Microvolt T-Wave Alternans During Exercise and Pacing in Patients with Acute Myocardial Infarction

Long-term Cardiac Arrhythmias recorded by an Insertable

Loop Recorder in Patients with

Depressed Left Ventricular Function after Acute Myocardial Infarction

CARISMACardiac

Arrhythmias and

RIsk

Stratification

after

Myocardial infArction

PE Bloch Thomsen,MD,PhD Gentofte

University Hospital

Copenhagen, Denmarkpebt@ geh.regionh.dk

CARISMA investigators

Principal investigators:

H. Huikuri, Finland, PE Bloch Thomsen, Denmark

P. Raatikainen

University of Oulu, FinlandR.M. Joergensen

University of Copenhagen, Denmark

J. Hartikainen

University of Kuopio, FinlandV. Virtanen

University of Tampere, Finland

J. Boland

Hopital

Citadelle, Liège, BelgiumO. Anttonen

Paijat-Hame

Hospital, Lahti, Finland

L.A.V. Boersma

St. Antonius

Hospital, Nieuwegein, NetherlandsE.S. Platou

University of Oslo, Norway

E. Stoupel

Hopital

Erasme, Brussels, BelgiumJ. Rokkedal, N. Hoest

Amtssygehuset

Glostrup, Denmark

European multicenter, prospective, observational study

Disclosures

Research grant and speaker fee• Boston Scientific Guidant• Medtronic BRC • St. Jude Medical

CARISMA was sponsored by

• Medtronic Bakken

Research Center

• Cambridge Heart Inc

Assess the predictive value of electrophysiologic

testing and

non-invasive screening tests for life-threatening tachyarrhythmias

in

patients surviving AMI with EF ≤

0.40

CARISMA –

Objective 1

(HRS, Hot Line Session, Denver, May 10, 2007)

CARISMA –

Objective 2

Document the incidence and assess the prognostic significance of cardiac

arrhythmias obtained from an implantable

ECG loop recorder

Implantable loop recorder

Weight 1/2 oz, 8 cc. Longevity up to 2 years. ECG storage 42 min, automatic arrhythmia detection algorithms

Sampling rate 100 Hz

Inclusion criteria

•

Patients within 3 to 21 days of AMI + CKMB or Troponin elevation+ Typical chest pain or ECG changes

•

EF ≤

40%, 2-D echo ( WMI ≤

1.3)

• Planned CABG/ ICD • NYHA IV• Informed consent not obtained

Exclusion criteria

Study design

312 pts

informed consent

1393 (24%) EF ≤

40%

5869 pts with AMI

ILR implantation

297 pts5-21 days

post-MI

3-21 days post-MI

Quarterly follow-up 2 year post-MI

Patient characteristics Enrollment:

2002-2005

Baseline# of pts

312

Gender (men)

77%Age (years)

65 ±

11

LVEF

31% ±

6AFib

permanent

9%

QRS > 120 ms

15%Diabetes 20%Prior MI 37%Hx

of CHF (II-III)

11%

RevascularizationPrimary PCI

30%

Thrombolysis

35%

Rx at dischargeASA

90%

Beta-blockers

96%ACE / AT II

89%

Statins

82%

Definitions Pre-specified arrhythmia

Sinus bradycardia

≤

30 bpm, ≥

8sSinus arrest

≥

5s

AV block (2°, 3°) ≤

30 bpm, ≥

8s

Non-sustained VT ≥

125 bpm, ≥16 beats Sustained VT ≥

125 bpm, ≥30s

AFib

≥

125 bpm

Incidence of arrhythmias recorded by the ILR

Mean follow-up 1.9 years

137 pts (46%) documented at least one of the pre-specified arrhythmias

86% were asymptomatic

Bradyarrhythmia: Time

to first

arrhythmia

by ILR

1.0

0.7

0.8

0.9

0.0

0 200 400 600 800Time (days)

Eve

nts

Free

1.0

0.7

0.8

0.9

0.0

0 200 400 600 800Time (days)

Eve

nts

Free

S. ArrestS. BradyAV block

Sinus arrest

(>5s) n= 16 (5%)

Sinus brady

(>8s) n= 20 (7%)

AV block (>8s) n=29 (10%)

1 s

1.0

0.5

0.6

0.7

0.8

0.9

0.0

0 200 400 600 800Time (days)

Eve

nts

Free

NSVT

VTsustVF

AFib

Tachyarrhythmia: Time to first

arrhythmia

by ILR

Ventricular Fib. n=8 3%VT Sust. n=9 3%VT Non-sust. n=39 13%

AFib

n=95 32%

Conclusion Incidence of arrhythmias

27% had new onset atrial

fibrillation

17% had high degree AV block or sinus bradyarrhythmia

17% had non-sust

VT or VT/VF

Univariate analysis Predictors of cardiac death

N = 25 (9%)

HR p-value

AV block < 30 bpm 7.0 0.0004Sinus brady < 30 bpm 5.8 0.004Non sustained VT 3.4 0.025

Multivariate analysis

High-degree AV block was the onlyindependent predictor of cardiac death

HR 4.8 [2.0-11.5] p < 0.001

Pre-specified arrhythmias were included as time dependent covariates in a multivariate Cox model.

Summary

CARISMA is the first study to report on long term arrhythmias and prognostics by an

implantable loop recorder in patients surviving an AMI with reduced left ventricular function

Conclusion

High-degree

AV block was the only independent predictor of

cardiac death

Future directions

The insertable

ECG loop recorder is a diagnostic tool that should be considered to guide medical and

device therapy in patients surviving myocardial infarction

BACK UP slides

Limitations

The CARISMA study was an observational study not designed to answer the question whether an ILR is a clinical tool that should be implanted in future post MI patients with reduced left ventricular function

Device implants

57 patients received ICD5 of the 9 pts with sust

V T on ILR

11 of the 39 pts disclosing non-sust

VT

22 patients received pacemaker13 pts disclosed bradyarrhythmias

on ILR

Dying with the ILR

Cardiac death

25Dying with ILR

16

VT/VF

8

(1/7)Bradycardia

5

No recordings

3

# of pts

Device implants

57 patients received ICD45 primary prophylaxis12 secondary prophylaxis

22 patients received pacemaker

Study Design

312 (22%) patients

Informed consent

LVEF > 40%

6 weeks post-MI

Quarterly follow-ups

1393 (24%) / 5869

screened with EF <

40%

AMI

ILR implantation

297 patients1.

EP study

2.

Exercise test3.

24-hr Holter

4.

T-wave alternans5.

SAECG

6.

12-lead ECG

5-21 days post-MI

3-21 days post-MI

2 year post-MI

Circadian distribution of bradyarrhythmias N=

Symptomatic 1: YES 2: No

6

16 16

22

27

32

1917

119

7

4

10

6

0 0

43

24

6

3

7

13

Freq

0

10

20

30

40

Hour0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

N = 258

Circadian distribution New onset atrial fibrillation

Symptomatic 1: YES 2: No

1113

11

64

9

20

17

50

30

3836

32

36 35

29

15

22

47

23

20

14

108

Freq

0

10

20

30

40

50

Hour0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

(N=538)

Circadian distribution Ventricular tachyarrhythmia

Type V Tachyarrhythmia 1: VF 2: sust VT>=30s 3: NSVT>=125bpm

13

2

4 4 4

6

7

1

3

5

3

2

7

9

6

2 2 2

4

1

4 4

6

2

Freq

0

1

2

3

4

5

6

7

8

9

10

11

12

13

Hour0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

(N=102)

Circadian distribution High degree AV block

Symptomatic 1: YES 2: No

2

9

8

14

16

18

7

11

6

7

3 3

6

10 0

4

2

1

3

0 01

2

Freq

0

1

23

45

67

89

1011

1213

1415

16

1718

Hour0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23

N = 124

Limitations of the ILR

• 20-30

SA block

with

frequency > 30/min • 20-30

AV block

with

frequency > 30/min

• AFib

with

varying RR intervals > 480 ms• Non sust VT < 16 beats• VT with CL< 260 ms

may

be missed

• Undersensing of VF

Limitations of the CARISMA study

• No control

group

•Many exclusions

• No follow up of excluded patients

Endpoint DefinitionsComposite primary endpoint 1.

Sudden cardiac death of arrhythmic origin

2.

Resuscitated arrhythmic death3.

Spontaneous, symptomatic, sustained ventricular tachycardia

The arrhythmia should be ECG documented and be likely treatable by an ICD

Secondary endpoints1.

Total mortality

2. Cardiac death