2006 siracusa, congresso nazionale di cardiologia. minimizzazione del pacing ventricolare nel paziente portatore di defibrillatore impiantabile

1. S. Nardi, MD
Lab. Elettrofisiologia – Div. di Cardiologia
Azienda Ospedale S. Maria - TERNI
Nel “Cuore” della Magna Grecia
17-20 ottobre 2006 – Siracusa
Interesse clinico del modo di
pacing AAIsafeR nei pz con ICD
Fisiologicità e sicurezza nel gestire i
disturbi di conduzione atrioventricolare

2. “ Feel “ Ventricular Activity
Detection Atrial and Ventricular
Tachyarrhythmias
(with several and dedicated Algorithm)
Physiologic Pacing
Background
What is the objectiveWhat is the objective
of ICD?of ICD?
Relase ATP & shocks when necessary
Sweeney MO, PACE ‘05
What does it mean
Physiologic Pacing ?

3. In 80 ies and 90 ies
Physiologic Pacing mean DDD
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

4. DAVID
MOSTMOST
DANISHDANISH
CTOPPCTOPP
UKPACEUKPACEPASEPASEA: AAI(R)
B: VVI(R)
C: DDD(R)
D: DDD(R): (with special programming )
C. W. Israel CW, Cardiostim `06
TRIALS

5. UK-PACE All-cause
mortality
CV mortality
Toff, NEJM `05
• 2021 pts
• ≥70 yrs
• High-grade AVB
TRIALS
CTOPP
Connolly, NEJM `00
AFibCV mortality,
stroke
Nr. 2568
first implant
(65% AVB)

6. MOST
Nr. 2010
first implant
DDDR
Pacing
1014
VVIR
pacing
996
1ary
Endpoint: Stroke + ACM Hosp. for CHF, Stroke, Death
Atrial FibrillationHosp. For CHF
Lamas G, NEJM ’02
TRIALS

7. DAVIDDAVID
N = 506 ICD pts
LVEF <40%, conventional
ICD indication (class 1
ACC/AHA) OMT FU, No
PM indication, no AT/AF
DDDR 70
n = 250
VVI 40
n = 256
Wilkoff BL, JAMA ‘02
Background
VVI
40
DDDR
70
HR
(p)
HF-H or
DEATH
16.1% 26.7% 1.61
(p=0.03)
CHF-H 13.3% 22.6% 1.54
(p=0.07)
DEATH 6.5% 10.1% 1.61
(p=0.15)
Single Blinded multicenter parallel
group RANDOMIZED TRIAL

8. Potential Flaws
in Randomized Controlled Trials
•CTOPP: Pts with low unpaced HR benefit from DDD
•UKPACE: Short programmed AVD (75-150 ms)
•PASE: High cross-over due to PM syndrome in VVIR
(intention-to-treat analysis)
•MOST: High cross-over due to PM syndrome in VVIR
(intention to treat analysis)
Ellenbogen, AJC `00; Tang, Circulation `01; Link, JACC `04, Toff, NEJM `05
UKPACEUKPACE

9. 0
2
4
6
8
10
12
14
16
RateofHeartFailure
Hospitalization
< 10% Cum VP > 90% Cum VP
DDDR VVI R
Sub-Study
(1339pts (67%)
with Know Cum%VP)
• Cum%VP greater in DDDR (90%) vs. VVIR (51%).
• The rates of CHF-H increased with Cum%VP
Sweeney MO,
Circulation ‘03
Median FU 31mo
• Lower rate ≥60
• Max rate ≥110bpm
• AVD 120-200ms
MOST

10. • 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.
MOST
Sweeney MO, Circulation ‘03
0
1
2
3
4
0 20 40 60 80 100
Cum % VP
RiskofAFrelativeto
VVIRpatientwithCum%VP=0
Sub-Study DDDR mode
(1339pts (67%) with Know Cum%VP)

11. 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 DDDR mode
(1339pts (67%) with Know Cum%VP)

12. 0
2
4
6
0 20 40 60 80 100
Cum% VP
RR of 1st CHF-H
The RR INCREASE between 0%
and 40% of Cum% VP, but doesen’t
change for >40% 45% have the
same RR of 65%)
The RR is REDUCED at ≈2% if RV
pacing is minimised
Conclusions
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
MOST
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

13. • 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
Executive Summary
• 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%

14. Sweeney, Circulation `06
What kills the Patients:
the DDD Mode or Inadequate
implantation/programming?

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

16. Spragg DD, Circulation ’03
Regional Alterations of Protein
Expression in CHF and RVP dogs

17. 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

18. AAI mode

19. RVA pacing

20. • Conventional RV pacing results in
“forced” ventricular
desynchronization, which mimics
LBBB and has adverse effects on
structure and function.
Sweeney, JACC `06
Executive Summary
• Most ICD pts (~80%) have reliable
AV conduction and narrow QRS.
These pts would benefit from
mode that promotes intrinsic AV
conduction.

21. 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

22. Considerations
Cost
Efficacy
AAI(R) mode
• Preserves a normal ventricular
activation sequence but requires
stable long-term AV conduction and
SR
• SND is a spectrum of electrical
disorders that includes AF and AV
block
Ineffective for V bradycardia during
- Paroxysmal and permanent AF and/or AV block
Too Risky?
Which Strategies
to Optimize Pacing ?

23. Study Mode
Selection
FU Incidence of
AF
Annualized
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 DDDRVVIR 3 years 16.6% 5.5% (DDDR)
Study FU 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%

24. 1. AAI(R) until stable AV conduction
(safety VP “back-up” if AVB occur)
2. Reduction unnecessary Cum %VP better then
conventional strategies with 4 criteria – AVB1st
2nd
3th
pausa max - (DDD with long AVD or search AV, DDI mode)
3. Detection and treatment of AVB (safety pacing mode
(temporary DDD-mode)
4. Switch back to AAI(R) (if recovery spontaneous AV cond)
5. Able to support exercise pts capacity
6. No technical limit of AAI mode
(undersensing/oversensing)
7. Switch AAI ⇒ DDI (in atrial arrhythmias)
8. Detailed diagnostic
AAISafeRmodespecifications
AAIsafeR
Operative Mechanism

25. * Sorin Group
AAIsafeR
Switch Criteria
• Switch “for 1 day”
AAI ⇒ DDD
(“1-day
DDD”):
 ≥ 45 ep. of AVB/ 24 h
≥ 15 ep. of AVB/24 h,
for consecutive 3 days
 Cum %Vp > 50% in 1 h
• Automatic restore DDD ⇒ AAI (“switch back” to AAI):
 if 12 spontaneous VS event in DDD
 after 100 VP event
 one tentative daily (h 8.00 AM) to restore AAI mode

26. “AAI” “DDD”
AAISafeRAAISafeR
1st
degree AVB at 103 b/m’ in SR
7 consecutive atrial events (AS
and or AP) with a PR interval >
maximum programmable limits
(programmable)
Switch I d AVB “Exercise Only”:
PR max: 200 – 450 ms (step 50ms)
Switch I d AVB “Rest+Exercise” PR
max: 350-400-450 ms
1st degree AVB

27. AAISafeRAAISafeR
2st degree AVB
• 3/12 blocked atrial events (AS
and/or AP) in a dynamic window
of 12 atrial cycles; immediate
switch in DDD(R) (dynamic
AVDs, programmable)

28. • 2 consecutive blocked atrial events (AS and or AP) induce
immediate switch in DDD(R) mode (dynamic AVDs, programmable)
AVBlockmanagement
AAISafeRAAISafeR
3st degree AVB
AVD programmable

29. Potential Pitfall
AAI(R) mode
AAI Syndrome
loose the adaptative “AV
conduction time” with progressive HR
increment
Mabo P, PACE `91
With progressive incremented of
Work-load (from rest to 60W),
HR increment and PR interval
does’t adapt.
The relationship spike-R / RR
can acheve at 100% for
consistent work-load (70W).

30. exercises capacityAAISafeRAAISafeR
AAIsafeR2
commuta
in
AAIsafeR2
commuta
in
modo
DDD(R)
modo
DDD(R)
If 1st
degree AVD occur during exercise,
(critical AVD) automatic switch in
DDD(R) (max PR tollerate 200-450 ms)
guarantite a more efficacy AV
synchronism (OAVD and CO) with
respect for exercise’s capacity of pts,
until the end of exercises
→ Option execise only

31. How to eliminate Undersensing/Oversensing
of AAI mode ?
Short Automatic refractory
period like DDD mode
(also post
VS or VP) minimizing ARP and
with better Atrial
arrhythmias detection
Atrial Autosensing
(dynamic atrial sensibility = 1/3
mean P wave)
Protection against Far-Field
(automatic changing of Atrial
Sensibility inside cardiac cycle )
Blanking
Atriale
Blanking
Ventricolare
As
Vs
80
ms
95
ms
Ap
Vs
80
ms
95
ms
PAC
Vs
Vs Vs
As Ap
Vs
PAC
PRAPRA PRAPRA
A-ARP
Absolute
ARP
AAISafeRAAISafeR

32. ≥ 60% of DDD/PM indications
could improve with AAIsafeR
Danish, German & Swiss PM Registries:
Herzschr Elektrophys `02
AAIsafeR
Savourè A, PACE ’05
Safety on 43 pts
Frohlig G, Europace ’06
123 pts (74±10yrs, 51% M), FU M1 in AAIsafeR mode
(1st 43 pts Holter pre-discharge)
SAFETY:
- No indesiderate events,
- No Ventricular pauses
- No false negative on safety switch AAI ⇒ DDD

33. SAVE/RSAVE/R
N = 54 pts
conventional PM
indication (SND, Bradi/tachi,
Parox AVB)
Study
• Spontaneous AV conduction at rest:
PR < 250 ms, Randomized pacing
mode at M1, no Permanent AVB at M1
DDD +
Long AVD
AAIsafeR
Nr pz 26 28 *
% VP (mean ±DS) 7.3 ± 19.8 % 0.04 ± 0.19 %
Mediana % VP 0 % 0 %
Min - Max % VP 0 – 95 % 0 - 1 %
Nr pz con %Vp =
0
18 (69 %) 27 (96 %)
0
10
20
30
40
50
60
70
80
90
100
% V pacing Pts with Vp=0%
AAIsafeR DDD long AVD
P=0.01P=0.01
P<0.006P<0.006
AAIsafeRinPMpts
EFFICACY
JM Davy, HRS ‘05

34. SAVE/RSAVE/R Study
EFFICACY
N = 183 pts
conventional PM
indication (SND,
Bradi/tachi, Parox
AVB)
AAIsafeRinPMpts
JM Davy, HRS ‘05

35. Long AV delay during
DDD(R) mode
how long to prevent VP ?
AVD 200 ms
AVD 270 ms
AVD 300 ms
AVD 350 ms

36. • Long AV delays may reduce
unnecessary VP and maintain
normal ventricular activation
sequence but require reliable
AV nodal conduction.
• Long AV delays may impose
limitations on optimal DDDR
operation:
– Reduced 2:1 block point due to
increased TARP
– Abandonment of mode-
switching or significantly
delayed AF recognition
Long AV delay during
DDD(R) mode
→ Endless Loop Tachycardia

37. Nielsen, JACC ‘03
AAIR
DDDR
Long AV Delay
DDDR
Short AV Delay
p=0.03
Pacing
Mode
AV
Delay (ms)
VP
(%)
AF
(%)
AAIR -- 0 7.4
DDDR-L
(300ms)
300 17 17.5
DDDR-S
(≤150ms)
≤150 90 23.3 n=177 pts; 2.9 yrs F/U
Long AV delay during
DDD(R) mode
AAIR (0% VP)
DDDR short AVD (≤150 ms; 90% VP)
DDDR long AVD (300 ms;
17% VP)

38. DDDR-DDDR-
s-AAIs-AAI
AAIAAI
RR
DDDR-DDDR-
ss
DDDRDDDR
-l-l
LA Diameter
0%
20%
40%
60%
80%
100%
A Pace V Pace
AAIR DDDR-l DDDR-s
0%
20%
40%
60%
80%
100%
A Pace V Pace AF
AAIR DDDR-l DDDR-s
Long AV delay during
DDD(R) mode
AAIR (0% VP)
DDDR short AVD (≤150 ms; 90% VP)
DDDR long AVD (300 ms;
17% VP)
Nielsen JC, JACC ‘03

39. - After an AS, the mode will not provide a Vp unless no Vs occurs before
reaching the lower rate
– After an Ap, which would only occur at the lower rate, a Vp will be
provided (if needed) at the programmed PAV.
DDI(R) mode
A limited solution
Higgins SL, Am J Cardiol ‘98
N = 139 ICD pts
LVEF <40%, conventional
ICD indication (class 1
ACC/AHA)
25 pts (18%) need pacing
• Permits long AV delays w/o the
possibility of upper rate limit tracking
during AF (unlike DDDR); However,
limitations of long AV delays in reducing
VP still persist.
• Operationally VVIR during AV block if sinus rate exceeds lower
rate limit. Competitive AP during sensor-modulation may precipitate
AF.

40. AAIsafeR:evaluationinICDpts
* Study approved in UK, France,
Italy, Germany, Holland, Denmark
AAISafeRAAISafeR
ICDICD Objective
Ovatio DR (16) Ovatio CRT (14)
(AAIsafeR mode)
Sex (% men) 75 79
Age 62 ± 10 68 ± 10
1st
ICD indication 56 % 66 %
CAD 56% CAD, 44% post-MI,
12% DCM, 12% ARVD
100% CHF, 64% CAD, 57%
post-MI
Pacing Indication 31%AVB, 31%SND,
38% none
28% AVB,
14% AVB + SND
LVEF (%) 43 ± 18 27 ± 6
NYHA Class I-IV 6 / 9 / 1 / 0 0 / 7 / 5 / 2

41. 24 h EKG Holter analyses reveal:
 No Ventricular cicle > “Max Ventricular pause programmed
 No switch on false positive
 No False Negative AAI ⇒ DDD swich
AAIsafeR:evaluationinICDpts
AAISafeRAAISafeR
ICDICD Safety and Efficacy
pts
No
Switches
Intermittent
Switch
Long
switches
Cum %VP 30 0% (23 pz) 0–1% (5 pts) 30–97% (2 pts)
Cum %AP 30 20±30% 32±42 % 5 ± 9 %
% V pacing 10 0 % (2 pz) 0–8% (6 pts) 8–12% (2 pz)
FU 24h
F-up M1 FU 24 h: 93% (28/30 pts) “No switch” or “Intermittent Switch”
FU M1: 80% (22/30 pts) “No switch” or “Intermittent Switch”

42. Sweeney, HRS `04, JACC
`06, Circulation `06
Relationship between
mechanical asynchrony and
HF development, as derived
from various randomized
clinical trials
MVPMVP

43. • Several TRIALS on physiologic pacing
have demonstrated that an AAI
support ≥ in Clinical outcome (⇓
HFH) vs VVI or DDI (low HR)
strategies, because preservation of
• AV synchronism;
• spontaneous sequence of Ventricular
activation (V synchronism and ⇓ %Vp) PP RR
INTRINSICINTRINSIC
Or DDD longOr DDD long
AorticAortic
pressurepressure
LVLV
pressurepressure
PPPP
PeakPeak
atrial systoleatrial systole
Start ofStart of
LV systoleLV systole
Diastolic
Mitral
Regurgitation
Maximum
Effective Preload
PP VV
PACEDPACED
AAIAAI PPPP
SynchronizedSynchronized
LV and atrialLV and atrial
systolessystoles
Sweeney MO, PACE ‘05
Executive Summary
• These data support a therapeutic
strategies in a contest of ICD
indication (1st
- 2st
), that an AP is
able to give an adequate
CHRONOTROPIC SUPPORT
and reduce CHF-H minimizing Cum %
VP.

44. AAISafeRAAISafeR
ICDICD Conclusions
In ICD indication pts (w/o CRT indication or permanent
AVB), AAIsafeR is Safe (no adverse event; No Ventricular
pauses > programming; No FN AAI ⇒ DDD)
AAIsafeR:evaluationinICDpts
In non selected population of ICD pts 7% (2/30)
switched to DDD of long duration after 1 day (20% at
M1) (due to probably latentt sitaution of advanced AVB)
In selected population of ICD pts « No switch » or « Intermittent Switch
» with Global efficacy in Cum %VP <1% (mean value 0.1%)
AAIsafeR is Safe reduce un-necessary RV pacing

45. AAISafeRAAISafeR
ICDICD Conclusions
PerspectivesforICDpts
 In pts w/o anti-bradicardia pacing support:
a valid alternative to “VVI (o DDI) low rate”
 In pts with SND (Chronotopic Incompetence):
a valid alternative to “DDI 60 bpm” or “AAIR” mode
 In pts with Paroxistic AVB:
a valid alternative to “DDD + long AVD” mode

46. Grazie per laGrazie per la
cortese attenzionecortese attenzione