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Infarct transmurality and infarct size assessed by delayed enhancement

magnetic resonance imaging: Association with time-to-treatment, ST-

segment resolution, and TIMI-flow grades

Holger Thiele, MD; Axel Linke, MD; Sandra Erbs, MD; Enno Boudriot, MD; Alexander Lebcke, MD;

Dietmar Kivelitz, MD; and Gerhard Schuler, MD

Department of Internal Medicine/Cardiology, University of Leipzig – Heart Center

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Background

• The TIMI flow, ST-segment resolution and time-to-reperfusion are associated with mortality in ST-elevation myocardial infarction (STEMI) after either fibrinolysis or percutaneous coronary intervention. Boersma et al. Lancet 1996;96:771-775De Luca et al. J Am Coll Cardiol 2003; 42:991-997GUSTO-I. N Engl J Med 1993; 329:1615-1623Stone et al. Circulation 2001; 104:636-641de Lemos et al. J Am Coll Cardiol 2001;38:1283-1294

• As a result of excellent spatial resolution delayed enhancement magnetic resonance imaging allows assessment of infarct transmurality and infarct size.Simonetti et al. Radiology 2001;218:215-223

• Whether these clinical, angiographic and ECG measures are also associated with infarct size and infarct transmurality, has not yet been investigated.

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Background

As a consequence of excellent spatial resolution DE-MRI might also allow to assess the assumed “wavefront phenomenon” of myocardial necrosis in humans.

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

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Hypothesis

We hypothesized that these measures (Time-to-

Reperfusion / ST-Resolution / TIMI-Flow) would also be associated with infarct size and infarct transmurality as assessed by delayed enhancement MRI.

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Patients with Angina (< 6 h) n=164

Methods and Materials: Patients (Leipzig Prehospital Fibrinolysis Study)

Prehospital Fibrinolysis (n=82) Facilitated PCI (n=82)

Lost to 6 month follow-up (n=1)

Primary Endpoint Analysis (Infarct Size) (n=66)Secondary Combined Endpoint Analysis (n=80)

Primary Endpoint Analysis (Infarct Size) (n=69)Secondary Combined Endpoint Analysis (n=79)

Lost to 6-month follow-up (n=0)

Excluded, no infarction (n=2)

Rescue Angioplasty (n=14)

Excluded, no infarction (n=2)

No Stent (n=4) not necessary (n=3) not possible (n=1)

12-lead-ECG STEMI

Exclusion criteria?, Informed consent?

Randomization and hospital assignment (3 PCI, 4 non-PCI-center)

Prehospital combination fibrinolysis ASA 500 mg, Heparin (60IE/kg BW), Abciximab (0.25 mg/kg BW), Reteplase

Double-Bolus 5 U

Thiele H, et al. Eur Heart J 2005; 26:1956-1963

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Methods: MR Image Analysis

Blinded observers:

Manual drawing of endocardial, epicardial, papillarypapillary, and

infarct contours

%Infarct Size = (Volume Infarct/Volume LV mass)

1

2

3

4

5

613

7

12

11

10

9

8

14

15

1617

Transmurality for each segment of 17 segment model:

> 50% transmurality

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Methods Patient Stratification

135 Patients

3 Groups:Defined by Tertile Symptom-Treatment-Interval

Lower Tertile (<120 min)

Middle Tertile (120-240 min)

Upper Tertile (> 240 min)

Median Symptom-Treatment-Time: 118 min.

135 Patients

3 Groups:Defined by ST-Segment Resolution

No ST-Resolution (<30%)

Intermediate ST-Resolution (30-70%)

Complete ST-Resolution (>70%)

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Results: Infarct Size and Transmurality – Time to treatment

0

2

4

6

8

10

12

14

16

18

< 2h 2-4 h > 4h

Infa

rct S

ize

(%L

V)

Prehospital lysis

8.2 (3.0;15.6)

14.3 (6.6;20.9)

14.5 (3.2;21.8)

Facilitated PCI

3.9 (0.9;7.8)

10.3 (1.8;14.5)

12.8 (9.1;18.6)

7.5 (2.5;14.0)

14.0 (5.8;20.5)

13.5 (3.0;17.0)

Infarct size

0

2

4

6

8

10

12

14

16

18

< 2h 2-4 h > 4h

Tra

nsm

ural

ity

Sco

re

5.0 (2.0;8.0)

11.0 (2.3;15.0)

12.0 (11.3;18.3)

Transmurality Score

P<0.001P=0.007

P=0.02 P=0.02

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Results: Infarct Size and Transmurality - ST-Resolution

0

2

4

6

8

10

12

14

16

>70% 70-30% <30%

Infa

rct

size

(%

LV

)

p<0.001

ST-segment resolution

4.2 (1.6; 10.5)

13.6 (8.0; 16.4)12.4 (7.7; 17.9)

0

2

4

6

8

10

12

14

16

>70% 70-30% <30%T

ran

smu

rali

ty S

core

p<0.001

5.0 (2.0; 10.8)

11.0 (8.8; 16.3)

13.0 (8.0; 19.5)

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0

2

4

6

8

10

12

TIMI 0-I TIMI II-III

Results: Infarct Size and Transmurality -Pre-PCI TIMI-Flow

IS (

% L

V)

p = 0.002

10.8%LV (IQR 7.6; 17.3)

3.9%LV (IQR 0.9; 9.6)

n=69, Facilitated PCI-Group

0

2

4

6

8

10

12

TIMI 0-I TIMI II-IIIT

rans

mur

alit

y S

core

p = 0.003

11.5 (IQR 8.0; 16.5; )

5.0 (IQR 2.0; 9.5)

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Wavefront Phenomenon - Human Data

Time (min)

20

0 60 120 180 240 300 360

30

40

50

60

70

80

90

1125 13

9

99

6

14

19

20

Prehospital Lysis

Facilitated PCI

Pro

bab

ilit

y T

ran

smu

rali

ty >

50%

(%

)

Time (min)0 60 120 180 240 300 360

80

70

60

50

40

30

20

10

2019

6

14

9

9

91311

25

Prehospital Lysis

Facilitated PCI

Pro

bab

ilit

y In

farc

t S

ize

>10

% (

%)

Each 30 min delay in time-to-treatment 20-25% risk increase transmurality >50%

Each 30 min delay in time-to-treatment 20-25% risk increase infarct size >10%

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The time from symptom-onset-to-treatment, ST-resolution and pre-PCI TIMI-flow influence the final infarct size and infarct transmurality for either prehospital fibrinolysis or prehospital initiated facilitated PCI.

This finding is in contrast to other studies with a primary PCI approach (STOPAMI 1+2 trial). These differences might be explained by the much shorter time to reperfusion in the current trial (mean 118 min vs. 180-215 min).

A prehospital initiated facilitated PCI approach is superior to prehospital fibrinolysis alone in particular in the early time period after symptom onset.

This underlines the assumed pathophysiological link between early flow restoration and perfusion in the infarct related artery, which is known as the “wavefront phenomenon”.

Summary and Conclusions

Major goal in STEMI treatment is very early complete reperfusion