STEMI - Cath Lab

STEMI in the Cath Lab

• primary PCI • primary PCI

Role of PCI in the management of STEMIRole of PCI in the management of STEMIagendaagenda

• the challenges• the challengeshow to achieve optimal reperfusionhow to achieve optimal reperfusionwhat to do with the occluded IRAwhat to do with the occluded IRAreplacing the function of death cellsreplacing the function of death cells

- angioplasty vs thrombolysisangioplasty vs thrombolysis

- added benefit of stent placement- added benefit of stent placement- timing

- culprit vessel vs all vessel intervention

- role of 2b/3a inhibitors

- timing



• transfer, rescue and facilitated PCI• transfer, rescue and facilitated PCI


Primary PCI

angioplasty vs thrombolysisangioplasty vs thrombolysis

primary PTCA vs thrombolysis randomized trials

primary PTCA vs thrombolysis randomized trials

Zijlstra 1Zijlstra 2RibeiroGrinfeld De WoodGrinesGibbonsRibichini Garcia GUSTO 2b

Zijlstra 1Zijlstra 2RibeiroGrinfeld De WoodGrinesGibbonsRibichini Garcia GUSTO 2b

29495

100112

90395103

83189

1138

29495

100112

90395103

83189

1138totaltotal 25992599

primary PTCA vs lysis in AMIprimary PTCA vs lysis in AMI

PTCAn 1290PTCAn 1290

death

reMI

death/ reMI

total stroke

ICH

death

reMI

death/ reMI

total stroke

ICH

4.4%

2.9%

7.2%

0.7%

0.1%

4.4%

2.9%

7.2%

0.7%

0.1%

6.5%

5.3%

11.9%

2.0%

1.1%

6.5%

5.3%

11.9%

2.0%

1.1%

lysisn 1316lysis

n 1316

00 0.50.5 1.51.511 22

odds ratio (95% CI)odds ratio (95% CI)

PTCAbetterPTCAbetter

lysisbetterlysis

better

0.66 (0.46-0.94)0.66 (0.46-0.94)

0.53 (0.34-0.80)0.53 (0.34-0.80)

0.58 (0.44-0.76)0.58 (0.44-0.76)

0.35 (0.14-0.77)0.35 (0.14-0.77)

0.07 (0.00-0.43)0.07 (0.00-0.43)

30-day outcomes30-day outcomes

WD Weaver JAMA 1997; 278: 2093-8WD Weaver JAMA 1997; 278: 2093-8

deathdeath 4.4%4.4% 6.5%6.5%

PTCA vs lysis30 day death/reMI, subgroup analysis

PTCA vs lysis30 day death/reMI, subgroup analysis

age <6060-70>70

age <6060-70>70

PTCAPTCA

0.10.1 0.20.2 110.50.5 22

OR (95% CI)OR (95% CI)lysislysis

DM yesno

DM yesno

MI anteriornon-anterior

MI anteriornon-anterior

prior MI yesno

prior MI yesno

4.3%4.3%6.3%6.3%

13.3%13.3%9.2%9.2%6.5%6.5%8.2%8.2%6.2%6.2%9.7%9.7%6.6%6.6%

8.2%8.2%12.8%12.8%23.6%23.6%19.3%19.3%11.8%11.8%14.5%14.5%12.0%12.0%22.7%22.7%11.5%11.5%

PTCA betterPTCA better lysis betterlysis better

risk group low interm. high

risk group low interm. high

2.9%8.0%

13.1%

2.9%8.0%

13.1%

7.2%12.7%24.1%

7.2%12.7%24.1%

23231515

881010161613131616

8877

27271515

88

NNTNNT

source: PCAT collaborators AHJ 2003;145:47-57source: PCAT collaborators AHJ 2003;145:47-57

primary PTCA vs lysisprimary PTCA vs lysis6-month outcomes: death/reMI6-month outcomes: death/reMI

00 0.50.5 1.51.511 22

odds ratio (95% CI)odds ratio (95% CI)PTCAPTCA

death

reMI

death/ reMI

death

reMI

death/ reMI

lysislysis

PTCA betterPTCA better lysis betterlysis better

0.73(0.55-0.98)0.73(0.55-0.98)

0.46(0.34-0.64)0.46(0.34-0.64)

0.63(0.50-0.78)0.63(0.50-0.78)

source: PCAT collaborators AHJ 2003;145:47-57source: PCAT collaborators AHJ 2003;145:47-57

6.2%

4.8%

10.3%

6.2%

4.8%

10.3%

8.2%

9.8%

16.3%

8.2%

9.8%

16.3%death/ reMIdeath/ reMI 10.3%10.3% 16.3%16.3%

primary PCI vs lysisprimary PCI vs lysis

PTCAPTCA

lysislysis

p = 0.002p = 0.002

deathdeath

p <0.001p <0.001

reMIreMI

p < 0.0001p < 0.0001

death/reMI/strokedeath/reMI/stroke00

55

1010

1515

2020%

patients%

patients

EC KEELEY. JAMA 2003;361:13-20EC KEELEY. JAMA 2003;361:13-20

long-term (6-18 m) outcomes23 CRT (7739 pts)

long-term (6-18 m) outcomes23 CRT (7739 pts)

Primary PCI

POBA vs StentPOBA vs Stent

primary PTCA vs stent randomized trials

primary PTCA vs stent randomized trials

FRESCOZWOLLEGRAMIPAMIPASTASTENTIM-2CADILLACPSAAMI

FRESCOZWOLLEGRAMIPAMIPASTASTENTIM-2CADILLACPSAAMI

150 227 104 900 136 211

1028 88

150 227 104 900 136 211

1028 88

total total 28442844

primary PTCA vs stentprimary PTCA vs stent6-month outcomes6-month outcomes

00 0.50.5 1.51.511 22

OR (95% CI)OR (95% CI)stentstent

death

reMI

death/ reMI

TVR

death/reMI/TVR

death

reMI

death/ reMI

TVR

death/reMI/TVR

3.3%

1.7%

4.9%

8.3%

13.7%

3.3%

1.7%

4.9%

8.3%

13.7%

3.8%

3.0%

6.8%

18%

25.9%

3.8%

3.0%

6.8%

18%

25.9%

PTCAPTCA

stent betterstent better PTCA betterPTCA better

0.85 (0.57-1.27)0.85 (0.57-1.27)

0.58 (0.35-0.96)0.58 (0.35-0.96)

0.72 (0.52-0.98)0.72 (0.52-0.98)

0.41 (0.32-0.52)0.41 (0.32-0.52)

0.45 (0.37-0.55)0.45 (0.37-0.55)

death/ reMIdeath/ reMI 4.9%4.9% 6.8%6.8%

number of events (death / reMI) prevented at 6-month F/U x 1000 patients treated

number of events (death / reMI) prevented at 6-month F/U x 1000 patients treated

thrombolysisthrombolysis

6060

POBAPOBA

1919 stentingstenting

POBAPOBAvsvs

stentingstentingvsvs

STAT study JACC 2001;37:985-91

STAT study JACC 2001;37:985-91

7474

Is timing an issue even for Primary PCI?

Survival Benefit by Time to Treatment with Lytics

Mortality by time to reperfusion with Primary PCINRMI-2 Registry (27,080)

C.P. CANNON. JAMA 2000;283:2941-7

Why is Primary PCI less time dependent than Lysis?

1) Lysis is less effective at restoring infarct artery patency as the clot ages



2) Myocardial salvage and infarct size after lytics are very sensitive to time to reperfusion



2) Myocardial salvage and infarct size after lytics are very sensitive to time to reperfusion

3) Cardiac rupture is more likely to occur as the time to lysis increases

Recommendations

• When performed by experienced* operators/centers, PCI is the reperfusion strategy of choice for patients with AMI

• PCI for AMI: door-to-balloon time < 2hrs (time window up to 12 hours accepted)

* operator: 75 PCI (any type) / year; center: 36 Primary PCI / year

After 12 hours???BRAVE-2Rationale: While thrombolysis has been shown to produce no benefit after 12 hours, no similar studies have looked at primary PCI in this group.

Study: 365 patients randomized to in an invasive arm or a conservative arm. The invasive group underwent angiography and then PCI if necessary, while the conservative group was treated with conventional medical therapy. The primary end point was infarct size determined by SPECT at five to 10 days.

Results: Infarct size (%LV) was significantly reduced in the invasive arm (8.0 vs 13%; p=0.002). No clinical differences.

Kastrati ACC 2005

http://www.acc.org/2005ann_meeting/home/home.htm








- timing





culprit vessel vs all vessel intervention

• The ACC/AHA guidelines on PCI give elective PCI of a non-infarct related artery at the time of AMI a class III recommendation with a C level of evidence.

• Exception: in case of cardiogenic shock, systematic intervention in multiple vessels may be required to optimize reperfusion of the heart.

Role of GP 2b/3a inhibitors

26.1%26.1%

11.2%11.2%9.7%9.7%

14.6%14.6%

4.5%4.5% 5.8%5.8%2.0%2.0%

6.0%6.0%

0%0%

10%10%

20%20%

30%30%

EPICEPIC RAPPORTRAPPORT NeumannNeumann ADMIRALADMIRAL

PlaceboPlacebo GP IIb/IIIaGP IIb/IIIa

p = 0.06p = 0.06 p = 0.03p = 0.03 p = 0.03p = 0.03 p = 0.01p = 0.01

N: 64 483 200 300 2082 N: 64 483 200 300 2082

GP IIb/IIIa Inhibitors For Primary PCI—30-Day Death, (re)MI or Urgent Revascularization

GP IIb/IIIa Inhibitors For Primary PCI—30-Day Death, (re)MI or Urgent Revascularization

6.8%6.8%4.5%4.5%

CADILLACCADILLAC

p = 0.02p = 0.02

the ADMIRAL studythe ADMIRAL study

61615858

6464

5757

6161

5757

abcixabcix

G. MONTALESCOT. NEJM 2001;344:1895-903G. MONTALESCOT. NEJM 2001;344:1895-903

LV function at 24hLV function at 24h

00

2020

4040

6060

8080

EF (%)EF (%)

placeboplacebooveralloverall

abcixabcix placeboplaceboCCU/cath labCCU/cath lab

abcixabcix placeboplaceboMICU/ERMICU/ER

p<0.05p<0.05 NSNS p<0.05p<0.05

Eptifibatide

Cutlip DE et al. Am J Cardiol 2001; 88: 62-4

Tirofiban

Lee DP et al. Circulation 2003; 107: 1497-501

Other 2b/3a inhibitors








- timing




door-to-balloon times in primary PCIdoor-to-balloon times in primary PCI

8%8%

21% 21%24%24%

17%17%

10%10%

20%20%

<60<60 60-9060-90 120-150120-15090-12090-120 150-180150-180 >180>18000

55

1010

1515

2020

% of patients% of patients

minminC.P. CANNON. JAMA 2000;283:2941-7C.P. CANNON. JAMA 2000;283:2941-7

NRMI-2 : 27080 consecutive patientsNRMI-2 : 27080 consecutive patients

When patients present to a primary unit without interventional capabilities:Therapeutic options

a) lyticsb) “transfer” to a facility with a cardiac

cath lab (with or without adjunctive therapy – “facilitated PCI”).

Any such “transfer” needs to be effected rapidly to take advantage of the early benefits of revascularization.

MAASTRICHT

PRAGUE 1

DANAMI 2

PRAGUE 2

AIR PAMI

MAASTRICHT

PRAGUE 1

DANAMI 2

PRAGUE 2

AIR PAMI

thrombolysis vs transfer & primary PCIthrombolysis vs transfer & primary PCIrandomized trialsrandomized trials

n

150

200

1572

850

138

total 2910

n

150

200

1572

850

138

total 2910

MAASTRICHT

PRAGUE 1

DANAMI 2

PRAGUE 2

AIR PAMI

MAASTRICHT

PRAGUE 1

DANAMI 2

PRAGUE 2

AIR PAMI

n

150

200

1572

850

138

n

150

200

1572

850

138

lysis

6.7%

14.0%

7.6%

10.0%

12.1%

lysis

6.7%

14.0%

7.6%

10.0%

12.1%

PCI

6.7%

7.0%

6.6%

6.8%

8.4%

PCI

6.7%

7.0%

6.6%

6.8%

8.4%

0.00.0 0.50.5 1.51.511 2.02.0

OR 95% CIOR 95% CI

lysis better lysis better PCI betterPCI better

1.0(0.28-3.61)1.0(0.28-3.61)1.0(0.28-3.61)1.0(0.28-3.61)

0.45(0.17-1.17)0.45(0.17-1.17)0.45(0.17-1.17)0.45(0.17-1.17)

0.86(0.59-1.27)0.86(0.59-1.27)0.86(0.59-1.27)0.86(0.59-1.27)

0.65(0.40-1.07)0.65(0.40-1.07)0.65(0.40-1.07)0.65(0.40-1.07)

0.68(0.22-2.08)0.68(0.22-2.08)0.68(0.22-2.08)0.68(0.22-2.08)

30-day mortality30-day mortalitythrombolysis vs transfer & primary PCIthrombolysis vs transfer & primary PCI

0.74(0.57-0.98)0.74(0.57-0.98)0.74(0.57-0.98)0.74(0.57-0.98)p=0.03p=0.038.8%8.8% 6.7% 6.7% 29102910pooledpooled

thrombolysis vs transfer & primary PCIthrombolysis vs transfer & primary PCI

† from admission† from admission

minmin

5050

100100

150150

200200

00MAASTRICHTMAASTRICHT DANAMI 2DANAMI 2 PRAGUE 2PRAGUE 2PRAGUE 1PRAGUE 1 AIR PAMI †AIR PAMI †


8585

1010

4949

1212

5151

t to treatment (from randomization)t to treatment (from randomization)

PCIPCI

1001008080 9999 9494

155155

thrombolysis vs transfer & primary PCIthrombolysis vs transfer & primary PCI

00

5050

100100

150150minmin

pooledpooled


PCIPCI

41

106106

57

9090

10 CRT’s10 CRT’s

6565 3333

If transfer PCI is considered:

Recommended time to arrival < 2 hours

(directly to cath lab – bypass ER)

If thrombolytic therapy is considered, but no signs of reperfusion: transfer for rescue PCI

ISAM, INJECT, HIT 4 data (3912 patients)ISAM, INJECT, HIT 4 data (3912 patients)

partial(30- 70%)

partial(30- 70%)

absent(<30%)absent(<30%)

2.7%2.7%4.7%4.7%

13.5%13.5%

complete(>70%)

complete(>70%)

00

55

1010

1515

death %death %

ST segresolutionST segresolution

30-day mortality by ST segment resolution at 180 min

30-day mortality by ST segment resolution at 180 min

Belenkie

RESCUE

PRAGUE

Vermeer

Belenkie

RESCUE

PRAGUE

Vermeer

rescue PCI in acute MI randomized trials

rescue PCI in acute MI randomized trials

28

151

200

149

28

151

200

149

totaltotal 528528

rescue PCIshort term outcome: death

rescue PCIshort term outcome: death

Belenkie

RESCUE

PRAGUE

Vermeer

Belenkie

RESCUE

PRAGUE

Vermeer

n PCI cons.n PCI cons.

28

151

200

149

28

151

200

149

6.3%

5.1%

7%

8.7%

6.3%

5.1%

7%

8.7%

33.3%

9.6%

14.0%

6.7%

33.3%

9.6%

14.0%

6.7%

00 0.50.5 1.51.511 2.02.0

odds ratio (95% CI)odds ratio (95% CI)

0.13 (0.01-1.40)0.13 (0.01-1.40)

0.51 (0.12-2.06)0.51 (0.12-2.06)

0.46 (0.16-1.30)0.46 (0.16-1.30)

1.24 (0.31-4.49)1.24 (0.31-4.49)

0.55 (0.30-1.01)0.55 (0.30-1.01) p=0.052p=0.052totaltotal 528528 6.7%6.7% 11.5%11.5%

2.5%

4.9%

0%

5%

10%

15%

20%

2.5%

4.9%

0%

5%

10%

15%

20%

Pre HospitalLysis

Pre HospitalLysis

PrimaryPCI

PrimaryPCI

P=0.09P=0.09Incidence of ShockIncidence of Shock

CAPTIM – Prehospital tPA vs 1°PCI1 Year ResultsCAPTIM – Prehospital tPA vs 1°PCI1 Year Results

Bonnefoy Lancet 2002Bonnefoy Lancet 2002

5.4%

7.3%

0%

10%

5.4%

7.3%

0%

10% P=0.27P=0.27

Death at 1 YearDeath at 1 Year

Pre HospitalLysis

Pre HospitalLysis

PrimaryPCI

PrimaryPCI

Studies of early angioplasty after thrombolytics

GRACIA I

Facilitated PCI• Use of pharmacological treatment to establish

early reperfusion before catheterization. This strategy combines the benefits of early revascularization with easier intervention (since the artery will already be open in many patients). Facilitation may be obtained with full dose GP 2b/3a inhibitors, full dose lytics, or a combination of half dose lytics + full dose GP 2b/3a inhibitors.

- While primary PCI appears superior to thrombolysis in direct

comparison studies, few patients have prompt access to the cath.

lab.

- While primary PCI appears superior to thrombolysis in direct

comparison studies, few patients have prompt access to the cath.

lab.

rationalerationale

- treatment delays are common and likely reduce the true benefit

of PCI

- treatment delays are common and likely reduce the true benefit

of PCI

- TIMI 3 grade flow prior to PCI is a determinant of success rate and

clinical outcomes

- TIMI 3 grade flow prior to PCI is a determinant of success rate and

clinical outcomes

Effect of Pre-procedural TIMI Flow on Cumulative Late Mortality after Primary PTCA

100%100%

98%98%

96%96%

94%94%

92%92%

90%90%00 11 22 33 44 55 6 6

0.5%0.5%

2.8%2.8%4.4%4.4%

log-rank log-rank P P for trend = 0.009for trend = 0.009

Grade 3Grade 3Grade 2Grade 2Grade 1Grade 1

MonthsMonths

N = 2,507 pts in PAMI-1, PAMI-2, PAMI Stent Pilot, PAMI Stent N = 2,507 pts in PAMI-1, PAMI-2, PAMI Stent Pilot, PAMI Stent N = 2,507 pts in PAMI-1, PAMI-2, PAMI Stent Pilot, PAMI Stent N = 2,507 pts in PAMI-1, PAMI-2, PAMI Stent Pilot, PAMI Stent

Su

rviv

al (

%)

Su

rviv

al (

%)

Stone Circ 2001Stone Circ 2001Stone Circ 2001Stone Circ 2001

6-Month 6-Month MortalityMortality

multivariate predictors of deathmultivariate predictors of death

age (continuous)

anterior MI

female gender

3-vessel disease

pre-PCI TIMI 0-2 flow

age (continuous)

anterior MI

female gender

3-vessel disease

pre-PCI TIMI 0-2 flow

OR (95% CI)

1.06 (1.02-1.10)

4.6 (2.1-10.0)

3.3 (1.6-6.7)

2.5 (1.2-5.6)

2.1 (1.2-37)

OR (95% CI)

1.06 (1.02-1.10)

4.6 (2.1-10.0)

3.3 (1.6-6.7)

2.5 (1.2-5.6)

2.1 (1.2-37)

p

0.001

0.001

0.008

0.01

0.04

p

0.001

0.001

0.008

0.01

0.04

GW STONE. Circulation 2001; 104:636-41GW STONE. Circulation 2001; 104:636-41

pre-PCI TIMI 0-2 flowpre-PCI TIMI 0-2 flow 2.1 (1.2-37)2.1 (1.2-37) 0.040.04

TIMI 0 Complete occlusion

TIMI 1 Penetration of obstruction by contrast but no distal perfusion

TIMI 2 Perfusion of entire artery

but delayed flow

TIMI 3 Full perfusion, normal flow

10.6

7

4.7

0

2

4

6

8

10

12

14

TIMI 0/1 TIMI 2 TIMI 3

Mortality at 42 Days

P < 0.005

TIMI 1TIMI 1

OPEN ARTERY THEORY:Better flow in the infarct artery improves survival

Chesebro JH et al. Circulation 1987;76:142-54

66667272

5454 56564747

404043433939

00

1010

2020

3030

4040

5050

6060

7070

8080 Full-Dose LyticFull-Dose Lytic

GP IIb/IIIa +LyticGP IIb/IIIa +Lytic

% T

IMI 3

Flo

w (

60-9

0 m

ins

)%

TIM

I 3 F

low

(60

-90

min

s)

% T

IMI 3

Flo

w (

60-9

0 m

ins

)%

TIM

I 3 F

low

(60

-90

min

s)

IMPACT-AMIIMPACT-AMI TIMI-14 SPEED TIMI-14 SPEED INTRO-AMI INTRO-AMIFull-Dose t-PA +Full-Dose t-PA + t-PA + r-PA + t-PA + t-PA + r-PA + t-PA + Eptifibatide Abciximab Abciximab EptifibatideEptifibatide Abciximab Abciximab Eptifibatide

IMPACT-AMIIMPACT-AMI TIMI-14 SPEED TIMI-14 SPEED INTRO-AMI INTRO-AMIFull-Dose t-PA +Full-Dose t-PA + t-PA + r-PA + t-PA + t-PA + r-PA + t-PA + Eptifibatide Abciximab Abciximab EptifibatideEptifibatide Abciximab Abciximab Eptifibatide

Early TIMI 3 Flow with Combination TherapyEarly TIMI 3 Flow with Combination Therapy

Facilitated angioplasty studies

Half-Dose t-PA Before PCI: PACT Trial (n=606)Half-Dose t-PA Before PCI: PACT Trial (n=606)

1533

19

28

0

20

40

60

80

100

Placebo 50 mg t-PA

TIMI 2

TIMI 3

1533

19

28

0

20

40

60

80

100

Placebo 50 mg t-PA

TIMI 2

TIMI 361*

34

% P

atie

nts

Ross JACC 1999Ross JACC 1999Ross JACC 1999Ross JACC 1999

*

*

*p < 0.001 vs placebo

LVEF 58.4% 58.2%Rec Ischemia 13.5% 17.9%Reocclusion 3.7% 5.9%Major Bleed 13.5% 12.9%Death at 30d 3.3% 3.6%

P = NS

Full-Dose TNK 3-12h Before PCI: GRACIA-2Full-Dose TNK 3-12h Before PCI: GRACIA-2

Characteristic TNK+PCI PCI

No. patients 103 102

TIMI flow grade 3 59%* 43%

Complete STRes (6h) 61%* 43%

Death, MI, RI-UR 9% 12%

Major bleeding 2% 3%

No differences in infarct size, LV function

*p < 0.05

Characteristic TNK+PCI PCI

No. patients 103 102

TIMI flow grade 3 59%* 43%

Complete STRes (6h) 61%* 43%

Death, MI, RI-UR 9% 12%

Major bleeding 2% 3%

No differences in infarct size, LV function

*p < 0.05

Aviles ESC 2003Aviles ESC 2003Aviles ESC 2003Aviles ESC 2003

facilitated PCI facilitated PCI randomized trialsrandomized trials

nn

6000

4000

1900

4000

200

507

100

6000

6000

4000

1900

4000

200

507

100

6000

ADVANCED- MI

ASSENT PCI

CARESS

FINESSE

GRACIA 2

ON-TIME

TIGER-PILOT

TIGER

ADVANCED- MI

ASSENT PCI

CARESS

FINESSE

GRACIA 2

ON-TIME

TIGER-PILOT

TIGER

studystudy

½ TNK+eptif/early eptif

TNK+enox/adj. GPIIb/IIIa

½ rPA+abcix•/ ½rPA+abcix

½rPA + abcix/early abcix/adj.abcix

TNK+enox/adj.abcix

pre-hosp tirofiban/cath lab tirofiban

ER tirofiban/cath lab tirofiban

½TNK+tirofiban•/ ½TNK+tirofiban

½ TNK+eptif/early eptif

TNK+enox/adj. GPIIb/IIIa

½ rPA+abcix•/ ½rPA+abcix

½rPA + abcix/early abcix/adj.abcix

TNK+enox/adj.abcix

pre-hosp tirofiban/cath lab tirofiban

ER tirofiban/cath lab tirofiban

½TNK+tirofiban•/ ½TNK+tirofiban

treatmentstreatments

• PCI to be performed only in case of no ST-segment resolution• PCI to be performed only in case of no ST-segment resolution

Main Results of ADVANCE-MIMain Results of ADVANCE-MI

2.6

10.1 10

25

0

5

10

15

20

25

Death orSevere CHF

MajorHemorrhage

Placebo +eptifibatide

1/2 TNK +eptifibatide

Giugliano AHA 2004

P = 0.09

P = 0.02

Trial stopped after 149 patients randomized !

• how to achieve optimal reperfusion

• what to do with the IRA found to be

occluded (on late angiography)

• the replacement of function of death cells





current challengescurrent challenges

• how to achieve optimal reperfusion• how to achieve optimal reperfusionpatency (TIMI 2,3) reperfusion (cTFC/MBG)patency (TIMI 2,3) reperfusion (cTFC/MBG)

survival (%) survival (%)

follow up (days)follow up (days)

00

8080

9090

100100

400400 600600 800800

survival in TIMI 3 flow patientssurvival in TIMI 3 flow patients

12001200 14001400

JPS HENRIQUES. Circulation 2003;107:2115-9JPS HENRIQUES. Circulation 2003;107:2115-9

200200

MBG 2/3 n 823

MBG 2/3 n 823

10001000

MBG 0/1 n 101

MBG 0/1 n 101

*p<0.001*p<0.001

*log rank:20.55, p>0.001*log rank:20.55, p>0.001

mechanism/s of impaired blood flowmechanism/s of impaired blood flow• vasoconstriction / vasospasm

• loss of capillary autoregulation

• microvascular plugging

vasoconstriction of microvascular vessels linked to

platelet/leucocyte aggregates, inflammatory cytokines,

endothelial dysfunction

• distal embolization of angiographically visible vessels

• tissue oedema

• vasoconstriction / vasospasm

• loss of capillary autoregulation

• microvascular plugging

vasoconstriction of microvascular vessels linked to

platelet/leucocyte aggregates, inflammatory cytokines,

endothelial dysfunction

• distal embolization of angiographically visible vessels

• tissue oedema

• pharmacologic agents

• direct stenting

• endovascular cooling

• distal protection devices

• pharmacologic agents

• direct stenting

• endovascular cooling

• distal protection devices

optimal reperfusionoptimal reperfusion

CRT’s of agents designed to improve tissue reperfusion

CRT’s of agents designed to improve tissue reperfusion

resultresult

-----++-----

-----++-----

agentagent

metoprololprostacyclin

fluosolmagnesiumrheoth RxabciximabadenosineHu 23F2G

glucose/insulin/KAMP 579

pexelizumabpexelizumab

metoprololprostacyclin

fluosolmagnesiumrheoth RxabciximabadenosineHu 23F2G

glucose/insulin/KAMP 579

pexelizumabpexelizumab

TIMI 2TIMI 4TAMI 9ISIS 4COREMUNICHAMISTADHALT MIECLAADMIRECOMPLYCOMMA

TIMI 2TIMI 4TAMI 9ISIS 4COREMUNICHAMISTADHALT MIECLAADMIRECOMPLYCOMMA

nn

1.39050

43058.050

2.780200236420407311920814

1.39050

43058.050

2.780200236420407311920814

trialtrial

effect of GP IIb/IIIa inhibition on recovery of CBF and LV function

effect of GP IIb/IIIa inhibition on recovery of CBF and LV function

• peak CBF(cm/sec)

• peak CBF(cm/sec)

00

1010

abcixabcix

2020 18.118.1

10.410.4

control control

N 80N 80 N 7200

0.20.2

0.40.4

abcixabcix controlcontrol

N 79N 79 N 72

0.440.44

0.150.15

F.J. NEUMANN. Circulation 1998;98:2695-2701F.J. NEUMANN. Circulation 1998;98:2695-2701

p=0.024p=0.024• wall motion index (SD/chord)

• wall motion index (SD/chord)

p=0.007p=0.007

•2 weeks F/U vs post PCI measurements•2 weeks F/U vs post PCI measurements

the AMISTAD trialinfarct size

the AMISTAD trialinfarct size

KW MAHAFFEY. JACC 1999;34:1711-20KW MAHAFFEY. JACC 1999;34:1711-20

00

5050

adenn 72

adenn 72

placebon 72

placebon 72

15%15%

45%45%% of LV% of LV

2020

1010

3030

4040

anterior MIanterior MI% of LV% of LV

00

1010

adenn 119adenn 119

2020

13%13%

20%20%

placebon 117

placebon 117

55

1515

allall

direct stenting

n 102

direct stenting

n 102

angio end pointslow flow (TIMI 3 2)no-flow (TIMI 0-1)distal embolization

clinical outcomes (6-m F/U)deathre-MITVR

angio end pointslow flow (TIMI 3 2)no-flow (TIMI 0-1)distal embolization

clinical outcomes (6-m F/U)deathre-MITVR

direct stenting in acute MI direct stenting in acute MI

C. LOUBEYRE et al. JACC 2002;39:15-21C. LOUBEYRE et al. JACC 2002;39:15-21

11.7%2.9%4.9%3.9%

0.9%2.9%8.8%

11.7%2.9%4.9%3.9%

0.9%2.9%8.8%

pre-dilatation

n 104

pre-dilatation

n 104

26.9%12.5%

7.6%6.7%

3.8%3.8%6.7%

26.9%12.5%

7.6%6.7%

3.8%3.8%6.7%

p=0.01p=0.02

p=0.01p=0.02

angio end pointangio end point 11.7%11.7% 26.9%26.9%slow flow (TIMI 3 2)slow flow (TIMI 3 2)

2.9%2.9% 12.5%12.5%

endovascular coolingendovascular cooling

SR DIXON. JACC 2002;40:1928-34SR DIXON. JACC 2002;40:1928-34 COOL-MI n 400 ptsCOOL-MI n 400 pts

% pts% pts

00MACEMACE

1010

0%0%

10%10%

median infarct sizemedian infarct size

2%2%

8%8%

% LV% LV

55

00

1010

55

cooling n 21 cooling n 21 control n 21 control n 21

new cathether-based techniquesnew cathether-based techniques

thrombectomy

distal protection

thrombectomy

distal protection

mechanismmechanism CRTs in AMICRTs in AMIX-AMINE

AIMI

EMERALD

X-AMINE

AIMI

EMERALD

N 200N 200

N 500

PROMISE

N 200

N 500

PROMISE

N 200

devicedeviceX-SIZER•

ANGIOJET

PERCU-SURGE

FILTER-WIRE

X-SIZER•

ANGIOJET

PERCU-SURGE

FILTER-WIRE

delayed PTCA for occluded IRA’sdelayed PTCA for occluded IRA’soutcomes: deathoutcomes: death

TAMI 6TOMIISPfistererHoriTOAT all

TAMI 6TOMIISPfistererHoriTOAT all

short termshort term

1 year F/U1 year F/UPfistererHoriTOAT all

PfistererHoriTOAT all

7144166666

263

7144166666

263

nn

166666

148

166666

148

8.8%4.0%

000

3.2%

8.8%4.0%

000

3.2%

PTCAPTCA

0000

0000

5.4%5.0%

05%0

3.6%

5.4%5.0%

05%0

3.6%

cons.cons.

05.0%

03.2%

05.0%

03.2%

00 0.50.5 1.51.511 22PTCA betterPTCA better cons. bettercons. better

1.69(0.21-15.7)1.69(0.21-15.7)

0.75(0.02-29.85)0.75(0.02-29.85)

0.0(0.0-3.64)0.0(0.0-3.64)

0.87(0.19-3.82)0.87(0.19-3.82)

0.0(0.0-3.64)0.0(0.0-3.64)

OR 95% CIOR 95% CI

0.01(0.0-4.4)0.01(0.0-4.4)

OOccluded ccluded AArtery rtery TTrial (OAT)rial (OAT)OOccluded ccluded AArtery rtery TTrial (OAT)rial (OAT)

1º endpoint: death/reMI/rehosp. CHF (NYA class IV) over 3 years1º endpoint: death/reMI/rehosp. CHF (NYA class IV) over 3 years

multicenter, randomized, controledmulticenter, randomized, controled

randomizationrandomization

n 3200 patientsoccluded IRA (TIMI 0,1)

n 3200 patientsoccluded IRA (TIMI 0,1)

PCI (3-28 days after MI) + risk factor modificationPCI (3-28 days after MI) + risk factor modification

no PCIno PCI

ASA-blockersACE inhibitors

ASA-blockersACE inhibitors

Apoptotic Rate in Occlued vs Open IRA

Abbate A et al. Circulation 2002










TOPCARE-AMI

• hazards of stem cell manipulation

• arrhythmogenic potential of implanted cells

• hazards of stem cell manipulation

• arrhythmogenic potential of implanted cells

open questionsopen questions

• economic issues• economic issues

• the capacity of the stem cells to find their

optimal myocardial ‘niche’

• the capacity of the stem cells to find their

optimal myocardial ‘niche’

• long-term fate of transplanted cells in the

recipient heart

• long-term fate of transplanted cells in the

recipient heart• optimal timing for transplantation• optimal timing for transplantation

STEMI - Cath Lab

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