Europace (2000) 2, 93–98
doi:10.1053/eupc.2000.0081, available online at http://www.idealibrary.com on
Alternative right ventricular pacing sites — where are we
For over 40 years, since the advent of permanent cardiac
pacing, the right ventricular apex (RVA) has been the
routine site for placement of the ventricular pacing lead,
although interestingly the first reported endocardial elec-
trode placements were, in fact, in the right ventricular
outflow tract (RVOT). Evidence has existed for many
years, however, to suggest that the RVA may not be the
most suitable position for ventricular stimulation. In a
series of elegant experiments in 1925, Wiggers demon-
strated that electrical stimuli applied to ventricular
muscle will cause a deterioration in function over the
long term; it has been shown subsequently that these
effects arise from abnormalities provoked at the cellular
level[4,5]. Further studies have shown that apical pacing
has adverse effects on volume, pressure and inotropic
state[6–10], with thinning of the myocardial wall around
the activation siteand the development of regional
hypertrophy in the long term. This also leads to
perfusion defects[12,13]which are associated with apical
wall motion abnormalities and impaired global left
ventricular function, a situation which progresses with
time. In combination these studies all suggest that,
whilst apical pacing is sufficient to treat the initial
arrhythmia and offers lead stability by means of the
trabeculae, it may introduce the potential for future
A disturbing finding that begins to reinforce the
suggestion that RVA pacing is potentially detrimental
is evident in work by Rosenqvist et al.. In a retro-
spective study of 168 patients comparing VVI vs AAI
implants for sinus node disease (SND) (undertaken at
separate hospitals), they found an increased incidence of
congestive heart failure in those patients treated with a
ventricular device. They concluded that pacing the RVA
for SND predisposed this group to developing heart
failure more than pacing in the atrium alone, and that
this must result, at least in part, as a consequence of
pacing in the RVA. Of additional importance was the
high incidence of atrial fibrillation in the VVI group.
These findings were confirmed ten years later by Nielsen
et al.who also demonstrated this same link between
pacing mode and progression to heart failure. Bedotto
et al. summed up the clinical implications of ventricular
pacing in 1990; prior to 1990, 40–50% of total world-
wide pacemaker implants were for SND in patients with
intact AV nodal conduction and many of these were
ventricular devices, even though the safety and efficacy
of atrial-based pacing in this cohort had already been
proven and the associated effects of pacing mode on
mortality identified[17,18]. Although it is difficult to
separate the potential contribution of the increased
incidence of atrial fibrillation in these patients, these
data began to emphasize the number of patients who are
exposed to an increased risk of developing cardiac
dysfunction in the long term and subsequent studies
have concurred with these initial findings.
In his original paper, Wiggers postulated that the
degree of functional impairment was inversely propor-
tional to the proximity of the stimulation site to the
His-Purkinje system, and hence that the activation
sequence is more important than synchrony of acti-
vation. Thus it is not unreasonable to assume that a
more physiological approach, by positioning the pacing
lead as near to the His-Purkinje system as possible, may
limit the potential damage caused by RVA pacing. It has
been suggested that this is of greatest importance in
young patients receiving first implants as juveniles.
The immature heart can accommodate changes in vol-
ume and pressure readily, but this ability to adapt will
diminish with age and could potentially lead to the
genesis of heart failure in young to middle age. Also,
restoration of more normalized activation and contrac-
tion sequences may be beneficial in producing optimal
haemodynamics for patients with concomitant struc-
tural heart disease, for whom cardiovascular reserve
may be limited and maintenance of AV synchrony
Interest in His bundle pacing was shown as early as
1967 in work by Scherlag et al. as a means of allow-
ing the ventricles to depolarize in a more normalized
fashion. This study demonstrated little difference in
QRS duration and indices of pressure recorded during
intrinsically conducted sinus rhythm, atrial pacing,
and His Bundle pacing. Subsequent studies have made
similar comparisons of His bundle, atrial, and RVA
pacing[5,21,23]and confirmed that the temporal relation-
ship between atrial and ventricular contraction and the
Manuscript submitted 5 January 2000, and accepted 9 January
? 2000 The European Society of Cardiology
sequence of ventricular depolarization were both impor-
tant to maintain good LV function, and that the impor-
tance of each factor was increased in the absence of the
The RVOT and right ventricular septum (RVS) are
the most frequently described alternative right ventricu-
lar pacing sites. Numerous acute haemodynamic studies
have shown an improvement in cardiac output with
pacing leads placed in these sites and this has led to
limited work in improving haemodynamics in impaired
hearts[26,27]. Results have been promising, with improve-
ments not only in the functional capacity of these
patients but also in their quality of life, but so far
there is little evidence of any long-term benefit derived
from these new techniques. It is also difficult to assess
any decrease in mortality, as the subjects typically have
a significant degree of heart failure or are candidates for
orthotopic cardiac transplant. Some studies advocate
the use of the RVOT as a pacing site only in abnormal
hearts, suggesting that there are no benefits to be gained
by RVOT pacing in normally functioning hearts[29,30].
It is clear that, at least theoretically, alternative right
ventricular pacing sites are preferable, but there is still
debate as to the degree of functional benefit, and where
exactly the lead should be placed.
Anatomical position of pacing lead
Buckinghamdescribes positioning of the ventricular
lead high in the outflow tract and then pulling back until
the lead tip ‘jumps’ and points in a lateral direction on a
postero-anterior fluoroscopic image, whereas Giudici
et al. describe placement in the RVOT defined as the
position most superior to the RV free wall that is still
below the infundibulum. The discrepancy lies in
where a physician feels the septum finishes and the
outflow tract starts. Buckingham emphasizes the need
for the combination of detailed anatomical descriptions,
12-lead ECGs and X-rays to determine exact electrode
Karpawich has attempted to identify and describe the
different anatomical positions that are commonly
referred to as either RVOT or high septal pacing, and
described both the anatomical and the 12-lead ECG
appearance post-implant for four positions within the
RV. This classification should enable a more accurate
assessment of efficacy of specific positions in the long
term and help to ascertain the optimal pacing site.
Another important consideration is the type of lead
used in these new positions. The very nature of the in-
fundibular region of the RV requires that an active fixation
lead is used as there are insufficient trabeculae to support
the use of passive fixation leads in this position. Schwaab
et al. have successfully used passive fixation leads in septal
positions, but they are placed further toward the RVA
where trabeculation is more apparent, fitting the descrip-
tion of apical-septal pacing as defined by Giudici and
Karpawich. The safety and efficacy of active fixation
leads in the RVA has been well validated; however,
positioning the lead in an RVS or RVOT position
may be associated with an increased risk of dislodge-
ment or even perforation, particularly with the thinner
tissue of the RVOT region. Although one study has
confirmed the reliability of active fixation leads in the
area, further data are required to validate the long-
term safety and efficacy of these leads in alternative
RV positions. It is, however, possible to place these
leads in such positions using simple and reproducible
Importance of QRS duration
As previously discussed, the QRS duration recorded on
the surface ECG reflects the time taken for signal
transmission throughout the ventricular myocardium,
hence prolongation reflects increased conduction times.
The QRS duration may be a useful marker of position
when placing the lead on the RVS, with the narrowest
QRS obtained potentially indicating a position nearest
to the intrinsic system. This theory has been success-
fully utilized at implant to help identify the best RVS
position[33,36,37], but whether this acute QRS duration
reflects long-term activation patterns, or indeed ven-
tricular function, remains to be determined. Paced QRS
duration has been shown to be inversely related to left
ventricular function in patients with heart failure, but
there are, as yet, no data to confirm a relationship in
patients starting with normal ventricles.
The contribution of AV synchrony
Atrial contraction is beneficial for optimal cardiac func-
tion, but the role of variation of AV delay in paced
patients, i.e. the duration of mitral valve opening and
hence atrial contribution to ventricular filling, remains
unclear. A correctly timed atrial contraction preceding
each ventricular contraction during AV sequential pac-
ing minimally alters loading conditions, but the loss
of atrial transport during VVI pacing is thought to
contribute to the functional suppression associated
with abnormal activation[8,10,39]. This suggests that the
correct AV interval is important to ensure adequate
ventricular filling[40,41]. If the AV delay is too short
ventricular filling is inadequate, if the AV delay is too
long atrial contraction may occur against the closed
mitral valve during ventricular systole and provoke
symptoms of ‘Pacemaker Syndrome’.
The relevance of maintaining AV synchrony when
pacing within the RV by comparing results between
atrial, His bundle, and RV apical pacing has shown, in
dogs, that contractility (defined as dP/dT) and cardiac
output (CO) are suppressed with a very short PR
interval, and improved when the PR approached a more
normal value. The variations in function, however, were
more pronounced in the apically paced dogs. At any
Europace, Vol. 2, April 2000
given PR interval, ventricular function was better in the
His bundle pacing group, i.e. with more normalized
contraction sequences, and more pronounced at short/
normal PR intervals. They concluded that the order of
depolarization and the maintenance of AV sequential
contraction are of equal importance for maintaining
good LV function, and that either are accentuated in the
absence of the other. Some studies have suggested that a
programmed value as near to normal as possible, i.e.
100 ms, may be a suitable concession to time consuming
Some studies have continued to investigate the impor-
tance of AV synchrony to ventricular function and have
concluded that correctly timed atrial systole, in the
presence of an abnormal activation sequence produced
by pacing at the RV apex, is equally important as
maintaining AV synchrony. Both factors combined
will help to increase cardiac performance but cannot
compensate for the changes produced by abnormal
conduction sequences, hence atrial pacing alone (AAI)
provides the best haemodynamics[24,25,44].
Current experience with RVS/RVOT
A number of acute evaluations of RVS and RVOT
pacing sites have demonstrated mixed results. Whilst
some studies have found an increase in cardiac output
and contractility (dP/dT) compared with RVA pac-
ing, others have been unable to detect any differences
from RVA pacingor in patients with pre-existing
Following on from the initial work of Scherlag et al.
work, Karpawich et al. investigated His bundle pac-
ing in canines using a trans-epicardial approach, directly
placing the tip of the pacing electrode within the septal
muscle to maintain direct contact with the bundle of His,
and placing an epicardial wire in the standard apical
position. Intracardiac ventricular electrograms en-
abled recording of depolarization sequences, with data
obtained from the septal leads comparing favourably
with those obtained from non-paced controls with near-
normal, rapid conduction velocities. The data from the
apical group showed significantly longer depolarization
sequences and conduction velocities. A study using
direct His bundle pacing in four patients with cardio-
myopathyreported similar findings to those of
Karpawich et al. in dogs, with near-normal conduction
times; however, lead displacement occurred in one
patient and the limited data were inadequate to validate
this technique. There are also concerns over the presence
of continuing conduction tissue disease distal to the
stimulation site (particularly in the older patient) which
may lead to further atrioventricular conduction prob-
lems and subsequent loss of ventricular capture. Data
from a randomized, prospective study of apical vs
RVOT pacing in an unselected groupshowed a
significant decrease in NYHA classification in patients
with RVOT pacing, but echocardiographic assessment
of filling dynamics showed no difference between the two
groups. These data suggested that any acute improve-
ments with pacing in the RVOT were not present after
1 year. Giudici et al. suggested loss of atrial kick as
opposed to less efficient depolarization as a cause for
reduced cardiac output in a study of 89 unselected
patients receiving single or dual chamber pacing for any
indication; data were collected in five patients at 6
months post-implant, demonstrating that the acute im-
provements in cardiac output with RVOT, compared
with apical pacing, were still present. These data imply
potential long-term benefits but, as the functional status
at implant is not stated for the patients forming the
second data set, interpretation of these findings is
A more recent study prospectively compared func-
tional status with RVOT vs RVA pacing in a cohort of
patients with chronic atrial arrhythmias and mixed
ventricular functional status. Both leads were con-
nected to a DDD device (RVA to ventricular port and
RVOT to atrial port) to enable crossover between the
two lead sites. The results were inconclusive and did not
detect a difference in functional status as measured by
radionuclide imaging between the two pacing sites, but
this could be attributed to a residual effect on cardiac
function from the first randomized pacing site. No
difference was found in QRS duration or axis which is
not unsurprising considering the anatomical position of
the RVOT lead and the wide QRS duration associated
with stimulation at this site. The study did, however,
confirm the reliability and safety of chronic RVOT
pacing with active-fixation leads.
Buckingham et al. attempted both RVOT and com-
bined apical and RVOT pacing in a group of patients
(n=14) with ventricular ejection fractions of less than
40%. This acute study found little difference in hae-
modynamic variables between pacing at each site and
simulataneous pacing at both sites. A non-significant
trend was observed toward improvement in contractility
during RVOT and simultaneous pacing compared with
apical pacing, which suggested that some benefit may be
gained by RVOT or dual-site pacing in heart failure.
Giudici et al. also performed an acute study by pacing
the apex and then the RVOT with a temporary lead in
patients with class III–IV heart failure and existing
apical leads. This showed that RVOT pacing im-
proved haemodynamics acutely and may be an option
for those with drug-refractory heart failure.
Alternative pacing sites in heart failure
VVI pacing alone has been shown to result in a higher
risk of sudden death compared with non-paced patients
with a similar degree of heart failure. A retrospective
study of long-term follow-up between VVI and DDD
pacing showed that DDD enhances survival to a greater
extent than VVI in patients with heart failure and AV
Europace, Vol. 2, April 2000
block, and this is attributed to the importance of
atrial transport in ventricular filling. More importantly,
Nielsen et al. demonstrated that VVI pacing for sinus
node disease was associated with the development of
congestive heart failure over a 5 year follow-up period,
strongly supporting the hypothesis that ventricular api-
cal devices are detrimental to ventricular function rather
than potentially beneficial.
Hochleitner et al. described successful treatment of
16 patients with severe, drug-refractory cardiac failure
using a dual chamber pacemaker. The ventricular
lead was placed in the RV apex and the AV delay fixed
at 100 ms. The results showed an increase in ejection
fraction measure by scintigraphy and a reduction in the
severity of mitral regurgitation; however, despite a sig-
nificant reduction in left ventricular internal dimension
there was no significant change in paired values for each
patient. The authors suggest that the alteration in pre-
load, rather than any alteration of myocardial contrac-
tility, is the main contributory factor in the improvement
in ejection fraction. It is also assumed that the contri-
bution to ventricular filling of an appropriately timed
atrial contraction, achieved by programming the AV
delay to 100 ms, is significant in reducing ventricular
dilatation, although the improvement was more notice-
able in the RV than the LV. The authors suggested that
these data support the use of DDD pacing as a thera-
peutic aid to patients with severe cardiac failure. These
surprising results led to further investigations to verify
the efficacy of DDD pacing with a short AV delay.
Subsequent studies have, however, been unable to repro-
duce the results of Hochleitner’s group, possibly because
these original data were uncontrolled and observational
The conclusions that can be drawn from these studies
is that DDD pacing with a short AV delay may help
some patients, but overall changes in function are insig-
nificant, and results are observational at best. It is
important to emphasize that many patients are chrono-
tropically incompetent, and thus improvements in
NYHA classification and symptoms may be attributed
to a more normalized heart rate response. It may be
possible that some patients will benefit from this type of
pacing therapy; however, the overall mechanism appears
crude and is not supported by long-term results. It may
also be more appropriate to encourage intrinsic conduc-
tion rather than apical pacing as the potential benefits of
correctly timed atrioventricular synchrony and reduc-
tion in mitral regurgitation may be negated by the
deleterious effects of apical pre-excitation.
The concept of alternative right ventricular site pacing
was investigated by Gold et al. in 13 patients with severe
heart failure but intact AV conduction by measuring
haemodynamics during intrinsic contractions and VDD
pacing at various AV delays. The results were similar
for intrinsic conduction and each AV delay, inferring
that septal pacing produced similar haemodynamic in-
dices to those produced by intrinsic conduction, and so
providing no functional benefit in these patients. A
study by Cowell et al. compared haemodynamic indices
obtained during RVS with RVA pacing acutely in 14
patients with heart failure, and found that CO was
increased significantly during RVS pacing, particularly
when the AV delay was optimized between 50–100 ms.
The safety and efficacy of ventricular pacing as a treat-
ment for heart block has led to a change in direction
for pacing research, with attention now focussing on
the functional rather than electrical effects of pacing.
The improvement in haemodynamic indices and qual-
ity of life in patients with heart failure treated with
pacing[41,49,58–61]has led to increased interest in new
indications for and approaches to pacemaker implan-
tation. These findings do suggest, however, that whilst
pacing may initially improve cardiac function in this
cohort, pacing the RVA may induce heart failure over
time, an irony that has been slow to gain acceptance but
is now put forward as a reason for adopting new
electrode sites. It is difficult to translate the successes
achieved in failing histologically abnormal hearts to
those that are relatively normal on presentation for
pacing, and there are currently little long-term data to
support the use of such positions as the RVOT or RVS
over the RVA; results have so far been conflicting as to
the potential benefits[49,50,55,56,62]. In order to consider a
new pacing site as standard, a consensus is required
regarding choice of site and there will be a need for
long-term, randomized, prospective studies comparing
pacing at this alternative site to pacing at the RV apex.
The objectives must include consideration of long-term
lead stability and extractability. Until these objectives
can be met, we will not be able to determine the
potential superiority of more physiological ventricular
pacing and begin to influence practice that has changed
little over 40 years.
Z. I. HARRIS
M. D. GAMMAGE
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