Cardiac Resynchronization and Defibrillation Therapies:

1
Cardiac Resynchronizationand Defibrillation
Therapies

• Complementary Approachesto the Managementof
  Heart Failure

2
Ventricular ResynchronizationPathophysiology
and Identification of Responders
3
Mechanisms of Dysfunction Dueto 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
  increasedenergetic 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. 20034(suppl
2)S3-S13.
4
Impact of Mechanical Dyssynchrony
MRI-Tagged 3-D Cine-Imaging
Adapted from Kass DA. Rev Cardiovasc Med.
20034(suppl 2)S3-S13.Adapted from Leclercq C,
et al. Circulation. 20011061760-1763.
5
Disparities in Regional WorkloadResulting From
Dyssynchrony
Adapted from Kass DA. Rev Cardiovasc Med.
20034(suppl 2)S3-S13.
6
Discoordinate Motion
Adverse Effects on Global Function From
RV-PacingInduced Dyssynchrony
Normal Sinus Rhythm
Acute Dyssynchrony (RV Pace)
80
40
LV Pressure (mm Hg)
0
30
60
90
LV Volume (mL)
Adapted from Kass DA. Rev Cardiovasc Med.
20034(suppl 2)S3-S13.
7
Do We ResynchronizeWith Biventricular or Left
Ventricular Pacing?
8
CRT Enhances Cardiac Mechano-Energetic Efficiency
.24
LV pacing
Plt 0.01 Plt 0.05 Mean SEM
Dobutamine

Plt 0.05
.22
40
.20

MVO2/HR
(Relative Units)
20
Change ()
.18


0
.16
.14
-20
dP/dtmax
MeanCorF
AVO2
MVO2
PP
500
600
700
800
900
1000
dP/dtmax
(mm Hg)
Adapted from Nelson GS, et al. Circulation.
20001023053-3059.
9
Single-Site LV PacingWorks Just as Well
LV Free Wall per Circulation
Biventricular
120
120
80
80
LV Pressure (mm Hg)
LV Pressure (mm Hg)
40
40
0
0
0
300
200
100
0
300
200
100
LV Volume (mL)
LV Volume (mL)
Adapted from Kass DA. Rev Cardiovasc Med.
20034(suppl 2)S3-S13.
10
Regional Wall Motion With CRT
Septum
Seconds
0.4
0
Regional Fractional Area Change
Lateral
Seconds
0.4
0
Pacing Off Pacing On
Adapted from Kass DA. Rev Cardiovasc Med.
20034(suppl 2)S3-S13. Adapted from Kawaguchi M,
et al. J Am Coll Cardiol. 2002392052-2058.
11
Global Chamber Effects of CRTAcute Human Studies
Pacing ON
Pacing OFF
2-Min Steady State
1193.0
1120.0
dP/dt
dP/dt
-841.0
-727.0
114.0
114.0
AOP
AOP
54.7
50.8
113.0
113.0
LVP
LVP
0.4
1.0
1151.0
1151.0
870.0
865.0
0.0
2.8
5.6
8.4
11.2
0.0
2.5
5.0
7.5
10.0
Seconds
Seconds
120
80
LV Pressure (mm Hg)
40
0
0
300
200
100
Adapted from Kass DA. Rev Cardiovasc Med.
20034(suppl 2)S3-S13.
LV Volume (mL)
12
Ventricular Reverse RemodelingWith
Resynchronization
Plt0.001
Plt0.001
7.5
30
End-Diastolic Dimension (mm)
Ejection Fraction ()
6.5
20
6.0
10
Placebo n81
CRT n63
CRT n61
Placebo n63
Adapted from Abraham WT, et al. N Engl J Med.
20023461845-1853.
13
How Important Are Pacing Site, Atrioventricular
Delay, and Ventricular to Ventricular Delay?
14
AV Interval Optimization
Adapted from Auricchio A, et al. Circulation.
1999992993-3001.
15
Synchronous vs Non-Synchronous BV Pacing Is
RV-LV Delay Important?
6


5
4
Systolic Function (Echo Index)
3
2
1
RV Preactivation S LV Preactivation
0
Plt0.01 vs. Simultaneous (s)Sogaard P, et al.
Circulation. 20021062078-2084.
16
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. 20034(suppl
2)S3-S13.
17
QRS as a Predictor of Response
QRS duration is only weakly correlated with acute
improvement1,2
However, change in QRS duration does not
correlate with acute improvement2
60
100
r 0.51
75
40
Change in dP/dtmax ()
50
Change in dP/dtmax ()
25
20
0
0
-25
-50
-30
50
-10
0
10
30
100
150
250
200
Surface QRS (msec)
QRS (msec)

D
1. Adapted from Auricchio A, et al. Circulation.
1999992993-3001.2. Nelson GS, et al.
Circulation. 20001012703-2709.
18
More Direct Methodsto Assess Dyssynchrony

• Interventricular delay
• RV/LV pressure plot (area in loop)
• Interventricular delay
• QRS onset-pulmonary flow onset QRS onset-aortic
  flow onset gt25 msec
• Intraventricular delay
• Strain rate TDI
• M-mode ECHO
• Echo contrast analysis
• QRS onset-end lateral wall contraction gt290 msec
• QRS onset-end lateral wall contraction gtQRS
  onset-mitral E-wave onset

Kass DA. Rev Cardiovasc Med. 20034(suppl
2)S3-S13.
19
M-mode Echo Assessmentfor Predicting Responders
20
r -.70P.001
0
-20
-40
? LVESVI (mL/m2)
-60
-80
-100
D
20
60
380
140
220
300
SPWMD (msec)
Adapted from Pitzalis MV, et al. J Am Coll
Cardiol. 2002401615-1622.
20
TDI Assessmentfor Predicting Responders
80
60
40
Change in LVEF ()
20
0
20
40
60
80
-20
-40
Percentage of LV Base With DLC
Adapted from Sogaard P, et al. J Am Coll Cardiol.
200240723-730.
21
Potential Causesfor 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. 20034(suppl
2)S3-S13.
22
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
  functionand energetics from CRT can be marked
• Defining intraventricular mechanical
  dyssynchronyseems at present to be the most
  reliable variable for predicting respondersbut
  more work is needed to define the most reliable
  dyssynchrony measurement and test its prospective
  utility

23
Pathophysiologyof Congestive Heart Failure
24
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.
20034(suppl 2)S14-20.
25
Congestive Heart FailureScope of the Problem

• Nearly 900,000 annual hospital admissions
  (increased 90 in past 10 years)1
• Most common discharge diagnosis for patients
  olderthan 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.

26
Heart Failure Hospitalizations
The Number of Heart Failure Hospitalizations Is
Increasing in Both Men and Women
600,000
500,000
400,000
Annual Discharges
300,000
200,000
100,000
0
'79
'81
'83
'85
'87
'89
'91
'93
'95
'97
'99
Year
CDC/NCHS hospital discharges include patients
both living and dead. AHA. 2002 Heart and Stroke
Statistical Update. 2001.
27
Diagnosis of CHFClinical 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 accuracyfor
  CHF1
• 20 to 40 of patients with CHF have
  normalsystolic function2

1. Dao Q, et al. J Am Coll Cardiol. 200137379-385.
2. Hunt SA, et al. ACC/AHA Guidelines for the
   Evaluation and Management of Chronic Heart
   Failure in the Adult 2001.

28
New York Heart Association Functional
Classification
Functional Class
Patient Limitations

• 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 I
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.
29
New York Heart Association Functional
Classification
Functional Class
Patient Limitations

• Marked
• Patient is comfortable at rest
• Less than ordinary activity leads to symptoms

Class III
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.
30
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.
2001382101-2113.
31
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.
2001382101-2113.
32
Heart FailurePathophysiology

• 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. Francis GS, Tang WH. Rev Cardiovasc Med.
   20034(suppl 2)S14-20.
2. Francis GS. Am J Med. 2001110(suppl 7A)37S-46S.
3. Shah M, et al. Rev Cardiovasc Med. 20012(suppl
   2)S2-S6.
4. Ceconi C, et al. Rev Port Cardiol. 199817(suppl
   2)1179-1191.
5. Mann DL. Circulation. 1999100999-1008.

33
Heart FailurePathophysiology

• Etiology of heart failure includes1-7
• Alterations in signal transduction pathways
• Switch to fetal gene programsincrease ?-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. Katz AM. Med Clin North Am. 200387303-316.
2. Francis GS. Am J Med. 2001110(suppl 7A)37S-46S.
   
3. Iwanaga Y, et al. J Am Coll Cardiol.
   200036635-642.
4. Francis GS, Tang WH. Rev Cardiovasc Med.
   20034(suppl 2)S14-S20.
5. Shah M, et al. Rev Cardiovasc Med. 20012(suppl
   2)S2-S6.
6. Wilson EM, et al. J Card Fail. 20028390-398.
7. Jugdutt BI. Curr Drug Targets Cardiovasc Haematol
   Disord. 200331-30.

34
Heart Failure Pathophysiology
Fall in LV Performance
Myocardial Injury
Activation of RAAS, SNS, ET, and Others
Peripheral Vasoconstriction Hemodynamic
Alterations
ANP BNP
Myocardial Toxicity
Remodeling and Progressive Worsening of LV
Function
Heart Failure Symptoms
Morbidity and Mortality
Shah M, et al. Rev Cardiovasc Med. 20012(suppl
2)S2-S6.
35
Heart FailureLeft 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 cAMPand calcium
• Decrease in vagal activity secondary to
  stretching of cardiac mechanoreceptors

1. Leri A, et al. J Clin Invest. 19981011326-1342.
2. Fonarow GC. Rev Cardiovasc Med. 20012(suppl
   2)S7-S12.
3. Cerati D, Schwartz PJ. Circ Res.
   1991691389-1401.

36
Heart FailureLeft 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. Mann DL, Willerson JT. Circulation.
1998982367-2369.2. Heerdt PM, et al.
Circulation. 20001022713-2719. 3.
Ogletree-Hughes ML, et al. Circulation.
2001104881-886.4. McCarthy PM, Hoercher K.
Prog Cardiovasc Dis. 20004337-46.
37
Heart FailureLeft Ventricular Dysfunction

• Transition from LV dysfunction to HF1-3
• Cell dropout (apoptosis)
• Myocyte elongation, hypertrophy
• Myocyte slippage

1. Mann DL. Circulation. 1999100999-1008. 2.
Francis GS. Am J Med. 2001110(suppl 7A)37S-46S.
3. D'Armiento J. Trends Cardiovasc Med.
20021297-101.
38
Effects of Resynchronizationon LV Performance
Yu CM, et al. Circulation. 2002105438-445.
39
Effects of Resynchronizationon LV Performance
Yu CM, et al. Circulation. 2002105438-445.
40
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

41
Device SelectionCRT Alone VersusCRT Plus
Implantable Cardioverter Defibrillator (ICD)
42
Risk-Stratification for Sudden Cardiac Death
Arrhythmia PVCs VT-NS VT-S VF
Heart Disease Absent Present Present Present
LV Dysfunction Absent Absent Present Present
Potential Risks for SCD Minimal Intermediate Intermediate High
PVCs
VT-NS
PVCpremature ventricular complexes
VT-NSnonsignificant ventricular
tachycardiaVT-Ssignificant ventricular
tachycardia VFventricular fibrillation. Prystow
sky EN. Am J Cardiol. 198861102A-107A.
43
CAST Survival
100
Placebo (N725)
95
Survival ()
90
Encainide or flecainide (N730)
85
P0.0003
450
0
400
500
50
100
150
200
250
300
350
Days After Randomization
CAST Investigators. N Engl J Med.
1989321406-412.
44
EMIAT All-Cause Mortality LVEF and by Group
Ejection fraction 31-40
Probability of Survival
Probability of Survival
Amiodarone Placebo
Ejection fraction lt 30
Months Since Randomization
Months Since Randomization
Julian DG, et al. Lancet. 1997349667-674.
45
CAMIAT All-Cause Mortalityand Nonarrhythmic
Death
Amiodarone Placebo
Cumulative Risk ()
P0.130
Cumulative Risk ()
P0.072
Months Since Randomization
Months Since Randomization
Cairns JA, et al. Lancet. 1997349675-682.
46
Primary Prevention Post-MI Trials
80
70
55
60
54
50
Mortality Reduction w/ICD Rx ()
40
31
30
20
10
0
MADIT227 Months
MADIT-II320 Months
MUSTT127 Months

1. Buxton AE, et al. N Engl J Med.
   19993411882-1890.
2. Moss AJ, et al. N Engl J Med. 19963351933-1940.
3. Moss AJ, et al. N Engl J Med. 2002346877-882.

47
MUSTT and MADIT Overview
MADIT (N196) 27 mos 71 26 9 18 65
MUSTT (N704) 39 mos 66 30 5 40 64
Mean time (MI to enrollment) Prior CABG or
PTCA LVEF (mean) VT-NS (mean beats)
Beta-blocker at discharge Class II-III (
patients)
Adapted from Prystowsky EN. Am J Cardiol.
200086(Suppl 1)K34-K39.
48
MUSTT Study

• Hypothesis Antiarrhythmic therapy guidedby EP
  testing can reduce the risk of arrhythmic death
  and cardiac arrest in patients with
• Coronary artery disease
• LVEF lt40
• Nonsustained VT(3 beats 30 sec rate gt100 bpm)

Buxton AE, et al. N Engl J Med.
19993411882-1890.
49
MUSTT Randomized PatientsArrhythmic Death or
Cardiac Arrest
1.0
EP-Guided
0.9
0.8
Control
0.7
Event-Free Rate
P0.04
0.6
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.
19993411882-1890.
50
MUSTT Randomized PatientsArrhythmic Death or
Cardiac Arrest
EP ICD
1.0
0.9
Control
0.8
0.7
EP no ICD
Event-Free Rate
0.6
Plt0.001
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.
19993411882-1890.
51
MUSTT Randomized PatientsTotal Mortality
1.0
EP ICD
0.9
0.8
Control
0.7
Event-Free Rate
0.6
EP no ICD
0.5
0.4
Plt0.001
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.
19993411882-1890.
52
MADIT and MADIT-IIInclusion Criteria
MADIT
MADIT
1
1
MADIT
-
II
MADIT
-
II
2
2


NYHA Class I, II, or III

Prior MI

Prior MI
lt

Prior MI

Prior MI

LVEF 30

lt


LVEF 35

Asymptomatic,

Asymptomatic,
non-sustained VT


Inducible, nonsuppressible
Inducible, nonsuppressible
VT at EP
VT at EP

• Moss AJ, et al. N Engl J Med. 19963351933-1940.
• Moss AJ, et al. N Engl J Med. 2002346877-882.

53
MADIT Survival by Treatment Groups
1.0
ICD
0.8
0.6
Conventional Therapy
Probability of Survival
0.4
0.2
P0.009
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. 19963351933-1940.
54
MADIT-II Survival byTreatment Group
1.0
0.9
Defibrillator Group
0.78
0.8
Probability of Survival
0.7
Conventional Group
0.69
0.6
P0.007
0.5
0
1
2
3
4
Years
Moss AJ, et al. N Engl J Med. 2002346877-882.
55
Secondary Prevention TrialsAVID, CASH, CIDS
80
70
60
50
Mortality Reduction w/ICD Rx ()
40
31
30
28
20
20
10
0
CASH23 Years
CIDS33 Years
AVID13 Years

1. AVID Investigators. N Engl J Med.
   19973371576-1583.
2. Kuck KH, et al. Circulation. 2000102748-754.
3. Connolly SJ, et al. Circulation.
   20001011297-1302.

56
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 (N507)
• Antiarrhythmics (N509)
• Amiodarone (N493)
• Sotalol (N13)
• Other (N3)

AVID Investigators. N Engl J Med.
19973371576-1583.
57
AVID Overall Survival
1.0
Defibrillator Group
0.8
Antiarrhythmic Drug Group
0.6
Plt0.02
Proportion Surviving
0.4
0.2
0.0
2
3
0
1
Years After Randomization
AVID Investigators. N Engl J Med.
19973371576-1583.
58
AVID Hazard Ratios forAll-Cause Mortality
0
0.2
0.6
0.4
0.8
1.0
1.4
1.2
1.6
Hazard Ratio
AVID Investigators. N Engl J Med.
19973371576-1583.
59
CASH Long-Term Overall Survival in ICD and Drug
Arms
Kuck K-H et al. Circulation. 2000102748-754
60
Update of CIDS Trial11-Year Follow-Up From One
Center

• Original study randomized amiodarone vs ICD in
  VT/VF survivors (N659)
• Long-term follow-up from 1 centeramiodarone
  (N60)
• All-cause mortality higher in amiodarone (N28)
  vs ICD (N16)
• Annual mortality rateamiodarone, 8.4ICD, 4.8
• Amiodarone patients
• 82 had side effect
• 50 had significant side effect

Bokhari FA, et al. Circulation. 2002106(19 suppl
II)II-497.
61
CIDS Update 11-Year Follow-Up
100 80 60 40 20 0
Actuarial Survival ()
P0.021
ICD Amiodarone
20 40 60 80
100 120 140
Months
Bokhari FA, et al. Circulation. 2002106(19 suppl
II)II-497.
62
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.
20034(supp/2)S47-S53.
63
Summary

• Trials of antiarrhythmic drugs failed to
  preventor significantly reduce SCD in patients
  post-MI
• CAST, CAST-II, EMIAT, CAMIAT
• The ICD conferred a reduction of approximately
  50in overall mortality in the randomized trials
  MUSTTand MADIT
• The ICD has been shown in multiple
  randomizedstudies to be the most significant
  therapy availablefor the primary prevention of
  SCD in patientswith a previous MI

64
Summary

• The ICD was associated with reductions in
  all-cause mortalityin 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
  determinethe most appropriate candidates