Dealing With Sudden Cardiac Death:

Who Deserve Device Implantation ?

Muhammad Yamin
Cardiology Division, Department of Internal Medicine, Faculty of
Medicine, Universitas Indonesia,Cipto Mangunkusumo National Hospital
Jakarta
 Outline
Introduction and magnitude of
problem

Evidence of ICD for SCD

prevention

Strategy for Secondary and

Primary Prevention

Real World Challenges

Conclusion
Why is an Implantable Cardioverter Defibrillator (ICD) required?
Causes of SCD

Out of hospital cardiac arrest survival: 8,1%

Gramley R et al , Eu r Car Rev, 2010

A 28 female sport teacher, recurrent syncope. Known to have been well
before. Admitted to ER due to malignant arrhythmia, normal
electrolytes

Torsades des Pointes

A 58 male with HFrEF, NYHA FC III, due to Ischemic
Cardiomyopathy. Echo: EF=28%

EKG: Non-sustained VT
What is the best strategy to prevent (recurrent) Sudden
Cardiac Death ?
 Prevention of Sudden Cardiac Death (SCD)

• Secondary Prevention : survivor of sudden cardiac arrest (aborted

sudden cardiac death) or fatal arrhythmia (VT/VF)

• Primary Prevention: individuals who are AT HIGH RISK for SCD

but not yet experience SCD

2017 AHA/ACC/HRS Guideline for management ventricular arrhythmia and the prevention of sudden
cardiac death Circulation. 2018;138:e272–e391.
Implantable Cardioverter Defibrillator (ICD)
“the implanted defibrillator system represents an imperfect
solution in search of a plausible and practical application.”
 Clinical Trials for SCD

• Non-ICD Trials: • ICD Trials

Secondary Prevention
EMIAT AVID
GESICA CIDS
CAMIAT CASH

Primary Prevention
MADIT
MADIT II
MUST
SCD-HeFT
COMPANION
Antiarrhythmics Versus Implantable Defibrillators
(AVID)

• Risk of SCD is lower in ICD arm versus

amiodarone (20% relative reduction)

• ICD: 4.3% absolute reduction in mortality

compared to drug therapy

AVID Investigators. N Engl J Med. 1997;337(22):1576-1583.

 CASH
(Cardiac Arrest Study Hamburg)

propafenone

• ICD : 23% (nonsignificant) reduction of all-cause

mortality rates compared with drug treatment
(amiodarone or metoprolol) SCD

• Cardiac arrest recurrence was lower with ICD

than with propafenone, again suggesting
proarrhythmia from Class I drug.

Siebels J. Am J Cardiol. 1993; 72:109F-113F.

 CIDS
Canadian Implantable Defibrillator Study

• Patient population: – Prior cardiac arrest, or

– Hemodynamically unstable
VT
• Study objective: To compare ICD therapy
against amiodarone in
patients with prior cardiac
arrest or hemodynamically
unstable VT
• Primary endpoint: Arrhythmic or other death within
30 days of initiating therapy
• Secondary endpoint: – All-cause mortality
– Non-fatal VT or VF

Connolly SJ. Am J Cardiol. 1993;72:103F-108F.

 CIDS
Canadian Implantable Defibrillator Study

• Risk of SCD is lower in ICD arm

versus amiodarone (20% relative
reduction)

• ICD: 4.3% absolute reduction in

mortality compared to drug therapy
 Summary of 20 Prevention Trials

Hazard ratio
Trial Name, Pub Year Other features

●
N = 1016
AVID Aborted cardiac arrest
1997 0.62

CASH
2000
N = 191
●
0.83
Aborted cardiac arrest

●
N = 659
CIDS Aborted cardiac arrest or
2000 0.82 syncope
p = 0.0023
Meta ● HR:0.73 (0.59,0.89)

0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8

ICD better
 Primary Prevention Trials:
MADIT/MUSTT/MADIT-II
Patient Inclusion Criteria MADIT1 MUSTT2 MADIT-II3

CAD/Post-MI X X X
Low LVEF X X X
(<35%) (<40%) (<30%)
NSVT X X
Inducible VT on EPS X X
Inducible, non-suppressible
VT on EPS X
1 Moss AJ. N Engl J Med. 1996;335:1933-40.
2 BuxtonAE. N Engl J Med. 1999;341:1882-90.
3 Moss AJ. N Engl J Med. 2002; 346:877-83.
 Results:
MADIT1 MUSTT2 MADIT-II3
MI, EF < 35%, NSVT, CAD, EF < 40%, NSVT, MI, EF < 30%
inducible VT at EPS, inducible VT at EPS
nonsuppressible with (95% MI Hx)
AA drug

196 pts: 704 randomized pts: 1232 pts:

101 Conv. Rx 353 no EP guided 60% ICD Rx
95 ICD Rx 352 EP guided: 40% Conv.Rx
190 AA drugs
161 ICDs

54% reduction in 55-60% reduction in 31% reduction in

mortality with ICD Rx mortality with ICD Rx mortality with ICD Rx
(27 months mean follow-up) (39 months mean follow- (20 months mean follow-
up) up)
1 Moss AJ. N Engl J Med. 1996;335:1933-40.
2 BuxtonAE. N Engl J Med. 1999;341:1882-90.
3 Moss AJ. N Engl J Med. 2002; 346:877-83.
 Major ICD Primary Prevention Trials:
Heart Failure (Ischemic and Non-ischemic)
Study MADIT II DEFINITE SCD HeFT
Sponsor Guidant St Jude MIH/Wyeth/Medtronic
Reported in NEJM Mar 2002 May 2004 Jan 2005
No of patients 1232 458 2521
Disease MI CM/CHF CHF
NYHA 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 ICD
1o end-point ACM ACM ACM
Study duration Jul 1997 – Nov 2001 July 1998 – June 2002 Sep 1997 – Jul 2001

Follow-up, months 20 29 45.5

 ICD Trials - Primary prophylaxis
MADIT I
ns VT MUSTT

DEFINITE

SCD-HeFT

DINAMIT

CAT

High risk
no VA MADIT II

CABG-Patch
LV-EF (%)
5 10 20 30 40
 ICD 10 Prevention Trial Results
Hazard Ratio
CABG-Patch
MUSTT
CAD, MI MADIT I
MADIT II
DINAMIT
CAD,
NICM SCD-HeFT
DEFINITE
NICM AMIOVIRT
CAT

0 0.5 1 1.5 2 2.5

ICD better No ICD better
 SCD-HeFT
(Sudden Cardiac Death in Heart Failure Trial)

COMPANION
(Comparison of Medical Therapy, Pacing, and
Defibrillation in Chronic Heart Failure)
(Cardiac Resynchronization Therapy (CRT-P/CRT-D)

Result: reduction of primary endpoint (combined all-cause

hospitalization and all-cause mortality) by 19% in both ICD
and Bivent + ICD arms
 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
 LV-function as predictor of SCD

risk MUSST, MADIT, MADIT-2, SCD-HeFT

DINAMIT, COMPANION, ………

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 (%)
PREVENTION OF SUDDEN CARDIAC DEATH
Etiology

1 Ischemic Heart Disease

2 Nonischemic Cardiomyopathy (NICM)

Hypertropic
3 Cardiomyopathy

4 Cardiac Chanelopathaties
 SECONDARY PREVENTION OF SUDDEN CARDIAC DEATH

1 Ischemic Heart Disease (IHD)

Secondary prevention in
pts with IHD

• SCA survivor due to VT/VF, SCA survivor*

or sustained
Cardiac syncope†

hemodynamically unstable VT or spontaneous

monomorphic VT*
stable VT not due to reversible LVEF≤35%
causes
Ischemia Yes No
• Patiet with IHD and unexplained warranting
revascularization ICD EP study
syncope who have inducible (Class I) (Class IIa)
sustained monomorphic VT Yes No

Revascularize Inducible
& reassess VT
SCD risk ICD candidate║
(Class I)
Yes No Yes No

ICD GDMT ICD Extended

(Class I) (Class I) (Class I) monitoring

2017 AHA/ACC/HRS Guideline for management ventricular arrhythmia and the prevention of sudden cardiac death Circulation.
2018;138:e272–e391.
 SECONDARY PREVENTION OF SUDDEN CARDIAC DEATH

2 Nonischemic Cardiomyopathy (NICM)

SCA survivor due to • Patient who • Cardiac arrest

VT/VF or experience experience syncope survivor, sustained
hemodynamically due to VA and who VT, or symptomatic
unstable VT or don’t meet VA
stable VT not due to indications for
reversible causes primary prevention
ICD

2017 AHA/ACC/HRS Guideline for management ventricular arrhythmia and the prevention of sudden cardiac death Circulation.
2018;138:e272–e391.
 Secondary and Primary Prevention of SCD in
Patients With NICM
Patients with NICM

SCA survivor/ NICM due to

Symptoms Class II-III
sustained VT LMNA mutation
No concerning No HF and No
(spontaneous/ and 2º risk
for VA LVEF ≤35%
inducible) factors

Yes Yes
Yes
Yes

Arrythmogenic ICD ICD

ICD candidate* candidate*
syncope
candidate*
suspected

Yes No, due to newly Yes

Yes No Yes Etiology uncertain diagnosed HF
(<3 mo GDMT)
ICD Amiodarone ICD EP Study ICD or not on optimal ICD
(Class I) (Class IIb) (Class IIa) (Class IIa) (Class I) GDMT (Class IIa)
If positive
If LVEF ≤35%
and WCD
Class II-III (Class IIb)
HF
Reassess
LVEF ≥3mo

Colors correspond to Class of Recommendation in Table 1.

*ICD candidacy as determined by functional status, life expectancy or patient preference.
2° indicates secondary; EP, electrophysiological; GDMT, guideline-directed management and therapy; HF,
heart failure; ICD, implantable cardioverter-defibrillator; LVEF, left ventricular ejection fraction; NICM,
nonischemic cardiomyopathy; SCA, sudden cardiac arrest; SCD, sudden cardiac death; VA, ventricular
arrhythmia; and WCD, wearable cardiac-defibrillator.
 3 Cardiomyopathy

Arrhythmogenic
Right Ventricular Hypertrophic
Cardiomyopathy Myocarditis Cardiac Sarcoidosis
Cardiomyopathy
(ARVC)
• Survivor SCA due to • VF or • Survivors SCA or have
VT/VF LVEF 35% or less
• Spontaneous
hemodynamical • LVEF > 35% with
• Resuscitated sustained VT ly unstable VT syncope and or
SCA • One or more following evidence of
• Sustained VT risk factors (Max LV myocardial scar by
cardiac MRI or PET
wall thickness ≥30mm,
• RVEF/LVEF SCD in 1 or more first- scan, and/or indication
<=35% degree relatives, 1 or for permanent pacing
more episodes implantation
• syncope unexplained syncope • LVEF >35% if
presumed due within the preceding 6 sustained VA is
to VA months). inducible
• spontaneous NSVT or
abnormal BP response
with exercise either
have or no have SCD
risk modifiers.

2017 AHA/ACC/HRS Guideline for management ventricular arrhythmia and the prevention of sudden cardiac death Circulation.
2018;138:e272–e391.
 4 Cardiac Chanelopathaties

Catecholaminergic
Congenital Long QT Early Repolarization “J-
Polymorphic Ventricular Short QT Syndrome
Syndrome wave” Syndrome
Tachycardia (CPVT)

• Ineffective or not • Recurrent sustained • Cardiac arrest or • Cardiac arrest or

tolerated with beta
blocker
• In asymptomatic
patients with long QT
syndrome and a
resting QTc greater
than 500 ms while
receiving a beta
blocker
VT or syncope with sustained VA sustained VA
adequate or max beta
blocker or
combination
medication therapy
• Spontaneous type 1
Brugada ECG,
cardiac arrest,
sustained VA or recent
unexplained syncope

2017 AHA/ACC/HRS Guideline for management ventricular arrhythmia and the prevention of sudden cardiac death Circulation.
2018;138:e272–e391.
 PRIMARY PREVENTION OF SUDDEN CARDIAC DEATH

1 Ischemic Heart Disease

• LVEF <= 35%, • LVEF <= 30%, • NSVT due to • Nonhospitalized

40 days post-MI 40 days’ post-MI prior MI, LVEF patients with
and 90 days and 90 days <= 40%, NYHA class IV
post post sustained VT or • Candidates for
revascularization revascularization VF cardiac
• NYHA class II or • NYHA class I HF transplantation
III HF despite despite GDMT or an LVAD
GDMT

2017 AHA/ACC/HRS Guideline for management ventricular arrhythmia and the prevention of sudden cardiac death Circulation.
2018;138:e272–e391.
 PRIMARY PREVENTION OF SUDDEN CARDIAC DEATH

2 Non Ischemic Cardiomyopathy (NICM)

• HF with NYHA class • HF with NYHA class • NICM due to a

II–III symptoms and I symptoms, LVEF of Lamin A/C mutation
an LVEF of 35% or 35% or less, despite who have 2 or more
less, despite GDMT GDMT risk factors (NSVT,
LVEF <45%, non
missense mutation,
and male sex)

2017 AHA/ACC/HRS Guideline for management ventricular arrhythmia and the prevention of sudden cardiac death Circulation.
2018;138:e272–e391.
How cost-effective is ICD ???
 Incremental Cost Effectiveness Analysis:
Cost per Life-Year Saved (U.S. $1,000)

Cost per Life-Year Saved (U.S. $1,000)

100 $91.5

Expensive
80

$57.3
60
Borderline
$44.3
Cost Effective
40
$28.4
Cost Effective $23.2
$18.2
20 $14.8
$10.2
Highly
Cost Effective 0
PTCA1 ICD1 CABG1 Hyper- Captopril1 Cardiac Peritoneal PTCA1
(Chronic (Chronic tension 2 (Post-MI, Transplant1 Dialysis2 (Chronic
CAD, CAD, (Mild, Men, EF  40%) (CHF) CAD,
Severe Mild Age 40) Mild
Angina, Angina, Angina,
2 VD) 3 VD) 1 VD, LAD)

1Kupersmith
J. Prog Cardiovasc Dis. 1995;37(5):307-346.
2Kuppermann M. Circulation. 1990; 81(1):91-100.
Number Needed to Treat to Save One Life
35

30 28
26
25 24
23
22
20
20

15
11
10 9

5 4
3

0
MUSTT MADIT MADIT-II AVID SAVE SOLVD CIBIS-II ISIS-2 Merit-HF 4S

(5 Yr) (2.4 Yr) (3 Yr) (3 Yr) (3 Yr) (4 Yr) (1 Yr) (2 Yr) (1 Yr) (6 Yr)

NNTx years = 100 / (%Mortality in Control Group – %Mortality in Treatment Group)

Increasing rate of ICD implantation in 2017 as compared with 2016

Total Implant in 2018: 92

Cipto Mangunkusumo Hospital Experience
CRT-D dan ICD (2015-2018)

Jumlah Pasien CRT-D dan ICD

(n=56)

9 (16.1%)

47 (83.9%)

CRT-D ICD
 CRT-D dan ICD

Proporsi Pasien CRT-D dan ICD

berdasarkan Jenis Kelamin
(n=56)
80

70
8.93% (5)
60

50 62.50% (35)

40

30
7.14% (4)
20
21.43% (12)
10

0
Laki-laki Perempuan
CRT-D ICD
CRT-D dan ICD

Keterangan :
Diketahui bahwa rerata usia pasien yang melakukan CRT-D
adalah 58 tahun dan ICD 53 tahun.
 Summary and Conclusions
• Sudden Cardiac Death : a major health problem

• Appropriate identification for secondary and primary prevention is

mandatory

• ICD has been an effective therapy for primary and secondary

prevention in various clinical setting
Matur Sembah Nuwun
 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
 Definition:

Sudden Cardiac Death (SCD):

-occurs within one hour of onset of symptoms in witnessed cases,
-within 24 hours of last being seen alive when it is unwitnessed.
Magnitude of problem

Worldwide incidence: 25% of total 17 millions

US annual SCD ; 180,000-300,0001

1 Adabag AS et al .Nat Rev Cardiol 2010;7:216–25. https://doi.org/10.1038/nrcardio.2010.3; PMID: 20142817.

CRT-D dan ICD

Proporsi Pasien Iskemik pada pasien yang

melakukan CRT-D dan ICD Keterangan :
100
Proporsi dari 56 pasien diketahui yang mengalami
Iskemik ada 33.9% (19 pasien) dan 66.1% (37 pasien)
90
Non Iskemik.
80

70

60 12.5% (7)

50

40

30 3.6 % (2)
53.6% (30)

20
30.3% (17)
10

0
Iskemik Non Iskemik

CRT-D ICD