Cardiology
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Hypothesis

• Complementary intracoronary streptokinase (ICSK)
  infusion immediately following primary PCI may
  further improve tissue level perfusion by
  dissolving thrombus (either in situ formed or
  embolized from the proximal origin) at
  microvascular level.
• To this end, the effect of low-dose (250 kU)
  ICSK, administered immediately after primary PCI,
  on myocardial perfusion was investigated
  prospectively.

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Inclusion / Exclusion Criteria

• Inclusion criteria
• Ongoing chest pain,
• ST segment elevation on electrocardiogram,
• Occlusion of the infarct-related artery at
  angiography (Thrombolysis in Myocardial
  Infarction TIMI 0-I flow)
• Exclusion criteria
• Culprit lesion in a saphenous vein graft,
• Additional narrowing gt50 distal to the culprit
  lesion,
• Left bundle branch block,
• History of prior myocardial infarction, and
• Contraindications to streptokinase, tirofiban,
  aspirin, clopidogrel or heparin.

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Patients and Randomization Immediately after
diagnostic angiography eligible patients (n 41)
were randomized to ICSK group
(n21) Control group (n20) (Primary PCI
250 kU intracoronary streptokinase)
(primary PCI) All patients recieved -
300 mg of aspirin, - A loading dose of 600 mg
of clopidogrel, - Intracoronary unfractioned
heparin at a dose of 100 U/kg during the
procedure, - Tirofiban as a bolus of 0.1 µg/kg
in 3 minutes followed by continuous infusion of
0.15 µg/kg/min for 12 hours, and - Low
molecular weight heparin initiated four to five
hours after primary PCI and continued for at
least 48 hours
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Study Design

• All patients underwent intracoronary hemodynamic
  measurement and angiographic analysis two days
  after primary PCI to evaluate microvascular
  function
• ST segment resolution
• Diastolic deceleration time
• Echocardiographic assessment of left
  ventricular volumes and function
• Coronary flow reserve
• Index of microvascular resistance
• Coronary wedge pressure (mean ad systolic)
• Pressure derived collateral flow index
• Myocardial blush grades
• Corrected TIMI frame count

Pre/post PCI ECG
Transthoracic echocardiography, 2 days after AMI
Assesing microvascular perfusion and LV volumes
in early phase of STEMI
Second angiography and intracoronary hemodynamic
measurements 2 days after AMI.
Long term assesments (at 6 months)
Control angiography (TIMI frame count, Myocardial
blush grade) Infarct size measurement (SPECT),
Echocardiographic assessment of left
ventricular volumes and function
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Assessment of Microvascular Perfusion by Invasive
Methods

• Thermodilution-derived Coronary Flow Reserve
  (CFR)
• Resting mean transit time / hyperemic mean
  transit time
• Pijls NHJ et al.. Circulation
  20021052482-2486
• Index of Microvascular Resistance (IMR)
• Distal coronary pressure x hyperemic mean
  transit time
• Fearon WF. et al.. Circulation.
  20031073129-3132
• Coronary Wedge Pressure (CWP) and
  Pressure-derived Collateral Flow Index (CFIp)
• CWP/Pa

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Intracoronary Hemodynamic Indices of
Microvascular Perfusion
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Angiographic (cTFC, MBG), Electrocardiographic
(STR) and Echocardiographic (DDT) Indices of
Microvascular Perfusion
Univariate Multivariate ICSK group
Control Mean diff. p ICSK
group Control p
0.80
29.36 (21.48)-(37.25)
30.30 (23.14)-(37.46)
0.69
-0.79 (-6.66)-(5.08)
34.44 8.26
33.6 9.45
Immediately after primary PCI
cTFC mean
0.001
27.51 (22.03)-(32.99)
19.10 (14.16)-(24.04)
lt0.001
-9.27 (-13.50)-(-5.03)
31.79 7.58
22.52 5.58
Two days after primary PCI
0.023
25.89 (18.76)-(33.02)
18.88 (13.57)-(24.18)
0.014
-6.2 (-11.00)-(-1.39)
27.62 6.46
21.42 4.98
Six months after primary PCI
0.70
-
-
0.16
-
13 (72)
10 (50)
0/1
Immediately after primary PCI
MBG
-
-
-
5 (28)
10 (50)
2/3
0.065
-
-
0.012
-
13 (68)
6 (29)
0/1
Two days after primary PCI
-
-
-
6 (32)
15 (71)
2/3
0.13
-
-
0.035
-
6 (46.2)
1 (8.3)
0/1
Six months after primary PCI
-
-
-
7 (53.8)
11 (91.7)
2/3
0.001
257 (-65)-(580)
750 (446)-(1054)
lt0.001
468 (261)-(676)
360292
828258
DDT in the LAD artery (milliseconds)
0.45
71.36 (56.66)-(86.07)
66.75 (53.04)-(80.45)
0.42
5.00 (-7.89)-(17.89)
63.2114.37
68.2120.13
Immediately after primary PCI
STR ()
0.39
71.05 (53.55)-(88.55)
77.26 (61.30)-(93.23)
0.04
16.30 (0.06)-(32.54)
51.2524.40
67.5522.91
60 minutes after primary PCI
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Left Ventricular End Systolic (ESV) and End
Diastolic Volumes (EDV), Ejection Fraction (LVEF)
and Infarct Size () Comparisons
Univariate
Multivariate
p (two tailed)
Control, mean 95CI
ICSK (), mean, 95CI
p (two tailed)
Control
ICSK ()
0.063
65.03 (47.76-82.30)
50.81 (31.25-66.37)
0.013
78.65 30.55 (n 20)
58.16 17.02 (n 21)
Two days after primary PCI
ESV ml
0.068
58.68 (25.10-92.27)
36.08 (9.07-63.10)
0.004
83.73 39.32 (n 15)
50.64 18.23 (n 17)
Six months after primary PCI
0.055
15.30 (-28.40)-(59.01)
-12.32 (-47.47)-(-22.83)
0.014
12.67 30.75 (n 15)
-13.27 25.40 (n 17)
Change in ESV
0.50
118.53 (93.35-143.71)
111.22 (88.52-133.91)
0.07
137.75 36.82 (n 20)
119.88 23.36 (n 21)
Two days after primary PCI
EDV ml
0.089
118.77 (76.98-160.56)
92.72 (59.11-126.33)
0.021
150.13 49.28 (n 15)
115.70 29.67 (n 17)
Six months after primary PCI
0.036
14.97 (-18.31)-(48.24)
-11.19 (-37.95)-(15.58)
0.04
11.90 23.50 (n 15)
-4.60 22.01 (n 17)
Change in EDV,
0.078
47.96 (39.86-56.06)
54.25 (46.95-61.55)
0.06
44.51 12.40 (n 20)
51.52 10.76 (n 21)
Two days after primary PCI
LVEF
0.24
51.56 (36.90-66.23)
57.68 (45.88-69.47)
0.020
46.19 12.21 (n 15)
56.18 10.69 (n 17)
Six months after primary PCI
0.82
2.71 (-37.75)-(43.16)
5.97 (-27.32)-(39.26)
0.24
3.46 19.02
14.37 31.14
Change in LVEF,
0.17
37.28 (21.57-52.99)
27.84 (14.35-41.32)
0.005
37.05 13.84 (n 18)
23 13.37 (n 18)
Infarct size , SPECT
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Comments and Conclusions

• Early phase results
• In this pilot trial, low-dose intracoronary
  streptokinase administration immediately
  following primary PCI was compared with standard
  primary PCI without use of intracoronary
  streptokinase.
• Almost all indices of microvascular perfusion
  concordantly pointed out that use of
  intracoronary streptokinase immediately after
  primary PCI yields better perfusion at the
  microvascular level.

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Comments and Conclusions 2

• Late term results
• At six months, there was no significant
  difference between the two study groups with
  regards to left ventricular size or function and
  infarct size, although there were some trends
  favoring the streptokinase group.
• The trial was not originally planned to be large
  enough to detect differences in long-term
  outcome, and indeed enrollment was terminated
  early based on the midterm data on microvascular
  perfusion.
• Since trends in favor of the intracoronary
  streptokinase group were detected, it is possible
  that the study was underpowered for these
  analyses.

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Comments and Conclusions 3

• The finding of the current study supports the in
  situ formed (autochthonous) microvascular
  thrombus hypothesis and pointed out that this
  thrombus should be taken into consideration for
  achieving more efficient reperfusion at
  microvascular level during primary PCI.
• The results of the study should be confirmed by a
  larger randomized study before applying this
  treatment modality in daily cardiology practice.

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Following NEJM Publication in 2007
Goal of IC SK After PCI Get the microvasculature
open
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IC Compared to IV Abciximab Reduces MACE in ACS
Pts Undergoing PCI
UA and MI
Plt0.0008
Plt0.09
20.2
N 403 pts IC 294 IV 109
49
15.6
10.2
Plt0.002
9.5
Plt0.04
4.6
2.8
0.3
0.3
Urgent Revascularization
Recurrent MI
Death
MACE
IV abciximab
IC abciximab
Wöhrle J et al. Circulation 20031071840.
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Clot Disaggregation Following IC Eptifibatide
Pre-PCI Angiogram
Pinto et al, Am J Cardiol 2006
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Retrospective Experience with IC Eptifibatide

• 59 patients treated with unbuffered IC
  eptifibatide
• TIMI Grade 3 flow in gt90 of patients following
  PCI
• Normal TIMI myocardial perfusion grade 3 flow
  (TMPG 3) present in 54.4 of patients following
  PCI (range 20-25 in past)
• There were no in-hospital deaths, reinfarctions,
  or TIMI major bleeding events
• No arrhythmias during IC eptifibatide
  administration

Pinto et al, Am J Cardiol 2006
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Impact of IC Adenosine on Clinical
Electrocardiographic Outcomes in the Setting
Primary PTCA
Placebo
Adenosine 4 mg in 2 ml via central lumen of PTCA
balloon
p lt 0.02
p lt 0.03
p lt 0.04
of Patients
Developing Q Waves
Death, MI, CHF, Recurrent Angina
Marzilli et al, Circulation 2000 1012154-2159