History of mechanical reperfusion of STEMI · • Acute STEMI (ST elevation ≥2 mm in ≥2...

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History of mechanical reperfusion of STEMIHistory of mechanical reperfusion of STEMI

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Consultant: Medtronic, Guidant, JJIS/Cordis, EV3Consultant: Medtronic, Guidant, JJIS/Cordis, EV3

Equity: Accumed Systems, Radiant Medical, TherOxEquity: Accumed Systems, Radiant Medical, TherOx

Grant Support: Medtronic, Guidant, JJIS/Cordis, Pfizer,Grant Support: Medtronic, Guidant, JJIS/Cordis, Pfizer,Astra Zeneca, Millenium, PharmaceuticalsAstra Zeneca, Millenium, Pharmaceuticals

Myocardial ReperfusionMyocardial Reperfusionafter AMI: Will Novelafter AMI: Will Novel

Therapies Change FutureTherapies Change FutureTreatment Paradigms?Treatment Paradigms?Treatment Paradigms?Treatment Paradigms?

William W. O’Neill, M.D.William W. O’Neill, M.D.

Executive Dean of Clinical AffairsExecutive Dean of Clinical Affairs

University of MiamiUniversity of Miami

3

AMI: DRAMATIC IMPROVEMENT IN OUTCOMES OVER

PAST 30 YEARS

Pre-CCU CCU era Reperfusion

B M J2012;344:e356

d efibrillationhemod ynamic monitoringbeta-bloc kad e

A S Athrombolytic RxP C ISystems of Care

MI: TreatmentMI: Treatment

“. . . nitroglycerin, which had formerly“. . . nitroglycerin, which had formerlyhelped the patient, will generally behelped the patient, will generally beuseless.”useless.”

“Large doses of morphine should be given“Large doses of morphine should be given“Large doses of morphine should be given“Large doses of morphine should be givensubcutaneously.”subcutaneously.”

“In a large number of instances, no other“In a large number of instances, no othermedication is necessary.”medication is necessary.”

Levine, S.A.Medicine 8:245,Levine, S.A.Medicine 8:245,19451945

FormerFormer President Clinton’s StentPresident Clinton’s StentProcedure Calls Attention to HeartProcedure Calls Attention to Heart

HealthHealth

Historical OverviewHistorical OverviewMortality STEMIMortality STEMI

1315

20

Per

cen

t(%

)

GISSIGISSIControlControl GISSIGISSI

SKSK

GUSTOGUSTO10.7

6.3

2.5 1.8

0

5

10

1985 1990 1992 2000

Per

cen

t(%

)

GUSTOGUSTOrtrt--PAPA

PAMIPAMIPTCAPTCA

CADILLACCADILLACStentStent

Interventional Cardiovascular MedicineInterventional Cardiovascular MedicineRoubin, Califf, O’Neill, Phillips, StackRoubin, Califf, O’Neill, Phillips, Stack

Churchill Livingstone, Inc. 1994Churchill Livingstone, Inc. 1994

Cardiogenic Shock Complicating AcuteCardiogenic Shock Complicating AcuteMyocardial Infarction SurvivalMyocardial Infarction Survival

60

80

100

%S

urv

iva

l

Reperfusion No Reperfusion

0

20

40

0 4 8 12 16 20 24 28 32 36 40 44 48

Months

%S

urv

iva

l

Immediate PTCA TrialsImmediate PTCA Trials

7

8

56

8

10

In-H

os

pit

al

Mo

rta

lity

(%) Immediate PTCA

Deferred

4

1

3

5

0

2

4

6

In-H

os

pit

al

Mo

rta

lity

(%)

TAMI(n=197)

ECSG(n=367)

TIMI-IIA(n=389)

Frequency in Achieving TIMI 3Frequency in Achieving TIMI 3FlowFlow

54

69

9389

96

60

80

100

%T

IMI

3F

low

12

32

0

20

40

%T

IMI

3F

low

ASA/ASA/HeparinHeparin

SKSK Accel. tPAAccel. tPA 1/2 tPA +1/2 tPA +Abcix.Abcix.

PTCAPTCA StentStent StentStentAbcix.Abcix.

PARPAR GUSTOGUSTOII

GUSTOGUSTOII

TIMITIMI1414

PAR/PAR/PAMIPAMI

StentStentPAMIPAMI

CADILLACCADILLAC

Lysis + PTCA: SAMILysis + PTCA: SAMI

PTCAPTCAAloneAlone

PCI +PCI +SKSK

ppValueValue

2424--hr ventriculography (LVEF,%)hr ventriculography (LVEF,%)

66--mo ventriculography (LVEF;%)mo ventriculography (LVEF;%)

Transfusion rate (%)Transfusion rate (%)

Rate of CABG (%)Rate of CABG (%)

5252

5151

88

1.61.6

5050

5151

3939

10.510.5

NSNS

NSNS

.0001.0001

.03.03Rate of CABG (%)Rate of CABG (%) 1.61.6 10.510.5 .03.03

•• Adjunctive IV streptokinase therapy failed to enhance LVAdjunctive IV streptokinase therapy failed to enhance LVfunction, and increased bleeding, CABG rates, hospitalization,function, and increased bleeding, CABG rates, hospitalization,and costsand costs

•• PTCA therapy of acute MI should not be routinely performed withPTCA therapy of acute MI should not be routinely performed withadjunctive IV streptokinase therapyadjunctive IV streptokinase therapy

O’Neill WW. Circ 1992;86:1710O’Neill WW. Circ 1992;86:1710--17171717

PAMI Trial Clinical CentersPAMI Trial Clinical Centers

InIn--Hospital Unstable IschemiaHospital Unstable Ischemiaand Deathand Death

5.1

6.5 6.5

10.4

12

6

8

10

12

14

Pa

tien

ts(%

)

PTCA

tPA

2.6 2.6 3.12

5.1

2.2

0

2

4

6

Re-MI Overall Low Risk High Risk* MI or Death

Pa

tien

ts(%

)

DeathDeath

* High risk = Age > 70 yrs, anterior infarction, admission heart rate > 100* High risk = Age > 70 yrs, anterior infarction, admission heart rate > 100

PCI vs ThrombolysisPCI vs ThrombolysisMetaMeta--analysesanalyses

22

20

25Lysis

PCI

Short term (4Short term (4--6 weeks)6 weeks)

P<0.0001P<0.0001

8.57.3 7.2

2.0

7.24.9

2.8

6.8

1.0

0

5

10

15

20

Death Death SHOCKexcl.

Reinfarction Recurrentischemia

Stroke

Perc

en

t(%

)

Ellen C Keeley, Judith A Boura, Cindy L Grines. Lancet 2003; 361:13Ellen C Keeley, Judith A Boura, Cindy L Grines. Lancet 2003; 361:13––20.20.

P=0.0002P=0.0002 P=0.0003P=0.0003 P<0.0001P<0.0001

P=0.0004P=0.0004

CADILLAC StudyCADILLAC StudyInIn--Hospital MortalityHospital Mortality

15

20

Per

cen

t(%

)

1.4 1 1.6 1.6

0

5

10

PTCA PTCA +Abciximab

Stent Stent +Abciximab

Per

cen

t(%

)

3030--Day MortalityDay Mortality

TNK +PCI 6.0% (50/828 )6.0% (50/828 )

PCI alone

Log rank test

p=0.04

3.8% (32/835 )3.8% (32/835 )

Van de Werf. ESC 2005Van de Werf. ESC 2005

39

THE INCIDENCE & PREVALENCE OF HF IS GROWING,FUELED BY INCREASED SURVIVAL IN STEMI

M ozaffarianD etal.Circulation2015;131(4):e29-322.

Ezekow itzJA etal.JAm CollCardiol2009;53(1):13-20.

CungT T etal.N EnglJM ed2015;373(11):1021-31.

Infarct

Positive Results With Animal Model

Regression95% confid.

Correlation: r = .90290

Infa

rct

are

a(%

)

0

10

20

30

40

50

60

70

80

2.5 3.5 4.5 5.5 6.5 7.5 8.5

Regression95% confid.

Correlation: r = .77652

MVO2 during ischemia

Infa

rct

Are

a(%

)

0

10

20

30

40

50

60

70

80

3.5 4 4.5 5 5.5 6 6.5 7 7.5 8

*Impella 5.0 LAD animal occlusion model study – B. Meyns et al 2000: JACC 2003

Massive Myocardial damage Up to 5-times Reduction in infarct size

Infarct without Impella Infarct with Impella unloading

95% confid.

MVO2 during reperfusion

2.5 3.5 4.5 5.5 6.5 7.5 8.5

Area at risk

Endovascular Cooling SystemsEndovascular Cooling Systems

ReprieveReprieveTMTM Catheter,Catheter,Radiant Medical Inc.Radiant Medical Inc.

Heat Exchange Devices

Celsius ControlCelsius ControlTMTM

Catheter, InnercoolCatheter, InnercoolTherapies Inc.Therapies Inc.

FortiusFortiusTMTM Catheter,Catheter,Alsius Corp.Alsius Corp.

HypothermiaControl

End-diastole

End-systole

40

50

60

40

50

60

%o

fL

eft

Ven

tric

le

All Patients Anterior MI < 6 hours

p=0.30 p=0.04

AMIHOT

Infarct SizeInfarct Size

0

10

20

30

0

10

20

30

%o

fL

eft

Ven

tric

le

Control(n=122)

AO(n=121)

Control(n=52)

AO(n=49)

13 11

23

9

45

STEMI patient indicated for PPCI

DTU SAFETY & FEASIBILITY STUDY

Patient meets all inclusion criteria• Age 21-80 years• First MI• Acute STEMI (ST elevation ≥2 mm in ≥2 contiguous or ≥4

mm ST-segment deviation sum in anterior leads)• Presents within 1-6 hrs symptom onset

Informed Consent

Enrollment and Randomization

30 min unloading, then PPCI Initiate unloading, immediate PPCI

Explant Impella after 3-4 hrs support

Infarct size by CMR, 3-5 days and 30 days post-PPCI

Primary EndpointsPrimary Endpoints•• Infarct size at 30 days as percent LV mass, by CMRInfarct size at 30 days as percent LV mass, by CMR•• Composite of MACCE at 30 daysComposite of MACCE at 30 days

•• Cardiovascular mortalityCardiovascular mortality•• ReRe--infarctioninfarction•• Stroke/TIAStroke/TIA•• Major vascular complicationMajor vascular complication

DANAMI-2DENMARK5.4 mill. inhabitants

5 PCI centers

24 referral hospitals

62% of Danishpopulation

Transport distanceup to 95 US miles(mean 35 miles) 100 US miles

The Prognostic Significance ofThe Prognostic Significance ofSystolic LV Function After MISystolic LV Function After MI

Weissler AM et al. AJC 1981;48:995Weissler AM et al. AJC 1981;48:995

Arterial Patency and Risk ofArterial Patency and Risk ofArrhythmic ComplicationsArrhythmic Complications

22

15

20

25

ArrhythmiArrhythmicc

ComplicaComplica

p=.00002p=.00002

1

0

5

10ComplicaComplications at 1tions at 1yr (SCD,yr (SCD,VT, VF)VT, VF)

(%)(%)DischargDischarg

eePatencyPatencyn=136n=136

DischargDischargee

OccludeOccludedd

n=37n=37Hohnloser. Circ 1994;90:1747Hohnloser. Circ 1994;90:1747

Patency Decreases Risk ofPatency Decreases Risk ofRuptureRupture

33

22

aa

bb

cc

a SKa SK

Incid

en

ce

of

Ru

ptu

re(%

)In

cid

en

ce

of

Ru

ptu

re(%

)

11

0000 2020 4040 6060 8080 100100

dd

a SKa SKb SK + tPAb SK + tPA

c tPAc tPAd PTCAd PTCA

TIMITIMI -- 3 Flow (%)3 Flow (%)

Incid

en

ce

of

Ru

ptu

re(%

)In

cid

en

ce

of

Ru

ptu

re(%

)

Kinn et al. Cathet Cardiovasc Diagn 1997;42:151Kinn et al. Cathet Cardiovasc Diagn 1997;42:151

MyocardialMyocardial

IschemiaIschemiaIschemiaIschemia

Kloner RA et al. Circ 1980;62:945Kloner RA et al. Circ 1980;62:945

Coronary Heart DiseaseCoronary Heart DiseaseDeaths in the U.S. 1973Deaths in the U.S. 1973 -- 19981998

"A Shift to the Right""A Shift to the Right"

150000

200000

250000

#D

eath

s

1973

1998

0

50000

100000

150000

< 35 35-44 45-54 55-64 65-74 75-84 85+

Age at Death

#D

eath

s

Time to Reperfusion and 6 Month MortalityTime to Reperfusion and 6 Month MortalityIn Low and High Risk PatientsIn Low and High Risk Patients

Florence,Florence, ItalyItaly GroupGroup

8

10

12

14

6M

onth

Mor

talit

y%

7.9%

12.9%

11.5%High RiskHigh Risk

Antoniucci AJC 2002;89:1248Antoniucci AJC 2002;89:1248

0

2

4

6

8

6M

onth

Mor

talit

y%

4.8%

7.9%

1.6% 1.3%1.3%0%

Time to Reperfusion (hrs)

< 2 2 - 4 4 - 6 >6

Low RiskLow Risk

Major Hospitals in MiamiMajor Hospitals in Miami--Dade and BrowardDade and BrowardCountyCounty

Bittl et al. NEJM 1996;335:1290Bittl et al. NEJM 1996;335:1290

Mechanism of Myocyte DeathMechanism of Myocyte Death

Ischemia

Energy Depletion

Mitochondrialdeath

IrreversibleLoss of

Transmembrane

ReperfusionInjury

Oxygen Radical

ComplementActivationTnf1, Fas

Caspase ActivationTransmembraneGradients

MembraneRupture

Ca++Efflux

Cell Death

Oxygen RadicalSpecies Generation

Cell Death

Caspase Activation

DNA Fragmentation

Apoptotic Cell Death

Time Interval:Time Interval:

0-40 minutes Hours Hours/Days

SymptomSymptom--toto--Balloon Time & Infarct SizeBalloon Time & Infarct Size

9

12 1212.5

10

15

%o

fL

eft

Ve

ntr

icle

(Me

dia

n)

99m99mTcTc--sestamibi SPECT Imagingsestamibi SPECT Imaging

Pooled Sestamibi Analysis

P=0.0005P=0.0005

(2,25)(2,25) (1,22)(1,22)(2,31)(2,31)

4

0

5

<2 2 to 3 3 to 4 4 to 6 >6

%o

fL

eft

Ve

ntr

icle

(Me

dia

n)

Symptom Onset-to-Balloon Time (Hours)

N=82N=82 N=289N=289 N=288N=288 N=332N=332 N=145N=145

(0,16)(0,16)

(0,21)(0,21)

O’Neill et al. JACC 2005;45[suppl A]:225AO’Neill et al. JACC 2005;45[suppl A]:225A

DoorDoor--toto--Balloon Time & Infarct SizeBalloon Time & Infarct Size

1112 11.5

15

20

%o

fL

eft

Ve

ntr

icle

(Me

dia

n)

Door-to-balloon <90mins Door-to-balloon >90mins

TimeTime--toto--PresentationPresentation


P=0.0025P=0.0025 P=0.26P=0.26

8

11 11.5

0

5

10

<3 >3

%o

fL

eft

Ve

ntr

icle

(Me

dia

n)

Symptom Onset-to-Door (Hours)

N=509N=509N=297N=297 N=135N=135 N=126N=126

(0,19)(0,19)

(2,26)(2,26)(2,22)(2,22) (2,33)(2,33)


DoorDoor--toto--Balloon Time & Infarct SizeBalloon Time & Infarct Size

16

27

21

20

30

%o

fL

eft

Ve

ntr

icle

(Me

dia

n) LAD, p=0.005

Non-LAD, p=0.95

Anterior vs. NonAnterior vs. Non--Anterior MIAnterior MI


(9,43)(9,43)

(6,41)(6,41)16

14

68

57

0

10

<60 60-90 90-120 >120

%o

fL

eft

Ve

ntr

icle

(Me

dia

n)

Door-to-Balloon Time (Minutes)

(0,16)(0,16)

(1,33)(1,33)

(0,14)(0,14)

(0,34)(0,34)

(0,16)(0,16)(0,16)(0,16)


The Chain of SalvageThe Chain of Salvage

PT ArrivalPT Arrival

ER IdentificationER Identification

Pre Cath TherapyPre Cath Therapy

Coronary PatencyCoronary PatencyCoronary PatencyCoronary Patency

Distal EmbolizationDistal Embolization

Microcirculatory ProtectionMicrocirculatory Protection

Metabolic SupportMetabolic Support“Reperfusion Injury”“Reperfusion Injury”

Amount of Direct Unloading CorrelatesAmount of Direct Unloading Correlatesto Infarct Sizeto Infarct Size

67.24.6

Infa

rct

Siz

eas

Pro

po

rtio

no

fA

rea

at

Ris

k(%

)

60

8065.06.3

54.08.0

41.65.8

Ligation of 1st diagonale in Animal Model.Area at risk is ~14% of LV

Impella study – Flameng et al 2000.Meyns et al., J Am Coll Cardiol 2003; 41:1087-1095

Infa

rct

Siz

eas

Pro

po

rtio

no

fA

rea

at

Ris

k(%

)

0

20

40

Control ImpellaHalf Flow

41.65.8

IABP ImpellaFull Flow

Time from onset of symptoms to treatment(1,572 patients)

Invasive

Referral Door-to-needlePre-hospital

DANAMI-2

Fi b

rin

ol y

sis

Door-to-needlePre-hospital

Hospitals

0 60 120 180 240

Invasive

Referral

Invasive

Min.

Door-to-balloon

Door-to-balloon

In-door-out-door

Transportation

Pre-hospital

Pre-hospital

Fi b

rin

ol y

sis

PC

I

Primary end point within 30 Days1,572 patients

Fibrinolysis

Cu

mu

lati

ve

eve

nt

rate

(%)

10

20

Log rank: p=0.0003

DANAMI-2

13.7%

NNT=18

(front loaded tPA)

PCI

Cu

mu

lati

ve

eve

nt

rate

(%)

0

10

Days0 5 10 15 20 25 30

Log rank: p=0.0003

8.0%

Primary end point: Death or reinfarction or stroke

Primary end point within 30 DaysReferral hospitals: 1,129 patients

Fibrinolysis

Cu

mu

lati

ve

eve

nt

rate

(%)

10

20

Log rank: p=0.002

DANAMI-2

14.2%

NNT=18

(front loaded tPA)

PCI

Cu

mu

lati

ve

eve

nt

rate

(%)

0

10

Days0 5 10 15 20 25 30

Log rank: p=0.002

8.5%

Primary end point: Death or reinfarction or stroke

7.98.3

10.410.0

8

10

12

8.0 8.1

8

10

12

8.0

8

10

12

<1 / monthN=4,740

P = 0.0008

<1 / monthN=4,740

P = 0.0008

1-3 / monthN=14,078P < 0.0001

1-3 / monthN=14,078P < 0.0001

>3 / monthN=14,078P < 0.0001

>3 / monthN=14,078P < 0.0001

Primary PCI: Door-to-Balloon time vs.Mortality Stratified by Institutional Volume

Primary PCI: Door-to-Balloon time vs.Mortality Stratified by Institutional Volume

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

4.8

6.2

0

2

4

6

8

0-60 61-

90

91-

120

121-

150

151-

180

>180

Mo

rta

lity

(%

4.3 4.2

5.6

6.9

0

2

4

6

8

0-60 61-

90

91-

120

121-

150

151-

180

>180

Mo

rta

lity

(%

3.7 3.63.9

5.65.8

0

2

4

6

8

0-60 61-

90

91-

120

121-

150

151-

180

>180

Mo

rta

lity

(%

Incidence of TIMIIncidence of TIMI--3 Flow3 Flow

93 92 91 90

60

80

100

%T

IMI-

3F

low

AMIHOT

COOL MI

EMERALD

ICE-IT

1,122 Patients in 4 Trials Conducted Sept 20011,122 Patients in 4 Trials Conducted Sept 2001--Dec 2003Dec 2003

0

19 2012

0

20

40

60

Pre PCI Post PCI

%T

IMI-

3F

low

ICE-IT

3030--Day MACEDay MACE

10

15

1,122 Patients in 4 Trials Conducted Sept 20011,122 Patients in 4 Trials Conducted Sept 2001--Dec 2003Dec 2003

21.5

2.1

0.8

4.5

0

5

Death MI TVR Stroke MACE

%

13.0%

10%

15%

Infa

rct

siz

e(%

LV

med

ian

)

(3, 28)(3, 28)

Impact Of TIMI Flow PreImpact Of TIMI Flow Pre--PCIPCIOn Infarct SizeOn Infarct Size

P<0.0001

6.0%

3.0%

0%

5%

TIMI 0/1 TIMI 2 TIMI 3

Infa

rct

siz

e(%

LV

med

ian

)

(0, 23)(0, 23)

(0, 13)(0, 13)

19.0%

12.5%15%

20%

25%

Infa

rct

siz

e(%

LV

med

ian

)Impact Of Infarct VesselImpact Of Infarct Vessel

On Infarct SizeOn Infarct Size

(3, 39)(3, 39)

P<0.0001

12.5%

7.0%

0%

5%

10%

LAD LCX RCA

Infa

rct

siz

e(%

LV

med

ian

)

(3.5, 21)(3.5, 21)

(0, 16)(0, 16)

28.0%26.0%

20%

25%

30%

Infa

rct

siz

e(%

LV

med

ian

)

(14, 44)(14, 44)(8, 42)(8, 42)

Impact Of TIMI Flow Post PCIImpact Of TIMI Flow Post PCIOn Infarct SizeOn Infarct Size

P<0.0001

10.0%

0%

5%

10%

15%

TIMI 0/1 TIMI 2 TIMI 3

Infa

rct

siz

e(%

LV

med

ian

)

(0, 22)(0, 22)

DoorDoor--ToTo--Balloon Time & Infarct SizeBalloon Time & Infarct Size

8

9

13

11

10

15

%o

fL

eft

Ve

ntr

icle

(Me

dia

n)

P=0.038P=0.038

99m99mTcTc--sestamibi SPECT Imagingsestamibi SPECT Imaging


(1,30)(1,30)

(2,25)(2,25)

8

0

5

<60 60-90 90-120 >120

%o

fL

eft

Ve

ntr

icle

(Me

dia

n)

N=304N=304 N=405N=405N=296N=296N=183N=183


(0,23)(0,23)(0,19)(0,19)


Time to Reperfusion and InTime to Reperfusion and In--hospital Mortalityhospital MortalityIn Shock and NonIn Shock and Non--shock Patientsshock Patients

Moses Cone Primary PCI RegistryMoses Cone Primary PCI Registry

50

60

70

In-h

osp

italM

ort

ality

% 50%50%

62%62%

Shock (n = 138)Shock (n = 138)

0

10

20

30

40

In-h

osp

italM

ort

ality

%

31%31%

5.8%5.8% 4.6%4.6% 4.8%4.8%

NonNon--shock (n = 1705)shock (n = 1705)

< 3< 3 33 -- < 6< 6 >> 66

Time to ReperfusionTime to ReperfusionBrodie AHJ 2003;145:708Brodie AHJ 2003;145:708

Perfusion Images

Control Hypothermia

Future Reperfusion AlgorithmFuture Reperfusion AlgorithmChest pain onsetChest pain onset

PCIPCI

TIMI III flowTIMI III flow

Protective measuresProtective measures

Filters, thrombectomyFilters, thrombectomy

TIMI III flowTIMI III flow

RecoveryRecoveryassessmentassessment

Good recoveryGood recovery Poor recoveryPoor recovery

Microcirculatory agentsMicrocirculatory agents

HomeHome Myocyte regenerationMyocyte regeneration

ST resolutionST resolution

MRIMRI

MCEMCE

Adverse EventsAdverse Events

TNK + PCITNK + PCI PCIPCI PP--valuevalue

ReRe--MIMI 4.14.1 1.91.9 0.010.01

Repeat TVRRepeat TVR 4.44.4 1.01.0 <0.001<0.001

Total StrokeTotal Stroke 1.811.81 00 <0.001<0.001

ICHICH 0.970.97 00 0.0040.004

Bleeding (any)Bleeding (any) 31.331.3 23.423.4 <0.001<0.001

Major bleedMajor bleed 5.75.7 4.44.4 0.260.26

Inclusion CriteriaInclusion Criteria

StudyStudy No.No. SxSx--OnsetOnset STST Study EndpointStudy Endpoint

AMIHOTAMIHOT 252252 <24 hrs<24 hrs ≥≥ 1mm1mm Infarct SizeInfarct SizeDay 14Day 14

COOL MICOOL MI 359359 <6 hrs<6 hrs ≥≥ 1mm1mm Infarct SizeInfarct Size

Trials Conducted Sept 2001Trials Conducted Sept 2001--Dec 2003Dec 2003

COOL MICOOL MI 359359 <6 hrs<6 hrs ≥≥ 1mm1mm Infarct SizeInfarct SizeDay 30Day 30

EMERALDEMERALD 501501 <6 hrs<6 hrs ≥≥ 2mm2mm Infarct SizeInfarct SizeDay 5Day 5--1414

ICEICE--ITIT 200200 <6 hrs<6 hrs ≥≥ 1mm1mm Infarct SizeInfarct SizeDay 30Day 30

*Cardiogenic shock excluded in all trials

DoorDoor--ToTo--Balloon Time & TIMI FlowBalloon Time & TIMI Flow

9390

93 91

80

100

%T

IMI-

3F

low

<60 mins

60-90 mins

90-120 mins


10 1116 16

0

20

40

60

Pre PCI Post PCI

%T

IMI-

3F

low

>120 mins


Impact of DBT on 30Impact of DBT on 30--Day MACEDay MACE

7.6

5.5

10

Ev

en

tra

te(%

)

Death

MACE

P=0.003 for deathP=0.003 for deathP=0.0034 for MACEP=0.0034 for MACE


0.6 0.7

4.7

2.5

1.6

2.4

5.5

0

5

<60 60-90 90-120 >120

Ev

en

tra

te(%

)



COOLCOOL--MIMI ICEICE--ITIT

Core Temperature At ReperfusionCore Temperature At Reperfusion

21.9

30 p=0.05p=0.05

22.7

30p=0.09p=0.09

Anterior MI GroupAnterior MI Group –– Mean Infarct SizeMean Infarct Size

17.9

9.3

21.9

18.2

0

10

20

All Cool <35 C >35 C Control

(%) 16.3

12.9

17.6

0

10

20

All Cool <35 C >35 C Control

(%)

(n=54)(n=54) (n=16)(n=16) (n=38)(n=38) (n=59)(n=59) (n=36)(n=36) (n=10)(n=10) (n=26)(n=26) (n=38)(n=38)

37

36

Onset to Door115 min

Door to PCI104 min

Start Temp

Tem

per

atu

reºC

Procedural Results - CoolingMinimum Temp = 33.2°C72% Achieved Target Temp88% < 34 °CTime to Minimum Temp = 75 min

35

34

33

1 2 3 4 5 6 7 8 9 10

Start Temp= 36.1°C

Elapsed Time (hours)

Tem

per

atu

re

TCT 2003

Temp at PCI = 35.0 °CCooling prior toPCI = 18 min

Significantly Faster CoolingSignificantly Faster Coolingwith New Systemwith New System

34.5

35.0

35.5

36.0

36.5

37.0

Te

mp

era

ture

(de

gre

es

C)

New System

COOL MI

31.5

32.0

32.5

33.0

33.5

34.0

34.5

0:00 0:10 0:20 0:30 0:40 0:50 1:00

Elapsed Time (hh:mm)

Te

mp

era

ture

(de

gre

es

C)

65 minutes to 33oC

20 minutes to 32oC

13 minutes to 33oC

OO (g)(g)

ventvent

O2

O2

O2O2

O2

O2

O2

O2

O2O2

O2

O2

O2 O2

P > 500 psig

OO22 gasgas500 psig500 psig

saline mistsaline mist

Batch modeBatch mode

OO22(g)(g)500 psig500 psig

1) bubble high1) bubble high--pressure Opressure O22

thru saline and saturatethru saline and saturatesolutionsolution2) vent gas and2) vent gas andstore understore underpressurepressure

AtomizerAtomizerchamberchamber

nozzle

saline mistsaline mist

O2 O2

SalineSalinesourcesource

‘on‘on--demand’demand’AO supplyAO supply

1) Saline is spritzed by atomizer1) Saline is spritzed by atomizerinto highinto high--pressure Opressure O22 environmentenvironment2) droplets saturate and collect in pool for2) droplets saturate and collect in pool forimmediate useimmediate use

OnOn--line modeline mode

0.570.62

0.6

0.8

1

Ch

an

ge

inR

WM

Sc

ore

Ind

ex

P=0.240.75

0.6

0.8

1

P=0.03

All Patients Anterior MI <6-hours

Regional Wall MotionRegional Wall MotionAMIHOT

0.57

0

0.2

0.4

0.6

Control AO

Ch

an

ge

inR

WM

Sc

ore

Ind

ex

N=119

N=115N=119

0.54

0

0.2

0.4

0.6

Control AO

N=49N=49

PercuSurge GuardWire in AMIPercuSurge GuardWire in AMI

73.8%

62.2%70.1%

60.6%60%

80%

100%

GuardWire (n=233) Control (n=216)

Primary EndpointPrimary Endpoint

STST--Segment Resolution at 30 MinutesSegment Resolution at 30 Minutes

P=0.39P=0.39P=0.77P=0.77P=0.36P=0.36 P=0.75P=0.75

28.3%

9.5% 12.5%

26.9%

0%

20%

40%

60%

Absent

(<30%)

Partial

(30% - 70%)

Complete

(>70%)

Mean

1º endpoint

26.8%23.5%

30

40

Infarct sizeInfarct size

by Tcby Tc--99m99m--SPECTSPECTInfarct size, %LV, with 72% imputation for deaths before 5 daysInfarct size, %LV, with 72% imputation for deaths before 5 days

P=0.35P=0.35P=0.15P=0.15

±±21.921.9

P=0.36P=0.36

17.8%

11.3% 10.9%

23.5%

15.6%

0

10

20

All (n=435) LAD (n=174) RCA/LCX (n=261)

±±12.412.4 ±±13.913.9

1º endpoint

±±18.718.7±±18.118.1

±±21.921.9

±±21.421.4

Mortality reduction (%)

40

60

80

100

%%

Relationship Between Mortality Reductionand Extent of Salvage

Relationship Between Mortality Reductionand Extent of Salvage

Modifying factors

• Collaterals

• Ischemic preconditioning

0

20

40

1 3 6 12 24

Extent of salvage (% of area at risk)

Treatment objectives

Time to treatment is criticalTime to treatment is criticalOpening the IRA (PCI > lysis)Opening the IRA (PCI > lysis)

HoursHours

CP1163618-6

• Ischemic preconditioning

• MVO2

Gersh et al JAMA 2005Gersh et al JAMA 2005

Cesare Gianturco Dilation CatheterCesare Gianturco Dilation Catheter19641964



Bittl et al. NEJM 1996;335:1290Bittl et al. NEJM 1996;335:1290

CAD Circa 2010CAD Circa 2010

CAD Circa 1950CAD Circa 1950

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