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Long Term Effects of
RV Pacing
Tehran Arrhythmia Center
April 2006
Pacing the right ventricle
To Pace or not to Pace?
Deleterious Effects of RV Apical Pacing


Altered left ventricular electrical and mechanical
activation
Altered ventricular function



Less work produced for given LVEDV
Delayed papillary muscle activation  Valvular insufficiency
Remodeling


Modified regional blood flow patterns
Increased oxygen consumption without increase in blood flow

Abnormal thickening of LV wall
Cellular disarray
 Fibrosis (away from pacing lead location)
 Fat deposition
 Calcification
 Mitochondrial abnormalities


60% change in blood flow between early and later activated regions
Altered left ventricular mechanical
activation

Potential detrimental effect of RV apical pacing in
the form of pacing-induced LV dyssynchrony
secondary to the abnormal activation sequence

Pacing-induced abnormalities of myocardial blood
flow

RV apical pacing alters LV papillary muscle
function, changing the timing sequence of the
mitral valve apparatus, thus causing MR.
Altered LV Electrical Activation Pattern
Normal Sinus Rhythm
Right Ventricular Apical Pacing
Cassidy DM, et al. Circ 1984;70:37-42

Two break-out locations on LV endocardium
Inferior border of the mid-septum
Superior basal aspect of free wall

Latest activation
Base of the inferior posterior wall

Muscular conduction (less Purkinje
fiber density)
Vassallo JA, et al. JACC 1986;7:1228-33

Single break-out location on LV endocardium
Similar to left bundle branch block

Latest activation
Similar to intrinsic

Inferioposterior base
Apical Pacing Histopathology

Adomain (1986)

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
Karpawich (1990) – Pediatric Canine Model

LV myofibril disarray was found after 4 months
of pacing from RV apex



90 degree misalignment of adjacent fibers
(stress related?)
Also noted appearance of prominent Purkinje
cells in subendocardium, variable-sized
mitochondria, and dystrophic calcification
Karpawich (1999) – Pediatric Patients


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
25X: Karpawich PP, et al. Am Heart J 1990;119:1077-83
Clinical Studies of Adverse Effects
of RV Pacing
Pace,Vol.29, March 2006
Clinical Studies of Adverse Effects
of RV Pacing
Heart Rhythm, Vol 2, No 2, January 2005
Danish Study
Overview
• Hypothesis:
In patients with SND, atrial pacing (AAI) will result in
less atrial fibrillation, thromboembolism, heart failure
and overall mortality than ventricular pacing (VVI).

Study Design:
Single center, prospective, randomization of
patients referred for first pacemaker implant
Danish Study
Endpoints

Primary:
-Mortality
-Cardiovascular death

Secondary:
-Atrial fibrillation
-Thromboembolic events
-Heart failure
-AV block
Danish Study
Patient Characteristics
AAl Group
VVI Group
110
115
76 + 8
75 + 8
Women
73
69
Men
37
46
Sinus bradycardia
18
18
Sino atrial block
49
46
Brady-Tachy Syndrome
43
51
No. of Patients
Age, y
Danish Study
Patient Characteristics
AAl Group
VVI Group
NYHA Class I
79
92
NYHA Class II
24
20
NYHA Class III
7
3
NYHA Class IV
0
0
Digoxin
22
11*
Beta Blocker
7
1
Calcium Blocker
13
11
Antiarrhythmic drugs
12
6
32 + 51
23 + 39
Aspirin
48
46
Warfarin
6
1
Furosemide, mg/d
* P = 0.04, atrial versus ventricular group
Danish Study
Overall survival by pacing mode
1-0
0-8
Atrial
pacing
0-6
p = 0.045
0-4
Ventricular
pacing
0-2
0
0
2
4
Number of patients at risk
during follow-up
6
8
Time (years)
Atrial
110 102 97
92
86
82
59 38
13
Ventricular
115 103 96
91
85
80
56 29
12
Andersen H, et al. Lancet 1997; 350: 1210-16.
10
Danish Study
Cardiovascular death by pacing mode
1-0
Atrial pacing
0-8
p = 0.0065
0-6
Ventricular pacing
0-4
0-2
0
Number of patients at risk
during follow-up
0
2
4
6
8
Atrial
110 102 97
92
86
82
59 38
13
Ventricular
115 103 96
91
85
80
56 29
12
Andersen H, et al. Lancet 1997; 350: 1210-16.
10
Time (years)
Danish Study
Cumulative risk of PAF by pacing mode
Proportion without AF
1-0
Atrial
pacing
0-8
0-6
p = 0.012
0-4
0-2
Ventricular
pacing
0
0
2
Ventricular
6
8
Time (years)
Number of patients at risk
during follow-up
Atrial
4
110 100 92
82 73 69
46
21
9
115
76 61 49
34
10
2
Andersen H, et al. Lancet 1997; 350: 1210-16.
99 86
10
Danish Study
Cumulative risk of chronic AF by pacing mode
Atrial
pacing
Proportion without chronic AF
1-0
0-8
p = 0.004
0-6
0-4
Ventricular
pacing
0-2
0
0
2
Number of patients at risk
during follow-up
8
6
4
Time (years)
Atrial pacing
110 102 96
91
80
74
49
26
10
Ventricular pacing
115 102 92
84
75
65
41
18
5
Andersen H, et al. Lancet 1997; 350: 1210-16.
10
Danish Study
Survival without death from CHF
Mortality as a result of CHF
1,00
Atrial pacing
p = 0.18
Ventricular pacing
,80
,60
0
AAI: 110 102 97
VVI: 115 103 96
Andersen H, et al. Lancet 1997; 350: 1210-16.
4
2
6
Time (years)
92
91
86
85
82
80
59
56
8
38 13
29 12
10
Danish Study
CHF Analysis

NYHA classification was higher in the ventricular group
vs. the atrial group (p=0.010) at long term follow up.

During follow up, NYHA class worsened in the ventricular
group vs. the atrial group (p<0.005)

Mean dose of diuretics increased in the ventricular group
vs. the atrial group (p=0.033)
Danish Study
Conclusions

In patients with SND, atrial pacing is
associated with a significantly higher
survival, less atrial fibrillation, fewer
thromboembolic complications, and
less heart failure compared to
ventricular pacing.
Canadian Trial of Physiologic
Pacing
CTOPP
CTOPP Study Overview

Hypothesis:
-Physiologic (DDDR or AAIR) pacing is superior to
single-chamber (VVIR) pacing because it is
associated with lower risks of atrial fibrillation, stroke,
and death.

Study Design:
-32 Canadian centers
-Prospective, randomized
CTOPP Study Endpoints
 Primary:
-Stroke or death due to cardiovascular causes
 Secondary:
-Death from any cause
-Atrial fibrillation
-Hospitalization for heart failure
CTOPP Study Protocol
Patients undergoing first
IPG implant
n=2,568
Ventricular-Based Pacing
Physiologic Pacing
n = 1,474
n = 1,094
Follow for an average of 3 years and compare:
•Stroke or death due to cardiovascular causes
•Death from any cause
•Atrial fibrillation
•Hospitalization for HF
CTOPP
Cumulative Risk of Stroke or
Cardiovascular Death
Cumulative Risk
0.4
0.3
Ventricular pacing
0.2
P = 0.33
Physiologic pacing
0.1
0
0
1
2
3
4
Years after Randomization
No. at risk:
Ventricular pacing
Physiologic pacing
1474
1094
Connolly S et al. N Engl J Med 2000; 342: 1385-91.
1369
1005
1259
954
847
637
366
287
CTOPP
Cumulative Risk of any AF
Cumulative Risk
0.4
0.3
Ventricular pacing
P = 0.05
0.2
Physiologic pacing
0.1
0
0
1
2
3
4
Years after Randomization
No. at risk:
Ventricular pacing
Physiologic pacing
1474
1094
1276
936
Connolly S et al. N Engl J Med 2000; 342: 1385-91.
1127
857
731
559
303
250
CTOPP
Cumulative Risk of Chronic AF
Cumulative Risk
0.4
0.3
P = 0.016
Ventricular pacing
0.2
0.1
Physiologic pacing
0.0
0
1
2
3
4
Years Since Randomization
Number V 1474
At Risk P 1094
1317
975
Skanes A, et al. J Am Coll Cardiol 2001; 38: 167-72.
1180
906
779
601
331
269
CTOPP
Conclusions

Physiologic pacing (dual-chamber or atrial)
provides little benefit over ventricular pacing for
the prevention of stroke or death due to
cardiovascular causes.

Physiologic pacing does provide a reduction in
the relative risk of paroxysmal and persistent
AF.
A Mode
Selection Trial
MOST Sub-Study
Effect of Pacing Mode and Cumulative Percent
Time Ventricular Paced on Heart Failure and
Atrial Fibrillation in Patients with Sinus Node
Dysfunction and Baseline QRS Duration
<120 Milliseconds in MOST
Michael O. Sweeney, Anne S. Hellkamp, Arnold J. Greenspon, Robert Mittleman,
John McAnulty, Kenneth Ellenbogen, Roger Freedman, Kerry L. Lee, Gervasio
A. Lamas, for the MOST Investigators
Circulation 2003, in press
MOST Sub-Study
Background:
 DDDR pacing preserves AV synchrony and reduces
CHF compared to VVIR pacing in SND.
 DDDR pacing results in prolonged QRS durations
(QRSd) due to ventricular desynchronization.
Hypothesis:
 DDDR pacing often results in prolonged QRS
duration (QRSd) due to ventricular desynchronization
in patients with normal baseline QRSd and may
increase risk of heart failure and atrial fibrillation.
Sweeney MO, et al. Circulation 2003, in press
MOST Sub-Study
Methods:
 Baseline QRSd obtained from 12-lead EKG prior to
IPG implant in MOST (a 2,010 patient, 6-year
randomized trial of DDDR vs. VVIR pacing in SND).

Cumulative % time ventricular paced was determined
from stored pacemaker diagnostic data.

Baseline QRSd <120 ms was observed in 1332
patients; 702 were randomized to DDDR; 640 to VVIR.
Sweeney MO, et al. Circulation 2003, in press
MOST Sub-Study: Results
Cum%VP was greater in DDDR (90%) vs. VVIR (51%).

The rates of CHF hospitalization increased with Cum%VP:
Rate of Heart Failure
Hospitalization

16
14
12
DDDR
VVIR
10
8
6
4
2
0
< 10% Cum VP
Sweeney MO, et al. Circulation 2003, in press
>90% Cum VP
MOST Sub-study:
Risk of HFH Relative to a DDDR Patient with
Cum % VP = 0
•Risk of HFH increased between 0% and 40% Cum VP, but was
level at Cum%VP above 40%.
Risk of HFH relative to
DDDR patient with Cum%VP=0
•Risk can be reduced to about 2% if ventricular pacing is minimized.
7
6
5
4
3
2
1
0
0
20
40
60
Cum%VP
Sweeney MO, et al. Circulation 2003, in press
80
100
MOST Sub-Study:
Risk of HFH Relative to a VVIR Patient with
Cum % VP = 0
•Risk of CHF was constant between 0% and 80% Cum VP and
increased by as much as 2.5-fold when Cum%VP exceeded 80%.
•Risk cannot be reduced regardless of minimization of ventricular
pacing.
Risk of HFH relative to
VVIR patient with Cum%VP=0
7
6
5
4
3
2
1
0
0
20
40
60
Cum%VP
Sweeney MO, et al. Circulation 2003, in press
80
100
MOST Sub-Study
Cum%Vp at 30 days and subsequent HFH events
DDDR/Normal QRS
1
0.975
P=0.047
Proportion event-free
0.95
0.925
0.9
0.875
Cum%Vp <= 40
0.85
Cum%Vp > 40
0.825
0.8
0
12
24
36
48
Months
Sweeney MO, et al. Circulation 2003, in press
MOST Sub-Study
Cum%Vp at 30 days and subsequent HFH events
VVIR/Normal QRS
1
0.975
Proportion event-free
0.95
0.925
P=0.0046
0.9
0.875
0.85
Cum%Vp <= 80
Cum%Vp > 80
0.825
0.8
0
12
24
Months
Sweeney MO, et al. Circulation 2003, in press
36
48
MOST Sub-study
Conclusions: CHF

Higher rates of CHF hospitalization were associated
with higher Cum% VP:
- Cum % VP<10% was associated with the lowest rates of CHF
hospitalization (DDDR 2%, VVIR 7%).
- Cum % VP >90% was associated with the highest rates of CHF
hospitalization (DDDR 12%, VVIR 16%).

Ventricular pacing in the DDDR mode more than 40%
confers a 3-fold increased risk of heart failure
hospitalization but can be reduced to about 2% if
ventricular pacing is minimized.
Sweeney MO, et al. Circulation 2003, in press
4
4
Risk of AF relative to
VVIR patient with Cum%VP=0
Risk of AF relative to
DDDR patient with Cum%VP=0
MOST Sub-study: AF Risk
3
2
1
0
3
2
1
0
0
20
40
60
Cum%VP
80
100
0
20
40
60
80
Cum%VP
Risk of AF increases linearly with Cum%VP up to 8085% in both DDDR and VVIR
Sweeney MO, et al. Circulation 2003, in press
100
MOST Sub-study: AF Risk
1
Cum%Vp in first 30 days and subsequent AF events
DDDR/Normal QRS
%Vp <=40%
%Vp 40-70%
%Vp 70-90%
0.95
Proportion event-free
0.9
0.85
0.8
0.75
0.7
0.65
0.6
0
12
24
Months
Sweeney MO, et al. Circulation 2003, in press
36
48
MOST Sub-study: AF Risk
Cum%Vp in first 30 days and subsequent AF events
VVIR/Normal QRS
1
%Vp <=40%
%Vp 40-70%
%Vp 70-90%
0.95
Proportion event-free
0.9
0.85
0.8
0.75
0.7
0.65
0.6
0.55
0
12
24
Months
Sweeney MO, et al. Circulation 2003, in press
36
48
MOST Sub-study
Conclusions: AF
• Relationship between risk of AF and Cum%VP
was similar between pacing modes:
– Risk of AF showed a linearly increasing relationship
with increased Cum%VP from 0% pacing up to 8085% pacing in both pacing modes.
– Within this range, the risk of AF increased by 1%
for each 1% increase in Cum%VP (DDDR hazard
ratio 1.01 [1.004, 1.022] p=0.012; VVIR 1.01 [1.001,
1.01], p=0.025).
Sweeney MO, et al. Circulation 2003, in press
MOST Sub-Study:
Overall Conclusions

The adverse effects of forced ventricular
desynchronization probably explain the difficulty in
demonstrating a mortality and stroke benefit with
physiologic (DDDR) compared to ventricular (VVIR)
pacing in randomized trials.

These investigators concluded that RV pacing imposes
ventricular dyssynchrony even when AV synchrony is
preserved, thereby increasing the risk of heart failure
and AF.
Sweeney MO, et al. Circulation 2003, in press
Dual-Chamber and VVI
Implantable Defibrillator
Trial
DAVID
DAVID Trial
Overview

Hypothesis:
- Aggressive management of LV dysfunction with optimized drug
therapy and with dual chamber pacing could improve the
combined endpoint of total mortality and hospitalization for
heart failure, compared to similarly optimized drug therapy
supported by ventricular backup pacing.

Study design:
- Single blind, multicenter, parallel group, randomized trial
comparing DDDR (70 bpm lower rate) vs. VVI (40 bpm lower
rate) pacing modes
Wilkoff B, et al. JAMA. 2002; 288: 3115-3123.
DAVID Trial
Protocol
760 assessed for eligibility
510 eligible
250 excluded
149 Did not meet Rx criteria
55 refused
46 Other
4 Not randomized
2 Required pacing
1 Inadequate defibrillation threshold
1 Decided not to implant
506 randomized
VVI-40 (n=256)
•
•
•
•
•
•
•
•
•
1 had pacing mode set to DDD
1 LTF
10 Discontinued intervention
5 Bradycardia
1 CHF and AF
1 Brady induced Torsade
1 Heart Tx workup
1 AF w rapid V response
1 multiple shocks due to double counting
Wilkoff B, et al. JAMA. 2002; 288: 3115-3123.
DDDR-70 (n= 250)
•
•
•
•
•
•
•
•
3 had pacing mode set to VVI
2 LTF
5 Discontinued intervention
1 Angina
1 CHF and Lead Failure
1 CHF Hospitalization
1 Exacerbation of VT
1 Lead Migration
DAVID Trial
Results
VVI-40
DDDR-70
HR
(p-value, adj.)
CHF
Hospitalization
or Death
16.1%
26.7%
1.61
(p = 0.03)
CHF
Hospitalization
13.3%
22.6%
1.54
(p=0.07)
6.5%
10.1%
1.61
(p=0.15)
Death
Wilkoff B, et al. JAMA. 2002; 288: 3115-3123.
DAVID
VVI-40
DDDR-70
P-value
Sinus
97.1%
42.0%
<0.001
V-paced
2.9%
55.7%
<0.001
QRSd
117 + 29 ms
134 + 39 ms
<0.001
3 months
1.5% + 8.0%
57.9% + 35.8%
<0.001
6 months
0.6% + 1.7%
59.6% + 36.2%
<0.001
12 months
3.5% + 14.9%
58.9% + 36.0%
<0.001
6-month EKG:
Cum % VP:
Wilkoff B, et al. JAMA. 2002; 288: 3115-3123.
DAVID
Conclusions

Bradycardia pacing operation in dualchamber ICDs should be optimized for
individual patients.
-RV pacing in patients with LV dysfunction and no
bradycardia indication for pacing can be harmful.
-Programming of dual chamber devices to backup
ventricular pacing is justified in this patient
population.
Wilkoff B, et al. JAMA. 2002; 288: 3115-3123.
Left Ventricular-Based Cardiac Stimulation
Post AV Nodal Ablation Evaluation
(The PAVE Study)

The PAVE study was a prospective,
patient-blinded, randomized, multicenter
clinical trial comparing chronic biventricular
to right ventricular pacing in patients with
chronic atrial fibrillation undergoing AV node
ablation.
PAVE Study
(J Cardiovasc Electrophysiol, Vol. 16,
pp. 1160-1165, November 2005)
PAVE Study

Ablation of the AV node was permitted up to 4
weeks post-implantation

Pacemaker was reprogrammed to a VVIR mode
with a lower rate of 80 ppm for the next 4 weeks
so to mitigate the risk of polymorphic ventricular
tachycardia. All patients received rate-esponsive
pacing, with the sensor optimized 4 weeks after
implantation.
6-minute hallway walk distance
(J Cardiovasc Electrophysiol, Vol. 16,
pp. 1160-1165, November 2005)
6-minute hallway walk distance

For patients with symptomatic heart failure
(NYHA Class II or III), the hallway walk
distance measured at 6 months was 53%
greater for patients randomized to
biventricular pacing in comparison to
patients receiving right ventricular pacing
(78.9 ± 92.2 m vs 51.6 ± 86.2 m, P = 0.01).
LV ejection Fraction
(J Cardiovasc Electrophysiol, Vol. 16,
pp. 1160-1165, November 2005)
NYHA Class
(J Cardiovasc Electrophysiol, Vol. 16,
pp. 1160-1165, November 2005)
(J Cardiovasc Electrophysiol, Vol. 16,
pp. 1160-1165, November 2005)
Mortality in PAVE Study

There were 13 deaths (8%) in the
biventricular pacing group and 19 deaths
(18%) in the right ventricular pacing patients
Conclusion of PAVE Study

The findings of the PAVE study suggest
that, in order to avoid the adverse effects of
cardiac dyssynchrony generated by RV
pacing, a biventricular pacing should be
considered for patients who require AV
node ablation for management of atrial
fibrillation and who have a left ventricular
ejection fraction 45‫ـ‬،% or who have NYHA
Class II or III symptoms.
Multicenter Automatic Defibrillator
Trial II (MADIT II) study

During a 20-month follow-up, patients (n = 369) with ICD.

ICD programming was not standardized, the development
of new or worsened CHF was more common in the ICD
arm (19.9%) compared with the conventionally treated
patients (14.9%) .

The higher incidence of CHF in the ICD group was in all
likelihood due to ventricular desynchronization rather than
myocardial injury from ICD shocks
MADIT II

Approximately 40% of the had dual chamber
units (mostly set at DDD 60 to 70 beats/min) and
60% had single-chamber units (mostly set at VVI
60 beats/min).

Patients with dual-chamber units paced the
ventricle about 85% of the time, whereas those
with single-chamber units paced the ventricle
only 15% of the time.
MADIT II

During a 20-month follow-up, patients (n = 369)
having high cumulative RV pacing (>50%), had a
higher incidence of new or worsened heart failure
and heart failure or death compared to patients
with infrequent right ventricular pacing.
Conclusion of MADIT II study

The slightly increased occurrence of heart
failure was clearly associated with dualchamber ICD units having a higher
frequency of ventricular pacing.
Comparison of Medical Therapy, Pacing,
and Defibrillation in Chronic Heart Failure
(COMPANION) trial

Cardiac resynchronization therapy with left
ventricular pacing decreased the combined
risk of death from any cause or first
hospitalization in patients with advanced
heart failure and prolonged QRS interval.
COMPANION trial

These investigators concluded that
reduction in the combined endpoints of
death and heart failure hospitalizations was
primarily due to cardiac resynchronization
therapy (CRT), since CRT and CRT with an
ICD resulted in similar effects.
What are the lessons learned from
clinical trials?
• Conventional RV apical pacing results in
“forced” ventricular desynchronization,
which mimics LBBB and has adverse effects
on ventricular structure and function.
Goals and Strategies to
Optimize Ventricular Pacing
The New Goals of Pacing
Therapy
 Several approaches have been
investigated:
 Manipulation of DDDR timing cycles (AV
delay) to minimize unnecessary RV pacing
 Use of AAI or DDI/R pacing modes
 Novel pacing algorithms
 Alternate RV pacing sites
Long AV Delays During Dual Chamber
Pacing

Long AV delays may reduce
unnecessary ventricular pacing and
maintain normal ventricular activation
sequence but require reliable AV nodal
conduction.
Long AV Delays During Dual Chamber
Pacing: An Incomplete Solution

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
-Susceptibility to endless loop tachycardias
Long AV delays do not sufficiently
reduce ventricular pacing

Two approaches to programming long AV delays to
permit native ventricular activation:
1. AV delays > resting PR intervals1
•
•
AV delays > resting PR intervals (22224 ms vs. 18423 ms)
Mean time Vp for all patients was 80%; > 50% for 88%
2. Long fixed AV delay (300 ms)2-3
•
•
•
Mean time Vp 17.7% overall but 39% in nearly 50% of patients
Resting PQ interval (17728 vs. 20438), atrial stimulus-Q interval at 100
bpm (21340 vs. 22049) or AV delay (2993.2 vs. 28821) did not predict
Vp
High incidence of endless loop tachycardia
• Can be reduced if rate-adaptive AV delays are used
1 Sgarbossa E et al PACE 1993; ;16:872A.
2 Nielsen JC et al PACE 1997:20:1574A.
3 Nielsen JC et al Europace 1999;1:113-120
AAI Pacing: Too Risky?
• AAI pacing preserves a normal ventricular activation
sequence but requires stable long-term AV
conduction and sinus rhythm
• SND is a spectrum of electrical disorders that
includes AF and AV block
• AAI pacing is ineffectual for ventricular bradycardia
during
– Paroxysmal and permanent AF
– AV block
Development of Persistent (Complete) AV Block in
Studies of Pacemaker Therapy for SND
Study
Mean FollowUp Time
Incidence of
CHB
Annualized
Incidence
Rosenqvist 1989
3 years
Median 2.1%
Range: 0-11.9%
Median: 0.6%
Range: 0-4.5%
Andersen 1997
8 years
3.6%
0.6%
Brandt 1992
5 years
8.5%
1.8%
Sutton 1986
3 years
8.4%
2.8%
Rosenqvist 1986
2 years
4.0%
2.0%
Rosenqvist 1985
5 years
3.3%
0.7%
Hayes 1984
3 years
3.4%
1.1%
(literature review)
Development of Chronic AF in Studies of
Pacemaker Therapy for SND and CHB
Study
Pacing
Mode
Mean
Follow-Up
Time
Incidence
of AF
Annualized
Incidence
Andersen 1997
AAI
5 years
8.8%
1.8%
Sutton 1986
AAI
3 years
4.5%
1.5%
Brandt 1992
AAI
5 years
7.0%
1.4%
PASE 1998
DDDR
only
18 months
19.0%
12.7%
CTOPP 2000
DDDR/
VVIR
3 years
16.6%
5.5%
(DDDR)
DDIR Mode: A Limited
Solution

Permits long AV delays without the possibility of upper rate
limit tracking during AF (unlike DDDR).
-However, limitations of long AV delays in reducing ventricular pacing
still persist.

Unique limitations imposed by DDIR mode
-Operationally VVIR during AV block if sinus rate exceeds lower rate
limit.
-Competitive atrial pacing during sensor-modulation may precipitate
AF.


Can be mitigated with a non-competitive atrial pacing algorithm
May be more applicable to the ICD population
-Lower prevalence of AV block compared to conventional brady
pacing population.
Novel Pacing Algorithms to
Optimize Ventricular Pacing

Current-generation devices have features
that work to minimize ventricular pacing in
appropriate patient populations:
-Using Medtronic’s Search AV algorithm,27% and
47.2% reductions in ventricular pacing have been
observed by Silverman and Ellenbogen,
respectively, in patients with 1:1 conduction.1,2
Novel Pacing Algorithms to
Optimize Ventricular Pacing
Silverman et al, NASPE 2000
Novel Pacing Algorithms to
Optimize Ventricular Pacing

Minimal ventricular pacing modes can be
used in all patients, but are most effective in
SND patients with reliable AV conduction and
normal ventricular activation.

Development will continue on new pacing
algorithms which have been identified as an
important means of minimizing ventricular
pacing.
Alternate Sites of Ventricular Pacing

Alternate site pacing :
- Other right ventricular sites (outflow or septal
sites)
- Left ventricular sites in either unifocal or
bifocal or biventricular modes.
Alternate Site Pacing
Pace,Vol.29, March 2006
Ongoing Studies of Alternate Site Pacing
Pace,Vol.29, March 2006
Right Ventricular Outflow Tract
(RVOT) Pacing

A pooled analysis of nine prospective studies
evaluating the hemodynamic effects of RVOT
pacing in 217 patients indicated significant
hemodynamic benefit compared with RV apical
pacing.
Right Ventricular Outflow Tract
(RVOT) Pacing

Among these studies, most of them reported
acute hemodynamic effects, while only two
studies reported long-term hemodynamic effects,
with one indicating no difference between the two
sites after 3 months of pacing and the other
reporting a significant increase in left ventricular
fractional shortening following 2 months of right
ventricular outflow tract.
RV Septal Pacing

In an acute study of 14 patients receiving dualchamber pacemaker for complete heart block,
the septum was mapped to provide the
narrowest QRS. The reduction of QRS duration
obtained with right ventricular septal pacing
correlated with homogenization of left ventricular
contraction and improved systolic performance,
albeit with minor differences in ejection fraction.
Shortest Distance to Purkinje Fibers?
Right Ventricular Outflow Tract (RVOT) and/or Right Ventricular Septum
Prevention of Remodeling with
Septal Pacing

Karpawich (1991)
RV apical placement versus midseptal placement
 Mid-septal lead position via
appearance of normal
paced QRS (no bundle
branch block)
Function
 Near normal ventricular
conduction velocity
Histology
 4 month follow-up
 No calcification,
degenerative changes, or
altered mitochondrial
morphology in the septal
paced group
LV Free Wall 4 months post Pacing
RV Apical Pacing
RV Septal Pacing
Karpawich PP, et al. Am Heart J 1991;121:827-33
His Bundle Pacing

His bundle pacing has been shown to result in the same
QRS duration and pressure development as sinus rhythm
and atrial pacing and better hemodynamics than RV apex
pacing.

Technical difficulties in applying such pacing relating to
lead positioning, reliable capture, and long-term stability.

Need for an intact bundle branch conduction system may
be a limiting factor.
His Bundle Pacing

A significant improvement in left ventricular performance
was reported in 12 patients with a narrow QRS, chronic
atrial fibrillation, and reduced ejection fraction (<40%).

The same investigators were successful in applying this
pacing technique in 39 of 54 patients with cardiomyopathy,
low ejection fraction (mean 23%), persistent atrial
fibrillation, and normal QRS (<120 ms). After a mean
follow-up of 42 months, 29 patients were alive with
improved symptoms and ejection fraction (mean 33%).
Bifocal RV Pacing
(apical and outflow tract)

Bifocal right ventricular (apical and outflow tract)
pacing has been proposed for patients with
heart failure where the coronary sinus approach
to effect biventricular pacing turns out to be
unsuccessful due to various reasons, such as
failure to cannulate the os or to advance the
lead.
Bifocal RV Pacing
(apical and outflow tract)

The long-term (over a 22-month period) clinical
response of 22 patients undergoing this approach
has been favorable with ensuing clinical
improvement.

In a subset of 50 patients with NYHA class II-III
symptoms in the ROVA study, there was partial
improvement reported with right ventricular bifocal
pacing.
Bifocal RV Pacing
(apical and outflow tract)

More data about the usefulness of bifocal right
ventricular pacing will be provided by the ongoing,
randomized, single blind, crossover study
(BRIGHT), which is recruiting patients with NYHA
class III heart failure, a left ventricular ejection
fraction <35%, LBBB, and QRS complex ≥120 ms.
Biventricular or Left Ventricular
Pacing

A few studies have compared RV apical pacing with LV or
BiV pacing, which has now become the standard method
to apply cardiac resynchronization therapy in patients
with refractory heart failure .

Overall, patients treated with BiV pacing had significantly
greater improvement in QRS duration, 6-minute walk test,
and quality-of life scores compared to RV pacing therapy.
Biventricular or Left Ventricular
Pacing

Preliminary data have indicated that
there were no significant differences
between single-site left ventricular
pacing and biventricular pacing for
cardiac resynchronization therapy
suggesting that RV pacing may be
redundant and left ventricular pacing
alone might suffice.
Biventricular or Left Ventricular
Pacing

Acute hemodynamic measurements in 27 patients with heart failure
having an epicardial left ventricular lead indicated that left ventricular
pacing alone was superior to right ventricular pacing, but also to
biventricular pacing as well.

OPSITE, a prospective randomized trial, compared, in a single-blind,
3- month cross-over design, right ventricular and left ventricular
pacing (phase 1) and right ventricular and biventricular pacing
(phase 2). The study was performed in 56 patients affected by
severely symptomatic permanent atrial fibrillation, uncontrolled
ventricular rate, or heart failure. Primary endpoints were quality of life
and exercise capacity, which were modestly improved mainly by
biventricular, rather than left ventricular pacing.
Overall Conclusions

First, for those patients already having conventional pacing
systems, particularly in the presence of LV dysfunction or
heart failure, pacemaker programming should be employed
to minimize RV pacing. IN patients with sinus node
dysfunction but with normal atrioventricular conduction, by
establishing functional AAIR pacing with use of the DDDR
mode with a long atrioventricular delay (≥250 ms).
However, it remains an inefficient way to reduce ventricular
pacing in at least 17–32% .
Overall Conclusions

Manufacturers need to redesign their
pacemakers to make such programming
feasible or have the pacemakers search for
atrioventricular conduction and withhold
unnecessary ventricular pacing; automatic
mode switching from AAIR to DDDR .
Overall Conclusions

IN patients with permanent AV block, we need to use
alternate sites of pacing for those receiving new pacing
systems.

For those patients who already have an implanted
conventional pacemaker, either a dual-chamber pacing
system in the presence of sinus rhythm or a singlechamber system in cases of permanent atrial fibrillation,
we should seriously consider upgrading them to
biventricular systems if moderate or severe left
ventricular dysfunction is present.
The Donkey Analogy
Ventricular dysfunction limits a patient's ability to
perform the routine activities of daily living…
Digitalis Compounds
Like the carrot placed in front of the
donkey
Diuretics, ACE Inhibitors
Reduce the number of sacks on the
wagon
ß-Blockers
Limit the donkey’s speed, thus saving
energy
Cardiac Resynchronization
Therapy
Increase the donkey’s (heart) efficiency
Tehran Arrhythmia Clinic
www.IranEP. org
[email protected]