2006 orvieto, giornate cardoilogiche orvietane. il trattamento non farmacologico dello scompenso cardiaco

Giornate Cardiologiche OrvietaneGiornate Cardiologiche Orvietane
Il trattamento non farmacologico delloIl trattamento non farmacologico dello
SCOMPENSO CARDIACOSCOMPENSO CARDIACO
Stefano Nardi, MD, PhD
AZIENDA OSPEDALIERA SANTA MARIA TERNIAZIENDA OSPEDALIERA SANTA MARIA TERNI
DIPARTIMENTO CARDIOTORACOVASCOLAREDIPARTIMENTO CARDIOTORACOVASCOLARE
STRUTTURA COMPLESSA DI CARDIOLOGIASTRUTTURA COMPLESSA DI CARDIOLOGIA
STRUTTURA SEMPLICE DI ARITMOLOGIASTRUTTURA SEMPLICE DI ARITMOLOGIA
LABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONELABORATORIO DI ELETTROFISIOLOGIA ED ELETTROSTIMOLAZIONE

CHFCHF: non pharmacological approach: non pharmacological approach

Reduced Mortality in HF
ACE-I & Beta Blockade
Reduce Mortality
11.5%
15.6%
12.4%
7.8%
0%
4%
8%
12%
16%
SOLVD-T MERIT-HF
+ CIBIS II
1YearMortality
Placebo Treatment
Digossina,
Diuretici,
Idralazina ACE-I
ß-blocker
and ACE-I
SOLVD
CONCENSUS
da -16 a -31% CIBIS II
COPERNICUS
- 35%
Mortalità
MortalityMortality
too Hightoo High

Mortalità ad 1 anno
ITALIAN NETWORK CHF
4,1 %4,1 %
11,7 %11,7 %
24,8 %24,8 %
36,7 %36,7 %
15,1 %15,1 %
(%)(%)
NYHA I
1
NYHA II
2,14
[1,33-3,44]
NYHA III
3,77
[2,32-6,12]
NYHA IV
5,54
[3,23-9,48]
Totale
Rischio
Relativo
• 600.000 CHF pts
• 87.000 morti / anno
• Mortalità a 5 anni >70%
• 44% CHF re-hospitalization
a 6 mesi dal primo evento
• % della spesa sanitaria per
CHF: 1,5 - 2%
• CHF prima causa di
ospedalizzazione nella
popolazione > 65 anni di età
• CHF prima patologia per
durata della degenza
ospedaliera
1 Framingham Heart Study (‘48 – ‘88) in Atlas of Heart Diseases.
2 AHA. Heart Disease and Stroke Statistics—’03 Update.
CHF Patients Survival Results1CHF Patients Survival Results1

a Vicious Cycle
Abnormal RV-
LV sequence
Mitral Regurgitation
Segmental
Dyskinesia
Dysynchronous
Contraction
Abnormal LV
activation
sequence
↑ Neurohormones
↓ LVEF
Dissynchrony
RV/LV
filling flow

Burkhoff D, Am J Phys ‘87
Different Pacing-site
in CANINE model
What does it meanWhat does it mean
Asynchronus activation ?Asynchronus activation ?

Spragg DD, Circulation ’03
Regional Alterations of Protein
Expression in CHF dogs

SinusSinus
nodenode
AVAV
nodenode
BundleBundle
branch orbranch or
diffuse blockdiffuse block
Delayed conductionDelayed conduction
• Abnormal RV-LV sequence
• Abnormal LV activation
sequence
• Segmentary dyskinesia
• Aggravation of mitral
regurgitation
• Disynchrony of RV and LV
filling flows
Dyssynchrony Ventricular ContractionDyssynchrony Ventricular Contraction
What is abnormal in the HF pts?What is abnormal in the HF pts?
• Delayed AV sequence
• Mitral regurgitation
• Decreased filling time

What does it means
DYSSYNCHRONYSM ?
0
5
10
15
20
25
30
1 Year-Mortality
Total Sudden Death
LBBB
No LBBB
Study pop
11.9
16.1
10.5
5.5 4.9
7.3
p<0.001
p<0.001
60%
70%
80%
90%
100%
0 60 120 180 240 300 360
Days in Trial
CumulativeSurvival
QRS
Duration
(msec)
<90
90-120
120-170
170-220
>220
Adapted from Gottipaty et al. JACC
1999; 33(2):145A (abstract 847-4)
INCHF
• VEST study analysis
• NYHA Class II – IV pz

Di Donato M, Circulation ‘04
Which is the relationship between
Dysshynchronysm and QRS duration ?
60%
70%
80%
90%
100%
0 60 120 180 240 300 360
Days in Trial
CumulativeSurvival
Ole-A. Breithardt, MD
ALTERED
WORK-LOAD

• Radionuclide
• MRI
• ECHO-cardiography
Which technique for
Patients selection ??
INTER-VCD (CARE HF)
Conventional Echo-Doppler
(Q-efflux Ao –Q-efflux Po >40 ms)
INTRA-VCD
M-mode (validate only in QRS wide) PW-
TDI Strain Rate
Echo 3D

• Optimizes AV contraction sequence
• Reduces pre-systolic mitral regurgitation
• Improves atrial preloading of the ventricle
• Increases filling time
Mechanism IMechanism I
Atrio-Ventricular SynchronyAtrio-Ventricular Synchrony
Rationale for CRTRationale for CRT
What does pacing changeWhat does pacing change??

• Optimizes ventricular activation
• Increases pumping effectiveness
• Reduces regional wall stress (WMSI)
• Decreases mitral regurgitation
• Resynchronizes ventricular filling flows
• Decreases filling pressures
Mechanism IIMechanism II
Ventricular CoordinationVentricular Coordination
Rationale for CRTRationale for CRT
What does pacing changeWhat does pacing change??

OAVD Restores AV Synchrony
PP RR
INTRINSICINTRINSIC
AorticAortic
pressurepressure
LVLV
pressurepressure
PPPP
PeakPeak
atrial systoleatrial systole
Start ofStart of
LV systoleLV systole
Diastolic
Mitral
Regurgitation
Maximum
Effective Preload
PP VV
PACEDPACED
PPPP
SynchronizedSynchronized
LV and atrialLV and atrial
systolessystoles
Auricchio, PACE `98

Kass et al,Kass et al,
Circulation 99Circulation 99
IntrinsicIntrinsic
PacedPaced
00 100100 200200 300300
00
4040
8080
120120
RV SeptumRV Septum
00 100100 200200 300300
00
4040
8080
120120
BiventricularBiventricular
00 100100 200200 300300
00
4040
8080
120120
RV ApexRV Apex
00 100100 200200 300300
00
4040
8080
120120
LV FreewallLV Freewall
LV VolumeLV Volume (mL)(mL)
LVPressureLVPressure
(mmHg)(mmHg)
LVPressureLVPressure
(mmHg)(mmHg)
LV VolumeLV Volume (mL)(mL)
Acute studies

Cumulative Enrollment in C.R.Cumulative Enrollment in C.R.
Randomized TrialsRandomized Trials
0
1000
2000
3000
4000
1999 2001 2003 2005
Result s Present ed
CumulativePatients
PATH CHF
MUSTIC SR
MUSTIC AF
MIRACLE
CONTAK CD
MIRACLE ICD
PATH CHF II
COMPANION
MIRACLE ICD II
CARE HF
DOUG SMITHDOUG SMITH

Auricchio et al., NASPE ‘99
PATH-CHF:
Inclusion Criteria (42 pts)
• Dilated cardiomyopathy of any etiology
• NYHA Class III (> 6 months) or NYHA IV
• Optimal individual drug therapy
• QRS duration >120 msec
• PR Interval >150 msec
• Sinus rate > 55 bpm
• No conventional pacemaker indication
PATHCHF

325
350
375
400
425
450
475
pre-implant
n=20
4 weeks
n=20
8 weeks
n=20
12 weeks
n=20
6 months
n=20
12 months
n=20
Meters
Long Term Benefit
PATHCHF
0
10
20
30
40
50
60
pre-implant
n=20
4weeks
n=20
8weeks
n=20
12weeks
n=20
6months
n=20
8months
n=20
10months
n=20
12months
n=20
MinnesotaScore
Quality of Life6 - MWT

Long Term Benefit:
Peak Oxygen Uptake
0.9
1
1.1
1.2
1.3
1.4
0 1 2 3 4 5 6 7 8 9 10 11 12
Months
PeakVO2(l/min)
PATHCHF
0
10
20
30
40
daysofhospitalization
1 Year1 Year
Pre-ImplantPre-Implant
1 Year1 Year
Post-ImplantPost-Implant
PP == .003.003

MIRACLE
• Moderate or severe HF (NYHA III-IV)
• Stable optimal HF medical therapy regimen
for >1month
- Diuretics (93-94%)
- ACE-I or ARB (90-93%) if tollerated
- β-blocker (55-62%) at stable regimen for>3
months
• QRS duration ≥150 msec
• LVEF ≤35% or LVEDD ≥55mm (echo measure)
• Sinus rate > 55 bpm Abraham WT, Fisher WG, Smith AL, et al.
N Engl J Med 2002;346:1845-1853

Benefits Sustained Through 2 yr:
MIRACLE Study Program
0
100
200
300
400
500
Mean
6-MWT(m)
1
2
3
4
0
20
40
60
80
100
6 (N=1124) 12 (N=693) 18 (N=320) 24 (N=68)
Months of Active CRT
Mean NYHA
Functional Class
Mean QoL Score
Improvement ↓
Baseline
Follow-up
Paired
Data
Displayed
P<0.001 P<0.001 P<0.001 P=0.01
P<0.001 P<0.001 P<0.001 P<0.001
P<0.001 P<0.001 P<0.001 P<0.001
Source: Abraham,
WT et al. AHA 2003

Change in MR Jet AreaChange in MR Jet Area
-4-4
-3-3
-2-2
-1-1
00
11
ControlControl
(n=118)(n=118)
CRTCRT
(n=116)(n=116)
cmcm22
P<0.001P<0.001 P=0.009P=0.009
Change in LVEDDChange in LVEDD
-6-6
-4-4
-2-2
00
22
ControlControl
(n=118)(n=118)
CRTCRT
(n=116)(n=116)
mmmm
P<0.001P<0.001
Absolute Change in LVEFAbsolute Change in LVEF
-2-2
00
22
44
66
88
ControlControl
(n=146)(n=146)
CRTCRT
(n=155)(n=155)
%%
Baseline (mm)Baseline (mm)
69 ± 10
70 ± 10
Baseline (cmBaseline (cm 2
)
7.2 ± 4.9
7.6 ± 6.4
Baseline (%)Baseline (%)
22 ± 6
22 ± 6
Paired median change from baseline at 6 months
Cardiac Function and Structure
MIRACLE

Effects on
Cardiac Function and Oxidative Stress
0,14
0,16
0,18
0,20
0,22
0,24
500 600 700 800 900
dP/ dtmax (mm/ Hg/ s)
MVO2/HR(RelativeUnits)
Dobutamin
LV Pacing
P< 0.05
Nelson et al. Circulation 2000
Myocardial Oxidative
Metabolism
0
0,02
0,04
0,06
LV RV
kmono(min-1
)
p=
0.86
p=
0.62
n=8
Myocardial Efficiency
Work Metabolic Index
0
2
4
6
8
10
12
mmHG·L·m-2
Baseline CRT
p =0.024
Ukkonen et al. Circulation 2003
n=7
MIRACLE

Mortality/Morbidity
from Published Randomized, Controlled
Trials
Risk reduction with CRT
Study
(n random.) FU
Mor-
tality &
Hosp.
Mortal. &
HF Hosp.
Mor-
tality
HF
Mort.
HF
Hosp.
MIRACLE
(n=453)
6 Mo NR 39%* 27% NR 50%*
MIRACLE ICD
(n=369)
6 Mo 2% 0% 0% NR NR
Contak CD
(n=490)
3-6 Mo NR NR 30% NR 18%
Meta-analysis
(n=1634)
3-6 Mo NR NR 23% 51%* 29%*
* P < 0.05

RandomizeRandomize
1:2:21:2:2
• OptimalOptimal
PharmacologicPharmacologic
Therapy (OPT)Therapy (OPT)
• OPTOPT
• BV pacingBV pacing +
• OPTOPT
• BV pacingBV pacing
• DefibrillationDefibrillation
+
CoComparison ofmparison of MMedical Therapy,edical Therapy, PPacingacing anandd
DefibrillatDefibrillationion in Chronic Heart Failurein Chronic Heart Failure
((COMPANIONCOMPANION))

COMPANION CARE - HF
Cleland J. G.F, NEJM ‘05Bristow, NEJM ‘04

• Reduced LVEF remains the single most
important risk factor for overall mortality
and SCD.1
• Increased risk is measurable at EF above
30%, but an EF ≤30% is the single most
powerful independent predictor for SCD.2
1
Prior SG, Aliot E, Blonstrom-Lundqvist C, et al. Task Force on Sudden Cardiac Death of the European Society of
Cardiology. Eur Heart J, Vol. 22; 16; August 2001.
2
Myerburg RJ, Castellanos A. Cardiac Arrest and Sudden Cardiac Death, in Braunwald E, Zipes DP, Libby P, Heart
Disease, A textbook of Cardiovascular Medicine. 6th
ed. 2001. W.B. Saunders, Co., p. 895.
Relationship of SCDRelationship of SCD
and LV Dysfunctionand LV Dysfunction

 Several RANDOMIZED studies have demonstrated that ICD reduce MORTALITY
(~30-50%), both in primary and in secondary prevention

• 126 pts underwent CRT
• If criteria for ICD
(US guidelines,
including MADIT)
CRT-D
• If no, CRT-P
CRT-D vs CRT-P in Severe LV dysf.
Ermis et al. JCE, ‘04
Miglioramento del 41%
(p =0,01)
I pazienti che non presentano rischi noti di Morte
Improvvisa li sviluppano col passare del tempo …
ecco perché necessitano di un ICD di back-up

Mortalità
totale
Frazione di
eiezione
Morte per
causa aritmica
Diss. E-M
Elettrica
Infettiva
Neoplastica
Neurologica
Ecc.
All’aumentare della LVEF si riduce la mortalità
per CHF ma aumenta quella per causa aritmica
Challenges in electrical management of
CHF
NYHA II
Other
24%
CHF
12%
Sudden
death
64%
N=103
NYHA III
Sudden
death
59%
CHF
26%
Other
15%
N=232
NYHA IV
Sudden
death
33%
CHF
56%
Other
11%
N=27 MERIT-HF

ACE-I & Beta Blockade
Reduce Mortality
11,5%
15,6%
12,4%
7,8%
0%
4%
8%
12%
16%
SOLVD-T MERIT-HF
+ CIBIS II
1YearMortality
Placebo Treatment
Further Reduction
with CRT + ICD
for Higher Risk Patients
HF
Mortality
Sudden
Cardiac
Death
CRT
ICD
Weight of Evidence: CRT

Digossina,
Diuretici,
Idralazina ACE-I
ß-blocker
and ACE-I ß-blocker,
ACE-I and
CRT-D
COMPANION
- 36%
SOLVD
CONCENSUS
da -16 a -31% CIBIS II
COPERNICUS
- 35%
MortalitàCONCLUSIONSCONCLUSIONS

D’Ascia C, Eu Heart J ‘06
CRT
Baseline 1wk 1mo 3mo off-immed off-1wk off-4wk
100
125
150
175
200
225
*
*
*
*
†
* *
*
†
Leftventricularvolume(mL)
*
VO2(ml/min/mVO2(ml/min/m22
))
DODO22 (ml/min/m(ml/min/m22
))
Critical DOCritical DO22
DISOXIADISOXIA
Critical VOCritical VO22
NormalNormal
Reverse
Remodelling
TNF-alpha expression
Apoptosis
Fibrosis

2002
Classe IIa:
Symptomatic pts, Class NYHA
III or IV, DCM (hydiopatic or
ischemic) prolonged QRS interval
(≥ 130 ms), LVEDD≥ 55 mm, LVEF
≤ 35%.
News 2005
Classe I:
III, Synus Rhythm, OMT for
CHF, Dyssynchrony
(Level of Evidence A)
Aggiornamento delle linee guida
ACC/AHA (2002 2005)→
Terapia CRT

ESC 2005
Classe IIa:
Symptomatic pts in NYHA Class III
or IV in OMT for CHF,
Dyssinchrony and reduced LVEF
ACC/AHA 2005
Classe I:
III, Synus Rhythm, OMT for
CHF, Dyssynchrony
(Level of Evidence A)
Confronto tra LINEE GUIDA
ESC e ACC/AHA (2005)
Terapia CRT
CRT for improve symptoms and CHF-
H (Level of Evidence A)
CRT for improve risk of death
(Level of Evidence B)

CLASS I SR, LVEF ≤ 35%, QRS > 120ms, NYHA III-IV, OMT
CLASS
II
Atiral Fibrillation LVEF ≤ 35%, QRS > 120ms,
NYHA III-IV in OMT
LVEF ≤ 35%, QRS ≤ 120 ms, NYHA III-IV,
OMT Dysshynchronism (Echo),
SR, LVEF ≤ 35%, QRS > 120ms
Symptomatic NYHA class II, PM or ICD
indication (in primary prevention)
Chronic RVA pacing, LVEF ≤ 35%, NYHA III-
IV, OMT, Severe Dyssynchronism (Up-grading),
LINEE GUIDA AIAC 2006
CRT

High anatomic
of CS system
Optimization of CRT
(n° vene, presenza di
valvole, angolature,
tortuosità ecc.)

• Reduction of responsivity in
ischemic disease (SCAR, Non
contractile segment etc)
(Gasparini M, PACE ’03)
• In Ischemic DCM the
asynchronysm can interest each
LV wall, whereas CRT is more
efficacy in lateral or postero-
lateral wall
(Yu CM, Circulation ‘04)
• Pacing not efficacy
• Comorbidity
• Severe CHF or hemodinamic
instability
Why are the Non-Responders ?

• No MR
(Reuter S et a. Am J Cardiol ‘02) or
severe MR
(Achilli A, Italian Heart J ‘04)
• Elevated LVEDV and LVESV
(Bax JJ, JACC ‘04)
• Permanent AFib - controverso:
ablazione NAV? Speranza di
recupero RS con riduz. IM e
reverse LV remodeling?
• Class NYHA IV

CHF Population
6.5 Mio
NYHA III + IV (30 -
35%)
1.95 Mio
Wide QRS (10 - 30%)
Resynchronization Rx
Target Population:
195’000
650’000
Incidence = 580’000 (9.0%)
Mortality = 300’000 (4.6%)
CHF Population in EuropeCHF Population in Europe

Relative Cost of CRT
Cost per patient
$0$20$40$60
CRT+ I CD
CRT
Hip/ knee replace
PTCA
CABG
Dialysis
$ thousands
Total Annual Expenditures
$0 $5 $10 $15 $20
$ Billions
Doug Smith:
Doug Smith:
CONCLUSIONSCONCLUSIONS

0
5000
10000
15000
Baseline Post-implant
Intensive care
Cardiology
Others
Patient Cost Baseline: 12,784 Euro
Patient Cost (Implant included): 12,362 Euro
Patient Cost Post-implant: 1,680 Euro
Hospital costs per patient
Cost Effectiveness
Analysis of Biventricular
Pacing in HF
Curnis A 2001
CONCLUSIONSCONCLUSIONS

Creating Realistic
patients expectations
• Approximately two-third of patients
should experience improvement, but
some patients may not experience
immediate improvement
• Have patients set their own goals
of what they would like to do
following CRT:
Grocery shopping, Decreasing Lasix dose,
Walking to the mailbox without stopping,
Lying flat to sleep

Necessari ulteriori studi con “follow-up” a
più lungo termine per capire il giusto
“LINK” esistente tra efficacia in ACUTO,
mantenimento del risultato in cronico e
CONSEGUIMENTO DEGLI “END POINT”
Perfezionare le conoscenze sui meccanismi
della CHF
Migliorare la tecnologia, rendere le
procedure sempre più fattibili
minimizzando i rischi

GRAZIE PER LAGRAZIE PER LA
CORTESECORTESE
ATTENZIONEATTENZIONE

• Have patients set their own goals of what they
would like to do following CRT:
Grocery shopping, Decreasing Lasix dose
Walking to the mailbox without stopping,
Lying flat to sleep
• Encourage them to be part of the group that
responds to their therapy
Creating Realistic expectations
Cardiac Resynchronization TherapyCardiac Resynchronization Therapy

InSync Italian Registry
QRS duration (msec) 172+32
Ejection fraction (%) 25+7
LV end Diast. Diameter (mm) 71+9
NYHA functional class 3,15+0,61
6 min walking test (m) 269+142
Chronic Atrial Fibrillation 17,4%
190 patients M= 82,8%; Age= 68+ 8
ETIOLOGY:
Ischemic 46,6%; Idiopatic 37,9%; Other 15,5%
InSync
Italian
Registry

InSync
Italian
Registry
M. Zardini et al, Eur Hear 2000
LVEF %
0
10
20
30
40
BASELINE FOLLOW-UP
%
6m HWT
0
100
200
300
400
500
BASELINE FOLLOW-UP
m
NYHA class
0
1
2
3
4
BASELINE FOLLOW-UP
QOL Score
0
10
20
30
40
50
60
70
80
BASELINE FOLLOW-UP
p < .0001
p < .0001 p < .0001
p < .0001
Clinical Outcome

Results Active
pacing
Inactive
pacing
p
6-min w (m) 399 ± 100 326 ± 134 .0001
QOL score 29.6 ± 21.3 43.2 ± 22.8 .0002
VO2 (ml/min/Kg) 16.2 ± 4.7 15 ± 4.9 0.02
S.Cazeau et al NEJM 2001;344:873-80S.Cazeau et al NEJM 2001;344:873-80
MUSTIC
Results (67 pts)

VO2(ml/min/mVO2(ml/min/m22
))
DODO22 (ml/min/m(ml/min/m22
))
OO22ERER
Critical DOCritical DO22
DISOXIADISOXIA
Critical VOCritical VO22
DODO22 == QQCC X CaX CaOO22
VOVO22 == DODO22 XX OO22ERER
NormalNormal
DODO22 ==QQCC x (1,34 xx (1,34 x Hb x SaHb x SaOO22) x 10) x 10

QOL & Functional Capacity
6 Months in Moderate to Severe HF
-20
-15
-10
-5
0
P<0.001 P=0.02 P=0.017P<0.001
QoL Score
(MLWHF)
Avg. Change
0%
20%
40%
60%
80%
MIRACLE MUSTIC SR MIRACLE ICD Contak CD
P<0.001 P=0.006P=0.007
Data sources:
MIRACLE: Circulation 2003;107:1985-90 MUSTIC SR: NEJM 2001;344:873-80
MIRACLE ICD:JAMA 2003;289:2685-94 Contak CD: JACC 2003;2003;42:1454-59
 Control CRT
NYHA Class
Proportion
Changing 1
or more
Classes
Improve. ↓
Not
Reported

Exercise Capacity
6 Months in Moderate to
Severe HF
-20
0
20
40
60 P<0.001 P=0.36 P=0.029
P<0.001
6 Min Walk
Avg. Change
(m)
00
0
1
2
3
MIRACLE MUSTIC SR MIRACLE ICD Contak CD
P<0.001
P=0.029
P=0.04
P=0.003
Data sources:
MIRACLE: Circulation 2003;107:1985-90 MUSTIC SR: NEJM 2001;344:873-80
MIRACLE ICD:JAMA 2003;289:2685-94 Contak CD: JACC 2003;2003;42:1454-59
 Control  CRT
Peak VO2
Avg. Change
(mL/kg/min)

Effect on LV StructureEffect on LV Structure
6 Months in Moderate to
Severe HF
-40
-20
0
P<0.001
P=0.06
LVEDV
Avg. Change
(mL)
-6
-4
-2
0
2
MIRACLE MIRACLE ICD Contak CD
P<0.05 P=0.81 P=0.001
 Control  CRT
LVEDD
Avg. Change
(mm)
NOT
REPORTED
Data sources:
MIRACLE: Circulation 2003
MIRACLE ICD:JAMA 2003
CONTAK CD: J Am Coll Cardiol 2003

0
2
4
6
P<0.001
P=0.12
P=0.029
LVEF
Avg. Change
(Absolute %)
-3
-2
-1
0
MIRACLE MIRACLE ICD Contak CD
P<0.001
P=0.58
Data sources:
MIRACLE: Circulation 2003
MIRACLE ICD:JAMA 2003
CONTAK CD: J Am Coll Cardiol 2003  Control  CRT
MR Jet Area
Avg. Change
(cm2)
Not
Reported
Effect on LV FunctionEffect on LV Function
6 Months in Moderate to Severe
HF

CRT Does Not Promote
Ventricular Arrhythmias
• Analyzed 1,044 patients
with ICDs from 2 trials:
– CONTAK CD
– MIRACLE ICD
• Odds ratio (CI):
0.92 (0.67 – 1.27)
Patients with VT or
VF during Follow-up
17,2%
18,4%
No CRT CRT
Proportion
Bradley DJ, et al. JAMA 2003

Left Ventricular End
Systolic Diameter
200
250
300
350
400
cm3
Base 6 Mo
P=0.01
CRT Promotes Reverse Remodeling
in Class II CHF
Left Ventricular End
Diastolic Diameter
200
250
300
350
400
cm3
Base 6 Mo
P=0.04
Left Ventricular
Ejection Fraction
20
22
24
26
28
30
%
Base 6 Mo
P=0.02
• Control (n=85) ♦ CRT (n=69)
MIRACLE ICD II

• Radionuclidi
• RMN
• ECOcardiografia
Patients selection
INTER-VCD
Eco-Doppler convenzionale (Q-
efflusso Ao –Q-efflusso Po >40 msec)
INTRA-VCD
Eco M-mode (validate only in QRS wide) PW-TDI
Strain Rate
Echo 3D
Quando isolata, BASSO VALORE PREDITTIVO

DCM - Ischemic
Advanced
age
NYHA Class IV
PeAF No MR
Maggiori
LVEDV
LVESV

Related Risks
Com plicat ions ( 1)
4,8
3,7
1,5
1,0
1,8
0,3
10,6
10,0
2,3
2,4
1,7
0,3
0 5 10 15
Unsucess. Implant
LV Lead
Coronary Sinus
Infection
30 day mortality
Procedure death
Percent of Pat ient s
MIRACLE+CONTAK
CD+MIRACLE ICD
InSync III/Attain
4193
Reduced Procedure Time w it h
I ncreased Experience (2)
60
120
180
240
300
Up t o first
5
Next 6 t o
10
Next 11
more
Cent er-based experience
ImplantTime(minutes)
P < 0.001
Study Period Attempts
Primary
LV Lead
MIRACLE 11/98 – 12/00 591 Attain 2187
Contak CD 2/98 – 12/00 517 EasyTrak
MIRACLE ICD 10/99 – 8/01 636 Attain 4189
InSync III 11/00 – 6/02 334 Attain 4193
1. Greenberg, et al.
PACE 2003;26(4p2):
952 (Abstract 93)
2. Unpublished data.
Medtronic. Inc.

Relazione di Frank-Starling
P intraventric.
(mmHg)
= sviluppo di forza
50
100
150
200
250
50 100 150 200 250
Volume ventricolare sinistro (ml)
= lunghezza iniziale della fibra miocardica
sistole
diastole
Definizione:
entro limiti fisiologici, tanto più il cuore si riempie durante la diastole,
tanto maggiore sarà la quantità di sangue pompata in aorta in sistole

1 Framingham Heart Study (1948 – 1988) in Atlas of Heart Diseases.
2 American Heart Association. Heart Disease and Stroke Statistics—2003 Update.
CHF Patients Survival ResultsCHF Patients Survival Results11
100
90
80
70
60
50
40
30
20
10
0
Probabilityofsurvival,%
Men (Men (nn = 237)= 237)
Women (Women (nn = 230)= 230)
Time after CHF diagnosis, years
0 2 4 6 8 10
80% of men and 70%
of women who have
CHF will die within 8
years.2
80% of men and 70%
of women who have
CHF will die within 8
years.2

NYHA CLASS
Annualsurvival(%)
Hospitalizations/year
100
75
50
25
0
I II III IV
1
10
Survival
Hospitalization
.1
Hospitalization / NYHA-class

VolumeVolume
OverloadOverload
PressurePressure
OverloadOverload
Loss ofLoss of
MyocardiumMyocardium
ImpairedImpaired
ContractilityContractility
LV Systolic Dysfunction
EF < 35%
↓↓ CardiacCardiac
OutputOutput
HypoperfusionHypoperfusion
↑↑ End Systolic VolumeEnd Systolic Volume
↑↑ End Diastolic VolumeEnd Diastolic Volume
Pulmonary CongestionPulmonary Congestion
LV Systolic Dysfunction

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
Reverse Remodeling
Cardiac Resynchronization
Yu CM, Circulation ‘02

QoL 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
Adjusted SF 36 means Hobbs FDR, et al. Eur Heart J 2002
Quali sono le ragioni della CRT ?

LBBB
LABB +
Incomplete LBBB
NO LBBB
25.2%
67.9.%
6.9%
0
2000
4000
6000
8000
5517
3476
1771
TOTAL POPULATION
NO LBBB
LBBB + LABB +imcomplete LBBB
n°
Prevalence of wide QRS and LBBB
in the Study population (N°=5517)
INCHF

Completed 6-MonthCompleted 6-Month
Follow-upFollow-up
(n = 201)(n = 201)
Completed 6-MonthCompleted 6-Month
Follow-upFollow-up
(n = 215)(n = 215)
16 Death 12
2 Heart transplant 0
1 Infection/explant 1
5 Missed 6M FU 0
ControlControl
(n = 225)(n = 225)
CRTCRT
(n = 228)(n = 228)
RandomizedRandomized
6-Month Protocol6-Month Protocol
(n = 453)(n = 453)
Enrollment &
“Follow Up”
MIRACLE

Submaximal Exercise
Distance Walked in 6 MinutesDistance Walked in 6 Minutes Change from Baseline*Change from Baseline*
00
1010
2020
3030
4040
5050
6060
00 33 66
Follow-up Period (Month)Follow-up Period (Month)
MetersMeters
11
P=0.004P=0.004
P=0.003P=0.003
P=0.005P=0.005
Baseline (meters)Baseline (meters)
291 ± 101
305 ± 85
CRTCRT
ControlControl
MIRACLE
Abraham WT, Fisher
WG, Smith AL, et al.
N Engl J Med
2002;346:1845-1853

QOL
Change from Baseline*Change from Baseline*
00
55
1010
1515
2020
2525
00 33 66
Follow-up Period (Month)Follow-up Period (Month)
ScoreImprovement(points)ScoreImprovement(points)
11
P=0.001P=0.001
P<0.001P<0.001P<0.001P<0.001
CRTCRT
ControlControl
Minnesota Living with Heart Failure Questionnaire
Baseline (score)Baseline (score)
59 ± 21
59 ± 20
MIRACLE

NYHA Functional Class
00
2020
4040
6060
8080
100100
120120
NumberofPatientsNumberofPatients
Improved 2 orImproved 2 or
more classesmore classes
Improved 1Improved 1
classclass
No ChangeNo Change WorsenedWorsened
ControlControl CRTCRT
6%6%
32%32%
59%59%
4%4%
16%16%
52%52%
30%30%
2%2%
P<0.001P<0.001
MIRACLE
Abraham WT NEJM `02

4 weeks
4 weeks
One Year
4 weeks
Acute Testing at Implant
Randomization Prior to Discharge
Pre-OP Evaluation
Best Unichamber Biventricular
No Pace No Pace
Biventricular Best Unichamber
Best Chronic Pacing Mode
FlexStim
PATH CHF:
Study Design PATHCHF

Study Design
Pre-dischargePre-discharge
Random-Random-
izationization
ControlControl
CRTCRT
CRTCRTDouble-Double-
BlindBlind
BaselineBaseline SuccessfulSuccessful
ImplantImplant
——6 Months—6 Months—
≤≤ 1 week1 week
MIRACLE
• Primary Efficacy NYHA
Functional Class Quality of life (Minnesota Living
with HF) 6-minute Walk Distance
• Secondary Efficacy Included
VO2 peak, Exercise Time, LVEF, LVEDD, MR, QRS
Duration, Clinical Composite Response
• Other Protocol Specified Endpoints
Death or Worsening Heart Failure (Safety)
# Days Spent in Hospital (Health Care Utilization)
OMTOMT

Risk of Sudden Death:Risk of Sudden Death:
GISSI-2 TrialGISSI-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
Survival
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
Survival B
p log-rank 0.0001
0.86

Baseline
ex CPX
Implant
Attempt
Successful
Implant
Control
ICD
CRT
CRT + ICD
Pre-discharge
Randomization
6 Month
Follow-up
6 Month
Follow-up
CRT
Double
Blinded
Stable
Medical
Therapy
≤ 1
week
• Class NYHA II
• Intent to treat analyses
• Comparison between groups
• Core labs: metabolic exercise,
echocardiography, and
neurohormone data
CRT
Long term follow up
every 6 months
CPX
MIRACLE ICD II

210 Class II 429 Class III/IV
98 Completed 6M FU 82 Completed 6M FU
2 Death 2
1 Missed 6M FU 1
101 Control (ICD+OPT) 85 CRT (CRT+ICD+OPT)
639 Enrolled and Implant Attempted
19 Unsuccessful 191 (91%) Successful
186 Randomized
5 not randomized
- 1 death
- 4 LV lead dislodge.
MIRACLE ICD II

Composite Response
36% 34%
31%
58%
22% 20%
0%
20%
40%
60%
Improved No Change Worsened
Proportion
Control (n=101) CRT (n=85) Chi-square test
P = 0.01
MIRACLE ICD II

Effect on Ventricular Arrhythmias
• 25/101 pts (Control)
89 VT/VF events
• 18/85 pts (CRT)
61 VT/VF events
25%
21%
0%
5%
10%
15%
20%
25%
Control CRT
p = 0.61
During 6 Month
Randomization Period
MIRACLE ICD II

79
MADIT II
Marzo 2002
Precedenti Linee Guida ACC/AHA per
ICDs September 2002
COMPANION
Maggio 2004
SCD-HeFT
Gennaio 2005
La strada alle nuove linee guida
ESC updated Maggio
2005
ACC/AHA updated Agosto2005
CARE-HF
Aprile 2005

80
MADIT II
Marzo 2002
Precedenti Linee Guida ACC/AHA per
ICDs September 2002
COMPANION
Maggio 2004
SCD-HeFT
Gennaio 2005
ESC updated Maggio 2005
ACC/AHA updated Agosto2005
CARE-HF
Aprile 2005
0
1000
2000
3000
4000
1999 2001 2003 2005
Result s Present ed
CumulativePatients
PATH CHF
MUSTIC SR
MUSTIC AF
MIRACLE
CONTAK CD
MIRACLE ICD
PATH CHF II
COMPANION
MIRACLE ICD II
CARE HF
La strada alle nuove linee guida

Hospitalization for HF
MeanMean ±± SEMSEM
NN == 1616
0
10
20
30
40
daysofhospitalization
1 Year1 Year
Pre-ImplantPre-Implant
1 Year1 Year
Post-ImplantPost-Implant
PP == .003.003
PATHCHF

MUSTIC
• Dilated cardiomyopathy of any etiology
• NYHA Class III (not Class IV)
• Optimal individual drug therapy
• LBBB and QRS duration >150 msec
• Not mentioned AVD
• LVEF<35% and LVEDD>60mm
• 6-MWT<450m
• SR & no conventional PM indication

Composite Response
39%39%
34%34%
27%27%
67%67%
17%17% 16%16%
0%0%
20%20%
40%40%
60%60%
ImprovedImproved No ChangeNo Change WorsenedWorsened
ProportionProportion
Control N=225Control N=225 CRT N=228CRT N=228
Chi-square test
83
363
↓↓ 77%77%
ControlControl
n=34n=34
CRTCRT
n=18n=18
P<0.001P<0.001
Total HF days
Hospitalized
MIRACLE

NYHA Class III/IV HF*,NYHA Class III/IV HF*,
EFEF ≤≤ 35%, QRS35%, QRS ≥≥ 130 ms,130 ms,
Stable HF Medical TherapyStable HF Medical Therapy
No indicationNo indication
for ICDfor ICD
IndicationIndication
for ICDfor ICD
MIRACLEMIRACLE
(InSync)(InSync)
MIRACLE ICDMIRACLE ICD
(InSync ICD)(InSync ICD)
* Separate protocol for MIRACLE ICD Class II* Separate protocol for MIRACLE ICD Class II
Inclusion
Criteria
MIRACLE ICD trials
W.T. Abraham for MIRACLE and MIRACLE ICD Investigators

BaselineBaseline
ImplantImplant
AttemptAttempt
SuccessfulSuccessful
ImplantImplant
ControlControl CRTCRT
Pre-dischargePre-discharge
RandomizationRandomization
1, 3, 61, 3, 6
MonthMonth
Follow-upFollow-up
1, 3, 61, 3, 6
MonthMonth
Follow-upFollow-up
CRTCRT
DoubleDouble
BlindedBlinded
StableStable
MedicalMedical
TherapyTherapy
≤≤ 11
weekweek
CRTCRT
Long term follow upLong term follow up
every 6 monthsevery 6 months
• 369 randomized patients369 randomized patients
• 182 CONTROL and 187 CRT182 CONTROL and 187 CRT
• Control: No pacingControl: No pacing
• Treatment (CRT): atrial synched pacingTreatment (CRT): atrial synched pacing
• OMT for HF stability maintainedOMT for HF stability maintained
• ICD active in all patients of MIRACLE ICDICD active in all patients of MIRACLE ICD
MIRACLE ICD study design
182182 187187
369369

Survival
80%
85%
90%
95%
100%
0 1 2 3 4 5 6
Months Since Randomization
%ofPatientsSurviving
Control n=402 CRT n=415
P=0.42
MIRACLE and MIRACLE ICD Trials

Control 225 214 204 197 191 179 70
CRT 228 218 213 209 204 201 99
Patients At RiskPatients At Risk
70%70%
75%75%
80%80%
85%85%
90%90%
95%95%
100%100%
00 11 22 33 44 55 66
Months After RandomizationMonths After Randomization
EventFreeEventFreeSurvivalSurvival(%)(%)
CRTCRT
ControlControl
P = 0.033P = 0.033
Relative risk = 0.60;Relative risk = 0.60;
95% CI (0.37, 0.96)95% CI (0.37, 0.96)
Time to Death or
Worsening HF requiring Hospitalization
MIRACLE

Patients selection
• Which is the value of QRS within ?
- 30% pts with wide QRS no Mechanic Asinchronism
(Yu, Heart ‘03)
- Which cut-off considerate for pts selection ?
- Relationship between QRS duration and LV dilation ?
Ventricoli meno dilatati ma con dissincronie regionali
non alterano l’ECG di superficie (durata QRS
normale)? (Auricchio A, Yu CM – Heart ‘04)

• Età avanzata
• Genesi ischemica della miocardiopatia (controverso)
• Assenza di insufficienza valvolare mitralica
(Reuter S et a. Am J Cardiol 2002) o IM severa
(Achilli A, Italian Heart J ‘04)
• Maggiori volumi telediastolici e telesistolici
(Bax JJ, JACC ‘04)
• FA permanente - controverso: ablazione NAV?
Speranza di recupero RS con riduz. IM e reverse LV
remodeling?
• Classe NYHA IV (?)

EE AA EE AA
Mitral flowMitral flow
ICTICT IRTIRTETET
Aortic flowAortic flow
ICT+IRT = MPIICT+IRT = MPI
ETET
InSync
Italian
Registry
LMPILMPI
RMPIRMPI
1.2 ± 0.671.2 ± 0.67
1.35 ± 0.761.35 ± 0.76
0.8 ± 0.50.8 ± 0.5
0.81 ± 0.390.81 ± 0.39
0.0090.009
0.040.04
Baseline Follow-up p<

Burkhoff D, Am J Phys ‘87
Influence of Pacing-site

Sinus
node
AV
node
Bundle
branch or
diffuse block
Delayed conduction
• Delayed AV sequence
• Mitral regurgitation
• Decreased filling time
Delayed Ventricular ActivationDelayed Ventricular Activation
What is abnormal in the HF pts?What is abnormal in the HF pts?

Spragg DD, Circulation ‘03
Regional Alterations in Protein
Expression in the Dyssynchronous
Failing Heart

Physiologic pacing in ICDPhysiologic pacing in ICD
Spragg DD, Circulation ’03
Regional Alterations of
Protein Expression
11 CHF-dyssynchronous
Interstitial remodelling:
fibrosis α-TNF, apoptosis

Blanc et al., Circulation 1997 23 pts mean ± SD
90
100
110
120
130
140
150
SYSTOLICSYSTOLIC
Blood PressureBlood Pressure
RVARVA LV BVRVORVOBASBAS
mmHgmmHg
p<.01 p<.03
0
10
20
30
40
Pulmonary CapillaryPulmonary Capillary
Wedge PressureWedge Pressure
RVARVA LV BVBVRVORVOBASBAS
p<.01 p<.01
Acute studies

Kass, Circulation 99
%Change%Change
RVSRVS LVSLVS
SYSTOLIC PressureSYSTOLIC Pressure
0
2
4
6
8
10
RVSRVS LVSLVS
Max LV Dp/DtMax LV Dp/Dt
0
10
20
30
40
meanmean±±SDSD
LBBB
RBBB
p<.05p<.05
p<.01p<.01
p<.01p<.01
nsns
Acute studies

Effects of Ventricular
Dyssynchrony on Cardiac Function
Reduced diastolic filling time 1
Weakened contractility 2
Impaired Systolic function
(depressed Dp/Dt)
Protracted MR 2
Mechanical and
temporal dyssynchrony
Abnormal septal wall motion
Post systolic
regional contraction 3
1. Grines CL, et al Circulation 1989
2. Xiao HB, et al Br Heart J 1991
3. Søgaard P, et al. J Am Coll Cardiol 2002
Diminished SV
LVRV

• WHO?
 Which criteria ?
• WHEN?
 Which NYHA class ?
• WHERE?
 RV+LV / LV ?
• WHY?
 Symptoms / Mortality ?
CRT:CRT: KEY QUESTIONSKEY QUESTIONS

Why the need of CRT ?
Debole
Contrazione
Attivazione
Sistemi
Neuro-ormonali
Ritenzione
idrico-salina
CHF
Attivazione
Asincrona

Who are the Non-Responders ?
• STRUMENTALE
parametri Eco-
TDI-SR, ECO3D
(no
reverse remodelling)
• CLINICI
Sopravvivenza,
NYHA class, CHF-H,
6MWT, VO2 etc
• BIPHASIC CURVE

Who are the Non-Responders ?
• Improve LVEF less then 25%
(Penicka M, Circulation ’04)
• Reduction < 10% LVESV
(Yu CM, Circulation ‘05)
• Reduction LVESV index <15%
(Pitzalis MV, JACC ‘02)
• Class NYHA invariate or
improvement less then 25% of 6-
MWT
(Bax et a. JACC 2004)
• Invariate NYHA class or 6MWT,
death, CHF-H, No change or
improvement < 10% of VO2 peak
(Lecoq G, EHJ ’05, MUSTIC, PATH-CHF,
COMPANION)
• BNP plasma level, MR entity, HRV,
persistence of Inter and Intra-

Optimization of Pacing
VV delay
Ottimizzare l’intervallo
VV comporta un ulteriore
incremento della FE anche
nei responders
(Sogaard, Circulation ‘02)
Il 50% dei paz. mostra
beneficio nella
preattivazione VS (20-60
msec), il 50% nella
preattivazione VD (in
acuto) (Porciani, Am J Card
(Bordachar P, JACC ‘04)

• Inaccurata selezione dei
pazienti sulla base degli indici
predittivi
• Presenza di comorbidità
elevata
• Stimolazione biventricolare
tecnicamente inefficace
• Severe CHF or hemodinamic
instability

What does it mean wide QRS ?What does it mean wide QRS ?
LBBB more prevalent with Impaired LV
Systolic Function
38%
24%
8%
Moderate/Severe
HF (2)
Impaired LVSF
(1)
Preserved LVSF
(1)
1 Year Survival
11%
16%
QRS <
120ms
QRS >
120 ms
P < 0.001
1. Masoudi, et al. JACC ‘03
2. Aaronson, et al. Circ 97
Long-term (45 Mo)
Survival
34%
49%
QRS <
120 ms
QRS >
120 ms
Iuliano et al. AHJ 2002
N=669
P < 0.001
Baldasseroni S. EHJ `02
N=5,517

What does it means
DYSSYNCHRONYSM ?
• VEST study analysis
• NYHA Class II – IV pz
• 3,654 ECGs digitally
scanned
• Age, creatinine, LVEF,
heart rate, and QRS
duration found to be
independent predictors
of mortality
• Relative risk of widest
QRS group 5x greater
than narrowest
60%
70%
80%
90%
100%
0 60 120 180 240 300 360
Days in Trial
CumulativeSurvival
QRS
Duration
(msec)
<90
90-120
120-170
170-220
>220
Adapted from Gottipaty et al. JACC
1999; 33(2):145A (abstract 847-4)

%
Mortality rate in patients with or
without LBBB (5517 pts)
0
5
10
15
20
25
30
1 Year-Mortality
Total Sudden Death
LBBB
No LBBB
Study population
11.9
16.1
10.5
5.5 4.9
7.3
p<0.001
p<0.001
No LBBB
Unadjusted 1
Adjusted 1
RR of Total Death
No LBBB
Unadjusted 1
RR of Sudden Death
Adjusted 1
1.70
(1.34-2.21)
1.36
(1.15-1.61)
LBBB
1.58
(1.21-2.06)
LBBB
1.34
(1.05-1.42)
INCHF
LBBB: 25,2%

Synchronizing the Ventricles:
Separation of E- and A- Waves
Surface ECG
IVRT IVRT
A-waveA-wave
Aortic Flow
E-waveE-wave
Spectral
Doppler
PR PR
LVFTLVFT
Aortic Flow
Karloff, PACE ‘87

Cumulative Enrollment in C.R.Cumulative Enrollment in C.R.
Randomized TrialsRandomized Trials
0
1000
2000
3000
4000
1999 2001 2003 2005
Results Presented
CumulativePatients
PATH CHF
MUSTIC SR
MUSTIC AF
MIRACLE
CONTAK CD
MIRACLE ICD
PATH CHF II
COMPANION
MIRACLE ICD II
CARE HF
•• Actual ProjectedActual ProjectedDOUG SMITHDOUG SMITH

Kerchhoffs RC, J CV Electr 03
Influence of Pacing-site in
CANINE model

Influence of Pacing-site in
CANINE model
Kerchhoffs RC, J CV Electr 03

Ansalone G, GIEC ‘05
Pts with LBBB, after CRT PW-
DTI, shows an improvement of
mitralic CO respect E-A interval,
with reduction of systolic
velocity peak
Patients selection
INTRA-VCD
Eco M-mode (validate in QRS wide)
TDI Strain Rate
Echo 3D

laterale (35%)
anteriore (26%)
posteriore (23%)
infero-settale (16%)
(Ansalone, Am Heart J ‘01)
Inferiore (45%)
Laterale (30%)
Posteriore (25%)
Settale (16%)
Anterosettale (5%)
(Yu, JACC ‘05)
Optimization of CRT
I segmenti maggiormente interessati dal ritardo sono:
If the objective of CRT is pacing the more delayed wall, the
selection of the site of stimulation will be relevant

Improvement in Peak VOImprovement in Peak VO22
-0.5-0.5
0.00.0
0.50.5
1.01.0
1.51.5
2.02.0
ControlControl
(n=145)(n=145)
CRTCRT
(n=158)(n=158)
ml/kg/minml/kg/min
P=0.009P=0.009
Improvement inImprovement in
Total Exercise TimeTotal Exercise Time
00
3030
6060
9090
120120
ControlControl
(n=146)(n=146)
CRTCRT
(n=159)(n=159)secondsseconds
P=0.001P=0.001
BaselineBaseline
(ml/kg/min)(ml/kg/min)
13.7 ± 3.8
14.0 ± 3.5
BaselineBaseline
(secondsseconds)
462 ± 217
484 ± 209
Metabolic Exercise
MIRACLE
Nelson et al. Circulation ‘00
Ukkonen et al. Circulation ‘03

Current treatment of CHF
Functional improvement
Mortality reduction
– pump failure
– sudden death
DrugsDrugs
LV/LV/BiVBiV PacingPacing ?
ICDICD
DrugsDrugs
LV/LV/BiVBiV
ICD ?ICD ?
≈ 15% of all conventional ICD could be eligible for BVP

2006 orvieto, giornate cardoilogiche orvietane. il trattamento non farmacologico dello scompenso cardiaco

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