Alternate Site Pacing

Paul A. Levine MD FHRS FACC

Vice President, Medical Services
St. Jude Medical CRMD

Clinical Professor of Medicine

Loma Linda University School of Medicine
Clinical Associate Professor of Medicine
University of California, Los Angeles
 Therapeutic Goal

To cure the abnormal condition

or
To restore the patient as close to normal as
possible to optimize the quality of life

Primum non noceri

FIRST DO NO HARM

2
Ventricular Lead Placement
3
 Indication for Pacing
Clinically stable “asymptomatic” VV I pacing

Transient inhibition demonstrated an unreliable

escape rhythm
NOTE: Intrinsic sinus rhythm (˜105 bpm)
Early 1960’s - devices and leads were unreliable.
Implantation required thoracotomy for implant
with significant morbidity and mortality

4
 Complete Heart Block
Temporary VVI Pacing

3.0
Cardiac
Index 2.0
L/min/m2 1.0
0
IVR 50-65 70-83 85-
Heart Rate (bpm)100

Segel , J. Clin Invest 1964; 43: 1541

5
 Complete Heart Block
Temporary VVI Pacing

8
Grade I
6
Cardiac Grade II
Index
4 Grade III
L/min/m2
2 Exercise -IVR

0 Exercise
- PMKR
200 400 600 800
Oxygen Uptake (ml/min/m2)
Segel , J. Clin Invest 1964; 43: 1541
6
 “Normal” VVI pacing

200
mmHg

100
0

VV I Sinus VV I Sinus
Very elderly patient with dizzy spells until a pacemaker was implanted -
then she had syncope

7
 Normal VVI pacing - AV block

Coincidental
AV Synchrony

8
 Pacemaker Syndrome

Adverse hemodynamics and/or

electrophysiology associated with a
NORMALLY functioning pacing system
inducing either overt symptoms or limiting the
patient’s ability to achieve an optimal
functional status

9
 Normal Rate - Intrinsic Rhythm

Pseudo-Pacemaker Syndrome
In the mid 1970’s to early 1980’s, the focus was on the AV interval and
maintaining atrial transport while supporting the ventricular rate.

10
 Role of Atrial Transport

“At the same moment when the auricles alone

are beating, if you cut off the top of the
heart, you will see blood gush out at each
beat. This shows how blood enters the
ventricles, not by suction or dilatation but
by the beat of the auricles.”

W. Harvey - de Motu Cordis, 1628

11
 Atrial vs Ventricular Pacing

5 VV I paced rate
>
Cardiac 4 Intrinsic rate
Output
3
L/min
2

Sinus VVI

Junctional
Hartzler, Amer J Cardiol 1977; 40: 232 12
 Atrial vs Ventricular Pacing

7.0
Pacing rate in
6.0
both modes was
5.0 the same for each
patient
4.0
3.0
2.0

V Pace A Pace
Hartzler, Amer J Cardiol 1977; 40: 232
13
 Frank-Starling “Law of the Heart”

 Frank (1885) - isolated muscle fibers

 Starling (1914) - sheep hearts

Increased myocardial fiber stretch results in

increased contractility and improved cardiac
performance

14
 “Starling’s Law of the Heart”

NORMAL
ventricular
function
Cardiac
Output Restoring AV
synchrony with “atrial
Stroke
kick” results in marked
Volume
improvement in cardiac
function when
ventricular function is
normal
“Fiber Stretch” - EDP, PCWP

15
 “Starling’s Law of the Heart”

NORMAL
ventricular
function
Cardiac
Output Depressed LV function.
Stroke The relative gain with
Volume atrial transport is minimal
BUT every little bit of
help possible is
essential!

“Fiber Stretch” - EDP, PCW

16
 Atrial Transport at the “optimal” AV Delay

• At the optimal AV interval, the arterial pressure is the

highest and venous pressure is the the lowest.
– (and cardiac output is the best)
• The greatest effect of atrial transport on ventricular
function occurs at an AV delay between 70 to 200 ms.

Gessell, Amer J Physiol 1911; 29: 32

17
 VVI AAI
80 y.o. man with
unstable angina
and EF 22%.
LV P
C Non-surgical
disease
W
150 60 Drugs induced
mm bradycardia
Hg limiting their use
100 40
VVI pacing caused
abrupt
deterioration with
50 20
increase in angina
and CHF

0 0
18
 Optimal AV Synchrony

• Increases diastolic volume at the instant

(end-diastole) when diastolic volume
determines ventricular performance
• Allows the ventricles the “luxury” of a high
end-diastolic pressure without having to
“pay the price” of a high pressure
throughout diastole (congestion)

19
 AV (PV) delay behavior with first generation
DDD
Rates
60
Fixed AV
ppm
delay
with
increasin
100
g atrial
ppm
rates

130
ppm

20
 AV (PV) delay behavior with first generation
DDD
130 ppm 1:1 conduction
ECG
AEGM

Assessment of
AV nodal
conduction
with AAI
pacing
Right
Atrial
Pressure
21
 Role of AV Synchrony

“The mechanical activity of the LV as reflected

in the peak systolic pressure, the arterial pulse
pressure, the …, varied as a function of the
end-diastolic pressure or end-diastolic
segment length just before the onset of
contraction.”

Braunwald E, J Clin Invest, 1960; 39: 1874

22
 Response of Normal AV nodal conduction compared to
behavior of first generation DDD

AV/PV
Delay Medtronic Elite®
Telectronics Autima® Barbieri -
PACE 1990
Intermedics Cosmos®
Pacesetter AFP®

60 80 100 120 140 160 180

Heart Rate (bpm)

23
 Response of Normal AV nodal conduction compared to
RRAVD in DDDR systems

First generation RRAVD

introduced late 1980’s - early
1990’s

AV/PV
Delay
Barbieri -
Medtronic Thera®
PACE 1990
Telectronics Meta DDDR®
Intermedics Relay®
Pacesetter Synchrony®
60 80 100 120 140 160 180

Heart Rate (ppm)

24
 Interim conclusion

• Rate is critical for cardiac function

• AV synchrony is also important but the AV
delay must be optimal for the given
physiologic state

25
 Ventricular Activation Sequence

N = 12, Intact AV nodal conduction, normal PR

interval
AAI DDD VVI
Cardiac Output 6.2 5.6 5.3
LV ejection fx 70% 65% 68%
LVEDV (cc) 147 146 135

Rosenqvist, Am J Cardiol 1991; 67: 148

26
 Ventricular Activation Sequence
N = 11, Sinus Node Dysfunction
AAI DDD VVI
Cardiac Index (L/min/m2)
Rest 3.85 3.55 2.90
Exercise 7.8 7.0 6.2
LV Ejection Fraction (%)
Rest 61 58 52
Exercise 65 60 55

LeClercq, Amer Heart J 1995; 129: 1133 Rest 70 ppm

Exer 120 ppm

27
 Ventricular Activation Sequence
Hemodynamics of LBBB

• Evaluation of hemodynamics of LBBB

• n = 9, normal baseline LV function
AAI DVI p value
Rate 97 ppm 97 ppm ns
+dp/dt 1541 1319 < 0.001
-dp/dt 1506 1209 < 0.001
LVESV 48 cc 63 cc < 0.001
EF 66% 56% < 0.001
Syst. BP 161 145 < 0.01

Askenazi, Amer J Cardiol 1984; 53: 99

28
 Adverse histologic effect of VVI pacing
(? activation sequence)
• n = 12 normal canines
• AV nodal ablation with VVI pacing from RV
apex (LBBB) for 3 months
• Histologic examination showed myofibrillar
disarray in 9 of the 12 animals
– Role of loss of AV synchrony and rate modulation was not
addressed
Adomian, Amer Heart J 1986; 112: 79

29
 DAVID Study
Comparison of VVI-ICD to DDD-ICD

ICD patients, intact

AV nodal conduction
Forced ventricular
pacing at preset AV > 70% V Pace
delay resulted in
disordered activation < 4% V Pace
sequence
DDD pacing was
associated with
increase in combined
endpoint of mortality
and CHF
JAMA Dec 25, 2002
30
 Prospective Randomized Multicenter Trials:
AAI/DDD vs VVI
Impact of RV Apical Pacing

• AAI vs DDD (Preliminary to DANPACE)

– DDD with “normal” AV delay (150 ms) forcing ventricular
pacing associated with increased incidence of AF (JACC, 2003)
• MOST
– Higher percentage of ventricular pacing associated with both
CHF and increased incidence of atrial fibrillation (JACC, 2003)
– This was a retrospective analysis of the data and not a primary
designed endpoint of the study

31
 Adverse Consequences of RV apical pacing in the setting
of intact AV conduction

• DAVID Study (2003)

– Increased incidence of heart failure and all cause
mortality
• MOST Study (2002)
– Increased incidence of heart failure
– Increased incidence of atrial fibrillation
• AAI vs DDD Study (2003)
– Increased incidence of atrial fibrillation

For DAVID, MOST (and others), the only way to achieve V

pacing was by selecting too short an AV delay!

32
 Ventricular Activation Sequence

• Optimal hemodynamics occur with a normal ventricular

activation sequence
• A disordered ventricular activation sequence may
contribute to progressive ventricular dysfunction
– DAVID; MOST; MADIT II, PAVE studies
• Should the AV delay be increased without limit if this
will allow for a normal ventricular activation sequence?

33
 Normal Activation Sequence vs Optimal AV
Delay
n = 5, Marked First Degree AV block
Sinus DDD delta p
Resting HR 92 74 -20% <0.05
End Exer HR 113 111 -- ns
Exer Duration (s) 303 520 +72% <0.02
Cardiac Output 7.6 9.8 +29% <0.05
PCWP - exercise 15 10 -33% <0.05

Mabo P, PACE 1992; 15: 509

34
 Normal Activation Sequence vs Optimal AV
Delay
N = 9, First Degree AV block; narrow QRS
AAI DDD p
AR/AV (mean) 245 ms 157 ms
AR/AV (range) 212-300 125-175 ms
C.O. 4.6 L/m 5.1 L/m < .02

If AR interval > 220 ms (A stim to onset of QRS), improved

cardiac output with AV pacing despite disordered ventricular
activation sequence

Jutzy R, J Card Pace Electrophysiol, 1992; 2: A33

35
 Normal Activation Sequence vs Optimal AV
Delay

• AAIR vs DDDR at rest and exercise, n = 15

• Sinus Node Dysfunction, Intact AV conduction
• Pacing at 60 ppm and 100 ppm
• In DDD, AV delay set to longest value which still resulted in
full ventricular capture
• If AR interval < 220 ms, AAI > DDD
• If AR interval > 220 ms, DDD > AAI
Vardas PE, PACE 20: 1997: 1762-1768

36
 Clinician vs Device
“PR interval”
Clinician: PR interval measured from
PR ONSET of P wave to ONSET
of QRS complex

PR interval measured from

PR intrinsic deflection of
atrial depolarization to the
Device: ID of ventricular
depolarization

37
 Calculation of PR interval according to
Pacemaker
Onset of P and QRS complexes

Onset of QRS
Onset of P wave according to
according to pacemaker
pacemaker

38
 “PR” interval vs “AR” interval

180 170

Latency

AV > 300 ms to assure native

conduction with PR (native) 180 ms

39
 Ventricular Activation Site

• 18 month comparison of RVA to RVOT

– No underlying structural heart disease
– Indication: Complete Heart Block
• Prospective randomized trial comparing
RVA to RVOT
– RVOT selected after mapping to identify the site
that provided the narrowest paced QRS

Tse HF, J Am Coll Cardiol 2002; 40: 1451-1458

40
 Regional Ejection Fraction
RVOT 6M

100 RVOT 18 M
P < 0.05
RVA 6
M
80
EF % RVA 18
60 M

40

20

0
Lateral Inferior Apical Septal Anterior

Tse HF, J Am Coll Cardiol 2002; 40:1451-1458

41
 Adverse Consequences of RV apical pacing in the setting
of AV Block

• PAVE Study (2003)

– Chronic AF with induced AV block due to RF ablation
– Randomized to RV vs BiV
– No restriction on LVEF
• Mean LVEF was normal

42
 PAVE Trial Improvement in 6 minute walk -BV over RV
(BV:N=84,LV:N=28,RV:N=66)

90
80
17.2
Meter Improvement

70 26.07
15.79
60
BV
50 p=0.03 RV
40
LV
30
20
10
0
Pre-Implant 6 weeks 3 months 6 months
Time Frame

43
 PAVE Trial Improvement in peak VO2 -Within groups (in ml/kg/min)
(BV:N =35 and RV:N =10)
1

0.8
Improvement of VO2

0.6
0.71
0.4 BV
1.16
0.2 RV

0
6 weeks 3 months 6 months
-0.2

-0.4
Visit
* Within BV group – 0.86 ml/kg/min improvement
from 6 weeks to 6 mo. (p=0.026)

44
 Pacing in CHF - LV Stimulation

• Patients with compromised LV function and LBBB

• Original approach - LV epicardial leads placed via

thoracotomy or thoracoscopy
• New approach - Lead positioned in coronary sinus and then
manipulated into cardiac vein [Transvenous LV epicardial
pacing]
– Cardiac veins are located on epicardial surface of the heart

45
 LV Lead Placement

• LV lead placement and the site of stimulation can

have a significant impact on acute hemodynamic
improvement and may play a critical role in the
outcome of CRT

46
 LV Lead Placement

Lateral

Posterior

Anterior Middle Cardiac

47
 Optimal LV Lead Placement
• Acute investigations describe the LV mid-lateral wall as
the best pacing site during resynchronization therapy.
This is based on the optimal increase in pulse pressure
and peak dP/dT

• Optimal placement may be defined as stimulating the site

of latest activation, as determined by echo

D. Gras, J. Cardiovasc Electrophysiology, 2002; 13:

Suppl 48
Optimal LV Lead Placement

Place lead tip

on LV
LV leadFree
Lateral in
anterior vein
Wall
and lead in
RV apex are
“BiV” but do
not provide
CRT

49
 Impact of BiVentricular & LV pacing compared
to Drug Rx
• Acute cath lab study involving 10 patients, all with
demonstrated benefit of LV/BiV pacing
• DCM; LV-EF < 35%; LBBB; NYHA III-IV
• Dobutamine infusion titrated to similar level of contractile
improvement
• Assessment of MVO2, Contractility efficiency; dP/dt;
pressure-volume loops

Nelson GS, CIRC 2000; 102: 3053-3059

50
 Drugs vs Pacing in LV Dysfunction

0.24
LV Pacing
M 0.22

V 0.20
Dobutamine
O2 0.18
P < 0.005
0.16

Intrinsic
500 Rhythm
600 700 800
dP/dtmax (mmHg/s)

Nelson, CIRC 2000; 102: 3053

51
 Conclusions

• Where ever possible, allow for a normal ventricular

activation sequence if the QRS and ventricular function
are normal.
• If AV block is present and the ventricular lead is
chronic, optimize paced and sensed AV delay
• If AV block is present and this is a new implant,
consider RVOT or LV or BiV pacing
– Pending Studies: B-LEFT, BiV for standard AV block
without CHF
• If AV conduction is normal but there is a Bundle Branch
Block
????

52
Atrial Lead Placement

53
 Options for Management of PAF

• Eliminate the triggers

– Overdrive pacing
– Overdrive algorithms of varying complexity
– Pharmacologic therapy
• Alter the substrate
– Pharmacologic therapy
– Site specific pacing

54
 Pacing Mode, SND and
Chronic Atrial Fibrillation
Study Yrs F/U VVI AAI/DDD
Rosenqvist 4 47% 7%
Sasaki 6 36% 0%
Langenfeld 5 37% 1%
Santini 5 40% 10%
Hesselson 8 80% 10%

All of the above studies were retrospective

(Simplest of all the overdrive algorithms – RAA pacing)

55
 Danish Study
• Prospective randomized trial comparing AAI to
VVI in patients with sinus node dysfunction
• Single center N = 225
• End points
– Atrial Fibrillation, Systemic emboli
– Congestive Heart Failure
– Mortality

Andersen HR, LANCET 1997; 350: 1210

56
 Danish Study - Development of Atrial
Fibrillation

Anderson HR, LANCET 1997

57
 Bi-Atrial Pacing

• In patients with inter-atrial conduction times of >

90 ms
• Improves atrial electrical synchronization
• Decreases P wave duration
• Requires two leads - one in RA and one
stimulating LA (via coronary sinus)

Daubert JC, JACC 1995; 25: 230A

58
 Bi-Atrial Pacing

• 86 patients, P wave duration > 120ms. FU of 33

months , 7+5 episodes /6 months, 2.7+1.8 AADs
• After 33mos FU, 64 % pts remain in SR including
33% with no AF.
– Reduction of P wave duration from 187 + 29 ms to 106 +
14 ms.
– Response predicted by P wave duration < 160 ms

D’Allones et al JCE 2000

59
 Dual-Site (RA) Atrial Pacing

• Pacing from two sites in the right atrium - high right atrium
and ostium of coronary sinus
• Pacing at relatively high rate (80 ppm)
• Evaluated time to first recurrence of AF vs time between
episodes pre-implant
– HRA 71 days vs 12 days (p = 0.001)
– CS ostium 47 days vs 5 days (p = 0.06)
– Dual site 85 days vs 10 days (p = 0.001)
Saksena S, JACC; 1996: 28: 687-694

60
 Dual-Site RA Pacing

• n = 30, cross-over designed study

– Antiarrhythmic drug therapy continued
• Arrhythmia free-interval
– Control period prior to pacing: 9 +/- 10 days
– Single Site: 143 +/- 110 days (p < 0.0001)
– Dual Site: 195 +/- 96 days (p< 0.005 to single site and p<
0.0001 to control)
• Free of AF recurrence
– Single site: 62%
– Dual site: 89% Delfaut P, JACC 1998: 32:
1900-8

61
 Dual Site RA Pacing in
Refractory Paroxysmal AF
% pts NJ Experience (1994-2000)
100

80

60
% Survival
40 N =113
% Freedom from CV
20 Does not exclude
% Freedom from Permanent AF continued paroxysmal AF
0
0 6 12 18 24 30 36 42 48 52
Follow-up (mos)
Courtesy – Atul Prakash, M.D.
62
 The Dutch Study - DRAPPAF

• Prospective randomized within-patient crossover

study
• Dual-site Right Atrial Pacing for Prevention of
Atrial Fibrillation
• End points:
– Time to first recurrence of AF
– Need for DC cardioversion
– Development of Chronic AF

Ramdat AR, Amer J Cardiol 2000; 86: 20K-24K

63
 The Dutch Study - DRAPPAF

• N = 26
• Group 1 - dual site first followed by single site (HRA)
– No difference between arms of the study
• Group 2 - single site first followed by dual site
– Fewer electrical cardioversion in dual site compared to
single site pacing
• Arrhythmia free interval was NOT modified by pacing
mode
Ramdat AR, Amer J Cardiol 2000; 86: 20K-24K

64
 Dual Site Right Atrial Pacing

• Drug-refractory paroxysmal atrial fibrillation in 20 patients,

single blind randomized trial
• Dual site pacing compared to RAA pacing
• End point - QOL and Atrial Fib burden (percent time spent in
atrial fibrillation)
• DDDR mode, base rate 70 ppm
– Percent atrial pacing: 85 - 87%
Levy T, et al, Internatl J Cardiol 2001; 85: 58-52

65
 Dual Site Right Atrial Pacing

RAA Dual Site p

# PAF episodes 77 52 ns
Duration of PAF 4.8 days 6.3 ns
% AF burden 14% 19% ns

• Significant improvement (QOL, episodes of AF) compared to

baseline - hence, pacing is effective.
• No significant difference based on site of pacing

Levy T, et al, Internatl J Cardiol 2001; 85: 58-52

66
 Low left atrial pacing from CS

• Acute EP Lab study - unselected patients undergoing EP

study
• Ability to induce AF using premature stimuli from HRA
• Pacing from distal CS caused low atrial depolarization
rendering it refractory to premature stimuli delivered from
HRA and precluded induction of atrial fibrillation
Papageorgiu P, CIRC, 1997; 96: 1893-1989

67
 Interatrial Septal Pacing

ea
ar
et
rg
ta

FRONTAL LAO 45°

DeVoogt, NASPE 2002

68
 Interatrial Septal Stimulation

• Prospective study in 34 pt (25 with PAF)

• Required active fixation lead (Capsurefix, Tendril DX)
• Implant procedure
– 6 Fr decapolar electrode catheter positioned in coronary sinus
to serve as landmark & AF defib.
– Temporary wire also placed in HRA - lateral wall to measure
interatrial conduction times
Padeletti, J Intervent Cardiac EP, 1999; 3: 35-43

69
 Low Interatrial Septal Stimulation

• P wave duration (p < 0.0001)

– Sinus: 118 ms  17 ms
– Septal pacing: 82 ms  12 ms
• P wave axis (p < 0.0001)
– Sinus : + 40 / Septal: - 75
• Incidence of Atrial Fibrillation
(p < 0.01)
– Pre-implant: 6.2 episodes/month
– Post-implant: 0.006 episodes/month
Padeletti, J Intervent Cardiac EP, 1999; 3: 35-43

70
Low Atrial Septal Wall Sinus

ECGs courtesy of Dr. W. DeVoogt

71
 Bachmann’s Bundle Pacing

• Paroxysmal atrial fibrillation and standard bradycardia

indication for pacing
– 69% had sinus node dysfunction
• N = 170 randomized to either right atrial appendage or
Bachmann’s bundle (high septal)
• Atrial overdrive maintained with base rate 80 ppm
• Chronic atrial fibrillation defined as atrial fibrillation lasting > 2
months in duration

Bailin S, J Cardiovasc EP 2001; 12: 912-917 72

 Bachmann’s Bundle vs RAA pacing

Freedom from Chronic Atrial Fibrillation

C 1.0 Log Rank Test p value = 0.01
U 0.9 Wilcoxin Test p value = 0.01
M S
U U 0.8 Bachmann’s bundle
L R 0.7
A V
T I 0.6 Right Atrial
I V
A 0.5 Appendage
V
E L 0.4 10 20 30
Months from Implant

Bailin S, J Cardiovasc EP 2001; 12: 912-917

73
 CAP + Site Specific Location

• N = 46, Randomized to RAA (24) or IAS (22) pacing

• All patients had PAF + Symptomatic Sinus Brady
• Within each arm, randomized to CAP on or off for 3 month periods

Rt. Atrial Appendage Inter-Atrial Septum P

Algorithm OFF ON OFF ON
% A Pacing 79 96* 83 97* * 0.001
Symptomatic PAF 2.1 1.9 0.2 0.2
PAF burden 140 m/d 193 147 41
Time to 1st AF 6.8 d 6.7 9.6 d 6.7
Stimulation site location impacted PAF but not the CAP
algorithm
Padeletti L, et al, Am Heart J 2001; 142: 1047-1055
74
 Guidant (APP) and Medtronic (AT500)

• Atrial septal pacing +/- algorithms (N = 17)

• Atrial septal pacing reduced AF burden >50%
• Activation of overdrive algorithms in AT500
– Reduction in % AF On 61%, Off 73%
(p = 0.53)
• APP (Guidant)
– % AF On 5.84, Off 3.73 (p = 0.13)

• Conclusion: septal pacing but NOT algorithm associated

with reduction in AF burden

Kale, Europace 2003; 5: 123-131

75
 Atrial Pacing
• Site specific pacing appears to have a positive
impact on arrhythmias
– Low Atrial Septum (Triangle of Koch)
– High Atrial Septum (Bachmann’s Bundle)
• Various overdrive algorithms may complement
the beneficial effect of site specific pacing

76
 Site specific pacing
• Atrium (other than RAA)
– Beneficial effect on arrhythmias
– Hemodynamic benefit - TBD
• Ventricle (other than RV apex)
– Hemodynamic benefit confirmed
– Impact on arrhythmias
• Ventricular arrhythmia – TBD
• Atrial arrhythmias – aggravating (RV apex)

77
Thank You