Preventing Sudden Death Current & Future Role of ICD Therapy€¦ · Sudden death Epidemiology Risk quantification ICD Therapy in 2013 Indications Expectations Unanswered questions

Preventing Sudden Death

Current & Future Role of ICD Therapy

Canada

Research

Chairs

ACC – March 2013

Derek V Exner, MD, MPH, FRCPC, FACC, FAHA, FHRS

Professor, Libin Cardiovascular Institute of Alberta

Canada Research Chair, Cardiovascular Clinical Trials

Choose your

electrician wisely!

Consulting &

Honoraria

Boehringer Ingelheim, GE Healthcare,

Medtronic, Sanofi-Aventis, St Jude Medical

Speakers’ Bureau

Biotronik, Boston Scientific, GE Healthcare,

Medtronic, St Jude Medical

Equipment

donations

AudiCor, Cambridge Heart, GE Healthcare,

Roche Diagnostics, Sorin / ELA

Research

Support

Cambridge Heart, Heart Force Medical, GE

Healthcare, Medtronic, St Jude Medical

Investor Analytics4Life

Salary &

Grants

Alberta AET, CIHR, CRC, HSF Alberta, JC

Anderson Legacy Foundation, WED.

Derek V. Exner - Disclosures

March 2013

Overview

Sudden death

Epidemiology

Risk quantification

ICD Therapy in 2013

Indications

Expectations

Unanswered questions

March 2013

Sudden Death / Sudden Cardiac Arrest

Cardiovascular death < 1 hour of symptoms

March 2013

More deaths than others combined

Magnitude

0

100,000

200,000

300,000

400,000

500,000

Deat

hs p

er y

ear

Breast Lung Stroke Sudden Cancer Cancer Death

March 2013

What Proportion of Sudden Deaths are Arrhythmic?

1. 20%

2. 40%

3. 60%

4. 80%

Sudden Death: Diverse Mechanisms

VF

Rapid

VT

Brady/EM

D

Other

Am J Cardiol 1989;117:151-9

Ambulatory

VT/VF Brady/EMD

Circulation 1989;80:1675-80

Awaiting Transplant

March 2013

Population Subgroups

Rea AJC 2004;93:1455-60.

0 25 50 75

HeartFailure

Prior MI

Population Attributable Risk

% of events (prevalence)

Individual risk (incidence)

0% 25% 50% 75%

March 2013

Who is Indicated for an ICD?

1. Prior cardiac arrest / sustained VT

2. CAD & EF < 35%

3. CAD & EF < 30%

4. 1 & 2

5. 1 & 3

0.2 0.5 1 2

Odds ratio(95% confidence interval)

0.59 (0.43, 0.81)AVID (n = 1,016) 8.2%

CIDS (n = 659) 0.81 (0.57, 1.14) 4.3%

CASH (n = 288) 0.71 (0.43, 1.18) 8.1%

MADIT I (n = 196) 0.30 (0.15, 0.59) 22.8%

CABG-Patch (n = 900) 1.11 (0.81, 1.52)

MUSTT (n = 514) 0.34 (0.22, 0.53) 23.0%

MADIT II (n = 1,232) 0.68 (0.50, 0.92) 5.4%

AMIOVIRT (n = 103) 0.86 (0.27, 2.75) 1.7%

CAT (n = 104) 0.76 (0.33, 1.80) 5.4%

COMPANION (n = 903) 0.64 (0.46, 0.90) 7.3%

SCD-HEFT (n = 1,676) 0.70 (0.56, 0.87) 6.8%

DEFINITE (n = 458) 0.66 (0.39, 1.11) 5.2%

DINAMIT (n = 674) 1.12 (0.76, 1.67)

Overall 0.72 (0.60, 0.86)

Favors ICD

MortalityReduction

Spontaneous or InducibleVentricular Arrhythmias

Heart Failure or LVDysfunction Alone

LV dysfunction inSpecific Circumstances

Risk Groups

BEST-ICD (n = 138) 1.17 (0.39, 3.48)

IRIS (n = 898) 1.01 (0.75, 1.36)

Exner Randomized Trials of ICD Therapy 2011 March 2013

Recommend for history of

hemodynamically significant or

sustained ventricular arrhythmia

(secondary prevention).

For ALL:

Strong

Recommendation

High Quality

Evidence

Consider for primary prevention:

i. Ischemic LVD, NYHA II-III, EF ≤

35%, measured > 1 m post MI, & >

3 m post revascularization ;

ii. Ischemic LVD, NYHA class I, & EF

≤ 30% > 1 m post MI, & < 3 m post

revascularization ;

iii. Nonischemic LVD, NYHA class II-III,

EF ≤ 35%, measured > 9 m after

optimal medical therapy.

Recommendations - Chronic Heart Failure Implantable cardioverter-defibrillator (ICD)

Primary Prevention ICD Therapy Use Is:

1. Too High

2. About Right

3. To Low

ON

152

AB

120

Atlantic 186

QC

170 SK

105

MB

185 BC

122

Territories 125

New ICD Implants per Million

Crysler Industry Data 2010 March 2013

Regarding My Enthusiasm for Primary Prevention ICD Therapy:

1. I am keen

2. I am not keen due to the risk of

shocks

3. I am not keen due to an inability

to predict who will benefit

4. I am not keen due to the risk of

long-term complications (leads,

redo procedures)

5. I am not keen due to poor

accessibility

0

25

50

75

100

Pro

port

ion (

%)

Relying Solely On Low LVEF

Most Identified Are Not At High

Risk

Fails to Identify Most of Those

at Risk

Exner. Curr Opin Cardiol 2009, 24:61–7 March 2013

Clinical Risk Stratification: MADIT II

Predictors of ICD benefit

• age > 70,

• NYHA 3 or 4,

• Elevated urea

(> 26 mg/dl /

(> 9.3 mmol/ L)

• QRSd > 120 ms,

• Atrial fibrillation.

Goldenberg et al., JACC 2008;51:288-96

None of the 5 risk factors

(n = 345; 31%)

HR for ICD therapy 0.96

(95% CI 0.44, 2.07); p = 0.91

> 1 risk factor (n = 786; 69%)

HR for ICD therapy 0.51

(95% CI 0.37, 0.70); p < 0.001

March 2013

Based on data from SCD-HeFT, over the initial 5 years, patients receiving a primary prevention ICD

should expect ?

1. 10% risk of shocks;

95% for VT/VF


80% for VT/VF


65% for VT/VF


50% for VT/VF

Shocks: Necessary & Appropriate ?

VT / VF 65%

OS 12% SVT

20% NSVT 3%

Poole et al. N Engl J Med 2008;359:1009-17

- 1 in 3 ICD recipients

in SCD-HeFT

received shocks

- Inappropriate

2-fold higher

risk of death

- Appropriate

5-fold higher

risk of death

March 2013

Shock Reduction Algorithms

Time to Development of Shocks for VT/VF

Time to Development of Inappropriate Shocks

Reduced from 30.7% to 26.1%

Reduced from 23.5% to 8.4%

99.2% of all VT/VF episodes detected without delay

Volosin, Exner, et al. JCE 2011;22:280-9 March 2013

Range of NID Settings

Original NID = 18/24 Virtual ICD NID = 18/24 NID = 24/32 NID = 30/40

Time to Development of Inappropriate shocks

March 2013 Volosin, Exner, et al. JCE 2011;22:280-9

MADIT-RIT: Shock Reduction

NEJM 2012;367(24):2275-83 March 2013

~ 80% reduction in

inappropriate ICD

therapies

MADIT-RIT: Reduced Mortality

NEJM 2012;367(24):2275-83 March 2013

~ 50% reduction in mortality

(6.6% vs. 3.2%)

ICD Therapy: Recent MI

Exner Randomized Trials of ICD Therapy 2011

0.2 0.5 1 2


0.59 (0.43, 0.81)AVID (n = 1,016) 8.2%

CIDS (n = 659) 0.81 (0.57, 1.14) 4.3%

CASH (n = 288) 0.71 (0.43, 1.18) 8.1%

MADIT I (n = 196) 0.30 (0.15, 0.59) 22.8%

CABG-Patch (n = 900) 1.11 (0.81, 1.52)

MUSTT (n = 514) 0.34 (0.22, 0.53) 23.0%

MADIT II (n = 1,232) 0.68 (0.50, 0.92) 5.4%

AMIOVIRT (n = 103) 0.86 (0.27, 2.75) 1.7%

CAT (n = 104) 0.76 (0.33, 1.80) 5.4%

COMPANION (n = 903) 0.64 (0.46, 0.90) 7.3%

SCD-HEFT (n = 1,676) 0.70 (0.56, 0.87) 6.8%

DEFINITE (n = 458) 0.66 (0.39, 1.11) 5.2%

DINAMIT (n = 674) 1.12 (0.76, 1.67)

Overall 0.72 (0.60, 0.86)

Favors ICD

MortalityReduction




Risk Groups

BEST-ICD (n = 138) 1.17 (0.39, 3.48)

IRIS (n = 898) 1.01 (0.75, 1.36)

0.2 0.5 1 2


0.59 (0.43, 0.81)AVID (n = 1,016) 8.2%

CIDS (n = 659) 0.81 (0.57, 1.14) 4.3%

CASH (n = 288) 0.71 (0.43, 1.18) 8.1%

MADIT I (n = 196) 0.30 (0.15, 0.59) 22.8%

CABG-Patch (n = 900) 1.11 (0.81, 1.52)

MUSTT (n = 514) 0.34 (0.22, 0.53) 23.0%

MADIT II (n = 1,232) 0.68 (0.50, 0.92) 5.4%

AMIOVIRT (n = 103) 0.86 (0.27, 2.75) 1.7%

CAT (n = 104) 0.76 (0.33, 1.80) 5.4%

COMPANION (n = 903) 0.64 (0.46, 0.90) 7.3%

SCD-HEFT (n = 1,676) 0.70 (0.56, 0.87) 6.8%

DEFINITE (n = 458) 0.66 (0.39, 1.11) 5.2%

DINAMIT (n = 674) 1.12 (0.76, 1.67)

Overall 0.72 (0.60, 0.86)

Favors ICD

MortalityReduction




Risk Groups

BEST-ICD (n = 138) 1.17 (0.39, 3.48)

IRIS (n = 898) 1.01 (0.75, 1.36)

0.2 0.5 1 2


0.59 (0.43, 0.81)AVID (n = 1,016) 8.2%

CIDS (n = 659) 0.81 (0.57, 1.14) 4.3%

CASH (n = 288) 0.71 (0.43, 1.18) 8.1%

MADIT I (n = 196) 0.30 (0.15, 0.59) 22.8%

CABG-Patch (n = 900) 1.11 (0.81, 1.52)

MUSTT (n = 514) 0.34 (0.22, 0.53) 23.0%

MADIT II (n = 1,232) 0.68 (0.50, 0.92) 5.4%

AMIOVIRT (n = 103) 0.86 (0.27, 2.75) 1.7%

CAT (n = 104) 0.76 (0.33, 1.80) 5.4%

COMPANION (n = 903) 0.64 (0.46, 0.90) 7.3%

SCD-HEFT (n = 1,676) 0.70 (0.56, 0.87) 6.8%

DEFINITE (n = 458) 0.66 (0.39, 1.11) 5.2%

DINAMIT (n = 674) 1.12 (0.76, 1.67)

Overall 0.72 (0.60, 0.86)

Favors ICD

MortalityReduction




Risk Groups

BEST-ICD (n = 138) 1.17 (0.39, 3.48)

IRIS (n = 898) 1.01 (0.75, 1.36)

0.2 0.5 1 2


0.59 (0.43, 0.81)AVID (n = 1,016) 8.2%

CIDS (n = 659) 0.81 (0.57, 1.14) 4.3%

CASH (n = 288) 0.71 (0.43, 1.18) 8.1%

MADIT I (n = 196) 0.30 (0.15, 0.59) 22.8%

CABG-Patch (n = 900) 1.11 (0.81, 1.52)

MUSTT (n = 514) 0.34 (0.22, 0.53) 23.0%

MADIT II (n = 1,232) 0.68 (0.50, 0.92) 5.4%

AMIOVIRT (n = 103) 0.86 (0.27, 2.75) 1.7%

CAT (n = 104) 0.76 (0.33, 1.80) 5.4%

COMPANION (n = 903) 0.64 (0.46, 0.90) 7.3%

SCD-HEFT (n = 1,676) 0.70 (0.56, 0.87) 6.8%

DEFINITE (n = 458) 0.66 (0.39, 1.11) 5.2%

DINAMIT (n = 674) 1.12 (0.76, 1.67)

Overall 0.72 (0.60, 0.86)

Favors ICD

MortalityReduction




Risk Groups

BEST-ICD (n = 138) 1.17 (0.39, 3.48)

IRIS (n = 898) 1.01 (0.75, 1.36)

0.20.512

Oddsratio(95%confidenceinterval)

0.59(0.43,0.81) AVID(n=1,016)8.2%

CIDS(n=659)0.81(0.57,1.14)4.3%

CASH(n=288)0.71(0.43,1.18)8.1%

MADITI(n=196)0.30(0.15,0.59)22.8%

CABG-Patch(n=900)1.11(0.81,1.52)

MUSTT(n=514)0.34(0.22,0.53)23.0%

MADITII(n=1,232)0.68(0.50,0.92)5.4%

AMIOVIRT(n=103)0.86(0.27,2.75)1.7%

CAT(n=104)0.76(0.33,1.80)5.4%

COMPANION(n=903)0.64(0.46,0.90)7.3%

SCD-HEFT(n=1,676)0.70(0.56,0.87)6.8%

DEFINITE(n=458)0.66(0.39,1.11)5.2%

DINAMIT(n=674)1.12(0.76,1.67)

Overall0.72(0.60,0.86)

FavorsICD

MortalityReduction

SpontaneousorInducibleVentricularArrhythmias

HeartFailureorLVDysfunctionAlone

LVdysfunctioninSpecificCircumstances

RiskGroups

BEST-ICD(n=138)1.17(0.39,3.48)

IRIS(n=898)1.01(0.75,1.36)

March 2013

Use of ICD Therapy Early After MI

Hohnloser et al, NEJM 2004;351:2481-8.

DINAMIT

• N = 674

• EF < 0.35 (6-40 d post-MI)

• Impaired HR variability

Steinbeck et al, NEJM 2009;361:1427-36.

IRIS

• N = 898

• EF < 0.40 (5-31 d post-MI)

• Elevated HR +/- NSVT

Hohnloser. NEJM 2004;351:2481-8. Steinbeck. NEJM 2009;361:1427-36.

March 2013

Hohnloser. NEJM 2004;351:2481-8. Steinbeck. NEJM 2009;361:1427-36.

DINAMIT IRIS

March 2013

Development of a Cardiac Arrest

Moss & Zareba J Electrocardiol 2003;36:101-8

Autonomic Nervous System

Underlying Fixed

Substrate

Dynamic Substrate

March 2013

Holter, Modified Moving Average TWA

J Appl Physiol 2002;92:541-9 J Am Coll Cardiol 2011;58;1309-24 March 2013

Heart Rate Turbulence (HRT)

# of RR interval

RR

inte

rval

(m

s)

PVC

Schmidt et al. Lancet 1999;353:1390-6. Bauer et al. JACC 2008;52:1353-65.

Reflex response to perturbation

1 291 pts (post-MI)

Holter < 14 d

> 3-fold higher risk of death (indep’t)

Validation in multiple studies.

Consistent utility.

March 2013

HRT onset

HRTslope

# of RR interval

RR

inte

rval

(m

s)

PVC

Heart Rate Turbulence (HRT)

Reflex response to perturbation

1 291 pts (post-MI)

Holter < 14 d

> 3-fold higher risk of death (indep’t)

Validation in multiple studies.

Consistent utility.

Schmidt et al. Lancet 1999;353:1390-6. Bauer et al. JACC 2008;52:1353-65. March 2013

Combined Parameter Assessment

Cardiac Death or Cardiac Arrest

Remaining

HRT + TWA & EF < 0.50

322 post-MI patients serial assessment (2-4 & 10-14 weeks) Later testing more accurate

6-fold higher risk with abnormal HRT + TWA

Sensitivity: 55%

Positive PV: 27%

Negative PV: 96%

Exner et al. JACC 2007;50:2275-84. March 2013

Risk Estimation Following Infarction Noninvasive Evaluation: ICD efficacy

EF 0.36 to 0.50

2-15 mo. post-MI

> 3 mo. post-revasc.

< 80 years & without

dialysis, perm AF or AAD

Holter

Abnormal

TWA + HRT

Registry

Usual Care Alone

Usual Care + ICD

Minimum follow-up: 2 years

Mean follow-up: 5 years

1° outcome: mortality

2° outcomes: cost & QoL

March 2013

Summary

March 2013

Sudden death remains an important issue

Post-MI patients are at risk

EF alone is a poor discriminator

The recommendations for ICD therapy are

based on many large randomized trials

Clinical risk scores exist to maximize

benefit

Shock reduction is here to stay

Unanswered questions persist (post-MI)

Documents

Preventing Sudden Death Current & Future Role of ICD Therapy€¦ · Sudden death Epidemiology Risk quantification ICD Therapy in 2013 Indications Expectations Unanswered questions