Cardiac Resynchronization Therapy:

Current Indications and Future Prospects

Saverio Iacopino, MD, FACC, FESC

CHF Population

6.5 Million

Incidence = 580’000 (9.0%)

Mortality = 300’000 (4.6%)

CHF Population in Europe

American Heart Association. Heart Disease and Stroke Statistics - 2005 Update.

Hospital Discharges for CHF

CHF Patients Survival Results

American Heart Association. Heart Disease and Stroke Statistics - 2005 Update.

Myerburg RJ. Heart Disease, A Textbook of Cardiovascular Medicine. 5th ed, Vol 1. Philadelphia: WB Saunders Co; 1997:ch 24.

Middlekauf HR. J Am Coll Cardiol. 1993;21:110-116.

Stevenson WE. Circulation. 1993;88:2953-2961.

HF and/or Decreased LV Function

ü About one-half of all deaths in HF patients are characterized as sudden due to arrhythmias

ü The risk of SCD increases as left ventricular function deteriorates (low LVEF)

Incidence of SCD in Specific Populations and Annual SCD Numbers

Adapted from: Myerburg RJ. Sudden Cardiac Death: Exploring the Limits of Our Knowledge. J Cardiovasc Electrophysiol Vol. 12, pp. 369-381, March 2001.

300,000 200,000 100,000 0

Incidence of Sudden Deaths Per Year (number)

Multiple risk subgroups

Patients with any previous coronary event

Patients with ejection fraction <35% or CHF

Cardiac arrest, VT/VF survivors

High-risk post-MI subgroups

General adult population

30 25 20 10 5 0

Incidence of Sudden Death (% of group)

Risk of Sudden Death: GISSI-2 Trial

Patients without LV Dysfunction

(LVEF >35%)

Maggioni AP. Circulation. 1993;87:312-322.

Patients with LV Dysfunction

(LVEF < 35%)

No PVBs

1-10 PVBs/h

> 10 PVBs/h

0.86

A

0.88

0.90

0.92

0.94

0.96

0.98

1.00

0 30 60 90 120 150 180

Days

Su

rviv

al

p log-rank 0.002

0.88

0.90

0.92

0.94

0.96

0.98

1.00

0 30 60 90 120 150 180

Days

Su

rviv

al

B

p log-rank 0.0001

0.86

Severity of Heart Failure

MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). LANCET. 1999;353:2001-07.

Modes of Death NYHA II

12%

64% 24%

CHF Other Sudden Death

Deaths = 103

NYHA IV

56%

11%

33% CHF Other Sudden Death

Deaths = 27

NYHA III 26%

15%

59%

CHF Other Sudden Death

Deaths = 232

The greatest opportunity for SCD prevention is in patients that have mild to moderate CHF.

NYHA CLASS

Ann

ual s

urvi

val (

%)

Hos

pita

lizat

ions

/yea

r

100

75

50

25

0 I II III IV

1

10 Survival

Hospitalization 0.1

Hospitalization/NYHA Class in HF

Quality of Life for HF patients

Hobbs FDR, et al. Eur Heart J 2002

Overall perception of health

36 45

55 48 48

52

56 58

70

Heart Failure NYHA Class IV

Heart Failure NYHA Class III

Heart Failure NYHA Class II

Chronic Bronchitis

Valve disease symptomatic

AF symptomatic

Angina

Depression

General population

SCD in Heart Failure

ü Despite improvements in medical therapy, symptomatic HF still confers a 20-25% risk of pre-mature death in the first 2.5 yrs after diagnosis. ü ≈ 50% of these premature deaths are SCD (VT/VF)

ü The role of device therapy?

1 Bardy G. The Sudden Cardiac Deatth-Heart Failure Trial (SCD-HeFT) in Woosley RL, Singh S, Arrhythmia Treatment and Therapy, Copyright 2000 by Marcel Dekker, Inc. , pp. 323-342,

2 Sweeney MO PACE 2001;24:871-888.

0

20

40

60

80

MADIT MUSTT MADIT-II

Overall Death Arrhythmic Death

0

20

40

60

80

AVID CASH CIDS

Overall Death Arrhythmic Death

1 Moss AJ. N Engl J Med. 1996;335:1933-40. 2 Buxton AE. N Engl J Med. 1999;341:1882-90. 3 Moss AJ. N Engl J Med. 2002;346:877-83 4 Moss AJ. Presented before ACC 51st Annual Scientific Sessions,

Late Breaking Clinical Trials, March 19, 2002. 5 The AVID Investigators. N Engl J Med. 1997;337:1576-83. 6 Kuck K. Circ. 2000;102:748-54. 7 Connolly S. Circ. 2000:101:1297-1302.

ICD mortality reductions in primary prevention trials

are equal to or greater than those in secondary

prevention trials.

1 3, 4 2

5 7 6

Reductions in Mortality with ICD Therapy

54%

75%

55%

76%

31%

61%

27 months 39 months 20 months

31%

56%

28%

59%

20%

33%

% M

orta

lity

Red

uct

ion

w/ I

CD

Rx

% M

orta

lity

Red

uct

ion

w/ I

CD

Rx

3 Years 3 Years 3 Years

SCD-HeFT Mortality Rate Overall Results

Months of Follow-Up

Mor

tali

ty R

ate

48 36 24 12 0

Amiodarone Placebo ICD

0.4

0.3

0.2

0.1

0.0 60

No. at Risk Amiodarone 845 772 715 484 280 97 Placebo 847 797 724 505 304 89 ICD 829 778 733 501 304 103

Hazard Ratio (97.5% Cl) P-Value Amiodarone vs. Placebo 1.06 (0.86-1.30) 0.53 ICD vs. Placebo 0.77 (0.62-0.96) 0.007

Bardy GH. N Engl J Med. 2005;352:225-237.

SCD-HeFT Overall Mortality Results

0.007 0.77 (0.62-0.96) ICD vs. Placebo

0.53 1.06 (0.86-1.30) Amiodarone vs. Placebo

P-Value Hazard Ratio (97.5% CI)

ICDs reduce mortality by 23%

Bardy GH. N Engl J Med. 2005;352:225-237.

CHF Population

6.5 Million

NYHA III + IV (30 - 35%)

1.95 Million

Wide QRS (10 - 30%) 650’000

Incidence = 580’000 (9.0%) Mortality = 300’000 (4.6%)

CHF Population in Europe

Prevalence of Inter- or Intraventricular Conduction Delay

1 Havranek E, Masoudi F, Westfall K, et al. Am Heart J 2002;143:412-417 2 Shenkman H, McKinnon J, Khandelwal A, et al. Circulation 2000;102(18 Suppl II): abstract 2293 3 Schoeller R, Andresen D, Buttner P, et al. Am J Cardiol. 1993;71:720-726 4 Aaronson K, Schwartz J, Chen T, et al. Circulation 1997;95:2660-2667 5 Farwell D, Patel N, Hall A, et al. Eur Heart J 2000;21:1246-1250

IVCD 15%

IVCD >30%

General HF Population1,2 Moderate to Severe HF Population3,4,5

Prevalence and Prognosis of Ventricular Dysynchrony

Ventricular dysynchrony impairs diastolic and systolic function 4-6: Reduced LV filling time; Increased mitral regurgitation; Depressed dP/dt

4. Grines, et al. Circulation 1989;79:845-53 5. Xiao, et al. Br Heart J 1991;66:443-7 6. Xiao et al. Br Heart J 1992;68:403-7

Increased All-Cause Mortality with Wide QRS at 45 Months (3)

34%

49%

QRS < 120 ms

QRS > 120 ms

3. Iuliano et al. AHJ 2002;143:1085-91

P < 0.001

LBBB More Prevalent with Impaired LV Systolic Function

38%

24%

8%

Mod/Sev HF (2)

Impaired LVSF (1)

Preserved LVSF (1)

1. Masoudi, et al. JACC 2003;41:217-23 2. Aaronson, et al. Circ 1997;95:2660-7

60%

70%

80%

90%

100%

0 60 120 180 240 300 360 Days in Trial

Cu

mu

lati

ve S

urv

ival

QRS Duration (msec)

<90

90-120

120-170

170-220

>220

Wide QRS – Proportional Mortality Increase

ü  NYHA Class II-IV patients ü  3,654 ECGs digitally scanned ü  Age, creatinine, LVEF,

heart rate, and QRS duration found to be independent predictors of mortality

ü  Relative risk of widest QRS group 5x greater than narrowest

1 Gottipaty V, Krelis S, Lu F, et al. JACC 1999;33(2): 145 [Abstr 847-4].

Vesnarinone Study1 (VEST study analysis)

Desincronia Ventricolare ü Elettrica: Ritardo di conduzione intraventricolare (BBsn)

ü Strutturale: disgregazione della matrice di collagene cardiaca che danneggia efficienza meccanica e conduzione elettrica ü Meccanica: Anormalità nel movimento delle pareti con incrementato carico di lavoro e sforzo, compromettendo i meccanismi ventricolari

Tavazzi L. Eur Heart J 2000;21:1211-1214

R L

A

P

10 20

30

40

50

60 70

80

90

100

110 120

130 Durrer. Total Excitation of the Isolated Human heart Circulation 1970 Scher:The sequence of Ventricular Excitation Am. J.Cardiol. 1964

Site and Length of the Line-of-Block

Line of Block

Lateral

Inferior

Anterior

Sep

tum

>150

mse

c 12

0 - 1

50 m

sec QR

S D

urat

ion

Anterior

Lateral

Inferior

Sep

tum

Auricchio et al. Circulation 2004

Electromechanical Decoupling

Electrical disturbance ü wide QRS ü LBBB

Mechanical dysynchrony

ü  Impaired intra- and inter-ventricular coordination

Toussaint J-F, et al. PACE 2002;25:178-182

Hemodynamic Consequences of Ventricular Dysynchrony

Start of QRS mc ao ac mo

ü  Reduced LV filling time 1,2

ü  Prolonged mitral regurgitation 1,2

ü  Impaired systolic function (depressed dP/dt) 3,4

ü  Abnormal septal wall motion1

ü  Mechanical and temporal dysynchrony 4

1. Grines C, et al. Circulation 1989;79:845-853 2. Xiao, et al. Br Heart J 1991;66:443-447

3. Xiao et al. Br Heart J 1992;68:403-407 4. Curry C, et al. Circulation 2000;101:e2

Effects of LBBB on LV Contraction and Relaxation (1)

LBBB

Normal

Ejection Filling IVRT IVCT

Jarcho J. N Engl J Med 2006;355:288-294

The Cardiac Conduction System and Biventricular Pacing

CRT Baseline

Proposed Mechanisms of Benefit

Intraventricular Synchrony

Atrioventricular Synchrony

Interventricular Synchrony

↑ dP/dt, ↑ EF, ↑ CO (↑ Pulse Pressure)

↓ MR

↓  LA Pressure

↑ LV Diastolic Filling

↑ RV Stroke Volume

↓ LVESV ↓ LVEDV

Reversed Remodeling

Cardiac Resynchronization

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

Blanc et al., Circulation 1997 23 pts mean ± SD

Systolic Blood pressure

RVA LV BV RVO BAS

mm

Hg

p<.01 p<.03

Pulmonary Capillary Wedge Pressure

RVA LV BV RVO BAS

p<.01 p<.01

Acute Studies

90 100 110 120 130 140 150

0 10 20 30 40

Kass et al, Circulation 99

Intrinsic

Paced 0 100 200 300

0

40

80

120

RV Septum

0 100 200 300 0

40

80

120 Biventricular

0 100 200 300 0

40 80

120 RV Apex

0 100 200 300 0

40

80

120 LV Freewall

LV Volume (mL)

LV P

ress

ure

(m

m H

g)

LV P

ress

ure

(m

m H

g)

LV Volume (mL)

Acute Studies

Over 8,000 Patients Studied in Clinical Trials MADIT CRT

REVERSE ♦

♦ ♦

CRT Improve Quality of Life (MLHFQ) MUSTIC Trial

S.Cazeau et al NEJM 2001;344:873-80

MR area LVESV and LVEDV Pacing No pacing

N = 25

MUSTIC Trial

S.Cazeau et al NEJM 2001;344:873-80

Baseline 1wk 1mo 3mo off-immed off-1wk off-4wk 10 15 20 25 30 35 40

*

* †

*

* *

† †

Mit

ral r

egu

rgit

atio

n (%

) Baseline 1wk 1mo 3mo off-immed off-1wk off-4wk

100 125 150 175 200 225

* *

*

*

†

* *

*

†

Lef

t ven

tric

ula

r vo

lum

e (m

L)

*

Control 225 214 204 197 191 179 70

CRT 228 218 213 209 204 201 99

Patients At Risk

70%

75%

80%

85%

90%

95%

100%

0 1 2 3 4 5 6 Months After Randomization

Even

t Fre

e Su

rviv

al (%

)

CRT

Control P = 0.033 Relative risk = 0.60; 95% CI (0.37, 0.96)

Time to Death or Worsening HF requiring Hospitalization MIRACLE

MIRACLE: Circulation 2003;107:1985-1990

COMPANION Composite of Death or Hospitalization for Any Cause Results

Days after Randomization

1080

100

960 840 720 600 480 360 240 120 0

80

60

40

20

0

OPT CRT CRT-D

Eve

nt-

Free

Su

rviv

al (%

)

(CRT vs. OPT) P = 0.014

(CRT-D vs. OPT) P = 0.010

Bristow M. N Engl J Med. 2004;350:2140-2150.

No. at Risk OPT 308 176 115 72 46 24 16 6 1 CRT 617 384 294 228 146 73 36 14 3 CRT-D 595 385 283 217 128 61 24 8 0

COMPANION All-Cause Death Results

Days from Randomization

Eve

nt-

Free

Su

rviv

al (%

) 100

90

80

70

60

50

OPT CRT CRT-D

(CRT vs. OPT) P = 0.059

(CRT-D vs. OPT) P = 0.003

Bristow M. N Engl J Med. 2004;350:2140-2150.

No. at Risk OPT 308 284 255 217 186 141 94 57 45 25 4 2 CRT 617 579 520 488 439 355 251 164 104 60 25 5 CRT-D 595 555 517 470 420 331 219 148 95 47 21 1

90 900 810 720 630 540 360 270 180 0 990 1080 450

CARE-HF - Death or Unplanned Hospitalization for CV Event Results

% P

atie

nts

Fre

e of

Dea

th f

rom

An

y C

ause

or

Un

pla

nn

ed H

osp

ital

izat

ion

for

a

M

ajor

CV

Eve

nt

100

0

P < 0.001

CRT

Medical Therapy

75

50

25

0 1500 1000 500

No. at Risk CRT 409 323 273 166 68 7 Medical Therapy 404 292 232 118 48 3

Days

Cleland JGF. N Engl J Med. 2005;352:1539-1549.

HR 0.63 (95% CI 0.51 to 0.77) 37% Relative Risk Reduction

CARE-HF Death from Any Cause Results

% P

atie

nts

Fre

e of

Dea

th f

rom

An

y C

ause

100

0

P < 0.002

75

50

25

0 1500 1000 500

No. at Risk CRT 409 376 351 213 89 8 Medical Therapy 404 365 321 192 71 5

Days

CRT

Medical Therapy

Cleland JGF. N Engl J Med. 2005;352:1539-1549.

HR 0.64 (95% CI 0.48 to 0.85) 36% Relative Risk Reduction

ICD and CRT Which Patient ?

ICD:

ü  Mild to moderate HF – NYHA Class I-III ü  LV ejection fraction ≤ 35% ü  Post-MI (≥ 40 days); post-CABG (≥ 3 months) ü  Optimal medical therapy ü  Survival > 1 yr

CRT: ü  Moderate to severe HF (NYHA Class III/IV) patients ü  Symptomatic despite optimal, medical therapy ü  QRS ≥ 120 msec ü  LVEF ≤ 35 ü  Sinus rhythm

CRT plus ICD: ü  Same as above with ICD indication

CMS ICD Coverage Reference Guide

NYHA Class II or III HF SCD-HeFT ischemic

No

Yes History of MI

NIDCM > 9 months NYHA Class II or III

heart failure and LVEF ≤ 35% SCD-HeFT

non-ischemic

History of inherited conditions with high risk of VT

History of cardiac arrest due to VF

Sustained VT, spontaneous or induced by EPS

Not eligible for defibrillator

No

No

No

No

LVEF ≤ 30% MADIT-II

LVEF ≤ 35% No No

Yes Yes

Yes

Yes

Yes

Yes

• NYHA Class IV • Cardiogenic shock or hypotension • CABG or PTCA within past 3 months • MI within past 40 days • Candidate for coronary revascularization • Irreversible brain damage from preexisting cerebral

disease • Other disease with survival < 1 year

Eligible for defibrillator

Not eligible for defibrillator

CAD, inducible sustained VT or VF

at EPS MADIT

No Yes

Yes

No

Yes

No

CMS CRT/CRT-D Coverage Reference Guide Symptomatic

HF despite stable, optimal

medical therapy

Prolonged QRS and

LVEF≤ 35%

NYHA Class IV heart failure

NYHA Class III heart failure

Meets coverage criteria for the implantation

of an ICD

Not eligible for

CRT device

Eligible for CRT pacemaker

(CRT-P)

Eligible for CRT defibrillator

(CRT-D)

No

No

Yes

Yes Yes

Reference CMS Local Coverage Decision and Bulletins for any specific coverage requirements specific to your region or state. Some local policies require a QRS duration > 130 ms.

Yes

No

Yes

No

CLASS II

Ischemic Cardiomyopathy (at least 40 days after IMA) Reduced EF (≤ 30%), NYHA I , Optimal Medical Treatment (Level B)

Ischemic (at least 40 days after IMA) & Non-Ischemic Cardiomyopathy 31% ≤ EF ≤ 35%, NYHA II/III Optimal Medical Treatment (Level B)

Ischemic & Non-Ischemic Cardiomyopathy (for Ischemic at least 40 days after AMI) Reduced EF (≤ 30%), NYHA II/III, Optimal Medical Treatment (Level A)

Ischemic Cardiomyopathy, Reduced EF (≤ 40%) Non Sustained VT and Sustained Inducible VT (Level B)

CLASS I

ICD - PRIMARY PREVENTION IN CARDIOMYOPATHY

AIAC Guidelines

AIAC Guidelines

Chronic Right Ventricular Stimulation, Reduced EF (≤ 35%) Severe Ventricular Dyssynchrony NYHA III-IV despite Optimal Medical Therapy (Upgrade)

Synus Rhythm, Reduced EF (≤ 35%) Ventricular Dyssynchrony (QRS > 120ms) Symptomatic (NYHA II) and with pacing indication or Primary Prevention ICD

Reduced EF (≤ 35%), QRS ≤ 120 ms Ventricular Dyssynchrony (Echo assessment) NYHA III-IV despite Optimal Mdical Therapy

Pts In Atrial Fibrillation, Reduced EF (≤ 35%) Ventricular Dyssynchrony (QRS > 120ms) NYHA III-IV despite Optimal Medical Therapy

CLASS II

Synus Rhythm, Reduced EF (≤ 35%) Ventricular Dyssynchrony (QRS > 120ms) NYHA III-IV despite Optimal Medical Therapy

CLASS I

CARDIAC RESYNCHRONISATION THERAPY

RECOMMENDATIONS FOR CRT-D USE The use of ICD in addition of CRT (CRT-D) should be based on recommendations

for ICD use in primary or secondary prevention of sudden cardiac death

Indications of CRT New Guidelines of ESC

ü Symptoms (Class I, level A)

ü Hospitalizations (Class I, level A)

ü Mortality (Class I, level B)

CRT using BIV pacing can be considered in patients with reduced EF and ventricular dyssynchrony (QRS widht > 120 msec), who remain symptomatic (NYHA III-IV) despite optimal medical therapy to improve:

WCC, Barcellona 2-6 September 2006

QRS=160 ms QRS=120 ms

-------Therapy OFF------- ---------Therapy ON---------

Cardiac Resynchronization Therapy: Creating Realistic Patient Expectations

ü Approximately two-third of patients should experience improvement (responders vs. non-responders)1

ü Some patients may not experience immediate improvement

CRT is adjunctive and is not intended to replace medical therapy. Patients will continue to be followed by HF Specialist and Physician managing implantable devices.

1 Abraham, WT, et. Al. Cardiac Resynchronization in Chronic Heart Failure. N Engl J Med 2002;346:1845-53

Patient Selection for CRT Reasons for Low (or no) Response to CRT

ü  Inappropriate patient selection

ü  Inappropriate lead positioning

ü  Inappropriate AV delay tuning

ü  Inappropriate CRT delivery (PM functioning)

ü  Inappropriate drug treatment

ü  Spontaneous or PM mediated arrhythmias

RESPONDER ü  Survival + at least 1 NYHA class down + 10% increase in peak

VO2, for at least 6 months. Alonso. AJC 1999 ü  Improvement > 1 NYHA class. Oguz. Eur J H Fail 2002 ü  LVESV decreased by > 15%. Stellbrink. J ACC 2001 ü  Persistent decrease of > 1 NYHA class, irrespective of the changes

of others parameters.

NON RESPONDER: ü No decrease in NYHA class + no decrease in the QOL score.

Reuter. AJC 2002 ü  Therapy considered as neutral or not beneficial (same NYHA

class or decline of status; need for heart transplant; death due to progressive, drug-refractory pump failure). Lunati. J CE 2002

Definition of Responder/Non Responder

Reasons for low (or no) response to CRT 1. Inappropriate patient selection

ü No Ventricular asynchrony +++ ü CRT may create ventricular asynchrony !!

ü End stage cardiomyopathy ü Severe RV dysfunction, High pulmonary hypertension

ü Additional indications for Heart Surgery ü Valve replacement, CABG

Reasons for low (or no) response to CRT 2. Inappropriate lead positioning

ü LV lead placed in the Great Cardiac Vein

ü RV lead close to the apex

ü High lat RA lead in inter atrial conduction block ü Short AVD: good BiV capture + poor LA contraction ü Long AVD: poor BiV capture + good LA contraction

Possible Venous Tributaries of the CS

CS venous anatomy allowing LV lead tip should usually be positioned in a basal/mid-basal lateral (region C) or basal/mid-basal postero-lateral (region D) location

Varying Patient Anatomy

Reasons for low (or no) response to CRT 3. Inapproriate setting of AV delay

Long AV Delay 160 ms: Opt A

Short AV Delay 50 ms: opt E

Optimized AV Delay 100 ms: opt E + A

Importance of AV delay optimization

Reasons for low (or no) response to CRT 4. Inappropriate CRT delivery: Up to 20% !

PVC

VS VR

VS VR

AR

VS VR

AR AS

VP

AS

VP

AS

VP VS VR

AR

VS VR

AR

IVCD IVCD IVCD IVCD IVCD SAV SAV SAV iAV iAV iAV iAV

PVARP PVARP PVARP PVARP PVARP PVARP PVARP

Reasons for low (or no) response to CRT 5. Inappropriate drug treatment

ü ACE inhibitors: ü increase in dosage, re-introduction

ü Diuretics: ü decrease in dosage +++

ü Beta-Blockers: ü Introduction ü increase in dosage

ü Combination: Amiodarone and beta-blockers

CRT Procedure and Device Related Risks

Procedure Related Complications in 571 Patients Attempted; Proportion (n)

Unsuccessful implant 7.5% (43)

CS Dissection or Perforation

(35; all re-covered w/o sequela)

6%

Bradycardia ⏐0.3% (2)

Death ⏐0.3% (2)

Device Related Complications in 6 months in 528 Patients Successfully Implanted ; Proportion (n)

LV Lead Revision

5.7% (30; all replaced or repositioned)

PM Pocket/ RV Lead Infection 1.3% (7; 4 of 7 re-implanted)

Abraham WT, et al. NEJM 2002;346:1845-53 (MIRACLE)

Unpublished data. MIRACLE study.

Reduced Procedure Time with Increased Experience

60 120 180 240 300

Up to first 5

Next 6 to 10

Next 11 more

Center-based experience

Imp

lan

t Tim

e (m

inu

tes) P < 0.001

1 2

3 4

CS dissection

When to Consider Epicardial Approach for LV Pacing

ü  Failure to implant LV lead: 0 to 10 % ü  LV lead in mid or great cardiac vein: 0 to 10 % ü  Interest of endocardial versus epicardial pacing

88% 90% 92% 93% 96%

70%

100%

InSy

nc

InSy

nc It

Mus

tic

Mir

acle

Med

OTW

LV pacing using epicardial approach

Incremental Cost-Effectiveness Cardiovascular Interventions

Hypertension Therapy (diastolic 95 - 104 mmHg)

Expensive

Borderline Cost-Effective

Cost-Effective

Highly Cost-Effective

Incr

emen

tal C

ost p

er L

ife-

Year

Sav

ed

Economically Unattractive

Lovastatin (chol. =

290 mg/dL, 50 yrs old,

male, no risk factors)

PTCA (chronic CAD, severe angina

1 VD)

CABG (chronic

CAD mild angina,

3 VD)

End Stage Renal

Disease Treatment

Exercise SPECT

(atypical angina who

can walk on treadmill)

Routine Coronary

Angiography (35 - 84 yrs old,

low risk MI, has CHF)

$8,461 $17,701

$40,750

$67,000

$135,000 $150,000

Carotid Disease

Screening (65 yrs old,

male, no symptoms)

$1,000,000

$120,000

Moss AJ. Satellite Symposium, “Cost-Effectiveness of Device Therapy in the Heart Failure Population", September 23, 2003. Kupersmith J. Progress in Cardiovascular Diseases. 1995;Vol XXXVII, No. 5:307-346. Stanton M. Circulation. 2000;101:1067-1074.

$0

$20.000

$40.000

$60.000

$80.000

$100.000

$120.000

$140.000

$160.000

$180.000

$200.000

$0

$20.000

$40.000

$60.000

$80.000

$100.000

$120.000

$140.000

$160.000

$180.000

$200.000

Incremental Cost-Effectiveness ICD, CRT, and CRT-D Therapies

COMPANION CRT-D1

Incr

emen

tal C

ost p

er L

ife-

Year

Sav

ed

COMPANION CRT1

MADIT-II ICD3

AVID ICD4

$28,000 $38,200 $50,000 $67,000

Expensive

Borderline Cost-Effective Cost-Effective

Highly Cost-Effective

Economically Unattractive

SCD-HeFT ICD2

$33,000

1 Feldman AM. www.theheart.org. ACC News. March 16, 2005. 2 Mark DB. www.theheart.org. AHA News. November 11, 2004. 3 Ak-Khatib S. Ann Intern Med. 2005;142:593-600. 4 Larsen G. Circulation. 2002;105:2049-2057.

ü  Which implication in patients with unstable haemodinamic profile ?

ü  CRT in chronic Atrial Fibrillation ?

ü  CRT in Right Bundle Branch Block ?

ü  QRS<120ms or QTc dispersion ?

Actual Key Questions

ü  “Up-grading” in RVA pacing ?

Over 8,000 Patients Studied in Clinical Trials MADIT CRT

REVERSE ♦

♦

Prevalence of AF in moderate-to-severe CHF varies between 25% and 50%

2%

The interaction between AF and HF means that neither can be treated optimally

without treating both

HF AF

promotes

aggravates

MADIT-CRT Question

Does early intervention with CRT-D

slow the progression of HF in high-risk

patients with mild HF (NYHA I – II)

when compared to ICD only therapy?

MADIT-CRT

Hypothesis: in minimally symptomatic high-risk pts with IHD (NYHA I or II) or NIHD (NYHA II), wide QRS (≥ .13s), and low EF (≤ .30), CRT will slow or

prevent the development of heart failure

ü  CRT-D vs ICD-only ü  1820 pts: 110 enrolling centers in US & Europe ü  Endpoint: HF or death, whichever comes first ü  Enrollment complete, in f/up phase

Note: Of 1820 enrolled patients, 300 have experienced a 1st end-point event.

Kaplan-Meyer Curves for Death and for HF/Death – Both Rx Arms

(CRT-D vs. ICD)

LV Sequential Pacing

LAO

SR RV LV(lv) LV(pl) LV(lvpl) BIV

(RV+lv)

Triple Site BIV

(RV+2 left)

Triple-site biventricular pacing

Multi-site Pacing