Prevention de la Mort SubitePrevention de la Mort Subite Treatment of Ventricular Arrhythmias and the Prevention of Treatment of Ventricular Arrhythmias and the Prevention of

Sudden Cardiac DeathSudden Cardiac Death

S. Nasr, M.D.

Clinical Cardiac Electrophysiologist

Association Franco-Libanaise de Cardiologie 11 Mai 2007 - Beirut, Liban

Cause of Death

52

54

56

58

60

62

64

1989 1990 1991 1992 1993 1994 1995 1996 1997 1998

%

Total Mortality: Contribution from Sudden Cardiac Death

Zheng et al., Circulation 2001

Holter recordingsfrom 157 cases with

fatal arrhythmiasBrady-arrhythmias

62%

17%

Bayes de Luna et al. Am Heart J 1989

VT VFPrimary VF 9%

13%Torsadede Pointes

Sudden Cardiac Death

Sudden Cardiac Death

Huikuri et al. NEJM 2001

Implantable Defibrillator

Myerburg et al., Circulation 1992

3020105210 3002001000

(% per year)(x 1000)

Incidence Events per Year

Adult population

CAD

History of acoronary event

Heart failure

Resuscitation

Resuscitationwith previous MI

Sudden Cardiac Death

Sudden Cardiac Death

• Secondary Prevention

• Primary Prevention

10 20 30 40 60

LV-EF (%)LV-EF (%)

CIDSCIDS

CASHCASH

Dutch trialDutch trial

AVIDAVID

VF, cardiac arrestVF, cardiac arrest

sustained VTsustained VT

ICD Trials - Secondary prophylaxis

Summary of 20 Prevention Trials

0.6 0.8 1.0 1.2 1.4

AVID

1.6 0.4

1997

N = 1016

0.62

Hazard ratio

ICD better

1.8

Other features

CASH2000

N = 191 Aborted cardiac arrest

CIDS2000

N = 659

0.82

Aborted cardiac arrest or syncope

Trial Name, Pub Year

0.83

Aborted cardiac arrest

HR:0.73 (0.59,0.89)

p = 0.0023Meta

●●

●

●

Recommendations for 20 Prevention

• Class I RecommendationsThe ICD is effective therapy to reduce mortality by a reduction in SCD in patients with LVD due to prior MI who present with hemodynamically unstable sustained VT, who are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year (Level of Evidence: A)

An ICD should be implanted in patients with non-ischemic DCM and significant LVD who have sustained VT or VF, who are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year (Level of Evidence: A)

5 10 20 30 40

CATCAT

CABG-PatchCABG-Patch

MUSTTMUSTTMADIT IMADIT I

ns VT ns VT

High riskHigh riskno VAno VA MADIT IIMADIT II

DINAMITDINAMIT

SCD-HeFTSCD-HeFT

DEFINITEDEFINITE

LV-EF (%)LV-EF (%)

ICD Trials - Primary prophylaxis

ICD 10 Prevention Trial Results

CABG-Patch

MUSTT

MADIT I

MADIT II

DINAMIT

SCD-HeFT

DEFINITE

AMIOVIRT

CAT

0 0.5 1 1.5 2 2.5

CAD, MI

NICM

CAD, NICM

Hazard Ratio

ICD better No ICD better

Risk stratification for sudden death in ICD trials

Ejection fraction(EF <30%, <35%, <40% + ...)

Etiology of depressed EF(CAD vs DCM)

EP study(inducible VT, VF)

Timing of remote myocardial infarction(< 40 days, > 40 days / 1 month)

[HRV]

NYHA class

QRS duration

Study MADIT II DEFINITE SCD HeFT

Sponsor Guidant St Jude MIH/Wyeth/Medtronic

Reported in NEJM Mar 2002 May 2004 Jan 2005No of patients 1232 458 2521Disease MI CM/CHF CHFNYHA I/II/III/IV 37/34.5/24/4.5 21.6/57.4/21.0/… …/70/30/…LVEF, % 30 (23) 35 (21) 35 (25)IHD/NIHD, % 100/… …/100 52/48

Device ICD ICD ICD1o end-point ACM ACM ACMStudy duration Jul 1997 – Nov 2001 July 1998 – June 2002 Sep 1997 – Jul 2001

Follow-up, months 20 29 45.5

Major ICD Secondary Prevention Trials

LV-EF is considered as the best parameter for risk stratification after MI

exponential increase of risk of SCD below EF 35-40%

LV-EF (%)

risk

LV-function as predictor of SCD

MUSST, MADIT, MADIT-2, SCD-HeFTDINAMIT, COMPANION, ………

LV

EF

< 25

≥ 25

23

0.2 0.4 0.6 0.8 1.0 1.2 1.4 Defibrillator

Better

831

401

1232

MADIT II

15

20

25

40

35

30≤ 30

Conventional Better

Major ICD 10 Prevention Trials and LVEF

> 30> 30

0.2 0.4 0.6 0.8 1.0 1.2 1.4

1390

285

1675

SCDHeFT

15

20

25

40

35

30

35

25

≤ 30

LV

EF

0.2 0.4 0.6 0.8 1.0 1.2 1.4

310310

458

2020

< 20< 20

DEFINITE

35

21

15

20

25

40

35

30

LV

EF

148148

Principle of Guidelines

40

35

30

25 Class: 1LOE: A

Class: IIa; LOE: B

Class: IIb; LOE: B

A B C

LVEF

40

35

30

25 Class: 1LOE: A

LVEF

• Multiple trials with EF < 30%• No trials of EF 30-35% or 35-40%

• EF difficult to measure

Examples of Guideline Recommendations

40

35

30

25Class: 1LOE: A

LVEF

Class: 1LOE: B

CHD NICM

≤ 30-40% ≤ 30-35%

Etiology of Heart Failure

Study MADIT II DEFINITE SCD HeFT Total

Ischaemic All (1232) N/A 52% (884) 2116

Non-ischaemic N/A All (458) 48% (792) 1250

AetiologyAetiology nn

IschaemicIschaemic 884884

Non-ischaemicNon-ischaemic 792792

IschaemicIschaemic 506506

Non-ischaemicNon-ischaemic 397 397

0.2 0.4 0.6 0.8 1 1.2 1.4

SCD HeFTSCD HeFT

COMPANIONCOMPANION(ACM only)(ACM only)

ICD better ICD not better

ICD Recommendation:≥40 days post MI

0

2

4

6

8

10

ICD OPT

Non-arrhythmic Arrhythmic

6.0

1.5

3.4

3.5Ann

ual m

orta

lity

rate

, %

0

5

10

15

< 18 MO 18-59 MO 60-119 MO > 120 MO

ICD OPT

Pro

bab

ilit

y o

f S

urv

ival 1.0

0.9

0.8

0.7

0.6

0.0

Defibrillator

Conventional

0 1 2 3 4Year

DINAMIT Hohnloser SH et al, 2004MADIT II Wilber DJ et al, 2004

MADIT II Moss AJ, 2002

Salukhe TV et al, 2004

00,10,20,30,40,50,6

MUSTT MADIT MADIT II

1 year 2 years 3 years

LY g

aine

d p

er d

evic

e

Mo

rtal

ity

/ 100

py

Life expectancy >1 y

Bardy G. et al., N Eng J Med 2005; 352: 225-37Bardy G. et al., N Eng J Med 2005; 352: 225-37

SCD-HeFT

NYHA II NYHA III

NYHA Functional ClassNYHA class, % MADIT II DEFINITE SCD HeFT

I 37 21.6 -

II 34.5 57.4 70

III 24 21 30

NYHANYHA nn

II 461461 I I 771771II 9999IIII 263263IIIIII 9696IIII 11601160IIIIII 516516 ICD better ICD not better

MADIT IIMADIT II

DEFINITEDEFINITE

SCD HeFTSCD HeFT

0 0.4 0.8 1.2 1.6 2 2.4

Recommendations for 10 Prevention

Class 1 Recommendation:ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in SCD in patients with non-ischemic DCM who have an LVEF ≤ 30% to 35%, are NYHA functional class II or III receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year

(Level of Evidence: B)

Class 1 Recommendation:ICD therapy is recommended for primary prevention to reduce total mortality by a reduction in SCD in patients with LVD due to prior MI who are at least 40 days post-MI, have an LVEF ≤ 30% to 40%, are New York Heart Association (NYHA) functional class II or III, are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year

(Level of Evidence: A)

NYHA Functional Class 1 and LVD

“The writing committee struggled with this issue since guidelines are meant to summarize current science and not take into account economic issues or the societal impact of making recommendations. However the committee recognizes that the economic impact and societal issues will clearly modulate how these recommendations are implemented”

NYHANYHA nn

II 461461 I I 771771II 9999IIII 263263

ICD better ICD not better

MADIT IIMADIT II

DEFINITEDEFINITE

0 0.4 0.8 1.2 1.6 2 2.4

NYHA Class I Recommendations

Class IIa

Implantation of an ICD is reasonable in patients with LVD due to prior MI who are at least 40 days post-MI, have an LVEF of ≤ 30% to 35%, are NYHA functional class I on chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year

(Level of Evidence: B)

Class IIb

Placement of an ICD might be considered in patients who have non-ischemic DCM, LVEF ≤ 30% to 35%, are NYHA functional class I receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year

(Level of Evidence: C)

Guidelines for the management of patients at risk of sudden death

ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult

ESC 2005 Guideline Update for the Diagnosis and Treatment of Chronic Heart Failure

ACC / AHA 2004 Guidelines for the management of Patients with ST-Elevation Myocardial Infarction

ACC / AHA / NASPE 2002 Guidelines Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices

ICD Indications

Group of patients ACC/AHA HF ESC HF ACC/AHA STEMI

ACC/AHA/NASPE for PM

and ICD

ACC/A/H/A/ESCVentricular Arrhythmias and

Sudden Cardiac Death

2005 update 2005 2004 2002 2006

s/p MI, EF 30%, NYHA II, III

Class I, LOE B

Class IIb, LOE B

Class IIa, LOE B

Class IIa,LOE B s/p MI

EF ≤ 30-40%NYHA II-III

Class ILOE A

s/p MI, EF 30-35%, NYHA II, III

Class IIa, LOE B

Class I, LOE A

Class IIa, LOE B N/A

s/p MI, EF 30-40%, NSVT, positive EPS N/A N/A Class I,

LOE BClass IIb,

LOE B

s/p MI, EF 30%, NYHA I

Class IIa, LOE B N/A N/A N/A s/p MI, EF ≤ 30-35% NYHA I

Class IIa; LOE B

NICM, EF 30%, NYHA II, III

Class I, LOE B

Class I, LOE A N/A N/A LVEF ≤ 30-35%

NYHA II-IIIClass ILOE B

NICM, EF 30-35%, NYHA II, III

Class IIa, LOE B

Class I, LOE A N/A N/A

NICM, EF 30%, NYHA I

Class IIb, LOE C N/A N/A N/A EF ≤ 30-35%

Class IIb; LOE B

Comparison between Guidelines

ICD Indications

Group of patients ACC/AHA HF ESC HF ACC/AHA STEMI

ACC/AHA/NASPE for PM

and ICD

ACC/A/H/A/ESCVentricular Arrhythmias and

Sudden Cardiac Death

2005 update 2005 2004 2002 2006

s/p MI, EF 30%, NYHA II, III

Class I, LOE B

Class IIb, LOE B

Class IIa, LOE B

Class IIa,LOE B s/p MI

EF ≤ 30-40%NYHA II-III

Class ILOE A

s/p MI, EF 30-35%, NYHA II, III

Class IIa, LOE B

Class I, LOE A

Class IIa, LOE B N/A

s/p MI, EF 30-40%, NSVT, positive EPS N/A N/A Class I,

LOE BClass IIb,

LOE B

s/p MI, EF 30%, NYHA I

Class IIa, LOE B N/A N/A N/A s/p MI, EF ≤ 30-35% NYHA I

Class IIa; LOE B

NICM, EF 30%, NYHA II, III

Class I, LOE B

Class I, LOE A N/A N/A LVEF ≤ 30-35%

NYHA II-IIIClass ILOE B

NICM, EF 30-35%, NYHA II, III

Class IIa, LOE B

Class I, LOE A N/A N/A

NICM, EF 30%, NYHA I

Class IIb, LOE C N/A N/A N/A EF ≤ 30-35%

Class IIb; LOE B

Comparison between Guidelines

ICD Indications

Group of patients ACC/AHA HF ESC HF ACC/AHA STEMI

ACC/AHA/NASPE for PM

and ICD

ACC/A/H/A/ESCVentricular Arrhythmias and

Sudden Cardiac Death

2005 update 2005 2004 2002 2006

s/p MI, EF 30%, NYHA II, III

Class I, LOE B

Class IIb, LOE B

Class IIa, LOE B

Class IIa,LOE B s/p MI

EF ≤ 30-40%NYHA II-III

Class ILOE A

s/p MI, EF 30-35%, NYHA II, III

Class IIa, LOE B

Class I, LOE A

Class IIa, LOE B N/A

s/p MI, EF 30-40%, NSVT, positive EPS N/A N/A Class I,

LOE BClass IIb,

LOE B

s/p MI, EF 30%, NYHA I

Class IIa, LOE B N/A N/A N/A s/p MI, EF ≤ 30-35% NYHA I

Class IIa; LOE B

NICM, EF 30%, NYHA II, III

Class I, LOE B

Class I, LOE A N/A N/A LVEF ≤ 30-35%

NYHA II-IIIClass ILOE B

NICM, EF 30-35%, NYHA II, III

Class IIa, LOE B

Class I, LOE A N/A N/A

NICM, EF 30%, NYHA I

Class IIb, LOE C N/A N/A N/A EF ≤ 30-35%

Class IIb; LOE B

Comparison between Guidelines

Summary and Conclusions

VA&SCD Guidelines focus on management of actual and threatened ventricular tachyarrhythmias, and

• Build on others that have preceded them - some recommendations have not changed.

• Introduce many new and some potentially controversial recommendations

• Favour the ICD and extend its indications: Class I CHF / little or no LV dysfunction / wider range of ejection fraction / non-ischemic cardiomyopathy

• Acknowledge that not all those who might benefit from ICD therapy can accept or can receive such treatment - alternative treatment is recommended for those who do not receive an ICD

Guidelines and Controversy

You can please all the people some of the time, and some of the people all the time, but you cannot please all the people all the time."  

Abraham Lincoln