2009 acerra, congresso regionale sicoa, la terapia elettrica dello scompenso cardiaco nel paziente con qrs stretto

La CRT in pts with standard PMLa CRT in pts with standard PM
indication and in pts with DCMindication and in pts with DCM
and short QRSand short QRS
Stefano Nardi MD, PhDStefano Nardi MD, PhD
RESPONSABILERESPONSABILE
Centro di ARITMOLOGIA CLINICA ed ELETTROFISIOLOGIA CARDIACACentro di ARITMOLOGIA CLINICA ed ELETTROFISIOLOGIA CARDIACA
Diaprtimento CardiotoracovascolareDiaprtimento Cardiotoracovascolare
AO S.Maria TerniAO S.Maria Terni

VOO
VVI
RR
AAIR <-> DDDR
Cardiac pacing evolution …
DDD
Rate…
AV synchrony…
What does it
mean
Physiological
pacing ?
Since 30-ies .......

What Does it mean
Physiologic Pacing ?
DDD can reduce PCWP
and improve CO
Ishikawa, Eur J
Card Pacing Electr ‘96
DDD improves prognosis
in CHF compared to VVI
Linde-Edelstam PACE ‚92
• 1 and 2 year mortality significantly lower
with DDD compared to VVI(R) pacing
MEDICARE
n = 36,312
VVI(R)
DDD(R)
Lamas, Circulation `95

Impact of RVA pacing
• Global alteration of electro-mechanic LV activation
Betocchi S. JACC ‘93, Bedotto J. JACC ‘90,
Stojnic B. PACE ‘96, Tse HF. JACC ‘97
• Alteration of LV Systolic function
– Reduction of work-load for each and specific LVEDD
– Activation’s delay of papillary muscles
– Detrimental effect on Mitral Regurgitation
• Regional and global LV alteration of diastolic function
0
20
40
60
80
40 60 70 80
LV volume (ml)
LV pressure
(mm Hg)
NSR
RVA

DelayedDelayed
conductionconduction
SinusSinus
nodenode
AVAV
nodenode
Mimic LBBBMimic LBBB
• Abnormal RV-LV sequence
• Abnormal LV activation sequence
• Segmentary dyskinesia
• Disynchrony of RV and LV filling flows
24 pts (19.5±8.1) with normal
Segmental Anatomy paced
from the RV apex (median 10
yrs (0.7–18.9) and compared
with 33 CTR
Tantengco MVT. JACC ‘01
Impact of RVA pacing

Ansalone G. It H J ‘99
Altered Left Ventricular
Performance

Altered Left Ventricular
Performance
• Lister (‘64)
– Greater reduction in CO when pacing
from ventricular sites associated
with longest total activation time →
muscle conduction
• Conduction velocity
differences (Purkinje = 2-4
m/s; Muscle = 0.2-1 m/s)
• Wiggers (‘25)
– “The initial slower rise of intraventricular pressure is prolonged, IVCT phase is
lengthened, the gradient is not so steep, the pressure maximum is lower, and the
duration of systole is increased.”
Artificial stimuli induce local fractionate contractions → Slow
Sweeney MO. JACC ‘06

Altered LV performance
• Boerth and Covell (‘71)
– Reduced LV pressure, wall stress, and dP/dt
despite normal perfusion
• Burkoff (‘86)
– The more muscle mass activated by muscle conduction
rather than Purkinje conduction, the weaker the beat
→ “ineffective muscle mass”
Canine model Burkhoff D, Am J Phys ‘87

Altered
Myocardial Perfusion
• Heyndrickx (1985)
– Coronary blood flow was higher despite
decreased cardiac output
• Prinzen (1990)
– Similarity in behavior of electrical
activation, fiber strain and blood flow
• Redistribution of strain and blood flow
with RV pacing
• Early activated regions ~ 60% blood flow of
late activated regions
– The regions of the heart activated via
the Purkinje system (simultaneous
activation) have greater fiber strain
and blood flow

Karpawich PP. PACE ‘99, Tse HF. JACC
‘02, Thambo JB. Circulation ‘04
• Detrimental effects on
ventricular remodeling
– Regional alteration of flow
“patterns”
– Improvement of O2
consumption without
increment of flow
– Abnormal and asymmetric
ipertrofy of LV wall
Altered
Myocardial perfusion
VO2(ml/min/mVO2(ml/min/m22
))
DODO22 (ml/min/m(ml/min/m22
))
Critical DOCritical DO22
DISOXIADISOXIA
Critical VOCritical VO22
NormalNormal
• Rosenqvist (‘88)
– Increased incidence of CHF in
RV paced pts

Right ventricular pacing
HISTOPATHOLOGY
• Karpawich (‘90) – Pediatric Canine Model
– LV myofibril disarray was found after 4
months of pacing from RV apex
• 90° misalignment of adjacent fibers (stress related?)
– Also noted appearance of prominent Purkinje
cells in subendocardium, variable-sized
mitochondria, and dystrophic calcification
• Adomain (‘86)
– Myofibril disarray was found in 75% of canine hearts
after 3 months of pacing from RV apex
• Greatest at base of left ventricular free wall
RV septal pacing: no disarray
Karpawich PP. Am Heart J 1991.
RV apical pacing: disarray
Karpawich PP. Am Heart J 1990.
• Karpawich (‘99) – Pediatric Pts
– Myofibril hypertrophy, intracellular vacuolation,
degenerative fibrosis, and fatty deposits in the LV
after more than 3 years RV apical pacing
– Independent of paced time, patient age, epi- or
endocardial electrode placement, and mode

Spragg DD, Circulation ’03
Regional Alterations of Protein
Expression in RVP dogs
TNF-alpha expression
Apoptosis and Fibrosis

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 RVP pts?What is abnormal in the RVP pts?
Cardiac Resynchronization TherapyCardiac Resynchronization Therapy
• Delayed AV sequence
• Mitral regurgitation
• Decreased filling time

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?

• As the LV becomes more spherical this
twisting ability of LV reduced (apical
counter-clockwise /basal clockwise) with
reduction both of LVEF and filling.
• As CHF progresses, the associated
dilation of the LV will often change both SIZE
and SHAPE of LV
Left Ventricular Remodelling
Size, Shape and MV apparatus
• As CHF progresses, the associated
dilation of LV will often pull the MV
apparatus out of proper anatomical
alignment (MR)
• The misalignment reduces the ability of MV
apparatus to assist LV in the contraction
(additional work-load)

Stronger
Directed
Vector




Weaker
Misdirected
Vector
• As the shape of the LV
becomes distorted, this force
vector diminishes
and its direction moves
away from the AoV.
• The result is inefficient
pumping and turbulence in
the LV.
Left Ventricular Remodelling
Aortic Valve

D’Ascia C, Eu Heart J ‘06
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

Prolate Spheroidal
Coordinates
Costa, Biomech Eng. ‘96
www.continuity.ucsd.edu
Ventricular Muscle
Fiber Orientation
Walker et al, J Thorac CV Surg. ‘05
CHF PATHOLOGY

Definition of Stress
Fung, A 1° Course in Continuum Mechanics, ‘94
LV PV loops
McCulloch, Theory of Heart, ‘91
CHF PATHOLOGY

Model of
Shortening
Deactivation
Guccione and McCulloch, J
Biomech Eng. ‘93 Feb;115(1):72-90
Muscle Contraction
Model Comparison

DAVID
MOSTMOST
DANISHDANISH
CTOPPCTOPP
UKPACEUKPACE
PASEPASE
C. W. Israel CW, Cardiostim `06
DAVID Trial
JAMA ‘02
RV stimulation may be more deleterious in patients with
advanced LV dysfunction (ICD candidates); DDDR-70
was worse than VVI-40; more pacing (60%) was seen in
DDDR-70; however, only 30.8% of the patients had a
QRS>130ms
MOST Trial
Sweeney M, et al. PACE ‘02
(mode selection trial in sinus-node dysfunction)
Hospitalization was not associated with mode but with
prevalence of more then 40% RV pacing
Danish Pacemaker Study
Andersen HR, et al. Lancet ‘97
AAI vs. VVI for SSS
Danish pacemaker study: AAI had slightly better
survival and was associated with lower occurrence of
CHF (native AV conduction is better)
Pacemaker Selection in the Elderly
Lamas GA, et al. NEJM ‘98
VVI vs. DDD for Sinus Node Dysfunction or AV block;
no difference in quality of life or outcome (CV or death)
Different Pacing Modalities
in Randomized Clinical Trials

Why was DDD not better
than AAI/VVI in several Trials ?
(DAVID, DANISH, PASE, CTOPP, MOST, UKPACE ?)
A: Because DDD doesn‘t work
B: Because DDD was programmed badly
C: Because leads were not implanted optimally
D: Because all these studies had severe
limitations
E: B, C + D

• Cumulative percentage of RVP is
an INDIPENDENT PREDICTOR
of AF development
0
1
2
3
4
0 20 40 60 80 100
Cum % VP
RiskofAFrelativeto
DDDRpatientwithCum%VP=0
• RR of AF INCREASE LINEARLY
with the RVP until about 80-85%,
both in the DDDR group and
VVIR group
• AF risk is REDUCE of 1% for each 1%
of reduction of Cumulative % of VP in
the DDD(R) group.
Sweeney MO, Circulation ‘03
0
1
2
3
4
0 20 40 60 80 100
Cum % VP
RiskofAFrelativeto
VVIRpatientwithCum%VP=0
MOST Sub-Study
(1339pts (67%) with Know Cum
%VP)

V pace < 40%:
For each 10% increase in V-pacing
54% relative increase in risk for HFH
V-pacing > 40%:
Relative risk for HFH ~constant
VP >40% 2.6-fold→
increase in HFH
Sweeney MO,
Circulation ‘03
MOST Sub-Study
%VP)

0
2
4
6
0 20 40 60 80 100
Cum% VP
RR of 1st CHF-H
• RR INCREASE between 0% and 40% of Cum
% VP, but doesen’t change for >40%
(45% and 65% have the same RR)
• The RR is REDUCED at ≈2% if
RV pacing is minimised
When Cum% VP<40% for each 10% of
reduction of Cum %VP, there is a
relative reduction of 54% of RR for
1st CHF-H
0
2
4
6
8
10
12
0-20 20-30 30-40 > 40
Cum% VP
RiskofHFH
DDDR
VVIR
RR of CHF-H: VVIR > DDDR,
regardless of %VP
RR is max for VVIR vs DDDR,
INDIPENDENTELY for % of VP
%VP)

• Normal ventricular activation
requires a synchronized
participation of the distal
components of the specialized
conduction system
• Conventional RV pacing results in
“forced” ventricular
desynchronization, which mimics
LBBB and has adverse effects on
structure and function.
Sweeney, JACC `06
Executive
Summary

Andersen HR, Lancet ‘97
DANISH
AAl
Group
VVI
Group
No. of Pts 110 115
Bradycardia 18 18
SA block 49 46
Brady/Tachy 43 51
1,00
,80
,60
0 2 4 6 8 10
Atrial Pacing
Ventricular Pacing
p = 0.18
SurvivalwithoutdeathfromCHF
Time (years)
p = 0.045
Atrial
pacing
Ventricular
pacing
Time (years)
0 2 4 6 8 10
0
0-2
0-4
0-6
0-8
1-0
Mortality as a
result of CHF
Overall survival by
pacing mode

Study Mean FU
Time
Incidence of
CHB
Annualized
Incidence
Rosenqvist ‘89
(review of 28 stud)
3 yrs Median 2.1%
Range: 0-11.9%
Median: 0.6%
Range: 0-4.5%
Andersen ’97 8 yrs 3.6% 0.6%
Brandt ’92 5 yrs 8.5% 1.8%
Sutton ’86 3 yrs 8.4% 2.8%
Rosenqvist ‘86 2 yrs 4.0% 2.0%
Rosenqvist ’85 5 yrs 3.3% 0.7%
Hayes ’84 3 yrs 3.4% 1.1%
Incidence of persistent AVB
in pts paced for SND
Background

Study
Pacing
Mode
Mean
FU
Time
Incidenc
e of AF
Annualize
d
Incidence
Andersen ’97 AAI 5 years
8.8% 1.8%
Sutton ’86 AAI 3 years
4.5% 1.5%
Brandt ’92 AAI 5 years
7.0% 1.4%
PASE ’98 DDDR
only
18
months
19.0% 12.7%
CTOPP ’00 DDDRV
VIR
3 years
16.6% 5.5%
(DDDR)
Incidence of Chronic AFib
in pts paced for SND
Background

Is VVI better
then DDD ?
Is AAI better
then VVI ?

What kills the Patients: the DDD
Mode or Inadequate Implantation/
Programming?
Seeking answers,Seeking answers,
but what about somebut what about some
unanswerable questions?unanswerable questions?

Nardi S, AIAC ’08 Poster Abstract
Clinical implication of different pacing modalitiesClinical implication of different pacing modalities
for reducing unnecessary ventricular pacingfor reducing unnecessary ventricular pacing
METHODSMETHODS
• Jan ’04 - Sept ‘07, 910 patients (71+18, M=67%) underwent at DC
PM implant for SND (33%), Parox AVB (39%) or BTS (28%)
Patients
(n=910)
Frequency
(%)
Sinus node
dysfunction
300 33
Persistent
or parox.
AV block
355 39
Bradycardia-
tachycardia
syndrome
255 28
Pts
(n=910)
(%)
Group 1 - Short
AVD (≤150msec)
231
(86%)
25
Group 2 – Long
AVD (300msec)
225
(84%)
25
Group 3 – AV
hysteresis
212
(88%)
23
Group 4 –
AAISafeR
242
(84%)
27

Group 1
Short AVD
Group 2
Long AVD
Group 3 AV
hysteresis
Group 4
AAISafeR
P
CP/VP
(%)
92.4* 38* 24.6* 4.6 <0.0001
*4
vs(1+2+3)
AF
(%)
24.2* 19.4* 16.8* 6.8 <0.001
*4
vs(1+2+3)
HFH
(%)
17.6* 14.3* 13.3* 4.7 <0.001
*4Nardi S, AIAC ’08 Poster Abstract
Clinical implication of different pacing modalitiesClinical implication of different pacing modalities
for reducing unnecessary ventricular pacingfor reducing unnecessary ventricular pacing
Close relationship between Cum%VP and AF incidence and HF-H
AAIsafeR represent the best pacing modality respect other.
METHODS:METHODS:
No statistically differences were observed between these four groups in
term of age, sex, NYHA functional class, LVEF and drugs therapy (p=NS)

• Conventional DDD systems
often result in a higher
level of RVA pacing due to:
– AVD programmed shorter than
intrinsic AV conduction
– Lower rate settings higher than
necessary
– Rate-responsive algorithms which
increase VP in response to stress
• Higher level of Cum %VP in DDDR has adverse long-term
effects that mitigate the benefit of AV synchrony.
Sharma AD, HRS `05
DAVID post-hoc analysis
Mean Cum%VP VVI: 3%
Mean Cum%VP DDD: 56%

Potential Flaws in RCTs on DDD
versus VVI
• PASE: - High cross-over due to pacemaker syndrome in
VVIR (intention-to-treat analysis)
• CTOPP: - Patients with low unpaced heart rates benefit
from DDD
• MOST: - very high cross-over due to pacemaker
syndrome in VVIR
• UKPACE: (inappropriately) short programmed AV delay
(75-150 ms)
Ellenbogen AJC 2000;86:59-63
Tang, Circulation 2001;103:3081-5
Toff, NEJM 2005;353:145-55
Link, J Am Coll Cardiol 2004;43:2066-71

Sweeney, Circulation `06
Relationship between mechanical asynchrony and
HF development, as derived from various
RANDOMIZED clinical trials

"Systole is better than asystole."
• If the heart needs to be paced, and there is heart block, the ventricle
needs to be paced somehow
Wilkoff, June ‘04
The last famous words ………….

Seeking answers, but what aboutSeeking answers, but what about
some unanswerable questions?some unanswerable questions?
Who is the ideal
candidate for a pure
RV pacing ?
Are we able to identify
pts that will develop a
iatrogenic CHF “pace-
mediated”?
None
ON

Why we pace RV apex?
– Because the primary objective
was cure symptomatic bradi-
cardya due to syncope
– Because this is the common way of
treating
– Because actually, standard electro-catheters are
projected for an easy and stable positioning in RV
apex– Because there were no convincing reasons for stimulate another site

Standard PM indicationStandard PM indication

• 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??

LV Conduction Delay:
Fusion of E- and A- Waves
Surface ECG
Spectral Doppler Fused E & A waves
Aortic Flow
Fused E & A waves
PR
LVFTLVFT
Aortic Flow
PR
Karloff, PACE ‘87

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

A New Paradigm for
Physiologic Ventricular
Pacing
Sweeney MO, JACC ‘06
Ventricular pacing, not a lack of AV synchrony, is aVentricular pacing, not a lack of AV synchrony, is a
more important predictor of LV dysfunctionmore important predictor of LV dysfunction
The New Goals of Pacing Therapy
Maintain normal ventricular activation sequenceMaintain normal ventricular activation sequence
whenever possible or pacing in a BV mannerwhenever possible or pacing in a BV manner

What we can do ?
• Try to identifie an “optimal” or a “better” region of VP
where stimulation is able to provide an “hemodinamic
effect” or a “mechanical dyssinchrony” that is not
so much different from “spontaneous synchronism”
1
– Alternative sites for RV pacing (RVOT, RVS, His)
– Bifocal RV pacing
– Isolate LV pacing
– BV pacing
Pacing at alternative ventricular site(s) to
attenuate the adverse effects imposed by
ventricular desynchronization when VP can
not be avoided and/or abnormal
ventricular conduction is already present.
2

What we can do ?
Identifie a “better” region where stimulation
is able to provide an “hemodinamic
effect” that is not so much different from
“spontaneous synchronism”– Alternative sites for RV pacing (RVOT, RVS, His)
– Bifocal RV pacing
– Isolate LV pacing
– BV pacing

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

RV Bifocal pacing - How it worksRV Bifocal pacing - How it works
RV LV RVRV LV LV
IVS IVS
RV Apical Biventricular RV Bifocal
In accordance with Matsushita and Coll. – Europace 2005; 7, Suppl.; 229 (abs)
Propagation of DEPOLARIZATION
IVS

‘ALTERNATIVE’ sites of
right Ventricular pacing
septal Stimulation (RVS)
RVOT stimulation
bi-focal stimulation (RVOT + RVA)
para-hisian pacing
PARA-HISIAN
Rev Esp Cardiol ‘01
RVS
Lieberman, PACE ‘04
RVOT
Bourke JP, Europace ‘02
BI-SITE

Intrinsic LBBB
His Bundle Pacing
Bifocal RV Pacing
Unipolar RVA Safety Pace (80 ms)
Morina Vazquez, PACE
‘05
Gold MR. JACC ‘99
Rev Esp Cardiol ‘01
Lieberman, PACE ‘04
Bourke JP, Europace ‘02

Intrinsic LBBB
His Bundle Pacing
Bifocal RV Pacing
Unipolar RVA Safety Pace (80 ms)
Morina Vazquez, PACE ‘05
‘ALTERNATIVE’ sites of
right Ventricular pacing
Gold MR. JACC ‘99

Victor F. JACC ‘99
“No statistical differences (16 pts, 3 mo FU)
between two sites of pacing (RVOT vs RVA)
for all parameter considered. These results
are valid bothg in pts with LVEF >40% that in
pts with LVEF <40%.”
Randomized Crossover
ROVA Trial (RVA vs RVOT
vs Dual site pacing)
‘’ RVOT and Dual–site pacing reduce
QRS duration whereas not improve
all other parameters (QOL, LVEF,
NYHA, 6-MWT) ‘’
Stambler BS, JCE ‘03
80 pts completed RVOT/RVA crossover and
50 pts completed dual site (SUB-STUDY)

Comparison of LV performance (12 pts) during high RVS
pacing and RVA pacing after His bundle ablation for
refractory Chronic AFib, in pts with mild LV dysfunction
Mera F, PACE ‘99
RVS activation increased the
resting first pass LV ejection
fraction (0.51 ±0.14vs 0.43 ±
0.10, P <0.01)
APEX
SEPTUM
LV fractional shortening improved
during RVS pacing (0.31 ± 0.05 vs
0.26 ± 0.07, P <0.01).
How Right VentricularHow Right Ventricular
Septal (RVS) Pacing work ?Septal (RVS) Pacing work ?
High RVOT
Low RVOT
High FW
Low FW

CARDIAC FUNCTION
- Reduction LVEDD
- Reduction of LVESD
- Improvement FS (fractional shortening)
- Improvement of LVEF
18 AF pts
CHF (LVEF<40)
P Deshmukh, Circulation ‘00
PRE
impianto
FUP
P.Deshmukh, PACE ‘04
39 AF pts
CHF (LVEF<40)
NYHA III IV
FU 42 mo
CARDIAC FUNCTION
- Improvement LVEF
- Reduction of NYHA
- Improvement of DP/dt
- Prolonged excercise time
- Superior Treppe effect
- Improvement Cardio-Pulmon riserve
How para-hisianHow para-hisian
pacing work ?pacing work ?

How Alternative sites
of RV pacing work
Acute Chronic Observsations
RVOT Improvement of
Hemodinamic
profile
Only 2/9 studies
showed beneficus
effect on long-term
hemodinamic profile
(few pts)
On 89 pts  Short term
improvement Open
question: which RVOT
site is better to
stimulate?
RVS CO, LVEDP, LVEF NA 3 studies on few pts
(15 12 and 22 pts)
HIS Improvement of
LV performance
Improvement of
LVEF
(51 pts in two studies)
RVOT: Giudici MC, AJC ‘97; Buckingham TA, PACE ‘97; De Cock CC, PACE ‘98; Buckingham
TA; PACE ‘98; Kolettis TM, Chest ‘00; Vlay SC, PACE ’04; O’Donnell D, PACE ’05;
Stambler BS, JCE ’03; Aonuma K, HR ’05
RVS: Cowell R, PACE ‘94; Karpawich PP, PACE ‘97; Schwaab B, JACC ’99; Mera F, PACE ’99
HIS: Amitani S, PACE ‘99; Deshmukh P, Circulation ‘00; Deshmukh PM, PACE ’04

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

Weight of Evidence: CRT
• More than 7000 patients evaluated in
randomized controlled trials
• Consistent improvement in QOL, functional
status, and exercise capacity
• Strong evidence for reverse remodeling
– ↓ LV volumes and dimensions
↑ LV ejection fraction
– ↓ Mitral regurgitation

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
Confronto tra LINEE GUIDA
ESC e ACC/AHA (2005)
Terapia CRT
CRT for improve symptoms and CHF-H
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

Background: Linee Guida
A seguito della pubblicazione degli studi Companion e Care-HF, le linee
guida Europee (ESC) ed Americane (ACC/AHA) hanno introdotto la
CRT come Terapia di classe I per pazienti con:
• Scompenso Cronico in classe III NYHA o IV stabile,
nonostante terapia medica ottimale
• FE ≤ 35%
• QRS ≥ 120 ms
• Ritmo sinusale  solo per ACC/AHA
Swedberg K et al, European Heart Journal (2005) 26, 1115–1140
Hunt S A et al, Circulation. 2005;112

Background: Linee Guida
CRT come Terapia di classe II per pazienti con:
• FA, scompenso cronico in classe III o IV NYHA stabile,
nonostante terapia medica ottimale, FE ≤ 35% e dissincronia
ventricolare (QRS > 120 msec) ;
• FE ≤ 35%, QRS ≤ 120 msec e dissincronia ventricolare
ECO documentata, scompenso cronico in classe III o IV
NYHA stabile, nonostante terapia medica ottimale;
• Classe NYHA II con indicazione alla stimolazione
ventricolare e/o ad ICD profilattico, in RS, QRS ≥ 120 ms,
FE ≤ 35%;
• Stimolazione ventricolare destra, scompenso cronico in
classe III o IV NYHA stabile, nonostante terapia medica
ottimale, FE ≤ 35% e dissincronia ventricolare (upgrade)
Swedberg K et al, European Heart Journal (2005) 26,
1115–1140 Hunt S A et al, Circulation. 2005;112

Terapia Resincronizzante Cardiaca
La CRT utilizzando un BVP, può essere considerata in pts
con ridotta FE e dissincronia ventrioulare (QRS width>120
ms), che rimangono simtomatici (NYHA III–IV) malgrado
una terapia farmacologica ottimale, per migliorare:
i sintomi
(Classe di raccomandazione I, livello di evidenza A)
le ospedalizzazioni
(Classe di raccomandazione I, livello di evidenza A)
e la mortalità
(Classe di raccomandazione I, livello di evidenza B)

New section: Gaps in evidence
• 'In pts with HF and a wide QRS complex, which pt
characteristics should lead to a CRT-D being preferred
over a CRT-P?'
• 'Is there any role for ECHO assessment of
dyssynchrony in the selection of pts for CRT?'
• 'Does CRT improve clinical outcomes in pts with a low
LVEF, wide QRS but mild symptoms (NYHA class II)?'
• 'Does CRT improve clinical outcomes in pts with a low
LVEF, severe symptoms (NYHA class III/IV) and a QRS
width <120 ms?'
• 'Does an ICD improve clinical outcomes in HF with an EF
>35%?'
• 'What aspects of remote monitoring might best detect
early decompensation?'
REVERSE
not published
in time!
RethinQ
Good
question...
PROSPECT
SENSE-
HF?

ICD e CRT
L’impianto di un ICD in combinazione con pacing bi-
ventricolare, può essere considerato in pazienti che
rimangono sintomatici, con HF grave (classe NYHA
III–IV), con FE ≤ 35% e durata del QRS >120 ms, per
migliorare morbidità e/o mortalità
(Classe di raccomandazione IIa, livello di evidenza B)

New guidelines launched 30/8
• Great hush-hush before
launch
– ESC members
embargoed
• Major launch event at
ESC
– Dickstein
– Priori
– Focus sessions on
different aspects of
the guidelines

Positive aspects of new
guidelines
• One set of HF guidelines to use for all international
MDT materials
– Same citations for CRT and ICD recommendations
• Clearer language used this time
• Clearer cut-off points
• More diagrams
• More focus on collaboration

New: Standardised wordings
Class of
recommendation
Recommended wording
I
Is recommended
Is indicated
IIa Should be considered
IIb May be considered
III Is not recommended

• 'CRT-P is recommended to
reduce morbidity and
mortality in pts in NYHA
III-IV class who are
symptomatic despite
OMT, and who have a
reduced EF (LVEF <35%)
and QRS prolongation
(QRS width >120 ms)'
Class 1 level A
New guidelines: CRT v CRTD
• 'CRT with ICD function is
recommended to reduce
morbidity and mortality in
pts in NYHA III-IV class
who are symptomatic
despite OMT, and who
have a reduced EF (LVEF
<35%) and QRS
prolongation (QRS width
>120 ms)'
Class 1 level A
Dickstein et al. Eur Heart J. 2008. DOI:10.1093/eurheartj/ehn309

New guidelines: CRT v CRTD
'The survival advantage of CRT-D vs CRT-P has not
been adequately addressed. Due to the documented
effectiveness of ICD therapy in the prevention of
SCD, the use of a CRT-D device is commonly
preferred in clinical practice in pts satisfying CRT
criteria including an expectation of survival with
good functional status for >1 year'
Class of recommendation I, level of evidence A

CRT indicated
HF NYHA III/IV?
Yes
No

Level IA
QRS>120 ms?
Yes
No

Reduced EF?
Yes
No

Level IB
CRT-D indicated
All patients on optimal medical therapy
LV Dilation?
Yes
No

Reasonable
expectation
of survival >1
year?
CRT: Clearer rules 2008
Old

CRT indicated
HF NYHA III/IV?
Yes
No

Level IA
QRS>120 ms?
Yes
No

EF <35%?
Yes
No

Level IA
CRT-D indicated
All patients on optimal medical therapy
Reasonable
expectation
of survival >1
year?
CRT: Clearer rules 2008
New

CRT: role of echo

Reduced LV function?
Yes
No
Sustained ventricular
tachycardia?
Yes
No
Experienced a
cardiac arrest
Yes
No
ICD indicated

 
Level IA
Level IA
All patients on optimal medical therapy with life expectancy >1 year
ICD: Clearer rules 2008
Old

LV EF <40%?
Yes
No
Documented
haemodynamically unstable
VT and/or VT with
syncope?
Yes
No
Survivor of ventricular
fibrillation?
Yes
No
ICD indicated


Level IA
Level IA

New

>40 days past MI?
Yes
No
Nonischaemic heart
disease?
Yes
No


EF ≤30-35%?
Yes
No

EF ≤30-40%?
Yes
No

Level IA
NYHA II/III
Yes
No

ICD indicated
Level IA
Old

>40 days past MI?
Yes
No
Nonischaemic heart
disease?
Yes
No


EF ≤35%?
Yes
No

EF ≤35%?
Yes
No

Level IA
NYHA II/III
Yes
No

ICD indicated
Level IB
New

ICD in primary prevention
'Data on the role of ICD in pts with non-ischaemic
DCM are limited. The SCD-HeFT trial enrolled pts
with both DCM and ischaemic LV dysfunction and
showed a 23% reduction in mortality. A meta-
analysis* of trials enrolling only non-ischaemic DCM
pts showed a 25% reduction in mortality in the
group of pts receiving an ICD (p=0.003). These data
suggest that the aetiology of HF may not justify a
different approach for the primary prevention of
SCD.
* Desai 2004. JAMA 292:2874

Notable in the new guidelines
• No range of EF; all <35%
• SCD-HeFT patients recommendations now 1B
• Devices for NYHA I not in guidelines
– Post MI
– NICM EF <30%
• CRTP and CRTD both have Class IA

Structured approach to care
with emphasis on collaboration

TerapiaTerapia
Publicazioni
scientifiche
• I risultatiI risultati
possono esserepossono essere
confrontati conconfrontati con
dati storicidati storici
Registry
Risultati
“real life”
Clinical Practice
Valutazione del grado di
accettazione degli studi
randomizzati nella pratica
clinica
Collezione prospettica di dati
clinici in pts che hanno già un
PM impiantato
Valutazione dei benefici
dell’utilizzo di funzioni
specifiche del PM
(es impatto di alcuni algoritmi
funzionali su specifici “end-
point”)
Ipotesi,
gruppi
di CTR,
valutazioni
economiche
CLINICAL Practice VS Registries

TerapiaTerapia
• Obbligatorietà criteri
di selezione pazienti
• Uniformità procedure
• Follow-up ed esami di
controllo definiti
• Predeterminazione e
condivisione dei criteri
di valutazione
Randomized Trials
Pubblicazioni
scientifiche
Risultati
“real life”
Ipotesi,
gruppi
di CTR,
valutazioni
economiche
CLINICAL Practice VS RANDOMIZED Trials
Clincal Practice
• Criteri di selezione dei
pts non obbligatori
• Procedure, Follow-up ed
esami secondo le
abitudini dei centri
• Criteri di valutazione più
soggettivi (giudizio del
medico e/o del pts)

Scientific Paper
• Results coud beResults coud be
matched withmatched with
hystoricalhystorical
clinical dataclinical data
Registry
“Real life”
results
Clinical Practice
Acceptance degree of
randomized studies in clinical
practice
Prospectic data retrived of
clinical aspects in pts already
implanted with a PM
Evaluation of clinical benefits
due to specific PM functions
(ex. Impact of special
modality on several specific
“end-point”)
Hp,
Control
groups,
economic
evaluation
CLINICAL Practice VS Registries
Courtesy of Dr. Botto
TherapyTherapy

 Collezione prospettica di dati clinici in pazienti
che hanno un pacemaker già impiantato
Ruolo dei Registri
nella Pratica Clinica
 Valutazione dei benefici dell’utilizzo di funzioni
specifiche del pace-maker (ad
es.:impatto di un determinato algoritmo su alcuni “end
point” con CHF, HF-H, AFib …)
 Fotografia “Real life” della nostra routine
clinica

TherapyTherapy
• Specific pts
selection criteria
• Uniformity of clinical
procedure
• Well defined Follow-up
and clinical exams
• Pre-determined and
sharing of evaluation
criteria
Randomized Trials
Scientifc
Papers
“Real life”
results
Hp,
Control
group,
economic
evaluation
CLINICAL Practice VS RANDOMIZED Trials
Clinical Practice
• Pts selection criteria
not mandatory
• Procedure, Follow-up
and exams according to
centre clinical practice
• Evaluation criteria
according to physician
and/or pts point of view

2009 acerra, congresso regionale sicoa, la terapia elettrica dello scompenso cardiaco nel paziente con qrs stretto

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