35%

Désynchronisation/Resynchronisation
• Atrio‐ventriculaire: du PR long à la dissociation complète Conduction ventriculo‐atriale
• Atriale: dissociation inter‐atriale
• Ventriculaire:
− Prévenir la désynchronisation
− Désynchroniser volontairement: l’exemple de la MCHO
− Resynchroniser quand nécessaire:
l’insuffisance cardiaque systolique
Conduction VA: 70% si conduction AV « normale »
30% dans BAV de haut degré
Substrat
hémodynamique du Syndrome du PM
electrophysiologique des TRE (St DDD)
I
IEGM RA
20
10
PCWP
0
JC Daubert, A Roussel et Al. Arch Mal Cœur Vx 1984; 77: 413‐420 Long PR: Electromechanical correlates
Sinus
node
AV
node
Allongement
temps conduction AV
ƒ Réduction ou suppression
contribution atriale gauche
ƒ Réduction du temps de
remplissage ventriculaire
ƒ IM diastolique
ƒ Allongement durée IM syst
Non-adaptation à l’effort
Effets hémodynamiques du PR long isolé
Rythme sinusal Stimulation VDD
P Mabo et Al, PACE
1991
Concealed long PR Male, 64 yrs, NYHA class IV, Dilated cardiomyopathy, LVEF=18%
Concealed Long PR: Intracardiac ECG
LA
RA
100
240
LV
RV
180
140
Désynchronisation/Resynchronisation
AV: Stimulation synchrone dans le bloc AV
La stimulation « physiologique » restaure le synchronisme AV et la fonction chronotrope
‐ 1ère implantation chez l’homme (VAT) en 1969
‐ 1er stimulateur DDD en 1981
‐ 2010: 76% des 60.000 stimulateurs implantés en France sont des modèles DDD®
Physiological Relationship between PR and RR intervals during Exercise
P Ritter et Al. Pacing Clin Electrophysiol 1987
La Preuve du Concept (ou de sa nullité): UK PACE
WD Toff, et Al N Engl J Med 2005;353:145-55
UK PACE
WD Toff, et Al N Engl J Med 2005;353:145-55
Rapport risque/bénéfice
Taux de complications liées à la procédure:
‐ VVI/VVIR: 3.5%
‐ DDD: 7.8%
P<0.001
Influence sur les pratiques: France 2009 (62000 PM SC/DC)!
VVI/VVIR
Toutes indications
Blocs AV
DDD/DDDR
23%
41%
77%
59%
Désynchronisation/Resynchronisation
• Atrio‐ventriculaire: du PR long à la dissociation complète
• Atriale: la dissociation inter‐atriale
• Ventriculaire:
− Prévenir la désynchronisation
− Désynchroniser dans de rares cas: l’exemple de la MCHO
− Resynchroniser quand nécessaire:
l’insuffisance cardiaque systolique
Concept de Resynchronisation Atriale
180 ms
RA
cs
RV
RV
SYNBIAPACE Study
SYNchronous BIAtrial PACING for atrial arrhythmia prevention
European, multicenter,randomized, cross‐over study
to compare the effects of 3 pacing modes
Support (DDI 40), DDD 70, and biatrial‐DDD 70
during 3 periods of 3‐months ech
in patients with
‐ recurrent drug‐refractory atrial tachyarrhythmias
‐ intra‐atrial conduction delay (P >120 ms)
(P >120 ms
P Mabo et Al, Eur Heart J 1998
SYNBIAPACE study
Primary endpoint:
Time to 1‐st recurrence in a sustained form (device memories)
Inhibited 29 + 34 days
Single‐RA 35 + 40 days
Biatrial 48 + 41 days
p < 0.05
P Mabo et Al, Eur Heart J 1998
SYNBIAPACE
SYNBIAPACE
1,2
%
Arrhythmia free survival
100 1
BIATRIAL
DDD
Inhibited
0,8
80
0,6
60
0,4
40
20
0,2
00
50
77
days
60
30
30
21
0
0
90 day
P Mabo et Al, Eur Heart J 1998
Resynchronisation atriale
Validation du concept: Etude SYNBIAPACE (1992)
Méthodologie faible
Objectifs mal choisis: charge FA
Résultats peu significatifs
Concept à re‐évaluer?
Hemodynamic Benefit of Atrial Resynchronization
Transmitral flow Aortic ejection flow
Single RA Biatrial
Biatrial
Single RA
Comparison of Single RA DDD pacing and Biatrial DDD pacing
In a patient with HFPEF. AVD = 150 msec
C Daubert et Al Eur Heart J 1991; G Jauvert et Al, Eur Heart J, 2000
Left
Le atrial pacing in diastolic heart failure
• French multicenter randomized crossover study
• Principal investigator: G Laurent, JC Eicher CHU Dijon France
• Supported by the French Ministry on Health (PHRC)
Patients: HFPEF with NYHA Class III‐IV symptoms, LVEF>50%, NSR, and evidence of “atrial dyssynchrony” (Eur J Heart Fail 2012; 14, 248–258)
Active pacing: overdrive left atrial pacing (CS lead)
Pacing ON
6‐weeks
12‐weeks
Pacing OFF
Pacing ON
12‐weeks
Pacing OFF
22‐weeks
•
Primary outcome: 6 min walking distance
•
Secondary outcomes: –
Atrial fibrillation burden (device counters)
–
–
–
–
Quality of life (Minnesota living with HF)
Number of hospitalization for decompensated heart
failure
BNP/Ntpro‐BNP blood level
Mortality
–
Patient’s pacing mode preference (active vs inactive)
•
Primary outcome: 6 min walking distance
•
Secondary outcomes: –
Atrial fibrillation burden (device counters)
–
–
–
–
Quality of life (Minnesota living with HF)
Number of hospitalization for decompensated heart
failure
BNP/Ntpro‐BNP blood level
Mortality
–
Patient’s pacing mode preference (active vs inactive)
Désynchronisation/Resynchronisation
• Atrio‐ventriculaire: du PR long à la dissociation complète
• Atriale
• Ventriculaire:
− Prévenir la désynchronisation
− Désynchroniser dans de rares cas: l’exemple de la MCHO
− Resynchroniser quand nécessaire:
l’insuffisance cardiaque systolique
Prévenir le désynchronisation
Préserver la séquence d’activation intrinsèque lorsqu’elle est normale
Preserving the Normal Activation Sequence
%
70
LVEF
65
65±6
60
55
61±8
58±6
60±4
52±8
50
45
40
56±7
p<0.01
p<0.01
p<0.01
p<0.01
Rest
Exercise
%
70
65
71±14
67±11
60
Septal LVEF
55
50
45
63±12
58±10
55±15
P<0.01
51±8
NS
P<0.01
NS
40
C Leclercq et Al. Am Heart J. 1995;129:1133‐41
Rest
Exercise
AAIR
DDDR
VVIR
No significant difference in mortality,
stroke, new or worsening HF….
MO Sweeney et Al. N Engl J Med 2008; 357: 1000‐1007
Désynchronisation ventriculaire pour lever l’obstruction dans la CMHO
APC
V esc.
Transient AV dissociation
C Daubert et al, 1994
Importance of Optimizing Left AV Timing in HOCM
Randomized controlled studies on Pacing
Therapy in HOCM
PIC in Europe (1997)
M‐Pathy in US (1999)
The only HOCM therapy assessed in randomized studies
PIC Study
• Inclusion criteria :
– Functional limitation (NYHA class II or III , peak VO2 < 85% age‐predicted VO2max)
– LVOT gradient > 30 mmHg at rest
– No standard pacemaker indication
• Study design:
Prospective randomized multicentre double‐blind crossover (12 weeks ‐
PM activated vs non activated) study to investigate the impact of pacing
therapy in HOCM refractory or intolerant to drug treatment
• Primary endpoint: Exercise duration
• N = 83 pts ‐ Gender (f/m) 33/50 ‐ Mean age = 53 years
L Kappenberger, C Daubert et al. Eur Heart J 1997; 18:1249
PIC Study ‐ Results
Baseline
DDD
AAI
DDD vs B
DDD vs AAI
LVOT gdt (mmHg)
71 +/- 29
35 +/- 27
52 +/- 34
<.00001
<.00001
NYHA class
2.5 +/- .5
1.7 +/- .7
1.4 +/-0.6
<.00001
<.00001
Exercise d. (min)
12.9 +/- 5 12.6 +/- 4
12.9 +/-4
ns
ns
QoL (Karolinska)
Significant improvement 9‐44% with active pacing
Placebo effect of PM implantation ¶ Exercise
tolerance Ò 21%
in pts who at baseline tolerated < 10 min Bruce
Recommendation
in international guidelines: Class IIb, LOE: B
protocol
Wrong concept or concept to reassess in outcome studies?
L Kappenberger, C Daubert et al. Eur Heart J 1997; 18:1249
De La Resynchronisation Atriale
180 ms
RA
cs
RV
RV
A la Resynchronisation Ventriculaire…
V1
V3
Anterior-posterior
V5
A 18‐years Clinical Experience
Cazeau S, Ritter P, Bakdach S, Daubert JC
Four chamber pacing in dilated cardiomyopathy
Pacing Clin Electrophysiol 1994;17:1974-9.
Prevalence of Conduction Abnormalities in Systolic heart failure
- Long PR Interval (>200 ms) :
20‐47 % of CHF patients Influence of HF drugs : Beta‐blockers
n
so
on
r
ho
el
< 120ms
> 120ms
Sc
150
100
50
le
m
La
m
p
A
ar
200
Sh
a
Number of
Patients 250
in
300
Aa
ro
ns
on
‐ Intraventricular Conduction Delay (>120 ms)
31%
46%
27% 53%
41%
0
Italian network on CHF (S Baldasseroni et al, Am Heart J,2002):
Prevalence of LBBB in 5517 CHF patients : 25.2%
Progression of Conduction Disturbances over Time
msec
(ms)350
300
PR
250
200
150
QRS
100
Time (months)
50
0
10
20
30
40 (months)
Xiao et al, Int J Cardiol 1996
Predictive value of LBBB: The Italian network on CHF
1‐year mortality in 5517 patients (NYHA III‐IV: 28%)
All
No
L
B
B
B
L
B
B
B
Independent on age, NYHA class, etiology, drug treatment
S Baldasseroni et al Am Heart J 2002
Mechanical consequences of ventricular dyssynchrony
Dog model of dyssynchronized heart failure
LV dysfunction by rapid pacing + LBBB
LV‐RV simultaneous pacing
No pacing
C Leclercq, D Kass, 2001, Johns Hopkins, Baltimore
Acute Hemodynamic Studies with
Temporary Pacing
In CHF patients with NSR and IVCD, Atrio‐biventricular or LV pacing
• Increases cardiac output (Foster, Cazeau, Leclercq)
• Decreases pulmonary pressures (Cazeau, Blanc, Leclercq)
• Increases pulse pressure (Blanc, Kass, Auricchio)
• Increases LV + dP/dt (Kass, Auricchio)
• Improves cardiac performance: PV loops (Kass, Auricchio)
This effect is achieved at diminished energy cost (Nelson)
Acute Effects of Atriobiventricular Pacing
Atrial Pacing Atriobiventricular Pacing BP : 100 /80
BP : 120 / 70
Male, 67 yrs, NYHA class IV, Ischemic cardiomyopathy, LVEF= 20%
Inclusion criteria in RCT’s evaluating CRT in HF
Trial
N Pts
NYHA
LVEF %
LVEDD mm
SR/AF
QRS ms
ICD
MUSTIC-SR
58
III
<35%
>60
SR
>150
No
MIRACLE
453
III,IV
<35%
>55
SR
>130
No
MUSTIC AF
43
III
<35%
>60
AF
>200
No
PATH CHF
41
III,IV
<35%
NA
SR
> 120
No
MIRACLE ICD
369
III,IV
<35%
>55
SR
>130
Yes
CONTAK CD
227
II,IV
<35%
NA
SR
>120
Yes
MIRACLE ICD II
186
II
<35%
>55
SR
>130
Yes
PATH CHF II
89
III,IV
<35%
NA
SR
>120
Yes/No
COMPANION
1520
III,IV
<35%
NA
SR
>120
Yes/No
CARE HF
814
III,IV
<35%
>30
SR
>120
No
CARE HF extens
813
III,IV
≤35%
>30
SR
>120
No
REVERSE
610
I,II
<40%
>55
SR
>120
Yes/No
MADIT CRT
1800
I,II
<30%
NA
SR
>130
Yes
RAFT
1800
II,III
<30%
>60
SR/AF
>130 >200*
Yes
>8000 pts enrolled in >14 RCT’s including 4 large morbidity-mortality trials
MUSTIC: Study Design SR Group
Randomized single blind crossover comparison ƒ Atrial‐synchronized biventricular pacing with optimal AV timing ƒ Inactive VVI pacing (40 bpm)
Visits
ne
i
l
se
a
B
n
io
t
ta
4 weeks
an
l
p
Im 2 weeks
T0
om
d
n
Ra
tio
a
z
i
A‐BIV pacing No pacing
M 3 3 months M 6
M12
n
3 mo.3 mo.6 mo. 6 mo.
No pacing A‐BIV pacing
no modification in drug treatment, except for
S Cazeau, et Al. N Engl J Med 2001; 344 : 873‐80
diuretics
MUSTIC: Crossover Phase
500
450
384
400
413
BiV-NoP
NoP-BiV
354
350
320
6‐min WD
299
39
+23%
p<0.001
43.8
250
46.4
Meters Meters
322
346
300
Baseline
Rando
CO1
CO2
Phase 1
Phase 2
Score Improvement
15200
QoL MLWHF
Baseline
60
23.2
25
33.2
3540
39
41.1
45
40.6
20 46.4
43.8
‐ 32% P < 0.001
55
0
1
1
1
S Cazeau, et Al. N Engl J Med 2001; 344 : 873‐80
Months since randomization
CARE HF: Morbidity‐Mortality Trial
(All‐cause Mortality or Unplanned Hosp. for Major CV Event)
Event-free Survival
1.00
HR 0.63 (95% CI 0.51 to 0.77)
0.75
CRT (n=159; 39%)
0.50
P < .0001
Medical Tx
0.25
No statistical significant
heterogeneity in subgroups
(n=224; 55%)
0.00
Number at risk
0
500
1000
1500
Days
JGF Cleland, et Al. N Engl J Med 2005
CARE HF: All‐Cause Mortality
1.00
Event-free Survival
HR 0.64 (95% CI 0.48 to 0.85)
0.75
CRT (n=82; 20%)
P = .0019
0.50
Medical Tx
(n= 120; 30%)
ARR: 10% at 29 months
0.25
0.00
0
Number at risk
500
1000
1500
Days
JGF Cleland, et Al, N Engl J Med 2005
CARE‐HF Extension Study
Time to Sudden Death
1.00
CRT
Medical
Therapy
Survival
0.75
0.50
Hazard Ratio 0.54 (95% CI 0.35 to 0.84; P=0.006)
0.25
CRT = 32 sudden deaths (7.8%)
Medical Therapy = 54 sudden deaths (13.4%)
0.00
0
400
800
1200
1600
Time (days)
JGF Cleland, C Daubert et Al Eur Heart J 2006
2010 Focused Update of ESC Guidelines on Device Therapy in Heart Failure
An Update of the 2008 ESC guidelines for the Diagnosis and Treatment of
Acute and Chronic Heart Failure and the 2007 ESC guidelines for Cardiac and
Resynchronization Therapy, developed in collaboration with EHFA and
EHRA
Authors/Task Force Members: Kenneth Dickstein* (Chairperson) (Norway), Panos E.
Vardas** (Chairperson) (Greece), Angelo Auricchio (Switzerland), Jean-Claude Daubert
(France), Cecilia Linde (Sweden), John McMurray (UK), Piotr Ponikowski (Poland), Silvia
Giuliana Priori (Italy), Richard Sutton (UK), Dirk van Veldhuisen (Netherlands)
ESC Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson) (France), Angelo Auricchio
(Switzerland), Jeroen Bax (The Netherlands), Claudio Ceconi (Italy), Veronica Dean (France), Gerasimos
Filippatos (Greece), Christian Funck-Brentano (France), Richard Hobbs (UK), Peter Kearney (Ireland),
Theresa McDonagh (UK), Bogdan A. Popescu (Romania), Zeljko Reiner (Croatia), Udo Sechtem (Germany),
Per Anton Sirnes (Norway), Michal Tendera (Poland), Panos Vardas (Greece), Petr Widimsky (Czech
Republic)
Document Reviewers, Michal Tendera (Coordinator) (Poland), Stefan D. Anker (Germany), Jean-Jacques
Blanc (France), Maurizio Gasparini (Italy), Arno W. Hoes (Netherlands), Carsten W. Israel (Germany),
Zbigniew Kalarus (Poland), Bela Merkely (Hungary), Karl Swedberg (Sweden), A. John Camm (UK)
EHJ 2010 doi:10.1093/eurheartj/ehq337
Recommendation in patients with
heart failure
in NYHA function class III/IV
Patient Population
Class
LoE
Refs
I
A
5-19
Recommendation
CRT-P/CRT-D*
is recommended
to reduce
morbidity and
mortality
NYHA function class III/IV
LVEF≤35%, QRS≥120 ms, SR
Optimal medical therapy
Class IV patients should be
ambulatory**
*
Reasonable expectation of survival with good functional status for >1 year for CRT-D.
Patients with a secondary prevention indication for an ICD should receive a CRT-D.
** No admissions for HF during the last month and a reasonable expectation of survival
>6 months.
EHJ doi:10.1093/eurheartj/ehq337
NYHA functional class I‐II
Prevention of Heart Failure
Progression
• REVERSE (C Linde, JC Daubert): 2088‐2009
• MADIT CRT (AJ Moss): 2009
• RAFT (AL Tang): 2010
4200 pts; Follow‐up: 2‐5 years
Percentage Hospitalized for HF or Died
REVERSE: European Cohort
Time to First HF Hospitalization or Death
30%
HR (95%CI): 0.38 (0.20-0.73)
P=0.003
25%
24.0%
20%
CRT OFF
15%
11.7%
10%
5%
CRT ON
0%
0
6
12
18
24
Months Since Randomization
Number at Risk
CRT OFF
CRT ON
82
180
79
176
76
173
70
168
39
77
C Daubert et Al, J Am Coll Cardiol 2009; REVERSE: European Cohort
Powered Secondary End Point: LVESVi
LVESVi (ml/m2 )
110
CRT OFF
100
96,6
92,5
94,5
91,6
88,8
90
93,9
80
P<0.0001
CRT ON
76,8
70
73,6
69,2
69,7
18
24
60
0
6
12
Months Since Randomization
P-value compares 24-month changes.
C Daubert et Al, J Am Coll Cardiol 2009; RAFT: Mortality
ASL Tang et Al, N Engl J Med 2010; 363: 2385‐2395
Recommendation in patients with heart
failure
in NYHA function class II
Recommendation
Patient Population
CRT preferentially by
CRT D is recommended
to reduce HF morbidity
and prevent disease
progression
NYHA function class II
LVEF≤35%, QRS≥150
ms, SR
Optimal medical
therapy
Class Leve
l
I
A
Refs
9, 2022
* The guideline indication has been restricted to patients with HF in NYHA
function class II with a QRS width ≥150 ms, a population with a high
likelihood of a favourable response.
EHJ doi:10.1093/eurheartj/ehq337
Predictive value of QRS duration in NYHA class I‐II patients
MADIT CRT
P for interaction= 0.001
REVERSE 24‐months
RAFT
P for interaction= 0.003
Predictive value of QRS morphology in NYHA class I‐II pts
LBBB
Non-LBBB
W Zareba et Al Circulation.2011;0:CIRCULATIONAHA.110.960898
Predictive value of QRS morphology in NYHA class I‐II pts
RBBB
IVCD
W Zareba et Al Circulation.2011;0:CIRCULATIONAHA.110.960898
REVERSE: 12‐month
LVEF Change by QRS Morphology
Predictive
value of QRS morphology
in NYHA class I‐II pts
LVEF Change (%)
LVEFchange (%)
10
LBBB
8
M Gold et Al 2012 SubmittedNon-LBBB
to publication
CRT OFF
CRT ON
6
4
2
0
CRT On
CRT Off
CRT On
W Zareba
et Al Circulation.2011;0:CIRCULATIONAHA.110.960898
Non-LBBB
LBBB
Non LBBB
LBBB
CRT Off
2012 CRT Guidelines of the Heart Failure Society
Class I, LOE: A
CRT is recommended for patients in sinus rhythm with a widened
QRS interval (>150 msec) that is not due to right bundle branch
block who have severe LV systolic dysfunction (LVEF<35%) and
persistent mild to moderate HF (NYHA functional class II-III)
despite optimal medical therapy
Class IIb, LOE B
CRT may be considered for ambulatory NYHA class IV patients in
sinus rhythm with QRS interval (>150 msec) who have severe
LV systolic dysfunction (LVEF<35%) despite optimal medical Tx
CRT may be considered for patients with a QRS interval of
>120 msec to <150 msec who have severe LV systolic dysfunction
(LVEF<35%) and persistent mild to moderate HF (NYHA functional
class II-III) despite optimal medical therapy
J Cardiac Fail 2012; 18: 94-106
Recommendations for the use of CRT in patients in sinus rhythm with NYHA functional class II‐III, or ambulatory class IV with persistently reduced ejection
fraction, despite optiimal medical trearment
Désynchronisation‐Resynchronisation
Histoire: La messe est dite!
ou Pré‐histoire? Merci à tous ceux qui ont contribué à décrypter les asynchronismes cardiaques, concevoir les outils pour les corriger, évaluer la resynchronisation et écrire sa pré‐histoire
•
•
•
•
•
•
•
•
•
•
•
Christine Alonso
Serge Cazeau
Christian de Place
Erwan Donal
Daniel Gras
Christophe Leclercq
Philippe Mabo
Jacky Ollitrault
Dominique Pavin
Philippe Ritter
André Roussel
•
•
•
•
•
•
•
•
•
•
•
Christophe Bailleul
Ivan Bourgeois
Marcel Limousin
Yves Pouvreau
Alain Ripart
William Abraham
John Cleland
Michael Gold
Lukas Kappenberger
Cecilia Linde
Richard Sutton