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Cardiac
Resynchronization
and Defibrillation
Therapies:
Complementary Approaches
to the Management
of Heart Failure
Ventricular
Resynchronization
Pathophysiology and
Identification of Responders
Mechanisms of Dysfunction Due
to Contractile Discoordination
 Reduced ejection volume
– Internal sloshing of cavitary blood volume from prematurely activated
region to late-activated one
– Increased end-systolic volume (stress)
 Mechano-energetic inefficiency
– Reduced systolic function despite maintained or increased
energetic expenditure
 Late systolic stretch
– Cross-bridge detachment, reduced contractility
– Delayed relaxation
– After-contraction/arrhythmia
 Mitral valve dysfunction
– Papillary muscle discoordination
Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13.
Impact of Mechanical Dyssynchrony
MRI-Tagged 3-D Cine-Imaging
A
Adapted from Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13.
Adapted from Leclercq C, et al. Circulation. 2001;106:1760-1763.
Disparities in Regional Workload
Resulting From Dyssynchrony
Early Activated
20
Late Activated
20
Fiber Stress
Fiber Stress
Area = Regional Work
0
0
-0.1
0.0
0.1
Fiber Strain
Regional Blood Flow
Glucose Metabolism
Adapted from Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13.
-0.1
0.0
0.1
Discoordinate Motion
Adverse Effects on Global Function From RV-Pacing–Induced Dyssynchrony
Normal Sinus Rhythm
Acute Dyssynchrony (RV Pace)
LV Pressure (mm Hg)
80
40
0
30
60
LV Volume (mL)
Adapted from Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13.
90
Do We Resynchronize
With Biventricular
or Left Ventricular Pacing?
CRT Enhances Cardiac
Mechano-Energetic Efficiency
.24
*P< 0.01
†P< 0.05
Mean ±SEM
P< 0.05
Change (%)
40
*
20
†
†
0
-20
MVO2/HR
(Relative Units)
*
LV pacing
Dobutamine
.22
.20
.18
.16
dP/dtmax
PP
Mean
CorF
AVO2
MVO2
.14
500
600 700
dP/dtmax
Adapted from Nelson GS, et al. Circulation. 2000;102:3053-3059.
800
900 1000
(mm Hg)
Single-Site LV Pacing
Works Just as Well
LV Free Wall per
Circulation
Biventricular
120
LV Pressure (mm Hg)
LV Pressure (mm Hg)
120
80
40
0
80
40
0
0
100
200
300
LV Volume (mL)
Adapted from Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13.
0
100
200
LV Volume (mL)
300
Regional Wall Motion With CRT
Regional Fractional Area Change
Septum
0
Adapted from Kawaguchi M, et al. J Am Coll Cardiol. 2002;39:2052-2058.
0.4
Lateral
0
Adapted from Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13.
Seconds
Seconds
Pacing Off
Pacing On
0.4
Global Chamber Effects of CRT:
Acute Human Studies
Pacing ON
Pacing OFF
LVP AOP dP/dt
2-Min Steady State
-841.0
114.0
54.7
113.0
0.4
1151.0
2.8
5.6
8.4
Seconds
50.8
113.0
1.0
1151.0
0.0
2.5
5.0
7.5
Seconds
120
80
40
0
0
Adapted from Kass DA. Rev Cardiovasc Med.
2003;4(suppl 2):S3-S13.
-727.0
114.0
870.0
11.2
LV Pressure (mm Hg)
0.0
1120.0
LVP AOP dP/dt
1193.0
100
200
LV Volume (mL)
300
10.0
865.0
Ventricular Reverse Remodeling
With Resynchronization
P<0.001
P<0.001
Ejection Fraction (%)
End-Diastolic Dimension (mm)
7.5
6.5
30
20
6.0
10
Placebo
n=63
Control
CRT
n=61
6-month
Placebo
n=81
CRT
Adapted from Abraham WT, et al. N Engl J Med. 2002;346:1845-1853.
CRT 6-month
CRT
n=63
How Important Are Pacing
Site, Atrioventricular Delay,
and Ventricular to
Ventricular Delay?
AV Interval Optimization
LV
BV
12
8
4
0
1
-4
-8
AV delay
(0 to PR – 30 msec)
Adapted from Auricchio A, et al. Circulation. 1999;99:2993-3001.
24
Change in dP/dtmax (%)
Change in Aortic PP (%)
16
LV
BV
18
12
6
0
1
-6
-12
AV delay
(0 to PR – 30 msec)
Synchronous vs Non-Synchronous BV
Pacing: Is RV-LV Delay Important?
Systolic Function (Echo Index)
6
*
*
5
4
3
2
1
RV Preactivation
0
* P<0.01 vs. Simultaneous (s)
Sogaard P, et al. Circulation. 2002;106:2078-2084.
S
LV Preactivation
Can We Predict Responders?
 Wide QRS complex
– Widely used, but only broadly correlates with acute response
– Weak predictor of chronic response
 Mechanical dyssynchrony
– More direct target of CRT
– Measures of wall dyssynchrony (MRI, ECHO, TDI) best
correlate with acute and chronic responsiveness
 Basal dysfunction
– Low contractile state and marked P-R delay are likely additional
features of responders
Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13.
QRS as a Predictor of Response
QRS duration is only weakly
correlated with acute
improvement1,2
100
r =0.51
Change in dP/dtmax
(%)
Change in dP/dtmax
(%)
60
40
20
0
100
However, change in QRS duration
does not correlate with acute
improvement2
150
200
250
Surface QRS (msec)
1. Adapted from Auricchio A, et al. Circulation. 1999;99:2993-3001.
2. Nelson GS, et al. Circulation. 2000;101:2703-2709.
75
50
25
0
-25
-50
-30
-10 0
10
30
% D QRS (msec)
50
More Direct Methods
to Assess Dyssynchrony
 Interventricular delay
– RV/LV pressure plot (area in loop)
– Interventricular delay
– QRS onset-pulmonary flow onset – QRS onset-aortic
flow onset >25 msec
 Intraventricular delay
–
–
–
–
–
Strain rate TDI
M-mode ECHO
Echo contrast analysis
QRS onset-end lateral wall contraction >290 msec
QRS onset-end lateral wall contraction >QRS onset-mitral
E-wave onset
Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13.
M-mode Echo Assessment
for Predicting Responders
+20
r =-.70
P=.001
D LVESVI (mL/m2)
0
-20
-40
-60
-80
-100
D 20
60
140
220
300
SPWMD (msec)
Adapted from Pitzalis MV, et al. J Am Coll Cardiol. 2002;40:1615-1622.
380
TDI Assessment
for Predicting Responders
80
Change in LVEF (%)
60
40
20
0
20
40
60
-20
-40
Adapted from Sogaard P, et al. J Am Coll Cardiol. 2002;40:723-730.
Percentage of LV Base With DLC
80
Potential Causes
for Lack of Response
 Poor lead placement
– Site matters; lateral placement is usually better
 Improper setting of AV delay
– Loss of preexcitation; suboptimal atrial filling,
exacerbation of mitral regurgitation
 Infarcted underlying substrate
– Cannot be stimulated and thus cannot be
resynchronized
Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13.
Summary
 Cardiac dyssynchrony reduces net systolic function and
energetic efficiency, inducing marked regional heterogeneity
of wall stress and molecular signaling
 CRT is most effective if targeted to hearts with discoordinate
contraction, rather than QRS widening
 In appropriate patients, improvement in systolic function
and energetics from CRT can be marked
 Defining intraventricular mechanical dyssynchrony
seems at present to be the most reliable variable for
predicting responders—but more work is needed to define
the most reliable dyssynchrony measurement and test its
prospective utility
Pathophysiology
of Congestive
Heart Failure
Heart Failure
Heart failure is a clinical syndrome (ie, there are
signs and symptoms) characterized in most
patients by dyspnea and fatigue at rest and/or
with exertion caused by underlying structural
and/or functional heart disease
Francis GS, Tang WH. Rev Cardiovasc Med. 2003;4(suppl 2):S14-20.
Congestive Heart Failure
Scope of the Problem
 Nearly 900,000 annual hospital admissions
(increased 90% in past 10 years)1
 Most common discharge diagnosis for patients older
than 65 years2
 6.5 million hospital days per year1
 Single largest expense for Medicare1
 Annual hospital/nursing home costs: $15.4 billion3
1. Hunt SA, et al. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult. 2001.
2. Graves EJ, Gillum BS. 1994 Summary: National Hospital Discharge Survey. National Center for Health Statistics; 1996.
3. AHA. 2002 Heart and Stroke Statistical Update; 2001.
Heart Failure
Hospitalizations
The Number of Heart Failure Hospitalizations Is Increasing
in Both Men and Women
Annual Discharges
600,000
500,000
400,000
300,000
200,000
Women
Men
100,000
0
'79
'81
'83
'85
'87
'89
Year
CDC/NCHS: hospital discharges include patients both living and dead.
AHA. 2002 Heart and Stroke Statistical Update. 2001.
'91
'93
'95
'97
'99
Diagnosis of CHF:
Clinical Challenge
 Signs and symptoms of heart failure, such
as shortness of breath and edema, have a broad
differential diagnosis1
 Chest x-ray findings have limited accuracy
for CHF1
 20% to 40% of patients with CHF have normal
systolic function2
1. Dao Q, et al. J Am Coll Cardiol. 2001;37:379-385.
2. Hunt SA, et al. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult; 2001.
New York Heart Association
Functional Classification
Functional Class
Patient Limitations
Class I
 None
 Ordinary physical activity does not cause
undue fatigue, palpitation, dyspnea, or
anginal pain
 Often were previously symptomatic but
are now in a well-compensated state
Class II
 Slight
 Patient comfortable at rest
 Ordinary physical activity results in
fatigue, shortness of breath, palpitations,
or angina
The Criteria Committee of the NYHA. Diseases of the Heart and Blood Vessels: Nomenclature and Criteria for
Diagnosis. 6th ed. 1964.
New York Heart Association
Functional Classification
Functional Class
Patient Limitations
Class III
 Marked
 Patient is comfortable at rest
 Less than ordinary activity leads
to symptoms
Class IV
 Severe
 Inability to carry on physical
activity without symptoms
 Patient is symptomatic at rest
 Any physical activity increases
symptoms
The Criteria Committee of the NYHA. Diseases of the Heart and Blood Vessels: Nomenclature and Criteria for
Diagnosis. 6th ed. 1964.
ACC/AHA Stages of Heart Failure:
Stages A and B
Stage A
Patients at high risk of developing heart failure as a result of the
presence of conditions that are strongly associated with the development
of heart failure. These patients do not have any identified structural or
functional abnormalities of the pericardium, myocardium, or cardiac
valves and have never shown signs or symptoms of heart failure
Stage B
Patients who have developed structural heart disease that is strongly
associated with the development of heart failure but who have never
shown signs or symptoms of heart failure
Hunt SA, et al. J Am Coll Cardiol. 2001;38:2101-2113.
ACC/AHA Stages of Heart Failure:
Stages C and D
Stage C
Patients who have current or prior symptoms of heart failure
associated with underlying structural heart disease
Stage D
Patients who have advanced structural heart disease and
marked symptoms of heart failure at rest despite maximal
medical therapy and who require specialized interventions
Hunt SA, et al. J Am Coll Cardiol. 2001;38:2101-2113.
Heart Failure
Pathophysiology
 Etiology of heart failure includes1-5:
– Structural changes such as loss of myofilaments
– Disorganization of the cytoskeleton
– Apoptosis and necrosis
– Changes in heart size and shape (remodeling)
– Disturbances in Ca2+ homeostasis
– Alterations in receptor density and coupling to G-proteins
– Alterations in G-proteins
1.
2.
3.
4.
5.
Francis GS, Tang WH. Rev Cardiovasc Med. 2003;4(suppl 2):S14-20.
Francis GS. Am J Med. 2001;110(suppl 7A):37S-46S.
Shah M, et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2-S6.
Ceconi C, et al. Rev Port Cardiol. 1998;17(suppl 2):1179-1191.
Mann DL. Circulation. 1999;100:999-1008.
Heart Failure
Pathophysiology
 Etiology of heart failure includes1-7:
– Alterations in signal transduction pathways
– Switch to fetal gene programs—increase -myosin heavy chain,
decrease -myosin heavy chain, increase ANP, increase BNP
– Increase collagen synthesis, increase matrix
metalloproteinases
– Na+ and water retention
– Reflex control disturbances
– Myocyte hypertrophy
– Altered myocardial energetics
1.
2.
3.
4.
5.
6.
7.
Katz AM. Med Clin North Am. 2003;87:303-316.
Francis GS. Am J Med. 2001;110(suppl 7A):37S-46S.
Iwanaga Y, et al. J Am Coll Cardiol. 2000;36:635-642.
Francis GS, Tang WH. Rev Cardiovasc Med. 2003;4(suppl 2):S14-S20.
Shah M, et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2-S6.
Wilson EM, et al. J Card Fail. 2002;8:390-398.
Jugdutt BI. Curr Drug Targets Cardiovasc Haematol Disord. 2003;3:1-30.
Heart Failure
Pathophysiology
Fall in LV Performance
Myocardial Injury
Activation of RAAS, SNS, ET,
and Others
ANP
BNP
Myocardial Toxicity
Morbidity and Mortality
Peripheral Vasoconstriction
Hemodynamic Alterations
Remodeling and
Progressive
Worsening of
LV Function
Shah M, et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2-S6.
Heart Failure Symptoms
Heart Failure
Left Ventricular Dysfunction
 Mechanisms by which elevated LV filling pressure could
contribute to mortality in HF include1-3:
– Stretch-induced angiotensin II release
– Mechanically induced myocardial structural remodeling
– Progressive atrioventricular valvular regurgitation
– Myocardial stretch-induced increase in intracellular cAMP
and calcium
– Decrease in vagal activity secondary to stretching of cardiac
mechanoreceptors
1. Leri A, et al. J Clin Invest. 1998;101:1326-1342.
2. Fonarow GC. Rev Cardiovasc Med. 2001;2(suppl 2):S7-S12.
3. Cerati D, Schwartz PJ. Circ Res. 1991;69:1389-1401.
Heart Failure
Left Ventricular Dysfunction
 Changes associated with LVAD bridge to transplant
experience 1990s1-4:
– Decrease in chamber size
– Enhanced -adrenergic response
– Reversal of defects in sarcoplasmic reticulum (SR)
Ca2+ cycling
– Normalization of gene expression
– Normalization of neurohormones and cytokines
1.
2.
3.
4.
Mann DL, Willerson JT. Circulation. 1998;98:2367-2369.
Heerdt PM, et al. Circulation. 2000;102:2713-2719.
Ogletree-Hughes ML, et al. Circulation. 2001;104:881-886.
McCarthy PM, Hoercher K. Prog Cardiovasc Dis. 2000;43:37-46.
Heart Failure
Left Ventricular Dysfunction
 Transition from LV dysfunction to HF1-3:
– Cell dropout (apoptosis)
– Myocyte elongation, hypertrophy
– Myocyte slippage
1. Mann DL. Circulation. 1999;100:999-1008.
2. Francis GS. Am J Med. 2001;110(suppl 7A):37S-46S.
3. D'Armiento J. Trends Cardiovasc Med. 2002;12:97-101.
Effects of Resynchronization
on LV Performance
225
Left Ventricular Volume (mL)
45
200
40
175
35
150
30
125
25
100
Baseline 1wk
Ejection Fraction (%)
1mo
3mo
offimmed
1000
off1wk
20
Baseline 1wk
off4wk
1mo
dP/dtmax (mm/Hg/sec)
900
800
700
600
500
400
Baseline
Yu CM, et al. Circulation. 2002;105:438-445.
1wk
1mo
3mo
offimmed
off1wk
off4wk
3mo
offimmed
off1wk
off4wk
Effects of Resynchronization
on LV Performance
Mitral Regurgitation (%)
40
Left Ventricular Filling Time (msec)
500
35
450
30
400
25
350
20
300
15
10
Baseline 1wk 1mo
250
offoff3mo
immed 1wk
off4wk
Isovolumetric Contraction Time (ms)
160
150
140
130
120
110
100
90
80
70
60
50
Baseline 1wk 1mo
3mo
Yu CM, et al. Circulation. 2002;105:438-445.
Baseline
offimmed
1wk
off1wk
1mo
off4wk
3mo
offimmed
off1wk
off4wk
Summary
 Heart failure is a major medical and economic burden that is
growing in incidence with the aging of America
 The pathogenesis of heart failure begins with an index event and is
characterized by progressive remodeling of the heart
 Neurohormones are an important part of the pathogenesis of heart
failure; only those drugs that inhibit the RAAS and SNS have been
shown to slow or reverse remodeling and improve survival
 Devices also can reverse the remodeling process and improve
survival
 Device placement will likely complement pharmacologic therapies
in the HF patient with dyssynchrony
Device Selection:
CRT Alone Versus
CRT Plus Implantable
Cardioverter Defibrillator
(ICD)
Risk-Stratification for Sudden
Cardiac Death
Arrhythmia
PVCs; VT-NS
VT-S; VF
PVCs
VT-NS
Heart Disease
Absent
LV Dysfunction
Absent
Potential Risks for
SCD
Minimal
Present
Absent
Present
Intermediate
PVC=premature ventricular complexes; VT-NS=nonsignificant ventricular tachycardia;
VT-S=significant ventricular tachycardia; VF=ventricular fibrillation.
Prystowsky EN. Am J Cardiol. 1988;61:102A-107A.
Present
Present
High
CAST: Survival
100
Placebo (N=725)
Survival (%)
95
90
Encainide or flecainide
(N=730)
85
P=0.0003
0
50
100
150
200
250
300
350
Days After Randomization
CAST Investigators. N Engl J Med. 1989;321:406-412.
400
450
500
Ejection fraction 31%-40%
Ejection fraction < 30%
Months Since Randomization
Julian DG, et al. Lancet. 1997;349:667-674.
Probability of Survival
Probability of Survival
EMIAT: All-Cause Mortality
LVEF and by Group
Amiodarone
Placebo
Months Since Randomization
Amiodarone
P=0.072
Months Since Randomization
Cairns JA, et al. Lancet. 1997;349:675-682.
Cumulative Risk (%)
Cumulative Risk (%)
CAMIAT: All-Cause Mortality
and Nonarrhythmic Death
Placebo
P=0.130
Months Since Randomization
Mortality Reduction w/ICD Rx (%)
Primary Prevention Post-MI Trials
80
70
60
55
54
50
40
31
30
20
10
0
MUSTT1
27 Months
1. Buxton AE, et al. N Engl J Med. 1999;341:1882-1890.
2. Moss AJ, et al. N Engl J Med. 1996;335:1933-1940.
3. Moss AJ, et al. N Engl J Med. 2002;346:877-882.
MADIT2
27 Months
MADIT-II3
20 Months
MUSTT and MADIT: Overview
MUSTT
(N=704)
MADIT
(N=196)
Mean time (MI to enrollment)
39 mos
27 mos
% Prior CABG or PTCA
66%
71%
LVEF (mean)
30%
26%
5
9
% Beta-blocker at discharge
40%
18%
Class II-III (% patients)
64%
65%
VT-NS (mean beats)
Adapted from Prystowsky EN. Am J Cardiol. 2000;86(Suppl 1):K34-K39.
MUSTT Study
 Hypothesis: Antiarrhythmic therapy guided
by EP testing can reduce the risk of
arrhythmic death and cardiac arrest in
patients with:
– Coronary artery disease
– LVEF <40%
– Nonsustained VT
(3 beats – 30 sec; rate >100 bpm)
Buxton AE, et al. N Engl J Med. 1999;341:1882-1890.
MUSTT Randomized Patients:
Arrhythmic Death or Cardiac Arrest
1.0
Event-Free Rate
0.9
EP-Guided
0.8
Control
0.7
0.6
P=0.04
0.5
0.4
0.3
0.2
0.1
0.0
0
3
6
9
12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
Months After Enrollment
Buxton AE, et al. N Engl J Med. 1999;341:1882-1890.
MUSTT Randomized Patients:
Arrhythmic Death or Cardiac Arrest
1.0
EP ICD
Event-Free Rate
0.9
Control
0.8
0.7
EP no ICD
0.6
P<0.001
0.5
0.4
0.3
0.2
0.1
0.0
0
3
6
9
12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
Months After Enrollment
Buxton AE, et al. N Engl J Med. 1999;341:1882-1890.
MUSTT Randomized Patients:
Total Mortality
1.0
EP ICD
Event-Free Rate
0.9
0.8
Control
0.7
0.6
EP no ICD
0.5
0.4
P<0.001
0.3
0.2
0.1
0.0
0
3
6
9
12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
Months After Enrollment
Buxton AE, et al. N Engl J Med. 1999;341:1882-1890.
MADIT and MADIT-II:
Inclusion Criteria
MADIT1
MADIT-II2
 NYHA Class I, II, or III
 Prior MI
 Prior MI
 LVEF <30%
 LVEF <35%
 Asymptomatic,
non-sustained VT
 Inducible, nonsuppressible
VT at EP
1. Moss AJ, et al. N Engl J Med. 1996;335:1933-1940.
2. Moss AJ, et al. N Engl J Med. 2002;346:877-882.
MADIT: Survival by Treatment Groups
1.0
Probability of Survival
ICD
0.8
0.6
Conventional
Therapy
0.4
0.2
P=0.009
0.0
0
3
6
9
12
15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60
Months After Enrollment
Moss AJ, et al. N Engl J Med. 1996;335:1933-1940.
MADIT-II: Survival by
Treatment Group
Probability of Survival
1.0
0.9
Defibrillator Group
0.78
0.8
0.7
Conventional Group
0.69
0.6
P=0.007
0.5
0
1
Moss AJ, et al. N Engl J Med. 2002;346:877-882.
2
Years
3
4
Mortality Reduction w/ICD Rx (%)
Secondary Prevention Trials:
AVID, CASH, CIDS
80
70
60
50
40
31
30
28
20
20
10
0
AVID1
3 Years
1. AVID Investigators. N Engl J Med. 1997;337:1576-1583.
2. Kuck KH, et al. Circulation. 2000;102:748-754.
3. Connolly SJ, et al. Circulation. 2000;101:1297-1302.
CASH2
3 Years
CIDS3
3 Years
AVID Trial
 Eligibility criteria
– Resuscitation from ventricular fibrillation
– Sustained VT with syncope
– Sustained VT with LVEF ≤40% and
severe hemodynamic compromise
(near-syncope; CHF; angina)
 Therapy
– ICD (N=507)
– Antiarrhythmics (N=509)
• Amiodarone (N=493)
• Sotalol (N=13)
• Other (N=3)
AVID Investigators. N Engl J Med. 1997;337:1576-1583.
AVID: Overall Survival
1.0
Defibrillator Group
Proportion Surviving
0.8
Antiarrhythmic Drug Group
0.6
P<0.02
0.4
0.2
0.0
0
2
1
Years After Randomization
AVID Investigators. N Engl J Med. 1997;337:1576-1583.
3
AVID: Hazard Ratios for
All-Cause Mortality
Age
<60 yr
60-69 yr
70 yr
LVEF
<0.35%
0.35%
Cause of
arrhythmia
CAD
Other
Rhythm
Ventricular
Fibrilation
Ventricualr
Tachycardia
Other
0
AVID Investigators. N Engl J Med. 1997;337:1576-1583.
0.2
0.4
0.6 0.8 1.0
Hazard Ratio
1.2
1.4
1.6
CASH: Long-Term Overall Survival
in ICD and Drug Arms
1.0
Proportion Surviving
0.9
0.8
0.7
0.6
0.5
0.4
P=0.081
0.3
ICD
0.2
Amiodarone/metoprolol
0.1
0.0
0
1
2
3
4
Years
Kuck K-H et al. Circulation. 2000;102:748-754
5
6
7
8
9
Update of CIDS Trial:
11-Year Follow-Up From One Center
 Original study randomized amiodarone vs ICD in VT/VF
survivors (N=659)
 Long-term follow-up from 1 center–amiodarone (N=60)
 All-cause mortality higher in amiodarone (N=28) vs ICD
(N=16)
 Annual mortality rate–amiodarone, 8.4%–ICD, 4.8%
 Amiodarone patients
– 82% had side effect
– 50% had significant side effect
Bokhari FA, et al. Circulation. 2002;106(19 suppl II):II-497.
CIDS Update: 11-Year Follow-Up
Actuarial Survival (%)
100
80
60
40
P=0.021
20
ICD
Amiodarone
0
20
40
Bokhari FA, et al. Circulation. 2002;106(19 suppl II):II-497.
60
80
Months
100
120
140
Selection of CRT vs CRT-ICD
 CRT
– Consider for patients who require chronic ventricular
pacing, especially those with LV dysfunction or mitral
regurgitation
 CRT-ICD
– Consider for patients who meet criteria for MADIT II,
and MUSTT/MADIT with VT induced
– Consider for any patient with an ACC/AHA/NASPE
Class I indication for an ICD
Prystowsky EN. Rev Cardiovasc Med. 2003;4(supp/2):S47-S53.
Summary
 Trials of antiarrhythmic drugs failed to prevent
or significantly reduce SCD in patients post-MI
– CAST, CAST-II, EMIAT, CAMIAT
 The ICD conferred a reduction of approximately 50%
in overall mortality in the randomized trials MUSTT
and MADIT
 The ICD has been shown in multiple randomized
studies to be the most significant therapy available
for the primary prevention of SCD in patients
with a previous MI
Summary
 The ICD was associated with reductions in all-cause mortality
in three randomized secondary prevention trials of SCD
– AVID, CASH, CIDS
 In 2002, the FDA approved the combination CRT-ICD for
treatment of heart failure in patients at risk for SCD
 The CRT-ICD may be more appropriate than CRT without
defibrillation in patients who meet eligibility criteria for primary
prevention post-MI trials
 Preliminary results of the COMPANION trial strongly suggest
that many CRT candidates will benefit even more from CRT-ICD
 Further studies of the CRT-ICD are warranted to determine
the most appropriate candidates