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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

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Cardiac resynchronization and defibrillation therapies

Cardiac Resynchronizationand Defibrillation Therapies:

Complementary Approachesto the Managementof Heart Failure


Ventricular resynchronization pathophysiology and identification of responders

Ventricular ResynchronizationPathophysiology and Identification of Responders


Mechanisms of dysfunction due to contractile discoordination
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. 2003;4(suppl 2):S3-S13.


Impact of mechanical dyssynchrony
Impact of Mechanical Dyssynchrony

A

MRI-Tagged 3-D Cine-Imaging

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
Disparities in Regional WorkloadResulting From Dyssynchrony

Early Activated

Late Activated

20

20

Area = Regional Work

Fiber Stress

Fiber Stress

0

0

0.0

0.1

0.0

0.1

-0.1

-0.1

Fiber Strain

Regional Blood Flow

Glucose Metabolism

Adapted from Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13.


Discoordinate motion
Discoordinate Motion

Adverse Effects on Global Function From RV-Pacing–Induced 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. 2003;4(suppl 2):S3-S13.


Do we resynchronize with biventricular or left ventricular pacing

Do We ResynchronizeWith Biventricular or Left Ventricular Pacing?


Crt enhances cardiac mechano energetic efficiency
CRT Enhances Cardiac Mechano-Energetic Efficiency

.24

LV pacing

*P< 0.01

†P< 0.05

Mean ±SEM

Dobutamine

*

P< 0.05

.22

40

.20

*

(Relative Units)

MVO2/HR

20

Change (%)

.18

0

.16

.14

-20

MeanCorF

AVO2

MVO2

dP/dtmax

PP

500

600

700

800

900

1000

dP/dtmax

(mm Hg)

Adapted from Nelson GS, et al. Circulation. 2000;102:3053-3059.


Single site lv pacing works just as well
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

100

200

300

0

100

200

300

LV Volume (mL)

LV Volume (mL)

Adapted from Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13.


Regional wall motion with crt
Regional Wall Motion With CRT

Septum

0

Seconds

0.4

Regional Fractional Area Change

Lateral

0

Seconds

0.4

Pacing Off

Pacing On

Adapted from Kass DA. Rev Cardiovasc Med. 2003;4(suppl 2):S3-S13.

Adapted from Kawaguchi M, et al. J Am Coll Cardiol. 2002;39:2052-2058.


Global chamber effects of crt acute human studies
Global Chamber Effects of CRT:Acute 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

2.5

5.0

7.5

10.0

0.0

Seconds

Seconds

120

80

LV Pressure (mm Hg)

40

0

0

100

200

300

Adapted from Kass DA. Rev Cardiovasc Med.

2003;4(suppl 2):S3-S13.

LV Volume (mL)


Ventricular reverse remodeling with resynchronization
Ventricular Reverse RemodelingWith Resynchronization

Control

6-month

CRT

CRT 6-month

P<0.001

P<0.001

7.5

30

Ejection Fraction (%)

End-Diastolic Dimension (mm)

6.5

20

6.0

10

Placebo

n=63

CRT

n=61

Placebo

n=81

CRT

n=63

Adapted from Abraham WT, et al. N Engl J Med. 2002;346:1845-1853.



Av interval optimization
AV Interval Optimization Ventricular to Ventricular Delay?

16

24

LVBV

LVBV

12

18

8

12

Change in dP/dtmax (%)

Change in Aortic PP (%)

4

6

0

0

1

1

-4

-6

AV delay(0 to PR – 30 msec)

AV delay(0 to PR – 30 msec)

-8

-12

Adapted from Auricchio A, et al. Circulation. 1999;99:2993-3001.


Synchronous vs non synchronous bv pacing is rv lv delay important
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

* P<0.01 vs. Simultaneous (s)Sogaard P, et al. Circulation. 2002;106:2078-2084.


Can we predict responders
Can We Predict Responders? Important?

  • 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 as a Predictor of Response Important?

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

-25

0

-50

-30

-10

0

10

30

50

100

150

200

250

Surface QRS (msec)

%

QRS (msec)

D

1. Adapted from Auricchio A, et al. Circulation. 1999;99:2993-3001.2. Nelson GS, et al. Circulation. 2000;101:2703-2709.


More direct methods to assess dyssynchrony
More Direct Methods Important?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
M-mode Echo Assessment Important?for Predicting Responders

+20

r =-.70P=.001

0

-20

-40

 LVESVI (mL/m2)

-60

-80

-100

D

20

60

140

220

300

380

SPWMD (msec)

Adapted from Pitzalis MV, et al. J Am Coll Cardiol. 2002;40:1615-1622.


Tdi assessment for predicting responders
TDI Assessment Important?for 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. 2002;40:723-730.


Potential causes for lack of response
Potential Causes Important?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
Summary Important?

  • 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 responders—but more work is needed to define the most reliable dyssynchrony measurement and test its prospective utility


Pathophysiology of congestive heart failure

Pathophysiology Important?of Congestive Heart Failure


Heart failure
Heart Failure Important?

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
Congestive Heart Failure Important?Scope 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

  • Hunt SA, et al. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult. 2001.

  • Graves EJ, Gillum BS. 1994 Summary: National Hospital Discharge Survey. National Center for Health Statistics; 1996.

  • AHA. 2002 Heart and Stroke Statistical Update; 2001.


Heart failure hospitalizations
Heart Failure Important?Hospitalizations

Women

Men

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.


Diagnosis of chf clinical challenge
Diagnosis of CHF: Important?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 accuracyfor CHF1

  • 20% to 40% of patients with CHF have normalsystolic function2

  • Dao Q, et al. J Am Coll Cardiol. 2001;37:379-385.

  • 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
New York Heart Association Functional Classification Important?

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.


New york heart association functional classification1
New York Heart Association Important?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.


Acc aha stages of heart failure stages a and b
ACC/AHA Stages of Heart Failure: Stages A and B Important?

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
ACC/AHA Stages of Heart Failure: Stages C and D Important?

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
Heart Failure Important?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

  • 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 pathophysiology1
Heart Failure Important?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

  • 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 pathophysiology2
Heart Failure Important?Pathophysiology

Fall in LV Performance

Myocardial Injury

Activation of RAAS, SNS, ET,

and Others

ANP

BNP

Peripheral Vasoconstriction

Hemodynamic Alterations

Myocardial Toxicity

Remodeling and

Progressive

Worsening of

LV Function

Heart Failure Symptoms

Morbidity and Mortality

Shah M, et al. Rev Cardiovasc Med. 2001;2(suppl 2):S2-S6.


Heart failure left ventricular dysfunction
Heart Failure Important?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 cAMPand calcium

    • Decrease in vagal activity secondary to stretching of cardiac mechanoreceptors

  • Leri A, et al. J Clin Invest. 1998;101:1326-1342.

  • Fonarow GC. Rev Cardiovasc Med. 2001;2(suppl 2):S7-S12.

  • Cerati D, Schwartz PJ. Circ Res. 1991;69:1389-1401.


Heart failure left ventricular dysfunction1
Heart Failure Important?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. Mann DL, Willerson JT. Circulation. 1998;98:2367-2369.2. Heerdt PM, et al. Circulation. 2000;102:2713-2719. 3. Ogletree-Hughes ML, et al. Circulation. 2001;104:881-886.4. McCarthy PM, Hoercher K. Prog Cardiovasc Dis. 2000;43:37-46.


Heart failure left ventricular dysfunction2
Heart Failure Important?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
Effects of Resynchronization Important?on LV Performance

Ejection Fraction (%)

Left Ventricular Volume (mL)

225

45

200

40

175

35

150

30

125

25

100

20

off-immed

off-1wk

off-4wk

Baseline

1wk

1mo

3mo

off-immed

off-1wk

off-4wk

Baseline

1wk

1mo

3mo

dP/dtmax (mm/Hg/sec)

1000

900

800

700

600

500

400

off-immed

off-1wk

off-4wk

Baseline

1wk

1mo

3mo

Yu CM, et al. Circulation. 2002;105:438-445.


Effects of resynchronization on lv performance1
Effects of Resynchronization Important?on LV Performance

Mitral Regurgitation (%)

40

35

30

25

20

15

10

off-immed

off-1wk

Baseline

1wk

1mo

3mo

off-4wk

Left Ventricular Filling Time (msec)

Isovolumetric Contraction Time (ms)

500

160

150

140

450

130

120

400

110

100

350

90

80

300

70

60

250

50

off-immed

off-1wk

off-4wk

Baseline

1wk

1mo

3mo

off-immed

off-1wk

off-4wk

Baseline

1wk

1mo

3mo

Yu CM, et al. Circulation. 2002;105:438-445.


Summary1
Summary Important?

  • 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

Device Selection: Important?CRT Alone VersusCRT Plus Implantable Cardioverter Defibrillator (ICD)


Cardiac resynchronization and defibrillation therapies

Risk-Stratification for Sudden Cardiac Death Important?

PVCs

VT-NS

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.


Cast survival
CAST: Survival Important?

100

Placebo (N=725)

95

Survival (%)

90

Encainide or flecainide (N=730)

85

P=0.0003

450

0

50

100

150

200

250

300

350

400

500

Days After Randomization

CAST Investigators. N Engl J Med. 1989;321:406-412.


Emiat all cause mortality lvef and by group
EMIAT: All-Cause Mortality Important? LVEF and by Group

Ejection fraction 31%-40%

Probability of Survival

Probability of Survival

Amiodarone

Placebo

Ejection fraction < 30%

Months Since Randomization

Months Since Randomization

Julian DG, et al. Lancet.1997;349:667-674.


Camiat all cause mortality and nonarrhythmic death
CAMIAT: All-Cause Mortality Important?and Nonarrhythmic Death

Amiodarone

Placebo

Cumulative Risk (%)

P=0.130

Cumulative Risk (%)

P=0.072

Months Since Randomization

Months Since Randomization

Cairns JA, et al. Lancet.1997;349:675-682.


Primary prevention post mi trials
Primary Prevention Post-MI Trials Important?

80

70

55

60

54

50

Mortality Reduction w/ICD Rx (%)

40

31

30

20

10

0

MADIT-II320 Months

MADIT227 Months

MUSTT127 Months

  • Buxton AE, et al. N Engl J Med. 1999;341:1882-1890.

  • Moss AJ, et al. N Engl J Med. 1996;335:1933-1940.

  • Moss AJ, et al. N Engl J Med. 2002;346:877-882.


Mustt and madit overview
MUSTT and MADIT: Overview Important?

MUSTT (N=704)

39 mos

66%

30%

5

40%

64%

MADIT

(N=196)

27 mos

71%

26%

9

18%

65%

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. 2000;86(Suppl 1):K34-K39.


Mustt study
MUSTT Study Important?

Hypothesis: Antiarrhythmic therapy guidedby 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
MUSTT Randomized Patients: Important?Arrhythmic Death or Cardiac Arrest

1.0

EP-Guided

0.9

0.8

Control

0.7

Event-Free Rate

P=0.04

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. 1999;341:1882-1890.


Mustt randomized patients arrhythmic death or cardiac arrest1
MUSTT Randomized Patients: Important?Arrhythmic Death or Cardiac Arrest

EP ICD

1.0

0.9

Control

0.8

0.7

EP no ICD

Event-Free Rate

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
MUSTT Randomized Patients: Important?Total Mortality

1.0

EP ICD

0.9

0.8

Control

0.7

Event-Free Rate

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
MADIT and MADIT-II: Important?Inclusion Criteria

MADIT

MADIT

1

1

MADIT

MADIT

-

-

II

II

2

2

§

§

NYHA Class I, II, or III

§

§

Prior MI

Prior MI

<

§

§

Prior MI

Prior MI

§

§

LVEF 30%

<

§

§

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. 1996;335:1933-1940.

  • Moss AJ, et al. N Engl J Med. 2002;346:877-882.


Madit survival by treatment groups
MADIT: Survival by Treatment Groups Important?

1.0

ICD

0.8

0.6

Conventional Therapy

Probability of Survival

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
MADIT-II: Survival by Important?Treatment Group

1.0

0.9

Defibrillator Group

0.78

0.8

Probability of Survival

0.7

Conventional Group

0.69

0.6

P=0.007

0.5

0

1

2

3

4

Years

Moss AJ, et al. N Engl J Med. 2002;346:877-882.


Secondary prevention trials avid cash cids
Secondary Prevention Trials: Important?AVID, CASH, CIDS

80

70

60

50

Mortality Reduction w/ICD Rx (%)

40

31

30

28

20

20

10

0

CIDS33 Years

CASH23 Years

AVID13 Years

  • AVID Investigators. N Engl J Med. 1997;337:1576-1583.

  • Kuck KH, et al. Circulation. 2000;102:748-754.

  • Connolly SJ, et al. Circulation. 2000;101:1297-1302.


Avid trial
AVID Trial Important?

  • 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
AVID: Overall Survival Important?

1.0

Defibrillator Group

0.8

Antiarrhythmic Drug Group

0.6

P<0.02

Proportion Surviving

0.4

0.2

0.0

2

3

0

1

Years After Randomization

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


Avid hazard ratios for all cause mortality
AVID: Hazard Ratios for Important?All-Cause Mortality

Age<60 yr60-69 yr³70 yr

LVEF<0.35%³0.35%

Cause ofarrhythmia CAD Other

RhythmVentricularFibrilation

Ventricualr Tachycardia

Other

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. 1997;337:1576-1583.


Cash long term overall survival in icd and drug arms
CASH: Long-Term Overall Survival in ICD and Drug Arms Important?

1.0

0.9

0.8

0.7

0.6

Proportion Surviving

0.5

0.4

P=0.081

0.3

ICD

0.2

Amiodarone/metoprolol

0.1

0.0

0

1

2

3

4

5

6

7

9

8

Years

Kuck K-H et al. Circulation. 2000;102:748-754


Update of cids trial 11 year follow up from one center
Update of CIDS Trial: Important?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
CIDS Update: 11-Year Follow-Up Important?

100

80

60

40

20

0

Actuarial Survival (%)

P=0.021

ICD

Amiodarone

20 40 60 80 100 120 140

Months

Bokhari FA, et al. Circulation. 2002;106(19 suppl II):II-497.


Selection of crt vs crt icd
Selection of CRT vs CRT-ICD Important?

  • 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.


Summary2
Summary Important?

  • 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 50%in 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


Summary3
Summary Important?

  • 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