ORIGINAL ARTICLE
Reflux Symptoms in Gastroparesis
Correlation With Gastroparesis Symptoms, Gastric Emptying,
and Esophageal Function Testing
Asad Jehangir, MD and Henry P. Parkman, MD
Goal: The goal of this study was to determine the relationship of
reflux with gastroparesis (Gp), looking both at symptoms and
objective testing.
Background: Gp patients often experience gastroesophageal reflux
symptoms. How the severity of reflux correlates with the severity of
Gp is not known.
Study: Patients referred to our academic center with symptoms of
Gp completed the Patient Assessment of Upper Gastrointestinal
Symptoms, Hospital Anxiety and Depression Scale, and Patient
Health Questionnaire (PHQ)-15. They underwent 4-hour gastric
emptying scintigraphy; and, if indicated, high-resolution esophageal
manometry and esophageal pH impedance (EpHI).
Results: Of 755 patients from July 2013 to May 2018, 432 had Gp with
Gastroparesis Cardinal Symptom Index (GCSI) total score of 3.2 ± 0.1
(mean ± SEM) and heartburn/regurgitation subscore of 2.0 ± 0.1.
A fourth (27.1%) of all Gp patients had moderate to very severe
heartburn/regurgitation symptoms. Heartburn/regurgitation subscore
had strong correlation with GSCI total score (r = 0.56, P < 0.01), and
weak correlation with 4-hour gastric retention (r = 0.11, P = 0.02). In
total, 103 Gp patients underwent EpHI monitoring; time esophageal
pH < 4 had no correlation with heartburn/regurgitation subscore.
Less than half (41.7%) of the patients undergoing EpHI had gastro-
esophageal reflux disease by EpHI. Gp patients with gastroesophageal
reflux disease had more severe 4-hour gastric retention, and more
frequently had decreased lower esophageal sphincter resting pressure
and esophageal motility disorders. Heartburn/regurgitation subscore
had moderate correlation with somatic symptoms, and weak correla-
tions with anxiety and depression.
Conclusions: The severity of reflux symptoms in Gp has strong
correlation with GCSI total score, weak correlation with gastric
retention, and no correlation with esophageal pH monitoring.
Key Words: gastroparesis, GERD, gastric emptying, esophageal
impedance, high-resolution manometry
(J Clin Gastroenterol 2019;00:000–000)
Received for publication October 29, 2018; accepted January 10, 2019.
From the Section of Gastroenterology, Department of Medicine,
Temple University School of Medicine, Philadelphia, PA.
A.J.: collected and analyzed the data, did literature review, and wrote the
manuscript. H.P.P.: planned the study, evaluated patients included in
the study, did literature review, and helped write the manuscript.
An abstract of this study was presented at the American College of
Gastroenterology (ACG) Annual Scientific Meeting in October 2018
in Philadelphia, PA and was nominated as the Presidential Poster.
The authors declare that they have nothing to disclose.
Address correspondence to: Asad Jehangir, MD, Section of Gastro-
enterology, Department of Medicine, Temple University School of
Medicine, 3401 North Broad Street, Philadelphia, PA 19140
(e-mail: asadjehangir@gmail.com).
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/MCG.0000000000001190
J Clin Gastroenterol  Volume 00, Number 00, ’’ 2019
Copyright r 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
This paper can be cited using the date of access and the unique DOI number which can be found in the footnotes.
G astroparesis (Gp), a disorder with delayed gastric emp-
tying without mechanical obstruction, affects about 2%
of the adult population.1,2 Gp patients can experience a variety
of gastrointestinal (GI) symptoms that can include nausea,
vomiting, early satiety, postprandial fullness, and abdominal
pain. There is a poor correlation between the typical symptoms
of Gp and physiological testing of gastric emptying—hence the
presence of these symptoms do not predict the underlying
pathophysiology.3 In addition to the typical symptoms of Gp,
the patients with Gp can also experience gastroesophageal
reflux symptoms like heartburn, regurgitation, and bitter taste
in the mouth. Gp patients, particularly those with severe reflux
symptoms, often report lack of improvement of their typical
symptoms of Gp on long-term follow-up despite standard of
care treatments for Gp.4
The relationship of gastroesophageal reflux disease
(GERD) to Gp is complex and not well understood. Theo-
retically, delayed gastric emptying in Gp increases the volume
of gastric contents, that can subsequently cause regurgitation
of stomach contents into the esophagus, presumably
by causing proximal stomach distension and lowering the
lower esophageal sphincter (LES) pressure.5 In a study by
McCallum et al,6 41% of the patients with gastroesophageal
reflux had delayed gastric emptying, with recent literature
using 4-hour gastric emptying scintigraphy (GES) suggesting
an overlap in 8% to 20% of patients.5 Several pediatric studies
on patients with gastroesophageal reflux have shown a pos-
itive correlation between gastroesophageal reflux symptoms
and delay in gastric emptying7–12; however, subsequent
studies did not show such association.13–15 In patients with
refractory GERD, screening for delayed gastric emptying is
recommended, as treatment of Gp with prokinetics may
improve reflux symptoms as well.16 Surgical treatments for
refractory GERD, such as fundoplication, may include
pyloromyotomy if delayed gastric emptying is present.17
Despite the known association of Gp with gastroesophageal
reflux symptoms, studies in patients with Gp to examine the
correlation of the severity of typical symptoms of Gp with the
severity of reflux symptoms are lacking. The prevalence of
GERD in Gp patients by ambulatory esophageal pH monitoring
is not known. We also have limited knowledge of the correlation
of reflux symptom severity to the number of reflux events on
ambulatory pH testing in Gp patients. Nearly two thirds of Gp
patients have abnormalities on esophageal high-resolution
esophageal manometry (HREM), suggesting that Gp patients
with GERD may also have concomitant esophageal motility
disorders.18 Among patients with symptoms of GERD, those
with normal 24-hour esophageal pH impedance (EpHI) testing
more often have symptoms of anxiety when compared with
patients who meet the criteria for GERD.19 GERD patients with
persistent reflux symptoms also frequently report symptoms of
somatization.20,21 The prevalence of anxiety, depression, and
www.jcge.com |1
Jehangir and Parkman
somatization among Gp patients with GERD symptoms
undergoing EpHI is not known.
The primary aim of this study was to determine the
relationship of the severity of Gp with the severity of reflux,
looking both at symptoms and objective testing for Gp and
GERD. Secondary aims of the study were to: (1) determine
the prevalence of esophageal motility disorders in Gp
patients with reflux symptoms using esophageal manometry
testing; (2) determine the presence of anxiety, depression,
and somatization in Gp patients with reflux symptoms
undergoing ambulatory pH monitoring.
MATERIALS AND METHODS
Patients referred to Temple University Hospital (TUH)
Motility Center with symptoms suggestive of Gp from July
2013 to May 2018 were studied. This study was reviewed and
approved by the TUH Institutional Review Board. Subjects
were recruited at the end of their regularly scheduled appoint-
ments after obtaining informed consent. Inclusion criteria were
the following: (1) adults aged 18 to 80 years old; (2) symptoms
suggestive of Gp with delayed gastric emptying. Exclusion cri-
teria included: (1) patients with symptoms of Gp but with
normal or rapid gastric emptying; (2) patients with achalasia or
esophagogastric junction obstruction, as GES and EpHI results
may not be reliable in these patients.
On their initial evaluation, patients were asked to fill
out questionnaires about their clinical condition. These ques-
tionnaires contained the following: Patient Assessment of Upper
Gastrointestinal Symptoms (PAGI-SYM), Hospital Anxiety
and Depression Scale (HADS), Patient Health Questionnaire
(PHQ-15), and questionnaire on demographics, past medical,
and medication history. Patients underwent 4-hour GES
scheduled within 2 weeks of their initial evaluation, if had not
already recently been performed.22 A subgroup of all patients
also underwent EpHI with high-resolution esophageal man-
ometry with impedance (HREMI) within 2 weeks of their initial
evaluation. The decision to perform EpHI with HERMI was
made by the physician assessing the patients, if clinically indi-
cated. The most common indications for EpHI included: (1)
evaluation of patients with symptoms of GERD refractory to
proton-pump inhibitors (PPIs); and (2) assessment of adequacy
of acid control in patients with complicated GERD.23
The patients were categorized as idiopathic Gp if they
had symptomatic delayed gastric emptying with no primary
underlying abnormality predisposing to Gp.1 Onset of Gp
symptoms in patients with prior history of diabetes, with
delayed gastric emptying on GES, were classified as diabetic
Gp. The patients with histories of surgeries that can sub-
sequently cause delayed gastric emptying (eg, Nissen
fundoplication, bariatric surgery, vagotomy etc.) who
postsurgically developed symptoms of Gp, with GES con-
firming delayed gastric emptying, were classified as post-
surgical gastroparesis (PSGp). The patients who had other
underlying etiologies for Gp-like neurological disorders (eg,
Parkinson disease, multiple sclerosis), autoimmune, con-
nective tissue, and collagen vascular disorders (eg, systemic
lupus erythematosus, scleroderma, Sjögren syndrome,
Ehlers-Danlos syndrome), or eating disorders (eg, anorexia,
bulimia) were grouped under atypical gastroparesis (AGp).1
Questionnaires
PAGI-SYM
This validated questionnaire is for GI symptoms of Gp,
functional dyspepsia, and GERD.24 Gastroparesis Cardinal
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J Clin Gastroenterol  Volume 00, Number 00, ’’ 2019
Symptom Index (GCSI) consists of 3 subscales of PAGI-
SYM (nausea/vomiting, postprandial fullness/early satiety
and bloating) to measure important symptoms of Gp.25
PAGI-SYM has 3 additional subscales including upper
abdominal pain subscale, lower abdominal pain subscale,
and heartburn/regurgitation subscale.
HADS
The HADS has 2 subscales to screen and quantify
depression and anxiety.26 HADS-Depression subscale has been
shown to have sensitivity and specificity of 77% and 81%,
respectively, to screen for depression.27 HADS-Anxiety subscale
also has a similar sensitivity (70%) and specificity (79%) to
identify anxiety.27
PHQ-15
PHQ-15 is a 15-item screening tool for somatization in
clinical practice and research.28 In patients with GI diseases,
a modified Patient Health Questionnaire-12 (PHQ-12) has
been used in the prior studies, that excludes 3 questions on
GI symptoms.29,30
Questionnaires on Demographics, Past Medical,
and Medication History
This questionnaire asked patients to report information
such as age, gender, race/ethnicity, height, weight, past medical
history (including history of anxiety and/or depression), and
medication history including PPIs and histamine-2 (H2) blockers.
GES
GES was performed using a low-fat, egg white meal with
imaging over 4 hours after meal ingestion.22 Patients were
instructed to stop medications that could affect GI motility (eg,
prokinetics and opioid analgesics) for 48 hours before the study
and to come to the Nuclear Medicine Section in the morning
after fasting overnight, that is, an 8-hour fast. Diabetics have their
glucose checked at the beginning of the study, with appropriate
treatment measures being taken if hypoglycemia (< 70 mg/dL) or
hyperglycemia ( > 250 mg/dL) is detected. GES is performed
using a standard low-fat, eggbeaters meal to measure solid
emptying. The meal consists of the equivalent of 2 large eggs
radiolabeled with 0.5-1 mCi Tc-99m sulfur colloid served with 2
pieces of white bread and jelly. Patients are given 120 mL water.
Following ingestion of the meal, imaging is performed at 0, 0.5,
1, 2, 3, and 4 hours with the patient standing upright for meas-
uring gastric emptying of Tc-labeled solids. Gastric emptying is
analyzed as percent of radioactivity retained in the stomach over
time using the geometric center of the decay-corrected anterior
and posterior gastric counts for each timepoint. Gastric retention
of Tc-99m > 60% at 2 hours and/or > 10% at 4 hours is con-
sidered delayed gastric emptying of solids.22
Esophageal Manometry
Patients arrived at the endoscopy unit on the morning of the
study after an 8-hour fast. Esophageal manometry was per-
formed according to the standard clinical protocol at TUH
Motility Lab using HREMI equipment (ManoScan, Medtronics
Inc.). The catheter was inserted via nasal intubation and
advanced into the stomach with the patient sitting upright. The
patient was then placed supine, positioning the catheter so that
upper esophageal sphincter (UES), LES and proximal stomach
were present on the computer monitor. After 5 minutes for body
temperature equilibration, a 30 seconds baseline landmark
recording was obtained. This was followed by 12 wet swallows
with 5 mL of room temperature saline given every 30 seconds.
J Clin Gastroenterol  Volume 00, Number 00, ’’ 2019
Twelve swallows were performed to help ensure at least 10
swallows available for analysis. The catheter was subsequently
removed, recording the pressures excorpus for subsequent ther-
mal calibration of the catheter. The studies were systematically
analyzed (ManoView software version 3, Medtronics Inc.) for
esophagogastric junction pressures at landmark (baseline pres-
sures without swallowing for 30 s) along with pressure profiles
during 12 wet saline swallows. The swallows were analyzed for
UES resting and residual pressures, LES resting and residual
pressures, distal esophageal contractile pressures, esophageal
contractile velocity, distal contractile integral (DCI), distal latency
(DL), and bolus clearance percentage. The HREMI tracings
were retrospectively reviewed to categorize them using the
Chicago Classification version 3.0.31 Esophageal pressure
topography plots facilitated visualization of the high-pressure
zones created by the LES and crural diaphragm. Isobaric
contour plots using a 20 mm Hg pressure threshold were used
to analyze the peristalsis parameters. When the esoph-
agogastric junction had a hiatal hernia (HH), the size of the
HH was the distance between the peak pressures of the LES
and the crural diaphragm at inspiration.
EpHI Monitoring
EpHI testing was performed after HREMI. After
topical nasal anesthesia, an esophageal pH probe (Medtronic
Inc., Shoreview, Minneapolis, MN) was placed so that the
distal pH probe was positioned 5 cm above the proximal
portion of the lower esophageal sphincter. The probe was
attached to an external electronic data recorder (Digitrapper
pH-Z, Medtronic Inc., Shoreview, Minneapolis, MN) for
continuous 24-hour esophageal pH monitoring. The probe
was removed the following day, and pH data were down-
loaded for analysis (AccuView Reflux Software version 6.0,
Medtronic Inc., Shoreview, Minneapolis, MN). Patients had
objective evidence of GERD if they had esophageal acid
(pH < 4) exposure time > 4.5%.32
Data Management and Statistical Analyses
A retrospective review of the questionnaires, GES, EpHI,
and HREMI was performed after compiling these in Micro-
soft Excel database. Analysis of variance was used for com-
parison of multiple groups, followed by the Student t test with
P-value adjusted with Bonferroni correction for multiple
comparisons. Mann Whitney U test was used to compare
symptoms recorded on ordinal scale. These results are
expressed as mean ± SE of mean. The χ2 test was used for
categorical data, with results expressed as percentages. The
Spearman correlation was used to determine the correlation as
weak (0.00 to 0.30), moderate (0.31 to 0.50), and strong (0.51
to 1.0). Unanswered questions were excluded from the
analyses.
RESULTS
Patients
Of 755 patients who completed GES from July 2013 to
May 2018, 445 had delayed gastric emptying (% retention at
2 h > 60% and/or % retention at 4 h > 10%; Table 1), 298 had
normal GES and 12 had rapid GES. Among patients with
delayed gastric emptying, we excluded 13 patients who were
later diagnosed with esophagogastric outlet obstruction (n = 10)
or achalasia (n = 3) on HERMI. Of the remaining 432 patients
with Gp, most of the patients had delayed gastric emptying at
both 2- and 4 hours (n = 296) or delayed gastric emptying at
4 hours only (n = 121), whereas 15 patients had delayed gastric
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This paper can be cited using the date of access and the unique DOI number which can be found in the footnotes.
Reflux in Gastroparesis
emptying at 2 hours only. The patients with Gp included 230
with idiopathic gastroparesis (IGp), 119 with diabetic gastro-
paresis (DGp), 50 with AGp, and 33 with PSGp.
Questionnaires
PAGI-SYM
Using the PAGI-SYM subscales, symptom severity in Gp
patients included postprandial fullness/early satiety subscale
3.7 ± 0.1 (mean ± SEM), bloating subscale 3.2 ± 0.1, nausea/
vomiting subscale 2.7 ± 0.1, upper abdominal pain subscale
3.2 ± 0.1, lower abdominal pain subscale 2.5 ± 0.1, and heart-
burn/regurgitation subscale 2.0 ± 0.1. A fourth (27.1%) of all
Gp patients had moderate to very severe heartburn/regur-
gitation symptoms (heartburn/regurgitation subscore of ≥ 3).
GCSI total score averaged 3.2 ± 0.1.
Among subtypes of Gp, patients with DGp had a higher
severity of symptoms on nausea/vomiting subscale than IGp
(P < 0.001). Patients with AGp had more severe postprandial
fullness/early satiety subscore than IGp (P = 0.001) and DGp
(P < 0.001), as well as more severe upper abdominal pain sub-
score compared with IGp (P = 0.003) and DGp (P = 0.002).
Heartburn/regurgitation subscore were more severe in PSGp
(P < 0.001) and AGp (P < 0.001) patients, when compared with
IGp. PSGp and AGp also had a trend for more severe GCSI
total score.
A strong correlation was seen between heartburn/regur-
gitation subscore and GCSI total score (r = 0.57, P < 0.01).
There was a moderate correlation of heartburn/regurgitation
subscore to nausea/vomiting, postprandial fullness/early sati-
ety, bloating, upper abdominal pain, and lower abdominal
pain subscores (Table 2). Among subtypes of Gp, DGp
patients had the strongest correlation of heartburn/regur-
gitation subscore with GCSI total score and all PAGI-SYM
subscores, except postprandial fullness/early satiety subscore.
PSGp had a moderate correlation of heartburn/regurgitation
subscore with nausea/vomiting subscore, but no correlation
with other PAGI-SYM subscores, possibly due to small
sample size in this subgroup.
Questionnaires on Demographics, Past Medical,
and Medication History
The mean age of the patients with Gp was 43.3 ± 0.8 years
(Table 1). The patients with PSGp were older when compared
with the other subtypes of Gp (P < 0.001), whereas patients with
DGp were older when compared with IGp (P = 0.002). The
mean age of onset of Gp symptoms was 35.9 ± 0.8 years, and
mean duration of symptoms was 7.3 ± 0.5 years. PSGp and
DGp patients were older at the onset of Gp symptoms com-
pared with IGp and AGp. However, there were no differences
between the subtypes of Gp with respect to the duration of
symptoms. There was a female preponderance (82.9%) in
patients with Gp; the female preponderance was noted across all
subtypes of Gp, however, AGp were most likely to be females
(90%), whereas DGp were least likely (65.5%). Female Gp
patients had a higher GCSI total score than men (3.3 ± 0.1 vs.
2.8 ± 0.1, respectively; P < 0.01), without any difference in
heartburn/regurgitation subscale score (2.1 ± 0.0 vs. 1.9 ± 0.2,
respectively; P = 0.50). DGp patients had a higher body mass
index when compared with IGp (P < 0.001) and AGp
(P = 0.001). The majority of the patients who reported their race
were whites (84%), however only 71.6% of DGp were whites,
compared with a higher prevalence of whites in other subtypes
(86.8% to 92%; P < 0.001). A considerable minority of Gp
patients reported history of depression (19.4%) and anxiety
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Jehangir and Parkman J Clin Gastroenterol  Volume 00, Number 00, ’’ 2019

TABLE 1. Demographics, Medication Use, Symptom Severity on PAGI-SYM and GES Results in Gastroparesis Patients, and its Subtypes
Demographics, Medication
Use, Symptom Severity and
GES All Gp Patients (n = 432) IGp (n = 230) DGp (n = 119) PSGp (n = 33) AGp (n = 50) P
Age (y) 43.3 ± 0.8 40.7 ± 1.1 46.5 ± 1.4* 53.8 ± 2.4* 40.8 ± 2.3 < 0.01
Age Sx started (y) 35.9 ± 0.8 33.7 ± 1.2 39.7 ± 1.6* 44.3 ± 2.9* 31.0 ± 2.3 < 0.01
Duration of Sx (y) 7.1 ± 0.5 6.8 ± 0.8 6.4 ± 0.9 8.4 ± 1.7 9.6 ± 1.6 0.30
Female (%) 82.9 90.4 65.5† 81.8 90 < 0.01
BMI (kg/m2) 26.4 ± 0.4 24.8 ± 0.4 30.3 ± 1.1† 27.3 ± 1.2 24.5 ± 1.2 < 0.01
Race (% white)‡ 84 86.8 71.6† 87.8 92 < 0.01
PPI use (%) 63 57.8 74.8§ 69.7§ 54 0.01
Histamine-2 blocker use (%) 11.1 9.6 10.9 18.2 14 0.45
N/V subscale 2.7 ± 0.1 2.5 ± 0.1 3.0 ± 0.1∥ 2.7 ± 0.2 2.7 ± 0.2 0.01
PPF/ES subscale 3.7 ± 0.1 3.7 ± 0.1 3.5 ± 0.1 3.8 ± 0.2 4.2 ± 0.1¶ < 0.01
B subscale 3.2 ± 0.1 3.2 ± 0.1 3.1 ± 0.2 3.6 ± 0.3 3.4 ± 0.2 0.32
UAP subscale 3.2 ± 0.1 3.2 ± 0.1 3.1 ± 0.2 3.7 ± 0.2 3.8 ± 0.2¶ 0.01
LAP subscale 2.5 ± 0.1 2.4 ± 0.1 2.4 ± 0.2 2.8 ± 0.3 2.9 ± 0.2 0.16
HB/Rg subscale 2.0 ± 0.1 1.8 ± 0.1 2.2 ± 0.1 2.7 ± 0.2# 2.5 ± 0.2# < 0.01
GCSI total score 3.2 ± 0.1 3.1 ± 0.1 3.2 ± 0.1 3.4 ± 0.2 3.5 ± 0.2 0.11
GES: retention at 2 h (%) 66.2 ± 0.7 65 ± 0.9 67.5 ± 1.6 70.2 ± 3.5 66.1 ± 2.1 0.22
GES: retention at 4 h (%) 32.9 ± 1.0 29.5 ± 1.2 37.5 ± 2.0** 39.8 ± 4.0 33 ± 2.7 < 0.01
AGp included patients with eating disorders (n = 19), Ehlers-Danlos syndrome (10), reflex sympathetic dystrophy (10), Sjögren syndrome (6), Parkinson
disease (5), systemic lupus erythematosus (5), scleroderma (2), multiple Sclerosis (1), and myasthenia gravis (1). PSGp included patients with fundoplication
(n = 17), hiatal hernia repair (6), esophagectomy (3), duodenojejunostomy (2), esophageal repair (2), vagotomy pyloroplasty (2), and bariatric surgery (1). Results
expressed as mean ± SE of mean or percentages. P-value calculated using the χ2 test, Mann Whitney U test, and analysis of variance with Bonferroni correction
for multiple comparisons as appropriate. On PAGI-SYM, patients rate the severity of their gastrointestinal symptoms over the prior 2 weeks as none (0), very
mild (1), mild (2), moderate (3), severe (4), and very severe (5). GCSI total score is calculated as the average of N/V, PPF/ES, and B subscales.
*PSGp and DGp patients were older at presentation and onset of symptoms.
†DGp patients had a higher BMI and prevalence of nonwhites and males.
‡Of 419 patients who reported their race, 352 were whites.
§DGp and PSGp patients had a higher prevalence of PPI use.
∥DGp had more severe N/V than IGp.
¶AGp had more severe PPF/ES than IGp and DGp, as well as more severe UAP compared with IGp and DGp.
#HB/Rg symptoms were more severe in PSGp and AGp, when compared with IGp.
**DGp had more severe gastric retention at 4 hours compared with IGp.
Values in bold are statistically significant.
AGp indicates atypical gastroparesis; B, bloating; BMI, body mass index; DGp, diabetic gastroparesis; ES, early satiety; GCSI, Gastroparesis Cardinal
Symptom Index; GES, gastric emptying scintigraphy; Gp, gastroparesis; HB, heartburn; IGp, idiopathic gastroparesis; LAP, lower abdominal pain; N, nausea;
PAGI-SYM, patient assessment of upper gastrointestinal symptoms; PPF, postprandial fullness; PPI, proton-pump inhibitors; PSGp, postsurgical gastroparesis;
Rg, regurgitation; Sx, symptoms; UAP, upper abdominal pain; V, vomiting.

TABLE 2. Correlation Between the Severity of Symptoms on PAGI-SYM Heartburn/Regurgitation Subscale and N/V, Postprandial Fullness/
Early Satiety, B, UAP and LAP Subscales, as well as 2- and 4-Hour Gastric Retention on GES in Patients With Gastroparesis, and its Subtypes
N / V, Postprandial Fullness / Early Satiety,
B, UAP and LAP Subscales, and GES Gp (All Patients) IGp DGp PSGp AGp
N/V subscale r = 0.41 r = 0.37 r = 0.47 r = 0.38 r = 0.44
P < 0.01 P < 0.01 P < 0.01 P = 0.03 P < 0.01
Postprandial fullness/early satiety subscale r = 0.39 r = 0.38 r = 0.40 r = 0.22 r = 0.53
P < 0.01 P < 0.01 P < 0.01 P = 0.25 P < 0.01
B subscale r = 0.38 r = 0.35 r = 0.52 r = 0.16 r = 0.32
P < 0.01 P < 0.01 P < 0.01 P = 0.37 P = 0.02
UAP subscale r = 0.44 r = 0.38 r = 0.54 r = 0.29 r = 0.34
P < 0.01 P < 0.01 P < 0.01 P = 0.11 P = 0.02
LAP subscale r = 0.38 r = 0.29 r = 0.52 r = 0.28 r = 0.30
P < 0.01 P < 0.01 P < 0.01 P = 0.12 P = 0.04
GCSI total score r = 0.56 r = 0.54 r = 0.60 r = 0.35 r = 0.53
P < 0.01 P < 0.01 P < 0.01 P = 0.06 P < 0.01
GES: retention at 2 h r = 0.08 r = 0.07 r = 0.05 r = 0.07 r = 0.23
P = 0.12 P = 0.30 P = 0.62 P = 0.74 P = 0.13
GES: retention at 4 h r = 0.11 r = 0.05 r = 0.08 r = 0.14 r = 0.20
P = 0.02 P = 0.46 P = 0.38 P = 0.46 P = 0.16
Values in bold are statistically significant.
AGp indicates atypical gastroparesis; B, bloating; DGp, diabetic gastroparesis; GCSI, Gastroparesis Cardinal Symptom Index; GES, gastric emptying
scintigraphy; Gp, gastroparesis; IGp, idiopathic gastroparesis; LAP, lower abdominal pain; N, nausea; PAGI-SYM, patient assessment of upper gastrointestinal
symptoms; PSGp, postsurgical gastroparesis; UAP, upper abdominal pain; V, vomiting.

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J Clin Gastroenterol  Volume 00, Number 00, ’’ 2019 Reflux in Gastroparesis

TABLE 3. Demographics, Medication Use, Type of Gastroparesis, TABLE 4. Esophageal pH Impedance Results in Patients With
Symptom Severity, and GES Results in Gastroparesis Patients Gastroparesis Who Underwent 24-Hour pH Impedance Testing,
Undergoing 24-Hour pH Impedance Testing, Including Patients Including Patients Who Met Criteria for GERD and Patients Who
Who Met Criteria for GERD as well as Patients Who did not Meet did not Meet Criteria for GERD
Criteria for GERD on pH Impedance Testing
All Gp
Demographics, Patients Gp Gp
Medication Use, All Gp Patients Gp Gp Undergoing Patients Patients
Type of Undergoing pH Patients Patients pH Impedance With Without
Gastroparesis, Impedance With Without Testing GERD GERD
Symptom Severity, Testing GERD GERD pH Impendence (n = 103) (n = 43) (n = 60) P
and GES (n = 103) (n = 43)* (n = 60)* P
% time pH < 4 6.3 ± 0.8 12.9 ± 1.3 1.9 ± 0.2 < 0.01
Age (y) 43.4 ± 1.6 44.7 ± 2.6 42.7 ± 2.6 0.53 (total)
Females (%) 80.6 74.4 85 0.18 % time pH < 4 7.0 ± 1.0 13.8 ± 2.0 2.4 ± 0.3 < 0.01
BMI (kg/m2) 27.0 ± 0.7 28.3 ± 1.2 26.1 ± 0.9 0.15 (upright)
Race (% white)† 93.1 97.7 86.7† 0.05 % time pH < 4 8.3 ± 1.9 18.6 ± 4.4 1.5 ± 0.6 < 0.01
PPI use (%) 67 76.7 60 0.07 (supine)
H2 blocker use (%) 9.7 14 6.7 0.22 Gastroesopha- 29.9 ± 6.4 62.0 ± 11.8 7.9 ± 0.9 < 0.01
Type of 0.12 geal reflux
gastroparesis (%) score
Idiopathic 47.6 34.7 65.3 Total episodes
Diabetic 26.2 55.6 44.4 All reflux 46.5 ± 4.0 59.8 ± 6.8 35.3 ± 4.0 < 0.01
Postsurgical 11.7 58.3 41.7 Nonacid reflux 0.21 ± 0.07 0.03 ± 0.03 0.37 ± 0.14 0.01
Atypical 14.6 26.7 73.3 Weakly acid 25.4 ± 2.8 26.8 ± 4.7 24.1 ± 3.4 0.64
N/V subscale 3.0 ± 0.1 3.0 ± 0.2 2.9 ± 0.2 0.89 reflux
PPF/ES subscale 3.9 ± 0.1 3.8 ± 0.2 3.9 ± 0.1 0.32 Acid reflux 20.9 ± 2.6 32.9 ± 4.5 10.7 ± 1.8 < 0.01
B subscale 3.5 ± 0.1 3.3 ± 0.2 3.5 ± 0.2 0.42 Acid reflux 3.6 ± 0.6 5.6 ± 0.6 2.2 ± 0.9 < 0.01
UAP subscale 3.6 ± 0.1 3.4 ± 0.2 3.7 ± 0.2 0.25 > 5 min
LAP subscale 2.5 ± 0.1 2.2 ± 0.2 2.8 ± 0.2 0.08 Longest acid 43.3 ± 11.1 76.8 ± 21.9 20.7 ± 10.3 0.02
HB/Rg subscale 2.4 ± 0.1 2.6 ± 0.2 2.4 ± 0.2 0.37 reflux (min)
GCSI total score 3.4 ± 0.1 3.4 ± 0.1 3.5 ± 0.1 0.65 Upright episodes
GES: retention at 67.3 ± 1.5 70.4 ± 2.5 65.0 ± 1.9 0.09 All reflux 37.6 ± 3.2 47.5 ± 5.3 29.3 ± 3.5 0.01
2 h (normal Nonacid reflux 0.15 ± 0.05 0.03 ± 0.03 0.26 ± 0.09 0.02
≤ 60%) (%) Weakly acid 20.4 ± 2.4 21.6 ± 3.8 19.4 ± 2.9 0.64
GES: retention at 4 h 33.0 ± 2.3 43.4 ± 3.9 25.5 ± 2.4 < 0.01 reflux
(normal ≤ 10%) Acid reflux 17.0 ± 2.1 25.7 ± 3.5 9.5 ± 1.7 < 0.01
Supine episodes
*Criteria for GERD: esophageal acid exposure time > 4.5%. P-value All reflux 9.0 ± 1.3 12.3 ± 2.4 6.2 ± 1.2 0.03
comparing Gp patients who met the criteria for GERD on esophageal pH Nonacid reflux 0.06 ± 0.04 0.00 ± 0.00 0.11 ± 0.08 0.17
impedance testing to those who did not meet the criteria for GERD. Results
expressed as mean ± SE of mean or percentages as appropriate.
Weakly acid 5.0 ± 0.8 5.2 ± 1.4 4.8 ± 1.1 0.84
†Two patients did not report their race and were excluded while com- reflux
paring race between GERD+ve and GERD−ve patients. Acid reflux 4.1 ± 0.8 7.3 ± 1.7 1.3 ± 0.4 < 0.01
Values in bold are statistically significant. episodes
B indicates bloating; BMI, body mass index; ES, early satiety; GERD, % of distal esophageal episodes in proximal esophagus
gastroesophageal reflux disease; GES, gastric emptying scintigraphy; Gp, All reflux 46.3 ± 3.0 50.0 ± 4.4 43.4 ± 4.0 0.28
gastroparesis; H2, histamine-2; HB, heartburn; LAP, lower abdominal pain; Nonacid reflux 37.1 ± 12.2 33.3 ± 33.3 40.4 ± 12.9 0.78
N, nausea; PPF, postprandial fullness; PPI, proton-pump inhibitor; Rg, Weakly acid 40.6 ± 3.5 39.5 ± 5.4 41.5 ± 4.6 0.78
regurgitation; UAP, upper abdominal pain; V, vomiting.
reflux
Acid reflux 42.6 ± 3.4 45.8 ± 4.7 39.7 ± 4.8 0.37
Values in bold are statistically significant.
(17.8%). There were no differences in the prevalence of P-value comparing Gp patients who met the criteria for GERD on
depression or anxiety between the subtypes of Gp (results not esophageal pH impedance testing to those who did not meet the criteria for
GERD. Results expressed as mean ± SE of mean.
shown). Nearly two thirds of Gp patients (63%) were on PPIs, GERD indicates gastroesophageal reflux disease; Gp, gastroparesis.
and a minority (11.1%) were on H2 blockers. DGp and PSGp
patients reported a higher prevalence of PPI use than IGp and
AGp. There was no difference in the prevalence of H2 blocker
use between the subtypes of Gp. EpHI Monitoring
In total, 103 (23.8%) of all Gp patients underwent 24-hour
GES EpHI monitoring (Table 3). The decision for patients to undergo
On GES, the mean retention at 2 hours was 66.2% ± 0.7%, manometry and pH monitoring was for their clinical evaluation
whereas the mean retention at 4 hours was 32.9% ± 1.0% and based primarily on their clinical symptoms. More than half
(Table 1). There were no differences between the subtypes of Gp of the patients (n = 60, 58.3%) undergoing EpHI testing had
in their gastric retention at 2 hours. Patients with IGp had less normal esophageal acid exposure/impedance measurements. Of
severe gastric retention at 4 hours compared with DGp these patients with normal esophageal acid exposure/impedance
(P < 0.001). In patients with Gp, heartburn/regurgitation sub- measurements, 5 patients had major esophageal motility dis-
score had a weak correlation with 4-hour gastric retention orders (absent contractility = 4, distal esophageal spasm = 1), 4
(r = 0.11, P = 0.02), but no correlation with 2-hour gastric patients had significant symptom-reflux association despite nor-
retention (r = 0.08, P = 0.12). mal esophageal acid exposure/impedance measurements and

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Jehangir and Parkman J Clin Gastroenterol  Volume 00, Number 00, ’’ 2019

TABLE 5. Correlation of the Severity of Symptoms on PAGI-SYM TABLE 7. Correlation of Gastric Retention on Gastric Emptying
Heartburn/Regurgitation Subscale and 24-Hour Esophageal pH Scintigraphy and Esophageal pH Impedance Results in Patients
Impedance Results in All Patients With Gastroparesis Who With Gastroparesis Who Underwent 24-Hour pH Impedance
Underwent pH Testing, Including Patients Who Met Criteria for Testing
GERD and Patients Who did not Meet Criteria for GERD
Esophageal pH 2-h Gastric 4-h Gastric
All Gp Patients Gp Gp Impendence Retention Retention
Undergoing pH Patients Patients
% time pH < 4 (total) r = 0.10, P = 0.33 r = 0.28, P < 0.01
Total Reflux Impedance With Without % time pH < 4 (upright) r = 0.12, P = 0.23 r = 0.24, P = 0.02
Episodes on pH Testing GERD GERD % time pH < 4 (supine) r = 0.03, P = 0.78 r = 0.19, P = 0.16
Impendence* (n = 103) (n = 43) (n = 60) Gastroesophageal reflux r = 0.11, P = 0.26 r = 0.28, P < 0.01
All reflux r = −0.11 r = −0.16 r = 0.14 score
P = 0.30 P = 0.33 P = 0.36 Total episodes
Nonacid reflux r = −0.07 r = −0.19 r = −0.01 All reflux r = 0.20, P = 0.06 r = 0.20, P = 0.07
P = 0.53 P = 0.25 P = 0.98 Nonacid reflux r = −0.10, P = 0.39 r = −0.17, P = 0.13
Weakly acid reflux r = −0.18 r = −0.22 r = −0.14 Weakly acid reflux r = 0.13, P = 0.25 r = 0.03, P = 0.78
P = 0.10 P = 0.18 P = 0.34 Acid reflux r = 0.16, P = 0.14 r = 0.32, P < 0.01
Acid reflux r = 0.08 r = −0.08 r = 0.04 Upright episodes
P = 0.47 P = 0.63 P = 0.79 All reflux r = 0.18, P = 0.09 r = 0.20, P = 0.06
Acid reflux episodes r = 0.08 r = 0.04 r = 0.02 Nonacid reflux r = −0.08, P = 0.49 r = −0.21, P = 0.06
> 5 min P = 0.45 P = 0.83 P = 0.88 Weakly acid reflux r = 0.13, P = 0.24 r = 0.04, P = 0.70
Longest acid reflux r = 0.02 r = −0.04 r = −0.01 Acid reflux r = 0.16, P = 0.14 r = 0.30, P = 0.01
episode P = 0.82 P = 0.82 P = 0.96 Supine episodes
% time pH < 4 r = 0.15 r = 0.12 r = 0.13 All reflux r = 0.07, P = 0.53 r = 0.04, P = 0.76
P = 0.13 P = 0.46 P = 0.33 Nonacid reflux r = −0.05, P = 0.63 r = −0.04, P = 0.71
Gastroesophageal r = 0.09 r = 0.08 r = 0.07 Weakly acid reflux r = 0.03, P = 0.81 r = −0.10, P = 0.38
reflux score P = 0.36 P = 0.64 P = 0.59 Acid reflux episodes r = 0.10, P = 0.39 r = 0.25, P = 0.02

*Both upright and supine reflux episodes. Values in bold are statistically significant.
GERD indicates gastroesophageal reflux disease; Gp, gastroparesis;
PAGI-SYM, patient assessment of upper gastrointestinal symptoms.

P < 0.01), as well as a trend for more severe 2-hour gastric

retention (70.4% ± 2.5% vs. 65.0% ± 1.9%; P = 0.09).
were diagnosed with reflux hypersensitivity, while most of the GERD+ve patients expectedly had a higher number of
remaining patients were diagnosed with functional heartburn all reflux episodes and acidic reflux episodes compared with
based on Rome IV criteria.33 Less than half of the patients GERD−ve patients (Table 4). These GERD+ve patients also
(n = 43, 41.7%) undergoing EpHI testing met the criteria for had a greater duration of the longest acid reflux and spent a
GERD (GERD+ve); 19 of these patients also had abnormal significantly longer time with esophageal pH < 4. However,
impedance measurements. GERD+ve patients had a trend to be GERD−ve patients were more likely to have nonacidic reflux
more likely to be whites (97.7% vs. 86.7%; P = 0.05) and more episodes. There were no differences between GERD+ve and
commonly use PPIs (76.7% vs. 60%; P = 0.07), compared with GERD−ve patients with respect to the percentage of all reflux
GERD−ve patients. There was no difference between GERD episodes in the distal esophagus that reached the proximal
+ve and GERD−ve patients with respect to their subtypes of Gp. esophagus. There was a trend for males to have a higher
There were also no differences in the severity of symptoms on number of all reflux episodes (62.1 ± 10.2 vs. 41.8 ± 4.0;
PAGI-SYM between GERD+ve and GERD−ve patients using P = 0.08) and acidic reflux episodes (30.7 ± 6.8 vs. 17.9 ± 2.5;
the heartburn/regurgitation subscale. GERD+ve patients had a P = 0.09) when compared with females.
more severe 4-hour retention (43.4% ± 3.9% vs. 25.5% ± 2.4%;
Correlation Between Reflux Symptoms and EpHI Results
In patients undergoing 24-hour EpHI, there was no cor-
TABLE 6. Symptom Association Probability in Gastroparesis relation between heartburn/regurgitation subscale and per-
Patients With Reflux Symptoms Undergoing Esophageal pH centage time esophageal pH < 4, number of all reflux episodes,
Impedance Testing acidic reflux episodes, weakly acidic reflux episodes, nonacidic
reflux episodes, duration of longest acid reflux episode, and
All Gp Patients Gp Gp
gastroesophageal reflux score (Table 5). During EpHI testing,
Undergoing pH Patients Patients
there was a poor association of the common symptoms
Impedance With Without
reported by the patients and all reflux events (Table 6). There
Testing GERD GERD
was no difference between GERD+ve and GERD−ve patients
Symptoms (n = 103) (n = 43) (n = 60) P
in their symptom association probability.
Heartburn (%) 51.1 ± 10.5 53.1 ± 3.6 46.9 ± 2.4 0.81
Regurgitation (%) 45.2 ± 11.7 53.6 ± 2.4 39.7 ± 3.0 0.57
Nausea/vomiting (%) 51.7 ± 11.6 44.1 ± 3.7 52.8 ± 3.9 0.60 Correlation Between Gastric Retention and EpHI Results
Abdominal pain (%) 48.6 ± 10.5 66.0 ± 2.2 41.5 ± 2.6 0.33 The 4-hour gastric retention on GES had weak corre-
Chest pain (%) 48.6 ± 8.0 50.1 ± 2.6 47.2 ± 2.6 0.90 lations to percent time esophageal pH < 4 on EpHI (r = 0.28,
P < 0.01) and gastroesophageal reflux score (r = 0.28,
Values are represented as mean ± SE, else indicated.
P-value comparing patients with GERD to patients without GERD.
P < 0.01; Table 7). Weak correlation was also seen between
GERD indicates gastroesophageal reflux disease; Gp, gastroparesis. 4-hour gastric retention and percent time esophageal pH < 4
in upright position (r = 0.24, P = 0.02), with no correlation

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J Clin Gastroenterol  Volume 00, Number 00, ’’ 2019 Reflux in Gastroparesis

TABLE 8. Esophageal Manometry Results in Gp Patients, and Comparison of Esophageal Manometry Results in Patients Who Met Criteria
for GERD on 24-Hour EpHI Testing to Those Who did not Meet Criteria for GERD
All Gp Patients Esophageal Manometry
Undergoing Esophageal Results in Gp Patients Who Esophageal Manometry Results in
Manometry Testing Met Criteria for GERD Gp Patients Who did not Meet
Esophageal Manometry Data (n = 103) (n = 43) Criteria for GERD (n = 60) P
LES resting pressure 22.6 ± 1.5 21.0 ± 2.3 23.8 ± 1.9 0.35
(normal 13-43 mm Hg)
% with low LES resting pressure 21.4 32.6 13.3 0.02
LES residual pressure (normal 6.8 ± 0.5 6.2 ± 0.8 7.1 ± 0.8 0.41
<15 mm Hg)
HH on manometry (%) 34.0 34.9 33.3 0.87
Mean length of HH among those 1.7 ± 0.2 2.0 ± 0.4 1.5 ± 0.2 0.21
who had hernia detected on
manometry (cm)
Amplitude of distal contractions 81.6 ± 4.9 77.7 ± 7.1 84.8 ± 6.7 0.50
(normal 43-152 mm Hg)
Mean DCI (normal 500- 1793.9 ± 270.3 1295.6 ± 145.4 2254.9 ± 495.1 0.07
5000 mm Hg cm s)
DL (normal 4.8-7.6 s) 7.5 ± 0.2 7.4 ± 0.3 7.6 ± 0.3 0.76
Esophageal contractile velocity 5.0 ± 0.9 6.5 ± 1.9 3.7 ± 0.5 0.17
(normal 2.8-6.3 cm/s)
Bolus clearance (%) 67.2 ± 4.5 62.4 ± 7.2 71.0 ± 5.6 0.35
UES resting pressure 79.0 ± 4.0 83.6 ± 7.0 75.2 ± 3.8 0.30
(normal 34-104 mm Hg)
UES residual pressure (normal 1.3 ± 0.5 1.7 ± 0.8 1.0 ± 0.7 0.52
<12 mm Hg)
Esophageal motility disorder bases on Chicago Classification
Major disorders of peristalsis (%)
DES 2 (1.9) 1 (2.3) 1 (1.7) 0.81
Jackhammer esophagus 1 (1.0) 1 (2.3) 0 (0) 0.24
Absent contractility 8 (4.9) 4 (9.3) 4 (6.7) 0.62
Minor disorders of peristalsis (%)
IEM 8 (7.8) 6 (14.0) 2 (3.3) 0.04
Fragmented peristalsis 16 (15.5) 8 (18.6) 8 (13.3) 0.47
All esophageal motility disorders 35 (34.0) 20 (46.5) 15 (25) 0.02
Values in bold are statistically significant.
P-value comparing esophageal manometry results in Gp patients with GERD on 24-hour EpHI testing to those who did not have GERD. Results expressed
as mean ± SE of mean or percentages.
DCI indicates distal contractile integral; DES, distal esophageal spasm; DL, distal latency; EpHI, esophageal pH impedance; GERD, gastroesophageal
reflux disease; Gp, gastroparesis; HH, hiatal hernia; IEM, ineffective esophageal motility; LES, lower esophageal pressure; UES, upper esophageal sphincter.

between 4-hour gastric retention and percent time esoph-
ageal pH < 4 in supine position. There was a moderate
correlation of 4-hour gastric retention to the total number of
acidic reflux episodes (r = 0.32, P < 0.01), with weak corre-
lations to the number of acidic reflux episodes in the upright
(r = 0.30, P = 0.01) and supine positions (r = 0.25, P = 0.02).
There was no correlation between 4-hour gastric retention
and number of weakly acidic, nonacidic, and total reflux
episodes. We also did not find any correlations between
2-hour gastric retention and EpHI results.
pressure to the number of weakly acid reflux episodes
(r = −0.26, P < 0.02, Table 9). Weak correlation was seen
between LES pressure and the number of weakly acidic reflux
episodes in the upright position, with no correlation seen in the
supine position. There was no correlation between LES resting
pressure and the number of total, nonacid, and acid reflux
episodes, percent time pH < 4, and gastroesophageal reflux
score. LES resting pressure had a weak negative correlation to
the gastric retention at 2 hours (r = −0.28, P = 0.01) and
4 hours (r = −0.27, P = 0.01).

HREM
LES Pressure
The mean LES pressure in the patients who had
HREMI (n = 116) was 22.6 ± 1.5 mm Hg (Table 8). Patients
who met criteria for GERD on EpHI testing were more
likely to have subnormal (< 13 mm Hg) LES resting pres-
sures than GERD−ve patients (32.6% vs. 13.3%, respec-
tively; P = 0.02). There was no difference between GERD
+ve and GERD−ve patients in their residual LES
pressures.
Among patients undergoing both HREMI and EpHI
(n = 103), there was a weak negative correlation of LES resting
HH
A third (34%) of the patients undergoing HREMI had
HH detected, with mean HH length of 1.7 ± 0.2 cm. There was
no difference between GERD+ve and GERD−ve patients
with respect to the presence of HH or the mean length of HH.
Patients with HH on manometry had a higher severity of
symptoms on heartburn-regurgitation subscale compared with
patients without HH (2.9 ± 0.2 vs. 2.3 ± 0.2; P = 0.04).
Other HREMI Parameters
There were no differences between GERD+ve and
GERD−ve patients with respect to the amplitude of distal

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Jehangir and Parkman J Clin Gastroenterol  Volume 00, Number 00, ’’ 2019

ineffective esophageal motility (8). Eleven patients had

TABLE 9. Correlation of LES Resting Pressure on High-resolution major disorder of peristalsis, including absent contractility
Esophageal Manometry and Esophageal pH Impedance Results in
Patients With Gastroparesis (8), distal esophageal spasm (2), and jackhammer esophagus
(1). GERD+ve patients were more likely to have esophageal
Correlation With LES Resting motility disorders compared with GERD−ve patients
Esophageal pH Impendence Pressure (46.5% vs. 25%; P = 0.02); with notably a higher prevalence
% time pH < 4 (total) r = −0.13, P = 0.21 of ineffective esophageal motility disorders (14% vs. 3.3%;
% time pH < 4 (upright) r = 0.04, P = 0.69 P = 0.04).
% time pH < 4 (supine) r = −0.13, P = 0.25
Gastroesophageal reflux score r = −0.11, P = 0.33
Total episodes
Correlation Between Reflux Symptoms
All reflux r = −0.22, P = 0.05 and Manometry Results
Nonacid reflux r = −0.11, P = 0.33 We did not find any correlation of heartburn/regurgitation
Weakly acid reflux r = −0.26, P = 0.02 subscale to LES resting or residual pressures, length of HH,
Acid reflux r = −0.09, P = 0.43 amplitude of distal contractions, DCI, DL, bolus clearance,
Upright episodes esophageal contractile velocity, UES resting, or residual pres-
All reflux r = −0.18. P = 0.12 sures (results not shown).
Nonacid reflux r = −0.14, P = 0.24
Weakly acid reflux r = −0.25, P = 0.03 Anxiety, Depression, and Somatization in Gp
Acid reflux r = −0.04 P = 0.71
Supine episodes Patients
All reflux r = −0.18, P = 0.12 Gp patients averaged 8.3 ± 0.2 on the HADS-anxiety
Nonacid reflux r = 0.04, P = 0.75 subscale, with a third (33.6%) of Gp patients scoring
Weakly acid reflux r = −0.15, P = 0.19 abnormal (ie, HADS-anxiety subscores of 11 to 21). Using
Acid reflux episodes r = −0.14, P = 0.23 the HADS-depression subscale, the average score was
Values in bold are statistically significant.
slightly lower at 7.3 ± 0.2, and about a fourth (23.8%) of Gp
LES indicates lower esophageal sphincter. patients scored abnormal (ie, HADS-depression subscores
of 11 to 21). There were no differences in males and females,
or the subtypes of Gp with respect to their HADS-anxiety or
HADS-depression scores (results not shown). In patients
contractions, DCI, DL, esophageal contractile velocity, getting evaluation for their GERD symptoms with EpHI
bolus clearance, UES resting pressure, and UES residual testing, there was no difference between GERD+ve and
pressure. GERD−ve in their reported history of anxiety or depres-
sion, as well as their HADS-anxiety or HADS-depression
Esophageal Motility Disorders scores (Table 10).
A third (34%) of Gp patients undergoing HREMI had Using PHQ-15, the average score for Gp patients was
esophageal motility disorders using Chicago Classification. 13.8 ± 0.3. The majority of Gp patients scored high (45.6%)
These patients more commonly had minor disorders of or medium (30.6%), with a minority scoring low (19.4%)
peristalsis (n = 24), including fragmented peristalsis (16) and or minimal (4.4%). Female Gp patients scored higher on

TABLE 10. Comparison of History of Anxiety and Depression, and Responses on HADS and PHQ Questionnaires in Patients With
and Without GERD on 24-Hour Esophageal pH Manometry Testing
History of Anxiety and
Depression, and Responses on All Gp Patients Gp Patients With GERD on pH Gp Patients Without GERD on pH
HADS and PHQ Questionnaires (n = 432) Impedance Testing (n = 43) Impedance Testing (n = 60) P
History of anxiety (%) 17.8 20.9 16.7 0.58
History of depression (%) 19.4 20.9 21.7 0.92
HADS total score (anxiety) 8.3 ± 0.2 7.5 ± 0.7 8.9 ± 0.6 0.14
HADS (anxiety) (%) Abnormal (33.6) Abnormal (27.9) Abnormal (35) 0.45
Normal or Normal or borderline (72.1) Normal or borderline (65)
borderline (66.4)
HADS total score (depression) 7.3 ± 0.2 7.2 ± 0.7 7.0 ± 0.6 0.83
HADS (depression) (%) Abnormal (23.8) Abnormal (25.9) Abnormal (23.3) 0.79
Normal or Normal or borderline (74.1) Normal or borderline (76.7)
borderline (76.2)
PHQ-15 score 13.8 ± 0.3 14.8 ± 0.7 15.4 ± 0.7 0.57
PHQ-15 levels of somatic symptom High (45.6) High (58.1) High (56.7) 0.85
severity (%) Medium (30.6) Medium (23.3) Medium (25)
Low (19.4) Low (18.6) Low (16.7)
Minimal (4.4) Minimal (0) Minimal (1.7)
PHQ-12 score 9.1 ± 0.2 9.7 ± 0.6 10.2 ± 0.6 0.28
On HADS, symptoms during the previous week are reported on a Likert-scale ranging from 0 to 3. Total depression or anxiety scores of 0 to 7 are normal, 8
to 10 are borderline abnormal, and 11 to 21 are abnormal. On PHQ-15, each symptom is scored from 0 (not bothered at all) to 2 (bothered a lot). PHQ-15 Scores
of 0 to 4 represent minimal somatic symptom severity, 5 to 9 low, 10 to 14 medium, and 15 to 30 high somatic symptom severity.
GERD indicates gastroesophageal reflux disease; HADS, Hospital Anxiety and Depression Scale; PHQ, Patient Health Questionnaire.

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J Clin Gastroenterol  Volume 00, Number 00, ’’ 2019 Reflux in Gastroparesis

between Gp and GERD.5,16 The severity of reflux symptoms

TABLE 11. Correlation of HADS-Anxiety, HADS-Depression, had moderate to strong correlation to the severity of typical
and PHQ-12 Scores to GSCI Total Score, HB/Rg Subscale, Gastric
Retention, and 24-Hour Esophageal pH Impedance Results in symptoms of Gp with weak correlation to 4-hour gastric reten-
Gastroparesis Patients tion on GES and no correlation to esophageal acid exposure
time on 24-hour EpHI testing. Gp patients with GERD symp-
GSCI Total Score, toms often had concomitant esophageal motility disorders.
HB / Rg Subscale, Gastroesophageal reflux symptoms were most severe in
Gastric Retention, patients with PSGp and AGp. Among patients with PSGp,
and 24-Hour fundoplication was the most common surgical reason for
Esophageal pH HADS- HADS- delayed gastric emptying, hence these patients may have
Impedance Depression Anxiety PHQ-12 more severe reflux symptoms at baseline. Several disorders
GCSI total score r = 0.26 r = 0.26 r = 0.36 seen in patients with AGp (such as Sjögren syndrome,
P < 0.01 P < 0.01 P < 0.01 scleroderma, and Parkinson disease) are often considered
HB/Rg subscale r = 0.22 r = 0.26 r = 0.43 risk factors for reflux disease.34 Males are known to have
P < 0.01 P < 0.01 P < 0.01 increased gastric acid production,35 and our study suggests
GES: Retention at 2 h r = 0.10 r = −0.01 r = 0.09 increased acid reflux events in male Gp patients; however,
(normal ≤ 60%) P = 0.05 P = 0.94 P = 0.06
GES: Retention at 4 h r = −0.01 r = −0.06 r = −0.01
we found no difference in the severity of reflux symptoms
(normal ≤ 10%) P = 0.90 P = 0.19 P = 0.89 between males and females.
% time pH < 4 r = 0.13 r = 0.09 r = −0.05 There was moderate to strong correlation between the
P = 0.21 P = 0.37 P = 0.61 severity of GERD symptoms and symptoms of Gp using the
All reflux r = 0.11 r = 0.14 r = −0.01 PAGI-SYM. Patients with Gp often experience chronic
P = 0.30 P = 0.21 P = 0.92 poorly controlled symptoms affecting their quality of lives.36
Nonacid reflux r = 0.03 r = 0.21 r = 0.04 Likewise, presence of reflux is associated with significant
P = 0.77 P = 0.06 P = 0.74 impairment of health-related quality of lives.37 The assess-
Weakly acid reflux r = 0.09 r = 0.11 r = −0.01 ment of the severity of reflux symptoms may be important in
P = 0.40 P = 0.30 P = 0.96
Acid reflux r = 0.18 r = 0.05 r = 0.05
Gp patients to effectively manage their symptoms, partic-
P = 0.11 P = 0.63 P = 0.67 ularly in patients with a high severity of Gp symptoms given
a strong correlation of the severity of reflux symptoms with
Values in bold are statistically significant. Gp symptoms. We found a weak correlation of the severity
GCSI indicates Gastroparesis Cardinal Symptom Index; GES, gastric of reflux symptoms to the 4-hour gastric retention in Gp
emptying scintigraphy; HADS, Hospital Anxiety and Depression Scale; HB,
heartburn; PHQ, Patient Health Questionnaire; Rg, regurgitation. patients. Prior literature also suggests that proximal stom-
ach distension may be important in the pathogenesis of
symptoms of Gp38 and GERD.39
In patients with dyspepsia, 34% of patients experiencing
PHQ-15 than male Gp patients (14.4 ± 0.3 vs. 11.3 ± 0.7 symptoms of heartburn and/or regurgitation have GERD.40 In
respectively; P < 0.01). Female Gp patients were more likely our study on patients with delayed gastric emptying, 41% of the
to have high level of somatic symptom severity (ie, PHQ-15 patients who underwent 24-hour EpHI testing had objective
scores of 15 to 30) than male Gp patients (49.4% vs. 27%, evidence of GERD. However, not all patients with Gp under-
respectively; P < 0.01). Patients with AGp scored higher on went EpHI in our study. Perhaps the patients with more typical
PHQ-15 (18.1 ± 0.7) than IGp (13.1 ± 0.4; P < 0.001), DGp symptoms of GERD preferentially underwent this test in their
(13.6 ± 0.5; P < 0.001) and PSGp (14.5 ± 0.9; P = 0.002). evaluation; this might have inflated the true number of GERD
AGp were more likely (76%) to have high level of somatic +ve patients in Gp. We found no correlation of the esophageal
symptom severity, than IGp (37.8%), DGp (47.1%), and acid exposure time to heartburn/regurgitation symptoms. Var-
PSGp (48.5%; P < 0.001). Gp patients averaged 9.1 ± 0.2 on iance of GERD symptom severity may be due to decreased
PHQ-12. Female Gp patients scored higher on PHQ-12 than threshold for symptom perception or increased visceral sensi-
males (9.1 ± 0.3 vs. 7.1 ± 0.5, respectively; P < 0.01). AGp tivity in some patients.41 However, only a minority of patients
patients also scored higher on PHQ-12 (12.7 ± 0.6) than IGp undergoing EpHI in our study were diagnosed with reflux
(8.5 ± 0.3; P < 0.001), DGp (8.9 ± 0.3; P < 0.001), and PSGp hypersensitivity. It is plausible that some Gp patients with reflux
(9.3 ± 0.6; P = 0.001). There were no differences between symptoms have somatization that contribute toward or sec-
GERD+ve and GERD−ve patients on their PHQ-15 and ondarily maintain symptoms of reflux. Over half of the Gp
PHQ-12 scores. patients who were evaluated for symptoms of reflux with EpHI
The symptom severity on heartburn/regurgitation sub- scored high on PHQ-15, and there was a moderate correlation
scale had moderate correlation to the PHQ-12 score (r = 0.43, between PHQ scores and symptom severity on heartburn/
P < 0.01), and weak correlations to the HADS-anxiety score regurgitation subscale (r = 0.43, P < 0.01).
(r = 0.26, P < 0.01) and HADS-depression score (r = 0.26, In a study by Gourcerol et al42 using EpHI, delay in gastric
P = 0.01; Table 11) in patients undergoing evaluation of their emptying had no effect on the esophageal acid exposure. How-
reflux symptoms with EpHI. There were no correlations of ever, in our study GERD+ve patients had more severe 4-hour
PHQ, HADS-anxiety, or HADS-depression scores to the gastric retention than GERD−ve patients. There was also a weak
4-hour gastric retention on GES or EpHI results. negative correlation between gastric retention and LES pressure,
which supports the hypothesis that delay in gastric emptying may
DISCUSSION cause proximal stomach distension and decrease LES pressure.
In this study characterizing gastroesophageal reflux in Our findings of higher prevalence of subnormal LES pressures on
patients with Gp, we found that a fourth of Gp patients expe- manometry in Gp patients with GERD corroborates the findings
rienced moderate to very severe reflux symptoms which is con- of Chrysos et al43 studying esophageal motor function in GERD
sistent with the prior literature suggesting a significant overlap patients. Our study also shows that in Gp patients with reflux

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Jehangir and Parkman
symptoms, presence of HH on HREMI is associated with more
severe reflux symptoms. HREMI helps in accurate assessment of
HH, particularly those <2 cm in size which may be difficult to
detect endoscopically, radiographically, or through conventional
manometry.44 There was no correlation of the severity of reflux
symptoms to the length of HH, although most of our patients
had a small HH with mean length of 1.7 cm. GERD+ve Gp
patients were more likely to have concomitant esophageal
motility disorders compared with GERD−ve patients, that could
have contributed to their reflux symptoms.
A previous study at our tertiary care center by Cherian
et al45 showed high HADS-anxiety and depression scores in
Gp patients. In our study as well, a third (33.6%) of all Gp
patients scored abnormal on HADS-anxiety scale, even though
only a minority (17.8%) of all Gp patients reported history of
anxiety. Similar trends of high HADS-anxiety scores were seen
in GERD+ve and GERD−ve Gp patients, suggesting some Gp
patients in general may suffer from anxiety. A fourth (23.8%) of
all Gp patients scored abnormal on HADS-depression scale,
whereas 19.4% reported a history of depression. There were
weak correlations of HADS-depression/anxiety scores and
the severity of reflux symptoms in Gp patients undergoing
EpHI testing. The majority of Gp patients reporting reflux
symptoms had moderate to high levels of somatization, with
females scoring higher on PHQ than males. Reflux symptoms in
Gp patients correlated better with psychological testing scores
than the objective esophageal pH data. In the future, studies on
screening and treating underlying mood disorders in Gp patients
with reflux symptoms and their impact on clinical outcomes
could be useful.
Patients with GERD can have day-to-day variability in
the number of reflux events on 24-hour EpHI testing, and one
limitation of our study is that the patients recorded their
symptom severity on PAGI-SYM at the time of their first
clinical evaluation at our Motility Center. However, EpHI
testing was performed later, but within 2 weeks of their eval-
uation. PAGI-SYM has good correlation with daily symptom-
monitoring over 2 weeks, with heartburn/regurgitation
subscale having the strongest interclass correlation coefficient
over a 2-week period of 0.82.24,46 In addition, these patients
also had a poor symptom-reflux association during EpHI
testing. In patients off PPI, Lyon Consensus recognizes
esophageal acid exposure time > 6% as definitely abnormal,
with values between 4% and 6% being inconclusive.47 Hence,
we may have overestimated the number of GERD+ve Gp
patients using esophageal acid exposure time > 4.5% as the
diagnostic criteria for GERD. In addition, a significant num-
ber of the patients in our study were on PPIs that may have
affected the interpretation of EpHI, as there is limited liter-
ature available on normal values of esophageal acid exposure
time in patients taking PPIs. The patients in our study were
generally referred from community settings and it is con-
ceivable that the patients referred to our tertiary care center
may represent a more severe spectrum of the disease. Our
study was a questionnaire-based study. Some of the questions
were not answered by all the patients and the missed questions
were excluded from the analyses; the number of missed ques-
tions was negligible and likely not to affect the results. Lastly,
as this is a questionnaire-based study, there is a potential of
recall bias as well. This would likely apply both to all the
subtypes of Gp, and both GERD+ve and GERD−ve groups.
In conclusion, despite the frequent use of antireflux
medications, a fourth of patients with Gp experience mod-
erate to very severe reflux symptoms. These reflux symptoms
correlate moderately to strongly to the severity of typical
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This paper can be cited using the date of access and the unique DOI number which can be found in the footnotes.
J Clin Gastroenterol  Volume 00, Number 00, ’’ 2019
symptoms of Gp, and weakly to the 4-hour gastric retention.
Reflux symptoms in Gp patients correlate poorly with objec-
tive measures of reflux, which is analogous with the prior lit-
erature suggesting poor correlation between Gp symptoms and
objective measurements of gastric emptying.3,38,48 Gp patients
with reflux symptoms frequently have concomitant esophageal
motility disorders. Assessment of the severity of reflux in Gp
patients, both symptomatically and possibly objectively, may
be important to effectively manage their symptoms.
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