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© © CM Gibson 2006 CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Reimer KA, et al. Circulation. 1977;56:786-794. Time Dependence of Reperfusion Therapy: Time Dependence of Reperfusion Therapy: “Wavefront” Phenomenon of Necrosis in Dogs “Wavefront” Phenomenon of Necrosis in Dogs Duration of occlusion 3 h Area supplied by occluded artery x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x x XXXX Necrosis Ischemic but viable Nonischemic 24 h 40 min
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© CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

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Page 1: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Cross-sections of left ventricle after experimentalcoronary artery occlusionCross-sections of left ventricle after experimentalcoronary artery occlusion

Reimer KA, et al. Circulation. 1977;56:786-794.

Time Dependence of Reperfusion Therapy:Time Dependence of Reperfusion Therapy:“Wavefront” Phenomenon of Necrosis in Dogs“Wavefront” Phenomenon of Necrosis in Dogs

Time Dependence of Reperfusion Therapy:Time Dependence of Reperfusion Therapy:“Wavefront” Phenomenon of Necrosis in Dogs“Wavefront” Phenomenon of Necrosis in Dogs

Duration of occlusion 3 h3 h

Area supplied byoccluded artery

x x

xx

xx

xxx

xx

xx

x xx

x

xx

x xx

xx

x x xx

xx

x

XXXXNecrosis Ischemic but viable Nonischemic

24 h24 h40 min40 min

Page 2: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Time is Muscle: Delays in Symptom to Door Time are Associated Time is Muscle: Delays in Symptom to Door Time are Associated with Poorer Flow in the Muscle Independent of Flow in Arterywith Poorer Flow in the Muscle Independent of Flow in Artery

Time is Muscle: Delays in Symptom to Door Time are Associated Time is Muscle: Delays in Symptom to Door Time are Associated with Poorer Flow in the Muscle Independent of Flow in Arterywith Poorer Flow in the Muscle Independent of Flow in Artery

16% rise in risk of a closed muscle for every hour of delay in STEMI (p=0.0005) Gibson, JACC 200416% rise in risk of a closed muscle for every hour of delay in STEMI (p=0.0005) Gibson, JACC 2004

Normal LargeCapillary Lumen

Clinical Picture: Clinical Picture:

Open ArteryOpen Artery

Closed MuscleClosed Muscle

Blistering of CapillariesBlistering of Capillaries

& Endothelium& Endothelium

“Blistered” / Swollen Endothelium /wall of the capillary

Normal non-infarctedwall without edema

Infarcted wall with edema (white areas)

Interstitial Edema Interstitial Edema

EHJ (2004) 25, 794–803EHJ (2004) 25, 794–803

Page 3: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

0

1

2

3

0

1

2

3

GUSTO I90-93

GUSTO I90-93

2.82.8

Med

ian

Tim

e (h

rs)

Bet

wee

n S

ymp

tom

O

nse

t an

d T

reat

men

tM

edia

n T

ime

(hrs

) B

etw

een

Sym

pto

m

On

set

and

Tre

atm

ent

GUSTO III95-97

GUSTO III95-97

InTIME II97-99

InTIME II97-99

ASSENT 300-01

ASSENT 300-01

ASSENT II97-98

ASSENT II97-98

GUSTO V99-01

GUSTO V99-01

Time from Symptom Onset to Study Treatment in Large Scale Thrombolytic Trials

Time from Symptom Onset to Study Treatment in Large Scale Thrombolytic Trials

2.82.8 2.72.7 2.72.72.72.7 2.92.9

Gibson CM, Circulation 2001;104:2632-2634Gibson CM, Circulation 2001;104:2632-2634

Page 4: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Adapted from Tiefenbrunn AJ, Sobel BE. Circulation. 1992;85:2311-2315.Adapted from Tiefenbrunn AJ, Sobel BE. Circulation. 1992;85:2311-2315.

Time-Dependent Benefit of Reperfusion TherapyTime-Dependent Benefit of Reperfusion TherapyTime-Dependent Benefit of Reperfusion TherapyTime-Dependent Benefit of Reperfusion Therapy

0

20

40

60

80

100

0 2 4 6 8 10 12

Reperfusion Time (hours)

% B

enef

it

Reimer/Jennings 1977

Bergmann 1982

GISSI-I 1986

0

20

40

60

80

100

0 2 4 6 8 10 12

Reperfusion Time (hours)

% B

enef

it

Reimer/Jennings 1977

Bergmann 1982

GISSI-I 1986

Page 5: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Adapted from Timm TC, et al. Circulation. 1991;84(suppl II):II-230.Adapted from Timm TC, et al. Circulation. 1991;84(suppl II):II-230.

6.2

3.23.7

5.2

0

1

2

3

4

5

6

7

1 2 3 4

Time From Symptom Onset (hours)

6.2

3.23.7

5.2

0

1

2

3

4

5

6

7

1 2 3 4

Time From Symptom Onset (hours)

Mo

rta

lity

Ra

te (

%)

Mo

rta

lity

Ra

te (

%)

PP=0.05=0.05PP=0.05=0.05

TIMI 2: 6-Week MortalityTIMI 2: 6-Week MortalityTIMI 2: 6-Week MortalityTIMI 2: 6-Week Mortality

Page 6: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Adapted from Lee KL, et al. Circulation. 1995;91:1659-1668. Adapted from Lee KL, et al. Circulation. 1995;91:1659-1668.

Importance of Time-to-Treatment: Results of GUSTO-IImportance of Time-to-Treatment: Results of GUSTO-IImportance of Time-to-Treatment: Results of GUSTO-IImportance of Time-to-Treatment: Results of GUSTO-I

0

2

4

6

8

10

12

0 1 2 3 4 5 6 7 8 9 10 11 12

Time From Onset of Symptoms to Treatment (hours)

0

2

4

6

8

10

12

0 1 2 3 4 5 6 7 8 9 10 11 12

Time From Onset of Symptoms to Treatment (hours)

2=149 (1 df )2=149 (1 df )

30-

Day

Mo

rta

lity

( %)

30-

Day

Mo

rta

lity

( %)

Page 7: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Rapid Treatment Is Associated Rapid Treatment Is Associated With Decreased MortalityWith Decreased Mortality

Rapid Treatment Is Associated Rapid Treatment Is Associated With Decreased MortalityWith Decreased Mortality

Data source: Boersma E, et al. Lancet. 1996;348:771-775.Data source: Boersma E, et al. Lancet. 1996;348:771-775.

Number of lives saved per 1,000 patients treated with fibrinolytics (based on 35-day mortality)Number of lives saved per 1,000 patients treated with fibrinolytics (based on 35-day mortality)

65

37

2629

0

10

20

30

40

50

60

70

0-1 h 1-2 h 2-3 h 3-6 h

Liv

es

sa

ve

d (

No

.)65

37

2629

0

10

20

30

40

50

60

70

0-1 h 1-2 h 2-3 h 3-6 h

Liv

es

sa

ve

d (

No

.)

Time from symptom onset to thrombolysisTime from symptom onset to thrombolysis

50,246 pt meta-analysis1983-9350,246 pt meta-analysis1983-93

Page 8: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006Adapted from Weaver WD, et al. JAMA. 1993;270:1211-1216.Adapted from Weaver WD, et al. JAMA. 1993;270:1211-1216.

1.2

8.7

4.9

11.2

0.0

2.0

4.0

6.0

8.0

10.0

12.0

Mortality Infarct Size

Tx <70 minutesfrom onset

Tx >70 minutesfrom onset

1.2

8.7

4.9

11.2

0.0

2.0

4.0

6.0

8.0

10.0

12.0

Mortality Infarct Size

Tx <70 minutesfrom onset

Tx >70 minutesfrom onset

PP=0.04=0.04PP=0.04=0.04 PP<0.001<0.001PP<0.001<0.001

Pe

rce

nt

Pe

rce

nt

MITI: Mortality, Infarct Size, and TimeMITI: Mortality, Infarct Size, and TimeMITI: Mortality, Infarct Size, and TimeMITI: Mortality, Infarct Size, and Time

Page 9: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

1.0

3.74.0

6.4

14.1

0

5

10

15

20

25

60 61-75 76-90 91

1.0

3.74.0

6.4

14.1

0

5

10

15

20

25

60 61-75 76-90 91

Berger PB, et al. Circulation. 1999;100:14-20.Berger PB, et al. Circulation. 1999;100:14-20.

PP=0.001=0.001PP=0.001=0.001

Door-to-Balloon Time (minutes)Door-to-Balloon Time (minutes)

Importance of Door-to-Balloon Time: Importance of Door-to-Balloon Time: 30-Day Mortality in the GUSTO-IIb Cohort30-Day Mortality in the GUSTO-IIb Cohort

Importance of Door-to-Balloon Time: Importance of Door-to-Balloon Time: 30-Day Mortality in the GUSTO-IIb Cohort30-Day Mortality in the GUSTO-IIb Cohort

Mo

rta

lity

(%)

Mo

rta

lity

(%)

>< PTCA not performedPTCA not performed

Page 10: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

11.14 1.15

1.41

1.62 1.61

0.6

0.8

1

1.2

1.4

1.6

1.8

2

0-6

0

61

-90

91

-12

0

12

1-1

50

15

1-1

80

>1

80

MV

Ad

jus

ted

Od

ds

of

De

ath

Cannon CP, Gibson CM et al, JAMA 2000Cannon CP, Gibson CM et al, JAMA 2000

Page 11: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Patency and Mode of ReperfusionPatency and Mode of ReperfusionPatency and Mode of ReperfusionPatency and Mode of Reperfusion

0

20

40

60

80

100

0 30 45 60 75 90 120 150

Pat

ency

Rat

e (%

)

Fibrinolysis

PTCA at 75minutes

PTCA at 120minutes0

20

40

60

80

100

0 30 45 60 75 90 120 150

Pat

ency

Rat

e (%

)

Fibrinolysis

PTCA at 75minutes

PTCA at 120minutes

Time (minutes)Time (minutes)

90-minutepatency

90-minutepatency

ED

arrival

ED

arrival

Drug

administration

Drug

administration

Adapted from Gibson CM. Ann Intern Med. 1999;130:841-847.Adapted from Gibson CM. Ann Intern Med. 1999;130:841-847.

Page 12: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Hypothetical Relationship Between Early Reperfusion, Hypothetical Relationship Between Early Reperfusion, Mortality Reduction, and Extent of Myocardial Salvage Mortality Reduction, and Extent of Myocardial Salvage Hypothetical Relationship Between Early Reperfusion, Hypothetical Relationship Between Early Reperfusion, Mortality Reduction, and Extent of Myocardial Salvage Mortality Reduction, and Extent of Myocardial Salvage

Gersh BJ, et al. Gersh BJ, et al. JAMAJAMA. 2005;293:979-986.. 2005;293:979-986.

00

2020

4040

6060

8080

100100

1212 2424Time From Symptom Onset to Reperfusion TherapyTime From Symptom Onset to Reperfusion Therapy

(hours)(hours)

Mort

ality

Red

ucti

on

, (%

)M

ort

ality

Red

ucti

on

, (%

)

Mortality Reduction (%)Mortality Reduction (%)

Extent of SalvageExtent of Salvage(% of area at risk)(% of area at risk)

Critical Time-dependent Critical Time-dependent PeriodPeriodGoal: Myocardial SalvageGoal: Myocardial Salvage

D-B – HarmD-B – Harm

A-B – No BenefitA-B – No Benefit

Shifts in Shifts in Potential Potential OutcomesOutcomes

A-C – BenefitA-C – BenefitB-C – BenefitB-C – Benefit

D-C – HarmD-C – Harm

00

Time-independent PeriodTime-independent PeriodGoal: Open Infarct-related Goal: Open Infarct-related ArteryArtery

44

DD

CC

BBAA

88 1616 2020

Page 13: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Door to Balloon Time

<60 min(44 min ± 12)

n=183

60-90 min(75 min ± 9)

n=296

90-120 min (103 min ± 8)n=304

>120min(156 min ± 30)

n=403p-value

Onset-to-Door (mins) 197 ± 182 140 ± 140 141 ± 151 113 ± 124 <0.0001

Onset-to-Balloon (mins) 235 ± 180 216 ± 140 244 ± 150 269 ± 126 <0.0001

Death 30-days 0.6% 0.7% 4.7% 2.5% 0.0037

MACE 30-days 1.6% 2.4% 7.6% 5.5% 0.0034

Infarct Size (% LV) 14.2 ± 15.8 13.2 ± 14.6 18.0 ± 18.0 17.4 ± 18.0 0.0023

Does a 90-Minute Door-to-Balloon Time Matter? Observations From Four Current Does a 90-Minute Door-to-Balloon Time Matter? Observations From Four Current Reperfusion TrialsReperfusion Trials

EMERALD, COOL MI, AMIHOT, ICE-ITEMERALD, COOL MI, AMIHOT, ICE-IT

Does a 90-Minute Door-to-Balloon Time Matter? Observations From Four Current Does a 90-Minute Door-to-Balloon Time Matter? Observations From Four Current Reperfusion TrialsReperfusion Trials

EMERALD, COOL MI, AMIHOT, ICE-ITEMERALD, COOL MI, AMIHOT, ICE-IT

O’Neill, et al. JACC,2005:Suppl A:45:225A.

Page 14: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Time from Symptom Onset to TreatmentTime from Symptom Onset to TreatmentPredicts 1-year Mortality after Primary PCIPredicts 1-year Mortality after Primary PCITime from Symptom Onset to TreatmentTime from Symptom Onset to Treatment

Predicts 1-year Mortality after Primary PCIPredicts 1-year Mortality after Primary PCI

De Luca et al, Circulation 2004De Luca et al, Circulation 2004

The relative risk of 1-year mortality increases by7.5% for each 30-minute delay

n=1791

Page 15: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Time from Symptom Onset to TreatmentTime from Symptom Onset to TreatmentPredicts One-year MortalityPredicts One-year Mortality

Time from Symptom Onset to TreatmentTime from Symptom Onset to TreatmentPredicts One-year MortalityPredicts One-year Mortality

4.4

1.5

5.74.7

1.2

6.3

8.5

0.8

11.9

9.7

0.0

13.0

0

3

6

9

12

15

4.4

1.5

5.74.7

1.2

6.3

8.5

0.8

11.9

9.7

0.0

13.0

0

3

6

9

12

15 p = 0.006p = 0.006

<2 hrs<2 hrs 2-4 hrs2-4 hrs 4-6 hrs4-6 hrs

p = 0.02p = 0.02

De Luca at al, JACC 2003De Luca at al, JACC 2003

>6 hrs>6 hrs

All Patients Low-Risk

p = NSp = NS

High-Risk

Page 16: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Time from Symptom Onset to Treatment Predicts One-year Mortality Time from Symptom Onset to Treatment Predicts One-year Mortality Among Patients with Occluded Epicardial ArteriesAmong Patients with Occluded Epicardial Arteries

Time from Symptom Onset to Treatment Predicts One-year Mortality Time from Symptom Onset to Treatment Predicts One-year Mortality Among Patients with Occluded Epicardial ArteriesAmong Patients with Occluded Epicardial Arteries

5.34.1

2.7

5.55.9

9.2

0

12.7

0

3

6

9

12

15

5.34.1

2.7

5.55.9

9.2

0

12.7

0

3

6

9

12

15 p = 0.013p = 0.013

<2 hrs<2 hrs 2-4 hrs2-4 hrs 4-6 hrs4-6 hrs

p = NSp = NS

De Luca at al, JACC 2003De Luca at al, JACC 2003

>6 hrs>6 hrs

Pre-PCI TIMI 2/3 Flow Pre-PCI TIMI 0/1 Flow

Page 17: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Predictors of Door-to-Balloon Delay in Primary Predictors of Door-to-Balloon Delay in Primary AngioplastyAngioplasty

Predictors of Door-to-Balloon Delay in Primary Predictors of Door-to-Balloon Delay in Primary AngioplastyAngioplasty

3.7

3.2

2.7

2.2

1.7

Mea

n D

oo

r-to

-bal

loo

n t

ime

(ho

urs

)M

ean

Do

or-

to-b

allo

on

tim

e (h

ou

rs)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 230 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

Time of hospital arrival (24 hour clock)Time of hospital arrival (24 hour clock)

n=40,017

Angeja BG, et al. Angeja BG, et al. Am J CardiolAm J Cardiol 2002;89:1156-1161) 2002;89:1156-1161)

Page 18: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

What is Primary Angioplasty ?What is Primary Angioplasty ?What is Primary Angioplasty ?What is Primary Angioplasty ?

• Primary Angioplasty: Door to balloon time <1 hour

• Secondary Angioplasty: Door to balloon time 1 - 2 hours

• Tertiary Angioplasty: Door to balloon time 2 - 3 hours

• Post MI Care: Door to balloon time 3 - 4 hours

• Elective Case: > 4 hours

• Primary Angioplasty: Door to balloon time <1 hour

• Secondary Angioplasty: Door to balloon time 1 - 2 hours

• Tertiary Angioplasty: Door to balloon time 2 - 3 hours

• Post MI Care: Door to balloon time 3 - 4 hours

• Elective Case: > 4 hours

CM Gibson 2006CM Gibson 2006

Page 19: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

PCI-Related Time Delay vs Mortality Benefitin 22 Randomized Studies of PCI vs Fibrinolytic Therapy

PCI-Related Time Delay vs Mortality Benefitin 22 Randomized Studies of PCI vs Fibrinolytic Therapy

-5

0

5

10

15

Ab

solu

te R

isk

Diff

ere

nc

e I

n D

ea

th (

%)

0 20 40 60 80 100PCI-Related Time Delay (min)

Nallamothu and Bates, AJC 2003Nallamothu and Bates, AJC 2003

23 RCTs For every 10 min delay to PCI: 1 % reduction in Mortality Difference

Between PCI & LysisN= 7419

p=0.006

DANAMI: on site PCI

90 DB – 50 DN = 40 min delay

DANAMI: with transfer

110 DB – 50 DN = 60 min delay

“USA AMI” with transfer:

171 DB – 32 DN =

139 min delay

DANAMI: on site PCI

90 DB – 50 DN = 40 min delay

DANAMI: with transfer

110 DB – 50 DN = 60 min delay

“USA AMI” with transfer:

171 DB – 32 DN =

139 min delay

Page 20: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

NRMI 2,3,4

452,544 Reperfusion Eligible

STEMI Patients

1,963 Hospitals

Transfer Out Patients

n=119,235

Missing Time Intervalsn=13,137

Did Not Receive PCIor Fibrinolytic Therapyas Initial Reperfusion

n=89,524

Study Population192,509 Patients

645 Hospitals230,648 Patients1,860 Hospitals

≥20 STEMI Patients Treated

Treatment of ≥10 patients with Primary PCI and ≥10 patients with Fibrinolytic Therapy

Pinto DS … Gibson CM, Circulation 2006Pinto DS … Gibson CM, Circulation 2006

Page 21: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Mortality Increases with Increasing PCI Related DelayMortality Increases with Increasing PCI Related DelayMortality Increases with Increasing PCI Related DelayMortality Increases with Increasing PCI Related Delay

PCI Related Delay (DB-DN) (min)

In H

osp

ital

Mo

rtal

ity

(%) For every 30 minute delay,For every 30 minute delay,

mortality increases 10%mortality increases 10%

Pinto DS … Gibson CM, Circulation 2006Pinto DS … Gibson CM, Circulation 2006

Page 22: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

0.8

1.25

1.5

Estimated Treatment Effect and 95% Confidence IntervalsConditional on PCI Related Delay (DB-DN)(min)

After Adjusting for Covariates

Estim

ated

Tre

atm

ent E

ffect

0.5

1.0

2.0

PCI Related Delay (DB-DN) (min)

60 75 90 105 120 135 150 165 180114

Od

ds

of

De

ath

wit

h

Fib

rin

oly

sis

PCI Related Delay (DB-DN) (min)

PC

I B

ette

rF

ibri

no

lysi

s B

ette

r

The Advantage of PCI Compared with Fibrinolyisis Decreases as the PCI Related The Advantage of PCI Compared with Fibrinolyisis Decreases as the PCI Related Delay IncreasesDelay Increases

The Advantage of PCI Compared with Fibrinolyisis Decreases as the PCI Related The Advantage of PCI Compared with Fibrinolyisis Decreases as the PCI Related Delay IncreasesDelay Increases

Pinto DS … Gibson CM, Circulation 2006Pinto DS … Gibson CM, Circulation 2006

Page 23: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

0.8

1.25

1.5

Estimated Treatment Effect and 95% Confidence IntervalsConditional on PCI Related Delay (DB-DN)(min)

After Adjusting for CovariatesEs

timat

ed T

reat

men

t Effe

ct

0.5

1.0

2.0

PCI Related Delay (DB-DN) (min)

60 75 90 105 120 135 150 165 180114

Od

ds

of

De

ath

wit

h

Fib

rin

oly

sis

PCI Related Delay (DB-DN) (min)

PC

I Bet

ter

Fib

rin

oly

sis

Bet

ter

Pinto DS … Gibson CM. Circulation. 2006Pinto DS … Gibson CM. Circulation. 2006 *Betriu A. Am J Cardiol. 2005; 95:100-101.*Betriu A. Am J Cardiol. 2005; 95:100-101.

Randomized Studies*

Page 24: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Prehospital Delay & Timing of Reperfusion Strategy Prehospital Delay & Timing of Reperfusion Strategy EquivalenceEquivalence

Prehospital Delay & Timing of Reperfusion Strategy Prehospital Delay & Timing of Reperfusion Strategy EquivalenceEquivalence

0-120

121+NonAnt MI65+ YRS Ant MI 65+

YRS NonAnt MI<65 YRS Ant MI <65

YRS

179

168 148

107 103

58 43

400

60

120

180

Prehospital Delay (min)

19,517

5,296

9,812

41,774

16,119

20,424

10,614

PC

I Rel

ated

Del

ay (

DB

-DN

) W

her

e P

CI a

nd

Fib

rin

oly

tic

Mo

rtal

ity

Are

Eq

ual

(M

in)

3,739

Pinto DS … Gibson CM, Circulation 2006Pinto DS … Gibson CM, Circulation 2006

Page 25: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Pre-hospital Delay (Min)

Age <65 years & Anterior Infarction

(n=patients, n=hospitals)

Age <65 years & Non-anterior Infarction

(n=patients, n=hospitals)

Age ≥65 years & Anterior Infarction

(n=patients, n=hospitals)

Age ≥65 years & Non-anterior Infarction

(n=patients, n=hospitals)

0-120 39 minMet goal without transfer: 2.6%

Met goal with transfer: 3.6%

(n=19,517 pts; n=269 hospitals)

56 minMet goal without transfer:

20.2%Met goal with transfer:

17.3%(n=41,774 pts; n=385 hospitals)

109 minMet goal without transfer: 94.1%

Met goal with transfer: 92.8%

(n=9,812 pts; n=180 hospitals)

154 minMet goal without transfer: 99.8%Met goal with transfer: 100.0%(n=20,424 pts; n=271 hospitals)

121+ 50 minMet goal without transfer: 7.9%Met goal with transfer: 11.9% (n=5,296 pts; n=117 hospitals)

103 minMet goal without transfer: 89.1%

Met goal with transfer: 82.2%(n=16,119 pts; n=244 hospitals)

142 minMet goal without transfer: 98.1%

Met goal with transfer: 97.1%

(n=3,739 pts; n=91 hospitals)

183 minMet goal without transfer: 100.0%

Met goal with transfer: 100.0%(n=10,614 pts; n=191 hospitals)

Time At Which PCI Looses Superiority In Survival Over Time At Which PCI Looses Superiority In Survival Over Fibrinolysis Varies Depending Upon Patient Risk Fibrinolysis Varies Depending Upon Patient Risk

Time At Which PCI Looses Superiority In Survival Over Time At Which PCI Looses Superiority In Survival Over Fibrinolysis Varies Depending Upon Patient Risk Fibrinolysis Varies Depending Upon Patient Risk

Pinto DS … Gibson CM, Circulation Pinto DS … Gibson CM, Circulation 20062006

Page 26: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

Time of OnsetTime of OnsetTime of OnsetTime of Onset

ED Time Point 1: ED Time Point 1: DOORDOOR

ED Time Point 1: ED Time Point 1: DOORDOOR

ED Time Point 2: ED Time Point 2: DATADATA

ED Time Point 2: ED Time Point 2: DATADATA

ED Time Point 3: ED Time Point 3: DECISIONDECISION

ED Time Point 3: ED Time Point 3: DECISIONDECISION

ED Time Point 4: ED Time Point 4: DRUGDRUG

ED Time Point 4: ED Time Point 4: DRUGDRUG

Time Interval IIIDecision to drug

Time Interval IIECG to decision to treat

Time Interval IDoor to ECG

NHAAP Recommendations. U.S. Department of Health NIH Publication: 1997:97-3787.NHAAP Recommendations. U.S. Department of Health NIH Publication: 1997:97-3787.

The Four DsThe Four DsThe Four DsThe Four Ds

Page 27: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

75

105

135

165

195

225

255

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Min

ute

s (M

ed

ian

)M

inu

tes

(Me

dia

n)

NRMI 1NRMI 1 NRMI 2NRMI 2 NRMI 3NRMI 3 NRMI 4NRMI 4

NRMI Non-Transfer-In PatientsNRMI Non-Transfer-In Patients

NRMI Transfer-In PatientsNRMI Transfer-In Patients

Door to Balloon Times By Transfer Status, Primary PTCA PatientsDoor to Balloon Times By Transfer Status, Primary PTCA PatientsDoor to Balloon Times By Transfer Status, Primary PTCA PatientsDoor to Balloon Times By Transfer Status, Primary PTCA Patients

228

111

171

100110: DANAMI Transfer110: DANAMI Transfer

90: DANAMI On Site90: DANAMI On Site

Page 28: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

0

5

10

15

20

25

30

35

40

45

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Pe

rce

nt

of

Pa

tien

tsP

erc

en

t o

f P

ati

ents

NRMI 1NRMI 1 NRMI 2NRMI 2 NRMI 3NRMI 3 NRMI 4NRMI 4

Non-Transfer-In PatientsNon-Transfer-In Patients

Transfer-In PatientsTransfer-In Patients

Door to Balloon Times Door to Balloon Times <<90 Minutes By Transfer Status, Primary 90 Minutes By Transfer Status, Primary PTCA PatientsPTCA Patients

Door to Balloon Times Door to Balloon Times <<90 Minutes By Transfer Status, Primary 90 Minutes By Transfer Status, Primary PTCA PatientsPTCA Patients

3.8

33.6

39.1

5.3

Page 29: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

20

25

30

35

40

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Pe

rce

nt

of

Pa

tien

tsP

erc

en

t o

f P

ati

ents

NRMI 1NRMI 1 NRMI 2NRMI 2 NRMI 3NRMI 3 NRMI 4NRMI 4

All Patients

Door to Balloon Times Door to Balloon Times <<90 Minutes90 MinutesDoor to Balloon Times Door to Balloon Times <<90 Minutes90 Minutes

34.5 %

29.4 %

Page 30: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

National Trends in AMI Management:National Trends in AMI Management:Door to Drug Time with ThrombolysisDoor to Drug Time with ThrombolysisNational Trends in AMI Management:National Trends in AMI Management:Door to Drug Time with ThrombolysisDoor to Drug Time with Thrombolysis

0102030405060708090

100

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999

Media

n tim

e, m

inute

s

NRMI 1 NRMI 2 NRMI 3 (Activase only) (All lytics) (All lytics)

60

91

34 39

NRMI 1: Includes patients where initial ECG was the method of MI diagnosis NRMI 2 and 3: Includes patients with ST on 1st 12-lead ECG results, where 1st 12-lead ECG date/time = 1st 12-lead ECG with ST and/or BBB date/time

Non-transfer-in patients

75th percentile, 52

25th percentile, 22

Page 31: © CM Gibson 2006 Cross-sections of left ventricle after experimental coronary artery occlusion Cross-sections of left ventricle after experimental coronary.

© © CM Gibson 2006CM Gibson 2006

National Trends in AMI Management:National Trends in AMI Management:Door to Balloon Time in PPTCADoor to Balloon Time in PPTCA

National Trends in AMI Management:National Trends in AMI Management:Door to Balloon Time in PPTCADoor to Balloon Time in PPTCA

80

90

100

110

120

1994 1995 1996 1997 1998 1999

Media

n tim

e, m

inute

s

NRMI 2 NRMI 3

116

108

Includes patients with ST on 1st 12-lead ECG results, where 1st 12-lead ECG date/time = 1st 12-lead ECG with ST and/or BBB date/time (non-transfer-in patients)