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

Clinical Trial Results . orgClinical Trial Results . org

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

Goal of IC SK Before PCI: Get the artery openGoal of IC SK Before PCI: Get the artery open


Acute MI Treated with Distal Protection and IC tPA (8 mg)

Acute MI Treated with Distal Protection and IC tPA (8 mg)

After Percusurge / Angiojet

After 8 mg IC tPA

Pre PCI

Clot

Clot


Patients and RandomizationImmediately after diagnostic angiography

eligible patients (n =41) were randomized to

ICSK group (n=21) Control group (n=20)

(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

Sezer et al, et al. NEJM 2007; 356(18): 1823-1834


All patients underwent intracoronary hemodynamic measurement and angiographic analysis two days All patients underwent intracoronary hemodynamic measurement and angiographic analysis two days after primary PCI to evaluate microvascular functionafter primary PCI to evaluate microvascular function

ST segment resolution ST segment resolution

Diastolic deceleration time Diastolic deceleration time

Echocardiographic assessment of Echocardiographic assessment of left ventricular volumes and functionleft ventricular volumes and function

Coronary flow reserveCoronary flow reserve

Index of microvascular resistanceIndex of microvascular resistance

Coronary wedge pressure Coronary wedge pressure (mean ad systolic)(mean ad systolic)

Pressure derived collateral flow indexPressure derived collateral flow index

Myocardial blush gradesMyocardial blush grades

Corrected TIMI frame countCorrected TIMI frame count

Study Design

Second angiography and intracoronary hemodynamic

measurements 2 days after AMI.

Ass

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Control angiography (TIMI frame count, Myocardial blush grade) Infarct size measurement (SPECT), Echocardiographic assessment of left ventricular volumes and functionLo

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(at 6

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Transthoracic echocardiography,

2 days after AMI

Pre/post PCI ECG



Assessment of Microvascular Perfusion by Invasive MethodsAssessment of Microvascular Perfusion by Invasive Methods

• Thermodilution-derived Coronary Flow Reserve (CFR)*Thermodilution-derived Coronary Flow Reserve (CFR)*

= = Resting mean transit time / hyperemic mean transit timeResting mean transit time / hyperemic mean transit time *Pijls NHJ et al.. Circulation 2002;105:2482-2486*Pijls NHJ et al.. Circulation 2002;105:2482-2486

• Index of Microvascular Resistance (IMR)**:Index of Microvascular Resistance (IMR)**:

= Distal coronary pressure x hyperemic mean transit time= Distal coronary pressure x hyperemic mean transit time**Fearon WF. et al.. Circulation. 2003;107:3129-3132**Fearon WF. et al.. Circulation. 2003;107:3129-3132

• Coronary Wedge Pressure (CWP) and Pressure-derived Collateral Flow Index Coronary Wedge Pressure (CWP) and Pressure-derived Collateral Flow Index (CFIp):(CFIp):

= CWP/Pa= CWP/Pa

• Thermodilution-derived Coronary Flow Reserve (CFR)*Thermodilution-derived Coronary Flow Reserve (CFR)*

= = Resting mean transit time / hyperemic mean transit timeResting mean transit time / hyperemic mean transit time *Pijls NHJ et al.. Circulation 2002;105:2482-2486*Pijls NHJ et al.. Circulation 2002;105:2482-2486

• Index of Microvascular Resistance (IMR)**:Index of Microvascular Resistance (IMR)**:

= Distal coronary pressure x hyperemic mean transit time= Distal coronary pressure x hyperemic mean transit time**Fearon WF. et al.. Circulation. 2003;107:3129-3132**Fearon WF. et al.. Circulation. 2003;107:3129-3132

• Coronary Wedge Pressure (CWP) and Pressure-derived Collateral Flow Index Coronary Wedge Pressure (CWP) and Pressure-derived Collateral Flow Index (CFIp):(CFIp):

= CWP/Pa= CWP/Pa

Guiding cath.Microvasculature

Balloon

CWP: mm Hg

Pa: mm Hg

Pressure wire



0.0020.0020.17(0.14)-(0.21)

0.17(0.14)-(0.21)

0.08(0.05)-(0.11)

0.08(0.05)-(0.11)

<0.001

<0.001

-0.09(-- 0.13)-(-0.06)

-0.09(-- 0.13)-(-0.06)0.17 + 0.070.17 + 0.070.08 + 0.050.08 + 0.05CFIp (mean, unitless)CFIp (mean, unitless)

<0.001<0.00129.46(21.80)-(37.12)

29.46(21.80)-(37.12)

15.17(8.26)-(22.08)

15.17(8.26)-(22.08)

<0.001

<0.001

-15.56(-21.27)-(-9.85)

-15.56(-21.27)-(-9.85)33.80 + 11.033.80 + 11.018.24 + 6.0718.24 + 6.07CWP, systolic (mmHg)CWP, systolic (mmHg)

0.040.0412.54(6.83)-(18.24)

12.54(6.83)-(18.24)

7.98(2.84)-(13.12)

7.98(2.84)-(13.12)0.0040.004-6.39

(-10.73)-(-2.05)-6.39

(-10.73)-(-2.05)17.20 + 7.9317.20 + 7.9310.81 + 5.4610.81 + 5.46CWP, mean (mmHg)CWP, mean (mmHg)

0.0020.0021.66(1.25)-(2.07)

1.66(1.25)-(2.07)

2.29(1.92)-(2.66)

2.29(1.92)-(2.66)

<0.001

<0.001

0.62(0.35)-(0.93)

0.62(0.35)-(0.93)1.39 + 0.311.39 + 0.312.01 + 0.572.01 + 0.57CFRCFR

<0.001<0.00129.05(22.17)-(35.92)

29.05(22.17)-(35.92)

11.73(5.53)-(17.92)

11.73(5.53)-(17.92)

<0.001

<0.001

-16.20(-21.75)(10.64)

-16.20(-21.75)(10.64)32.49 +11.0432.49 +11.0416.29 + 5.0616.29 + 5.06IMR (U)IMR (U)

ppControl

Group, Mean(95% CI)

Control Group, Mean

(95% CI)

Intracoronary Streptokinase Group, Mean

(95% CI)

Intracoronary Streptokinase Group, Mean

(95% CI)

ppMean

Difference 95% CI

Mean Difference

95% CI

Control Groupn:20

Control Groupn:20

Intracoronary Streptokinase

Groupn:21

Intracoronary Streptokinase

Groupn:21

MultivariateMultivariateUnivariateUnivariate

Intracoronary Hemodynamic Indices of Microvascular Perfusion Intracoronary Hemodynamic Indices of Microvascular Perfusion



Angiographic (cTFC, MBG), ic (STR) and Echocardiographic (DDT) Indices of Microvascular Perfusion

Angiographic (cTFC, MBG), ic (STR) and Echocardiographic (DDT) Indices of Microvascular Perfusion

0.0010.001257(-65)-(580)

257(-65)-(580)

750(446)-(1054)

750(446)-(1054)<0.001<0.001468

(261)-(676)468

(261)-(676)360+292360+292828+258828+258DDT in the LAD artery (milliseconds)#

DDT in the LAD artery (milliseconds)#

------7 (53.8)7 (53.8)11 (91.7)11 (91.7)2/32/3

0.130.13

----

0.0350.035

--6 (46.2)6 (46.2)1 (8.3)1 (8.3)0/10/1Six months after primary PCI

Six months after primary PCI

------6 (32%)6 (32%)15 (71%)15 (71%)2/32/3

0.0650.065

----

0.0120.012

--13 (68%)13 (68%)6 (29%)6 (29%)0/10/1Two days after primary PCITwo days after primary PCI

------5 (28%)5 (28%)10 (50%)10 (50%)2/32/3

0.700.70

----

0.160.16

--13 (72%)13 (72%)10 (50%)10 (50%)0/10/1Immediately after primary PCI

Immediately after primary PCI

MBGMBG

0.0230.02325.89(18.76)-(33.02)

25.89(18.76)-(33.02)

18.88(13.57)-(24.18)

18.88(13.57)-(24.18)0.0140.014-6.2

(-11.00)-(-1.39)-6.2

(-11.00)-(-1.39)27.62 + 6.4627.62 + 6.4621.42 + 4.9821.42 + 4.98Six months after primary PCISix months after primary PCI

0.0010.00127.51(22.03)-(32.99)

27.51(22.03)-(32.99)

19.10(14.16)-(24.04)

19.10(14.16)-(24.04)<0.001<0.001-9.27

(-13.50)-(-5.03)-9.27

(-13.50)-(-5.03)31.79 + 7.5831.79 + 7.5822.52 + 5.5822.52 + 5.58Two days after primary PCITwo days after primary PCI

0.800.8029.36(21.48)-(37.25)

29.36(21.48)-(37.25)

30.30(23.14)-(37.46)

30.30(23.14)-(37.46)0.690.69-0.79

(-6.66)-(5.08)-0.79

(-6.66)-(5.08)34.44 + 8.2634.44 + 8.2633.6 + 9.4533.6 + 9.45Immediately after primary PCIImmediately after primary PCI

cTFC meancTFC mean

Univariate Multivariate ICSK group Control Mean diff. p ICSK group Control p

Univariate Multivariate ICSK group Control Mean diff. p ICSK group Control p



0.170.1737.28(21.57-52.99)

37.28(21.57-52.99)

27.84(14.35-41.32)

27.84(14.35-41.32)0.0050.00537.05 + 13.84

(n: 18)37.05 + 13.84

(n: 18)23 + 13.37

(n: 18)23 + 13.37

(n: 18)Infarct size %,

SPECTInfarct size %,

SPECT

0.820.822.71

(-37.75)-(43.16)

2.71(-37.75)-(43.16)

5.97(-27.32)-(39.26)

5.97(-27.32)-(39.26)0.240.243.46 + 19.023.46 + 19.0214.37 + 31.1414.37 + 31.14Change in LVEF, %Change in LVEF, %

0.240.2451.56(36.90-66.23)

51.56(36.90-66.23)

57.68(45.88-69.47)

57.68(45.88-69.47)0.0200.02046.19 + 12.21

(n: 15)46.19 + 12.21

(n: 15)56.18 + 10.69

(n: 17)56.18 + 10.69

(n: 17)

Six months after

primary PCI

Six months after

primary PCI

0.0780.07847.96(39.86-56.06)

47.96(39.86-56.06)

54.25(46.95-61.55)

54.25(46.95-61.55)0.060.0644.51 + 12.40

(n: 20)44.51 + 12.40

(n: 20)51.52 + 10.76

(n: 21)51.52 + 10.76

(n: 21)

Two days after

primary PCI

Two days after

primary PCILVEF %

LVEF %

0.0360.03614.97

(-18.31)-(48.24)

14.97(-18.31)-(48.24)

-11.19(-37.95)-(15.58)

-11.19(-37.95)-(15.58)0.040.0411.90 + 23.50

(n: 15)11.90 + 23.50

(n: 15)-4.60 + 22.01

(n: 17)-4.60 + 22.01

(n: 17)Change in EDV, %Change in EDV, %

0.0890.089118.77(76.98-160.56)

118.77(76.98-160.56)

92.72(59.11-126.33)

92.72(59.11-126.33)0.0210.021150.13 + 49.28

(n: 15)150.13 + 49.28

(n: 15)115.70 + 29.67

(n: 17)115.70 + 29.67

(n: 17)

Six months after

primary PCI

Six months after

primary PCI

0.500.50118.53 (93.35-143.71)

118.53 (93.35-143.71)

111.22(88.52-133.91)

111.22(88.52-133.91)0.070.07137.75 + 36.82

(n: 20)137.75 + 36.82

(n: 20)119.88 + 23.36

(n: 21)119.88 + 23.36

(n: 21)

Two days after

primary PCI

Two days after

primary PCIEDVml

EDVml

0.0550.05515.30

(-28.40)-(59.01)

15.30(-28.40)-(59.01)

-12.32(-47.47)-(-22.83)

-12.32(-47.47)-(-22.83)0.0140.01412.67 + 30.75

(n: 15)12.67 + 30.75

(n: 15)-13.27 + 25.40

(n: 17)-13.27 + 25.40

(n: 17)Change in ESV %Change in ESV %

0.0680.06858.68(25.10-92.27)

58.68(25.10-92.27)

36.08(9.07-63.10)

36.08(9.07-63.10)0.0040.00483.73 + 39.32

(n: 15)83.73 + 39.32

(n: 15)50.64 + 18.23

(n: 17)50.64 + 18.23

(n: 17)

Six months after

primary PCI

Six months after

primary PCI

0.0630.06365.03(47.76-82.30)

65.03(47.76-82.30)

50.81(31.25-66.37)

50.81(31.25-66.37)0.0130.01378.65 + 30.55

(n: 20)78.65 + 30.55

(n: 20)58.16 + 17.02

(n: 21)58.16 + 17.02

(n: 21)

Two days after

primary PCI

Two days after

primary PCIESVml

ESVml

p(two

tailed)

p(two

tailed)

Control, mean 95%CI

Control, mean 95%CI

ICSK (+), mean, 95%CI

ICSK (+), mean, 95%CI

p(two

tailed)

p(two

tailed)ControlControlICSK (+)ICSK (+)

Univariate Multivariate Univariate Multivariate

Left Ventricular End Systolic (ESV) and End Diastolic Volumes (EDV), Ejection Fraction (LVEF) and Infarct Size (%) Comparisons

Left Ventricular End Systolic (ESV) and End Diastolic Volumes (EDV), Ejection Fraction (LVEF) and Infarct Size (%) Comparisons



Following NEJM Publication in 2007Following NEJM Publication in 2007

Goal of IC SK After PCI: Get the microvasculature openGoal of IC SK After PCI: Get the microvasculature open


0

5

10

15

20

25

0.30.3 0.30.3

4.64.62.82.8

9.59.5

15.615.6

10.210.2

20.220.2

P<0.002P<0.002P<0.04P<0.04

P<0.09P<0.09

P<0.0008P<0.0008

UrgentRevascularization

UrgentRevascularization

RecurrentMI

RecurrentMI

DeathDeath MACEMACE

IC Compared to IV Abciximab Reduces MACE in ACS Pts IC Compared to IV Abciximab Reduces MACE in ACS Pts Undergoing PCI Undergoing PCI

IC Compared to IV Abciximab Reduces MACE in ACS Pts IC Compared to IV Abciximab Reduces MACE in ACS Pts Undergoing PCI Undergoing PCI

Wöhrle J et al. Circulation 2003;107:1840.Wöhrle J et al. Circulation 2003;107:1840.

N = 403 ptsIC – 294IV – 109

N = 403 ptsIC – 294IV – 109

UA and MIUA and MI

IV abciximabIV abciximabIC abciximabIC abciximab

49%49%


Clot Disaggregation Following IC Eptifibatide: Pre-PCI Angiogram

Clot Disaggregation Following IC Eptifibatide: Pre-PCI Angiogram

Pinto et al, Am J Cardiol 2006


Retrospective Experience with IC EptifibatideRetrospective Experience with IC Eptifibatide

• 59 patients treated with 59 patients treated with unbuffered IC eptifibatide:unbuffered IC eptifibatide:

• TIMI Grade 3 flow in >90% of TIMI Grade 3 flow in >90% of patients following PCIpatients following PCI

• Normal TIMI myocardial Normal TIMI myocardial perfusion grade 3 flow (TMPG perfusion grade 3 flow (TMPG 3) present in 54.4% of patients 3) present in 54.4% of patients following PCI (range 20%-25% following PCI (range 20%-25% in past)in past)

• There were no in-hospital There were no in-hospital deaths, reinfarctions, or TIMI deaths, reinfarctions, or TIMI major bleeding events major bleeding events

• No arrhythmias during IC No arrhythmias during IC eptifibatide administrationeptifibatide administration

Pinto et al, Am J Cardiol 2006


Impact of IC Adenosine on Clinical & Electrocardiographic Outcomes in the Setting Primary PTCA

Impact of IC Adenosine on Clinical & Electrocardiographic Outcomes in the Setting Primary PTCA

18

00

20

40

60

80

100

Death

18

00

20

40

60

80

100

Death

85

59

0

20

40

60

80

10085

59

0

20

40

60

80

100

% Developing Q Waves

% Developing Q Waves

48

18

0

20

40

60

80

100

48

18

0

20

40

60

80

100

% Death, MI, CHF, Recurrent Angina% Death, MI, CHF, Recurrent Angina

p < 0.02p < 0.02 p < 0.04p < 0.04p < 0.03p < 0.03

Marzilli et al, Circulation 2000; 101:2154-2159Marzilli et al, Circulation 2000; 101:2154-2159

PlaceboPlacebo Adenosine 4 mg in 2 ml via central lumen of PTCA balloonAdenosine 4 mg in 2 ml via central lumen of PTCA balloon

% o

f P

atie

nts

% o

f P

atie

nts

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

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