Ambulatory esophageal pH monitoring by using a wireless system: A pilot study in Taiwan

Abstract

A new wireless esophageal pH monitoring device, the Bravo system, had been tested in the US with favorable results over conventional systems. However, its clinical application in eastern countries remains limited. The aim of the study was to assess the efficacy of the Bravo system in an Asian population, and compare it with the western results.
Thirty consecutive patients with clinically evident gastroesophageal reflux disease underwent esophageal pH monitoring by using the Bravo system. The Bravo capsule capable of measuring and transmitting pH data was introduced into the squamocolumnar junction and fixed on the esophageal mucosa through a locking pin. All patients were instructed to carry the receiver for a 48-hour study.
Twenty-nine (97%) of the 30 patients were successfully tested. In most cases (26/30, 87%) the capsules were placed without conscious sedation. All patients had successful capsule placement; however, two of them had failed the initial capsule attachment and required a second capsule. All patients had successful 24-hour recordings (30/30, 100%), while the successful 48-hour recording rate was 97% (29/30). A minor mucosal injury caused by inadvertent capsule extraction was the only complication (1/30, 3.3%).
Compared to the western experience, the new wireless pH monitoring system achieved a comparable attaching rate and recording efficacy. Potential complication was rare and self-limited.

Full text

Express Communication - 04358
INTRODUCTION
Gastroesophageal reflux disease (GERD) is one of
the most common disorders of the adult population.
It was estimated that up to 11% of the general pop-
ulation experience heartburn on a daily basis (1).
Ambulatory esophageal pH monitoring that quan-
tifies esophageal acid exposure is the standard for
establishing pathologic reflux, and has emerged as an
invaluable diagnostic tool in a substantial proportion of
patients with different manifestations of GERD (2).
The conventional system requires a transnasal pH
probe placed at 5cm above the manometrically deter-
mined lower esophageal sphincter and thus several
drawbacks ensue. The transnasal wire left in place dur-
ing test period causes discomfort, social embarrass-
ment, and reduce the willingness to be tested. Fur-
thermore, poor tolerability to the nasal wire may cause
modifications in diet and activity, which result in false-
negative studies (3). A wireless system is therefore
desirable.
A newly developed catheter-free esophageal pH-
metry, known as the BRAVOTM pH monitoring system
(Medtronic Inc., Skovlunde, Denmark), has recently
been approved by the United States Food and Drug
Administration (4). The BravoTM system uses a small
capsule attached on the esophageal mucosa as a pH
probe, which transmits the pH data to a small receiver
that the patient carries. Several studies of early clinical
experiences have been reported since 2001 (4-9). These
early reports had demonstrated a high success rate and
low risk of complication. Compared to conventional
catheter-based systems, the new system had achieved
comparable test efficacy and greater patient tolerabili-
ty (4). However, similar favorable results using the
BravoTM system had not been approved in the Asian
population.
A trend of increasing prevalence of GERD in Asian
countries has recently been noted, which is thought to
be related to western diet, obesity, increasing elderly
population, and possibly previous underestimation (10-
13). Application of ambulatory pH monitoring becomes
more crucial for the differentiation among the hetero-
geneous GERD patients in these areas. The present
study is a prospective collection of GERD patients
undergoing the BravoTM system in a major medical
center in Taiwan. By comparison to the western expe-
rience, this study is intended to verify the applicability
in a Chinese population.
METHODOLOGY
Thirty patients with manifestations associated
with GERD were consecutively enrolled from Decem-
1586
Ambulatory Esophageal pH Monitoring
by Using a Wireless System:
A Pilot Study in Taiwan
Chia-Hung Tu MD, Yi-Chia Lee MD, Hsiu-Po Wang MD1
, Ming-Shiang Wu MD, PhD
Han-Mo Chiu MD, Jaw-Town Lin MD, PhD
Department of Internal Medicine and 1Department of Emergency Medicine, College of Medicine
National Taiwan University, Taipei, Taiwan
Corresponding Author: Jaw-Town Lin MD, Department of Internal Medicine
National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan
Tel: +886 2 23123456, ext. 5695, Fax: +886 2 2394789, E-mail: jawtown@ha.mc.ntu.edu.tw
ABSTRACT
Background/Aims: A new wireless esophageal pH
monitoring device, the BravoTM system, had been
tested in the US with favorable results over conven-
tional systems. However, its clinical application in
eastern countries remained limited.
The aim of the study was to assess the efficacy of the
BravoTM system in an Asian population, and com-
pare with the western results.
Methodology: Thirty consecutive patients with
clinically evident gastroesophageal reflux disease
underwent esophageal pH monitoring by using the
Bravo TM system.
The BravoTM capsule capable of measuring and
transmitting pH data was introduced into the
squamocolumnar junction and fixed on the
esophageal mucosa through a locking pin. All
patients were instructed to carry the receiver for a
48-hour study.
Results: Twenty-nine (97%) of the 30 patients were
successfully tested. In most cases (26/30, 87%) the
capsules were placed without conscious sedation. All
patients had successful capsule placement; however,
two of them had failed the initial capsule attachment
and required a second capsule. All patients had suc-
cessful 24-hour recordings (30/30, 100%), while the
successful 48-hour recording rate was 97% (29/30). A
minor mucosal injury caused by inadvertent capsule
extraction was the only complication (1/30, 3.3%).
Conclusions: Compared to the western experience,
the new wireless pH monitoring system achieved a
comparable attaching rate and recording efficacy.
Potential complication was rare and self-limited.
Hepato-Gastroenterology 2004; 51:1586-1589
© H.G.E. Update Medical Publishing S.A., Athens-Stuttgart
KEY WORDS:
Ambulatory pH
monitoring;
Gastroesophageal
reflux disease;
Wireless system
ABBREVIATIONS:
Gastroesophageal
Reflux Disease
(GERD); Non-
Erosive Reflux
Disease (NERD)

ber 2003 to April 2004. All patients were ambulatory,
without significant medical illness, and with no history
of prior upper digestive tract surgery. Patients with
contraindications for upper gastrointestinal endoscopy
(i.e. upper airway disease, incooperability), esophageal
varices, bleeding diathesis, pacemakers and implant-
able cardiac defibrillator were excluded. A period of at
least 7 days devoid of proton-pump inhibitor and hista-
mine-2 receptor blocker and a 24-hour period devoid of
antacids were required before the test. Informed con-
sent was obtained from each patient and the study was
approved by the NTUH Ethics Committee.
After an overnight fast, subjects were placed in the
left lateral decubitus position. Endoscopy was per-
formed by a same group of experienced endoscopists,
who had been trained at the National Taiwan Univer-
sity Hospital. The stomach and duodenum were
inspected as well to exclude possible lesion.
The distal portion of the esophagus was evaluated
carefully to determine the presence of mucosal injury.
The definition of reflux esophagitis rested on the
demonstration of diffuse or streaking erythema,
mucosal friability, erosions, and ulcers, i.e. mucosal
breaks. The severity of GERD was assessed according
to the Los Angeles (LA) classification with standard
comparator photos (14). The location of the esophageal
squamocolumnar junction was recorded in centimeters
distal from the incisors.
Prior to the BravoTM procedure, all subjects had
nothing per os for at least 8 hours. Endoscopy was been
performed either simultaneously or within one month
before the pH monitoring. Conscious sedation with
titrated doses of midazolam and alfentanil was used if
requested by the patients. The delivery system was
introduced orally with the patient in the same left lat-
eral decubitus position assumed during endoscopy.
The BravoTM pH monitoring system consisted of a
pH capsule and a delivery system. The pH capsule,
measuring 6.3x5.5x26mm, was assembled on one end
of an 80-cm-long application catheter, and contained
sensor electrodes, a transmitter, and an internal bat-
tery. The other end of the catheter was the handle. The
suction chamber was a 4-mm-deep well in the capsule,
connecting to the vacuum line through the catheter
(Figure l A). With the vacuum off, the whole unit was
advanced through the mouth, until the capsule had
attached the esophageal wall at 6cm proximal to the
squamocolumnar junction (Figure 1B). After proper-
ly locating the capsule, the vacuum was turned on with
a source of at least 510 mmHg for 30 seconds. This
allowed the esophageal tissue to fill in the suction
chamber in the capsule. A locking pin was advanced
and driven through the captured esophageal tissue by
depressing an activating button on the handle, which
securely attached the capsule to the esophagus. A
plunger on the handle was rotated to release the cap-
sule from the catheter, and the implantation was com-
pleted by removing the delivery system. Once the cap-
sule had been placed in the esophagus (Figure 1C), it
began transmitting pH data via radiofrequency to a
pager-sized receiver worn. Patients were allowed to
maintain their regular diet and routine activities dur-
ing pH testing. They were instructed to take a proton
pump inhibitor (esomeprazole, NexiumTM
, 40mg) at 24
hours after placement of capsules according to the
study protocol. At 48 hours, the patients returned the
receivers and the data were uploaded to a pH software
(Figure 2). The capsule was expected to dislodge with-
in a few days and a chest film would be performed
when indicated (Figure 1D).
RESULTS
Twenty male and 10 female subjects were enrolled
in the study, aged from 29 to 83 years (57.6±14.3
Application of BravoTM System in Taiwan Hepato-Gastroenterology 51 (2004) 1587
FIGURE 1 The BravoTM esophageal pH-monitoring device. The capsule on the tip of the
application catheter before use. Close to it is a pager-sized receiver with antenna (A).
Esophagoscopic examination of a sedated patient while the capsule was suctioning on the
lower esophageal mucosa before it was released from the application catheter (B).
The capsule had successfully attached on the esophageal mucosa (C). A chest X-ray taken
6 days later showed the capsule (arrowheads) still at the previous location. However,
spontaneous dislodgement happened on the 7th day (D).
FIGURE 2 Examples of pH tracing in one patient with documented pathological reflux (upper)
and another patient with functional heartburn (lower).

years). The demographic data are shown in Table 1.
Twenty-four patients with documented GERD were
evaluated for drug effectiveness before surgery. Six
patients showed typical heartburn but their endoscop-
ic findings were normal, i.e. the non-erosive reflux dis-
ease (NERD) patients. The mean duration of place-
ment procedures (from calibration of pH capsule to
beginning of pH recording) was 15.2 minutes (range
from 10.5 minutes to 29.0 minutes). There were 4
patients that required conscious sedation, 16 patients
received simultaneous examination of endoscopy and
BravoTM procedure. All of the sedated patients received
the simultaneous tests.
The successful attaching rate of BravoTM capsule in
one session was 100% (30/30). Two patients required 2
capsules in one session. The only one procedure-relat-
ed complication was mucosal abrasion caused by inad-
vertent and forceful removal of the mucosa-fixed cap-
sule which failed to disconnect from the application
catheter. An esophagoscope was immediately inserted
to check for possible damage. Minor hemorrhage
ensued but stopped spontaneously a few minutes later
(Figure 3).
The failure of disconnection was considered as a
result of inappropriate and forceful lifting of the
plunger. A replacement capsule was subsequently
placed uneventfully. In another patient with grade 4
erosive esophagitis who had recently undergone
bougienation for lower esophageal stricture, the cap-
sule failed to adhere to the esophageal surface in the
initial attempt at the recommended location.
Although disconnected, the capsule was dragged
out by withdrawing the application catheter.
Examining the capsule revealed that the locking pin
which had been advanced across the suction chamber
might had not caught on any esophageal tissue probably
due to fibrosis. A second attempt with a new capsule at
8cm above the squamocolumnar junction soon after the
first one was successful without difficulty.
Successful recording of pH data in the first 24
hours was achieved in all cases, acquiring a mean dura-
tion of 23 hours and 15 minutes (range: 18 hours and
33 minutes to 24 hours, SD: l hour and 4 minutes) for
analysis. In most cases, there were only a few minutes
missing from recording. The mean duration of success-
ful acquisition in the second 24 hours was somewhat
shorter (mean: 22 hours and 54 minutes, SD: 1 hour
and 4 minutes, range: 5 hours and 9 minutes to 23
hours and 59 minutes), largely due to the shortest
recording of only 5 hours and 9 minutes. In that case
the patient forgot to carry the receiver when he was
out for personal reasons. There were no problems asso-
ciated with uploading and analysis of pH data. There-
fore, the overall successful one-day and two-day record-
ing rates were 100% and 97%, respectively.
DISCUSSION
This study shows the good efficacy of the wireless
esophageal pH monitoring system in clinical practice.
Ninety-seven percent of the thirty patients requiring
pH-metry had been successfully tested.
The test had gained a high level of patient satisfac-
tion and was associated with very low risk of complica-
tion. Although few similar reports using the BravoTM
system had been published from the United States
(4,5,7-9), this is the earliest clinical experience for the
Asian population. Ward et al. reported a capsule
1588 Hepato-Gastroenterology 51 (2004) C-H Tu, Y-C Lee, H-P Wang, et al.
TABLE 1 Demographic Data of the Patients Undergoing
Ambulatory pH Monitoring with the BravoTM System
Mean age (years) 57.6 (SD: 14.3)
Male : Female 20 : 10
Diagnosis
Erosive esophagitis
Grade A
*4 (13.3%)
Grade B 3 (10.0%)
Grade C 5 (16.7%)
Grade D 4 (13.3%)
Non-erosive reflux esophagitis 14 (46.7%)
*Los Angeles classification (14).
FIGURE 3 Esophageal mucosal abrasion with hemorrhage (arrowhead) caused by
abrupt extraction a BravoTM capsule which was still connected to the introduction
catheter (A). The bleeding stopped spontaneously after saline irrigation (B).
TABLE 2 Literature Reviews of BravoTM System Application
Successful Successful
capsule capsule Successful Successful
placement in placement in recording recording
Author Country Number Sedation first attempt one session for 24 hours for 48 hours
Streets CG, 2001 (8) USA 7NA*NA 7 (100%) NA 7 (100%)
Lin E, 2003 (7) USA 245 112 (46%) NA 238 (97%) NA 238 (97%)
Pandolfino JE, 2003 (4) USA 85 62 (73%) 83 (98%) 85 (100%) 82 (96%) 76 (89%)
Ward EM, 2004 (5) USA 60 60 (100%) 53 (88%) 59 (98%) NA 58 (97%)†
Bothwell M, 2004 (9) ‡USA 25 25 (100%) NA NA NA NA
Present study, 2004 Taiwan 30 4 (13%) 28 (93%) 30 (100%) 30 (100%) 29 (97%)
*NA: not available; †Thirty of the 58 studies were 24 hours; ‡Pediatric patients.

attachment failure and another failure in data
retrieval from the receiver in his total of 60 cases (5).
Two of our cases had attachment failure in the first
attempt, but a second attempt had succeeded in both
cases. Pandolfino et al. had failed 7 capsule attach-
ments in his first attempt, and had succeeded at the
second attempt in 6 of them (Table 2). According to
his description, attachment failure seemed unrelated
to inexperience in skills (4). The high rate of successful
testing (97%) in our study is comparable to the four
reported series in the US, range from 89% to 100%
(Table 2). In those studies, the causes of test failure
were well described. Lin et al. reported 7 (2.9%) pre-
mature capsule detachments (i.e. the capsule dropped
into the stomach before completion of 48-hour record-
ing) in 245 tests (7). Pandolfino et al. described 3 (3.5%)
premature detachments and 6 (7.1%) poor data recep-
tions in 85 cases (4). These constitute the majority of
the causes of reported test failures (Table 2). The only
one test failure in our study was a patient who failed to
keep the receiver with him during the second 24-hour
period. Though rarely reported, such occurrence is
always possible and unique for a wireless system.
Low complication rate is another similarity to the
previous reports from the US. The only complication in
this study probably originated from procedural errors
of the initial cases, which should be avoidable in more
experienced hands. A similar complication had been
reported in a pediatric patient under general anesthe-
sia; however, it is not clear whether there was a con-
tribution of technical error or introducer dysfunction
(9). Lin et al. reported 2 cases (0.8%) of retained cap-
sule (>14 days) requiring endoscopic extraction out of
his 238 cases (7). Pandolfino et al. also reported a case
(1.2%) of retained capsule (>15 days) in their 85 study
cases; however, two additional cases required endo-
scopic extraction because of intolerable discomfort
associated with the capsules (4). The longest duration
of retained capsule was 7 days in our study, and no
patient requested endoscopic removal.
An apparent difference from previous reports in
the US is that sedation was infrequently used in this
study. Only four of the thirty patients (13%) under-
went BravoTM capsule placement under conscious
sedation, whereas 46% to 100% of patients in three
larger series in the US were sedated (Table 2) (4,5,7).
This might be another example of difference in accept-
ability and availability of conscious sedation (15,16).
The four sedated procedures were the first, sixth,
tenth, and eleventh cases in this study, performed in
the early phase with this new device. As more unse-
dated procedures were successfully performed, we pre-
ferred non-sedation for the later cases because the cap-
sule attaching efficacy was good and a second look
esophagoscopy was considered unnecessary. In case of
failing attachment, the capsule could be brought out
with the introducer even with an advanced locking pin.
In conclusion, in the present study we have demon-
strated the highly successful rate and safety of this new
wireless ambulatory esophageal pH monitoring system
in an Asian population. As the prevalence of gastroe-
sophageal reflux disease in Oriental populations had
increased substantially to match that of the western
countries, the BravoTM system may provide an impor-
tant diagnostic alternative. Further studies are neces-
sary to analyze the cost-effectiveness and the benefit
from a prolonged period of recording.
ACKNOWLEDGEMENTS
The study was supported by the grants from
National Taiwan University Hospital and Taipei Insti-
tute of Pathology.
Application of BravoTM System in Taiwan Hepato-Gastroenterology 51 (2004) 1589
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