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