1180

Right Ventricular Outflow Versus Apical Pacing in Pacemaker

Patients with Congestive Heart Failure and Atrial Fibrillation
BRUCE S. STAMBLER, M.D., KENNETH A. ELLENBOGEN, M.D.,
XIAOZHENG ZHANG, M.D., THOMAS R. PORTER, M.D., FENG XIE, M.D.,
RAJESH MALIK, M.D., ROY SMALL, M.D.,# MARTIN BURKE, D.O.,
ANDREW KAPLAN, M.D., LAWRENCE NAIR, M.D., MICHAEL BELZ, M.D.,
CHARLES FUENZALIDA, M.D., MICHAEL GOLD, M.D.,## CHARLES LOVE, M.D.,
ARJUN SHARMA, M.D., RUSSELL SILVERMAN, M.D., FELIX SOGADE, M.D.,
BRUCE VAN NATTA, M.D., and BRUCE L. WILKOFF, M.D.,### for the ROVA Investigators
From University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio, USA; Medical College of Virginia, Virginia
Commonwealth University, Richmond, Virginia, USA; St. Jude Medical CRMD, Sylmar, California, USA; University of Nebraska,
Omaha, Nebraska, USA; Smith Clinic, Marion, Ohio,USA; #Lancaster General, Lancaster, Pennsylvania, USA; University of Chicago,
Chicago, Illinois, USA; Tri-City Cardiology Consultants, Mesa, Arizona, USA; Presbyterian Heart Group, Albuquerque, New
Mexico, USA; Virginia Mason Research Center, Seattle, Washington, USA; Denver Cardiology Associates, Aurora, Colorado, USA;
##University of Maryland, Baltimore, Maryland, USA; Ohio State University, Columbus, Ohio, USA; Sutter Health, Sacramento,
California, USA; Heart Care Center, East Syracuse, New York, USA; Medical Center of Central Georgia, Macon, Georgia, USA;
Memorial Medical Group, Long Beach, California, USA; and ###Cleveland Clinic Foundation, Cleveland, Ohio, USA

Right Ventricular Pacing Site in Heart Failure. Introduction: Prior studies suggest that right
ventricular apical (RVA) pacing has deleterious effects. Whether the right ventricular outflow tract (RVOT)
is a more optimal site for permanent pacing in patients with congestive heart failure (CHF) has not been
established.
Methods and Results: We conducted a randomized, cross-over trial to determine whether quality of life
(QOL) is better after 3 months of RVOT than RVA pacing in 103 pacemaker recipients with CHF, left
ventricular (LV) systolic dysfunction (LV ejection fraction 40%), and chronic atrial fibrillation (AF).
An additional aim was to compare dual-site (RVOT + RVA, 31-ms delay) with single-site RVA and RVOT
pacing. QRS duration was shorter during RVOT (167 45 ms) and dual-site (149 19 ms) than RVA
pacing (180 58 ms, P < 0.0001). At 6 months, the RVOT group had higher (P = 0.01) role-emotional
QOL subscale scores than the RVA group. At 9 months, there were no significant differences in QOL scores
between RVOT and RVA groups. Comparing RVOT to RVA pacing within the same patient, mental health
subscale scores were better (P = 0.03) during RVOT pacing. After 9 months of follow-up, LVEF was higher
(P = 0.04) in those assigned to RVA rather than RVOT pacing between months 6 and 9. After 3 months of
dual-site RV pacing, physical functioning was worse (P = 0.04) than during RVA pacing, mental health was
worse (P = 0.02) than during RVOT pacing, and New York Heart Association (NYHA) functional class was
slightly better (P = 0.03) than during RVOT pacing. There were no other significant differences between
RVA, RVOT and dual-site RV pacing in QOL scores, NYHA class, distance walked in 6 minutes, LV ejection
fraction, or mitral regurgitation.
Conclusion: In patients with CHF, LV dysfunction, and chronic AF, RVOT and dual-site RV pacing
shorten QRS duration but after 3 months do not consistently improve QOL or other clinical outcomes
compared with RVA pacing. (J Cardiovasc Electrophysiol, Vol. 14, pp. 1180-1186, November 2003)

heart failure, pacemakers, pacing

Introduction
For many years, permanent right ventricular (RV) pac-
ing leads have been traditionally implanted in the RV apex
(RVA). Recently, the deleterious effects of RVA pacing have
been increasingly recognized.1-6 Thus, alternative ventricu-
Supported by a grant from St. Jude Medical CRMD, Sylmar, California.
Address for correspondence: Bruce Stambler, M.D., University Hospitals of
Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106. Fax: 216-844-7196,
E-mail: bss4@po.cwru.edu
Manuscript received 30 April 2003; Accepted for publication 7 August 2003.
doi: 10.1046/j.1540-8167.2003.03216.x
lar pacing sites, including the RV outflow tract (RVOT), His
bundle, dual-site RV, left ventricular (LV), and biventricu-
lar have been investigated.7-16 The benefits of alternative RV
pacing sites remain controversial. Importantly, some previ-
ous studies evaluating optimal RV pacing site(s) were un-
controlled or unblinded, other studies only evaluated acute
and not chronic effects, and all prior studies were limited by
evaluation of only small numbers of patients with congestive
heart failure (CHF).7-14 Thus, whether RVOT or dual-site RV
pacing results in superior clinical outcomes compared with
RVA pacing has not been established due to a lack of consis-
tent findings, especially in CHF patients.
The primary purpose of the ROVA trial (Right ventricular
Outflow Versus Apical pacing) was to determine whether
pacemaker recipients with CHF, LV systolic dysfunction,
 Stambler et al.
and chronic atrial fibrillation (AF) have better quality of life
(QOL) during chronic pacing from the RVOT than the RVA.
Effects on New York Heart Association (NYHA) class, exer-
cise capacity, LV function, and mitral regurgitation also were
assessed. An additional aim was to compare dual-site RV
pacing with single-site RVA and RVOT pacing. Patients with
chronic AF were studied to avoid effects of atrial contraction
and AV delay on hemodynamics. To minimize the potential
confounding effects of pacemaker implantation and/or AV
junction ablation on the comparison of RVA with RVOT pac-
ing, pacing site randomization did not occur until 3 months
after implantation.
Methods
Patients were eligible if they had standard bradycardia in-
dications for VVIR pacing and were scheduled to undergo
permanent pacemaker implantation. All patients had NYHA
class II or III CHF, an LV ejection fraction (LVEF) 40%
(within 30 days of enrollment), and chronic AF (7 days).
Patients <21 years old or with a previous pacemaker, defib-
rillator, or leads implanted were excluded. During random-
ization (months 36) and cross-over (months 69) phases,
patients were excluded if they had inadequate pacing lead
position or performance, failed to maintain chronic AF, or
<90% ventricular pacing. The institutional review board of
each center approved the study protocol. All patients gave
written informed consent.
Study Design
The ROVA trial was designed as a randomized, single-
blind, cross-over comparison of RVOT versus RVA pac-
ing. The primary endpoint was health-related QOL assessed
by the Medical Outcomes Study short form health sur-
vey (SF-36) questionnaire and performed after 3 months
of ventricular pacing from each RV site (RVOT vs RVA).
The SF-36 instrument consists of 8 subscale scores rang-
ing from 0 to 100 (higher scores indicate superior QOL),
which measure general health perceptions, physical func-
tioning, role-physical, vitality, mental health, role-emotional,
social functioning, and bodily pain.17 From the 8 scores,
2 summary measures are aggregated as physical (compris-
ing the first 4 subscales) and mental (last 4 subscales)
components. Heart failure-related QOL also was assessed
using the Minnesota Living with Heart Failure question-
naire.18 Secondary endpoints included NYHA class, LVEF,
and severity of mitral regurgitation determined by echocar-
diography, exercise capacity assessed by a 6-minute walk
test, and lead-related complications including sensing/pacing
thresholds.
Patients underwent implantation of a standard dual-
chamber pacemaker (models 2364, 2360, 5330, and 5342,
St. Jude Medical, Sylmar, CA, USA) along with two bipolar,
active-fixation pacing leads (models 1388 and 1488, St. Jude
Medical): one lead was placed at the RVA and one lead was
implanted in the RVOT. The procedure for implantation of
the RVOT lead was prespecified in the study protocol as to be
performed by advancing the lead out the pulmonary artery,
withdrawing the lead until it dropped below the pulmonic
valve, and then advancing the lead into the high septum.
Proper lead positioning was confirmed by fluoroscopy and
ECG (Fig. 1). RVOT pacing was expected to produce a
Right Ventricular Pacing Site in Heart Failure 1181
left bundle branch block and inferior-axis ECG morphol-
ogy. The RVOT and RVA leads were connected to the atrial
and ventricular channels of the dual-chamber pacemaker,
respectively. Programming the pacemaker to AAI or VVI
modes provided single-site pacing from the RVOT or RVA,
respectively; whereas DDD mode with the shortest pro-
grammable AV interval (31 ms) produced dual-site RV pacing
(RVOT+RVA).
Postimplantation chest x-ray films and ECGs were sent
to the data-coordinating center (St. Jude Medical) for review
to confirm appropriate lead positions. Randomization at the
3-month visit did not occur until satisfactory lead positions
were confirmed. Patients with inappropriate lead positions
were excluded unless their leads were repositioned ade-
quately and the new site was confirmed as being acceptable.
Patients were seen in follow-up at months 3, 6, 9, and
12 after pacemaker implantation (Fig. 2). At each visit, pa-
tients had a clinical evaluation, completed QOL question-
naires, performed a 6-minute walk test, and underwent resting
12-lead ECG and echocardiography. Noninvasive interroga-
tion of the pacing system, including measurement of pac-
ing and sensing thresholds and impedances and confirmation
of >90% ventricular pacing via telemetered data, was per-
formed. One- and two-dimensional echocardiograms along
with Doppler ultrasound images using standard views were
videotaped and forwarded to the echocardiography core lab-
oratory (University of Nebraska Medical Center), which was
blinded to the RV pacing site. The core laboratory measured
LVEF and mitral valve regurgitant areas. From months 3 to
12, the lower pacing rate was 70 beats/min.
At the 3-month visit following the baseline clinical assess-
ment and confirmation of continued eligibility, patients were
randomly assigned to RVA or RVOT pacing for a 3-month
treatment period. Randomization occurred in blocks at each
site to ensure a balance between groups at each center. Pa-
tients were not informed of their treatment assignment. At
the 6-month visit, following the evaluation in the random-
ized pacing site, eligible patients were crossed over to pacing
from the other RV site (RVOT to RVA and RVA to RVOT)
for another 3 months.
At the 9-month visit, after the evaluation in the cross-
over pacing site, eligible patients were asked to participate
in a nonblinded, dual-site (RVOT+RVA, 31-ms delay) sub-
study from months 9 to 12. Patients were excluded from sub-
study participation if they had an RVOT to RVA conduction
time <31 ms (mean conduction time 71 25 ms). A final
evaluation was performed in dual-site substudy patients at a
12-month visit.
Statistical Analysis
The study was adequately powered to detect at least a
10% difference on most of the paired SF-36 subscale scores
between RVA, RVOT, and dual-site RV pacing using a two-
tailed paired t-test with 80% power. Continuous variables
were expressed as mean SD and compared using paired
t-tests. Differences of continuous variables among study
groups at follow-up visits were determined using analysis of
variance. Categorical variables were compared by Chi-square
analysis or Fishers exact tests and summarized by propor-
tion in each category. All statistical analyses were completed
using the SAS software package. A two-sided P < 0.05 was
considered statistically significant.
1182 Journal of Cardiovascular Electrophysiology
Figure 1. Lateral (left) and posteroanterior (right) chest x-ray films demonstrating pacing lead positions in the right ventricular outflow tract and at the
apex.
Results
Between February 1998 and July 2001, 103 patients at 30
centers were enrolled and underwent pacemaker implanta-
tion. Four patients with inappropriate RVOT lead positions
had their leads successfully repositioned and completed par-
ticipation in the trial. The mean age of patients was 69.5
12.4 years, and 75% were male. Fifty-four patients (52.4%)
were in NYHA class II and 49 (47.6%) were in class III
at enrollment. LVEF was 27.6% 8.2% (range 10%40%)
prior to enrollment. All patients had chronic AF. Coronary
artery disease was reported in 49%, hypertension in 40%, and
valvular disease in 33%. Thirty-four percent had a history of
myocardial infarction, and 25% previously had undergone
cardiac surgery. The indication for pacemaker implantation
was after AV junction ablation in 66 patients (64.1%), a slow
ventricular response in 29 (28.2%), third-degree AV block
in 2 (1.9%), and not reported in 6 (5.8%). Twelve patients
had left bundle branch block and 6 had right bundle branch
block. Within 48 hours of implant, 82% of patients were re-
ceiving diuretics, 81% digitalis, 57% angiotensin converting
enzyme inhibitors, 38% beta-adrenergic blockers, and 29%
Ca2+ channel antagonists.
QRS duration was shorter during RVOT than RVA pacing
(167 45 ms vs 180 58 ms, P < 0.0001). There was no
difference in capture thresholds or impedances between RVA
and RVOT leads (0.63 0.23 V vs 0.65 0.29 V at 0.5 ms,
and 563 155  vs 544 115 , respectively). Sensing
Vol. 14, No. 11, November 2003
thresholds were smaller at the RVOT than RVA (10.7 4.6
mV vs 12.0 4.4 mV, P = 0.04).
Baseline Evaluation
At the 3-month follow-up visit, 84 patients underwent
baseline evaluation after 3 months of RVA pacing (upper
and lower pacing rates: 116 18 beats/min and 83
14 beats/min, respectively) since implant. Prior to the
3-month visit, 5 patients died, 3 underwent implantable
cardioverter defibrillator placement (2 for cardiac arrest and
1 for recurrent ventricular tachycardia), 8 failed to main-
tain continued eligibility (<90% ventricular pacing, failure
to maintain chronic AF), 4 had lead-related problems (2 with
inappropriate lead positions, 1 with elevated thresholds, and
1 with a lead fracture) and did not undergo revision, and
3 were noncompliant and declined further participation. At
the end of the 3-month visit, 37 patients were randomly as-
signed to RVA pacing and 43 to RVOT pacing for the next
3 months. The two randomized groups were similar with re-
spect to baseline characteristics, as well as upper and lower
pacing rates.
QOL scores are given in Tables 1 and 2. QOL was signif-
icantly impaired in patients in the present study when com-
pared with groups with and without cardiovascular disease
previously reported (Table 1). At the 3-month visit, all 8 mean
QOL subscale scores of the SF-36 instrument were worse
than those reported for healthy individuals, 7 of 8 scores were
 Stambler et al. Right Ventricular Pacing Site in Heart Failure 1183

Study Endpoints
At the 6-month follow-up visit, role-emotional subscale
score was higher (+43%, P = 0.01) in patients assigned to
RVOT pacing for the previous 3 months compared with those
in the RVA group (Table 2). However, at 9 months there were
no significant differences in QOL scores between the RVOT
and RVA groups. In the paired cross-over analysis, comparing
within the same patient RVOT with RVA pacing for 3 months
each between months 3 and 9, mental health subscale scores
were better (+5% to 8%, P = 0.03) during RVOT than
RVA pacing. After 9 months of follow-up, LVEF was higher
(P = 0.04) in those assigned to RVA rather than RVOT pacing
between months 6 and 9. There were no other significant dif-
ferences between the RVOT and RVA pacing groups in any of
the QOL scores, NYHA class, distance walked in 6 minutes,
LVEF, or mitral regurgitation severity at the 6- or 9-month
visit or in the cross-over analysis. Outcomes did not differ
with respect to RVA compared with RVOT pacing based on
the primary indication for pacing (AV junction ablation vs
non-AV junction ablation).

Figure 2. ROVA (Right ventricular Outflow Versus Apical pacing) trial study
design. AF = atrial fibrillation; CHF = congestive heart failure; ECHO =
echocardiography; LVEF = left ventricular ejection fraction; QOL = quality
of life; RVA = right ventricular apex; RVOT = right ventricular outflow tract.
worse than those obtained from elderly pacemaker recipients
after 3 months of VVIR pacing, and 5 of 8 scores were worse
than those reported for patients with paroxysmal AF and for
patients with AF 3 months after AV junction ablation and
permanent pacing.19-21 The SF-36 and Heart Failure scores
at the 3-month visit were similar to patients with CHF in
previous reports.16,17 At the 3-month baseline visit, NYHA
class was 2.1 0.7, LVEF was 43.0% 13.6% (range 17%
66%), and patients were able to walk 295.8 127.4 m on the
6-minute walk test.
Dual-Site RV Substudy
Fifty patients participated in the dual-site RV substudy be-
tween months 9 and 12 following pacemaker implantation.
The clinical characteristics of substudy patients at enrollment
were similar to patients who did not participate in the sub-
study. Dual-site RV pacing shortened QRS duration (149
19 ms) compared with single-site RVA (180 23, P <
0.0001) and RVOT pacing (164 18 ms, P < 0.0001). After
3 months of dual-site RV pacing, physical functioning sub-
scale score was significantly worse (9%, P = 0.04) than
during RVA pacing and mental health subscale and mental
component summary scores were worse (6%, P = 0.02)
than during RVOT pacing (Table 2). NYHA class during
dual-site RV pacing was slightly better than during RVOT
(P = 0.03), but not different than RVA pacing (Table 2).
There were no other significant differences between dual-
site RV compared with RVOT and RVA pacing in the other
endpoints.

TABLE 1
Quality-of-Life Scores

SF-36 Subscale Scores ROVA Patients Healthy Subjects AF Patients APT Patients PASE Patients CHF Patients

General health 55.5 21.8 78 17 54 21 50.3 23.2 62.3 47 24

Physical functioning 48.3 28.2 88 19 68 27 52.5 29.3 53.9 48 31
Role-physical 34.5 38.7 89 28 47 42 40.6 42.2 53.6 34 40
Vitality 45.4 22.9 71 14 47 21 47.2 24.6 53.0 44 24
Mental health 73.6 19.8 81 11 68 18 69.7 17.8 77.0 75 21
Role-emotional 55.9 41.7 92 25 65 41 63.0 44.4 83.8 64 43
Social Function 73.8 27.5 92 14 71 28 67.3 28.2 73.0 71 33
Bodily Pain 66.1 28.1 77 15 69 19 66.3 27.0 69.7 63 31
Data are given as mean scores SD, except for PASE patients, which are mean scores.
ROVA (Right ventricular Outflow Versus Apical pacing) patients at the 3-month baseline visit (right ventricular apex pacing).
Healthy control subjects and paroxysmal atrial fibrillation (AF) patients from Dorian et al.19
AF patients from the Ablate and Pace Trial (APT).20
VVIR paced patients from the Pacemaker Selection in the Elderly (PASE) trial.21
Congestive heart failure (CHF) patients from Ware et al.17
1184 Journal of Cardiovascular Electrophysiology Vol. 14, No. 11, November 2003

TABLE 2
Effects of Right Ventricular Pacing Site

6 Months (Randomized Site) 9 Months (Cross-Over Site) 12 Months (Dual Site)

RVA RVOT RVOT RVA Dual RV

SF-36 QOL subscales

General health 56.7 21.8 55.1 24.4 52.4 23.3 55.7 25.6 54.0 24.3
Physical functioning 47.5 27.3 51.2 25.4 40.4 27.8 50.1 28.2 46.8 27.8
Role-physical 38.6 41.0 52.2 37.3 32.6 40.7 41.7 37.3 40.8 41.1
Vitality 50.2 18.2 46.0 25.7 45.5 23.3 41.4 26.0 43.9 26.2
Mental health 69.9 20.2 78.6 15.9 73.7 18.7 72.9 24.0 72.9 21.0
Role-emotional 55.6 41.4 79.3 33.7 47.5 46.4 67.8 39.3 60.3 44.9
Social function 78.4 24.7 79.6 24.7 67.4 26.7 76.7 29.9 74.5 26.3
Bodily pain 67.8 26.8 75.3 20.1 60.9 27.4 63.4 27.9 64.5 25.6
SF-36 summaries
Mental component 49.2 10.6 53.2 9.6 48.5 11.0 50.3 10.7 49.2 10.8
Physical component 37.7 11.6 37.8 10.3 34.3 11.3 36.4 10.3 36.1 10.9
Heart failure QOL scores 59.9 24.9 54.0 20.4 63.5 25.2 55.9 22.0 57.1 23.2
New York Heart Association functional class 2.1 0.7 2.1 0.7 2.2 0.7 2.1 0.7 1.9 0.7
6-minute walk distance (m) 342.5 138.7 315.5 131.8 307.8 141.5 346.0 127.7 347.1 134.9
Left ventricular ejection fraction (%) 41.9 13.4 43.8 14.4 34.3 13.4 47.2 17.6 40.5 13.4
Mitral regurgitation area (cm2 ) 6.9 4.3 4.7 3.8 7.2 6.2 4.6 2.5 5.0 4.2
P < 0.05, RVOT vs RVA at 6 months.
P < 0.05, RVOT vs RVA at 9 months.
P < 0.05, RVOT vs RVA at 6 vs 9 months (paired cross-over analysis).
P < 0.05, Dual-site vs RVA.
P < 0.05, Dual-site vs RVOT.
QOL = quality of life; RVA = right ventricular apex; RVOT = right ventricular outflow tract.

Discussion
Compared with normal intrinsic conduction through the
His-Purkinje system, pacing from the RV is associated with
abnormal electrical activation and contraction sequence,
systolic and diastolic dysfunction, perfusion mismatch, in-
creased energy expenditure, and histologic abnormalities.1-6
To date, whether an optimal RV site(s) for long-term perma-
nent pacing exists has not been determined based on the small,
single-center clinical studies available. The present study is
the first multicenter, prospective, randomized trial to com-
pare alternative RV pacing sites with RVA pacing in a large
group of patients with CHF. In the ROVA trial, no consistent
differences in clinical outcomes or functional assessments fa-
voring either RVOT or dual-site (RVOT+RVA) pacing over
RVA pacing were found in patients with NYHA class II or
III CHF, LV systolic dysfunction, and chronic AF. Although
RVOT and dual-site RV pacing significantly shortened QRS
duration compared with RVA pacing, quality of life, func-
tional class, exercise capacity, and ventricular function were
not improved after 3 months of pacing.
RV Paced QRS Duration
By shortening the paced QRS duration, alternative RV pac-
ing sites may more closely simulate the normal cardiac elec-
trical activation time and sequence.1,2,4 Normalization of the
paced QRS width is thought to be critical to the maintenance
of cardiac performance that potentially might be provided by
non-RV apical pacing sites, such as RVOT, RV septum, or
dual-site RV.2,12 Schwaab et al.12 demonstrated that synchro-
nization of LV contraction and increased systolic function
were significantly correlated with reduction in QRS duration
during optimized RV pacing. However, in most previous stud-
ies including that of Schwaab et al., the paced QRS duration
remained wide during RVOT or RV septal pacing and was not
significantly different from RVA pacing.7,10-12 Furthermore,
Schwaab et al.12 carefully localized the optimal RV pacing
site using detailed mapping and found that the paced QRS
duration and not anatomic RV lead location (septal vs api-
cal) was correlated inversely with LVEF. In the present study,
RVOT and dual-site RV pacing significantly shortened paced
QRS duration by about 15 and 30 ms, respectively, compared
with RVA pacing. These changes in QRS duration are simi-
lar in magnitude to that produced by biventricular pacing.16
However, even though the paced QRS complex was narrower
during single-site RVOT or dual-site RV pacing, the duration
still remained prolonged (i.e., >120 ms) with mean QRS du-
rations ranging from 149 to 164 ms. Right ventricular pacing
will not normalize QRS duration (i.e., <120 ms) unless per-
manent His-bundle pacing can be successfully achieved.15
Benefits of Alternative RV Pacing Sites
Similar to the present study, prior studies have not demon-
strated consistent clinical benefits of RVOT or dual-site RV
pacing over RVA pacing during acute studies or after long-
term evaluation. In one nonrandomized, nonblinded study,
cardiac output measured at implant was higher with RVOT
free wall than RVA pacing.7 However, at least three other
acute studies in patients with CHF and LV systolic dysfunc-
tion failed to show any significant differences in cardiac out-
put between RVOT or dual-site pacing and RVA pacing or in-
trinsic conduction.8-10 Utilizing a study design similar to the
ROVA trial, Victor et al.11 found no symptomatic or hemody-
namic improvement after 3 months of RVOT compared with
RVA pacing in 16 patients with chronic atrial tachyarrhyth-
mias, only 6 of whom had CHF or LVEF <40%. In contrast,
Mera et al.13 reported that in 10 patients with LV dysfunc-
tion, most of whom had CHF who underwent AV junction
 Stambler et al.
ablation for chronic AF, LVEF was higher after 2 months
of high septal RVOT than RVA pacing. More recently, Tse
et al.14 randomized 24 patients, none of whom had CHF or
LVEF <50%, to long-term RVOT or RVA pacing. Between
months 6 and 18 after initiation of pacing, LVEF declined
(55% 3% to 47% 3%) and myocardial perfusion defects
increased during RVA but not RVOT pacing.
In contrast to prior studies, the ROVA trial focused its
evaluation of RVOT versus RVA pacing only in patients with
CHF and LV systolic dysfunction. The study design permitted
a multicenter, randomized, blinded comparison of RV pac-
ing sites as well as cross-over between pacing sites, which
allowed alternative RV pacing sites to be compared in the
same patient. Importantly, randomization and comparison of
RV pacing sites did not begin until 3 months after implant.
This design likely minimized the confounding effects of AV
junction ablation and pacing and the potential for placebo ef-
fects. However, improvement in LVEF and NYHA class over
the first 3 months prior to pacing site randomization limited
the studys power to more fully assess the effects of alterna-
tive RV pacing sites in patients with severely depressed LV
function.
Quality of Life
Both physical function and mental well-being were sub-
stantially impaired in study patients with CHF, LV dysfunc-
tion, and chronic AF. The impairments in self-perceived QOL
were present at the baseline assessment 3 months after ini-
tiation of permanent ventricular pacing and were relatively
stable during follow-up. The subjective QOL impairments in
physical functioning were confirmed by the 6-minute walk
test, which demonstrated that patients had diminished ex-
ercise capacity. Although role-emotional and mental health
subscale scores were better during RVOT than RVA pacing
at 6 months and in the cross-over analysis, respectively, there
were no convincing QOL benefits favoring RVOT or dual-site
RV over RVA pacing.
Study Limitations
Potential limitations in the study design may have affected
our results. Beneficial or deleterious effects of longer pacing
durations (i.e., > 3 months) from alternative RV sites cannot
be addressed by this study. The pacing duration was deter-
mined in part by the cross-over study design and the expecta-
tion of relatively high mortality in the population. Although
study participants but not investigators were blinded to ran-
domization (RVA vs RVOT), investigator bias is unlikely.
Pacing site cross-over simply required pacemaker reprogram-
ming, but only one patient was withdrawn because of a per-
ceived benefit of one pacing site over the other. During the
dual-site RV substudy, patients were not blinded to the pro-
grammed pacing mode. However, during all study phases,
a core laboratory blinded to the RV pacing site interpreted
the echocardiograms. The SF-36 and Minnesota Living with
Heart Failure questionnaires are standardized and validated
instruments but may not have been adequate to detect subtle
changes in QOL. Although minimally appropriate treatment
effects for interventions based on QOL are not clear, changes
on the order of half of a SD unit of an SF-36 subscale are
considered significant and moderate in size.19 The ROVA
trial design postulated that an even smaller change in our
study population would be clinically meaningful (i.e., 10%
Right Ventricular Pacing Site in Heart Failure 1185
improvement in paired SF-36 scores). Because the present
study only evaluated dual-site pacing with a 31-ms RVOT
to RVA intraventricular delay, potential benefits of simulta-
neous dual-site RV pacing cannot be excluded. Finally, this
studys findings may not apply to other pacemaker popula-
tions, such as those without CHF or LV dysfunction and those
undergoing dual-chamber or biventricular pacing.
Conclusion
In patients with CHF, LV dysfunction and chronic AF un-
dergoing permanent pacing, RVOT and dual-site RV pacing
shorten but do not normalize paced QRS duration and do not
consistently improve QOL or other clinical outcomes after 3
months as compared with RVA pacing.
Appendix
Additional ROVA investigators included the following:
Henry Hsia, Temple University, Philadelphia, PA; Roger
Freedman, University of Utah, Salt Lake City, UT; Steven
Greenberg, St. Francis Hospital, Roslyn, NY; Arnold Green-
spon, Thomas Jefferson University, Philadelphia, PA; Bruce
Lerman, Cornell Medical Center, New York, NY; James Mar-
tin, University of Iowa, Iowa City, IA; John McKenzie, III,
Glendale Memorial Hospital, Glendale, CA; Foad Moazez,
Sunrise Hospital, Las Vegas, NV; John Mounsey, University
of Virginia, Charlottesville, VA; Prasad Palakurthy, Mercy
Hospital, Des Moines, IA; Michael Rome, Cardiac Study
Center, Tacoma, WA; Russell Reeves, Sorra Research Cen-
ter, Birmingham, AL; Andrea Russo, Presbyterian Medical
Center, Philadelphia, PA; and Fania Samuels, Hahnemann
University, Philadelphia, PA.
Acknowledgments: The authors gratefully thank Paul Levine, M.D., for his
support of the ROVA trial, review of the chest x-ray films, and comments on
the manuscript.
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