Abstract
Introduction:
Increased intraabdominal pressure in patients with elevated BMI may affect measurements of esophagogastric junction (EGJ) opening.
Methods:
Findings from adult patients who underwent both impedance planimetry with functional luminal imaging probe (FLIP) and high-resolution manometry (HRM) were compared by BMI.
Results:
Among patients with no EGJ outflow obstruction on HRM, abnormal EGJ classifications on FLIP were more common among those with elevated than normal BMI (61.1% vs 31.6%, p=0.037).
Conclusion:
Discordant results between FLIP and HRM on EGJ opening are more common in patients with elevated BMI. Body composition may impact EGJ function and measures on current testing modalities.
INTRODUCTION
Impedance planimetry with the functional luminal imaging probe (FLIP) is a useful tool to measure esophagogastric junction (EGJ) distensibility/opening1. High-resolution esophageal manometry (HRM) in patients with elevated body mass index (BMI) has shown a higher proportion with increased integrated relaxation pressure (IRP) despite little/no esophageal symptoms.2,3 Whether this represents a clinically significant finding or measurement artifact in this population has not been fully elucidated, but obtaining IRP in the upright position may improve diagnostic accuracy, which suggests a possible effect of increased intraabdominal pressure on HRM measures.4 Additionally, Chicago Classification v4.0 (CCv4.0) now requires IRP elevation in both upright and supine positions for conclusive diagnosis of EGJ outflow obstruction (EGJOO), which aims to limit positional effects on manometric parameters that may be, in part, related to body composition.5
In contrast to HRM, the effect of body habitus on esophageal biomechanical measurements by FLIP remains unknown. We hypothesized that changes in intraabdominal/transdiaphragmatic pressure in overweight patients may affect measurements of EGJ opening on FLIP. This study aimed to compare the rate of discordant EGJ findings on FLIP and HRM between patients with normal and elevated BMI.
METHODS
Adult patients who completed both FLIP and HRM at a tertiary care center in 2021-2022 were included. FLIP measures of EGJ opening were classified using the distensibility index during 60-mL and maximal diameter during 60 or 70-mL volumetric distention based on prior literature: normal (NEO), borderline normal (BnEO), borderline reduced (BrEO), and reduced (REO) EGJ opening (Supplementary Table 1).6 Patients were then dichotomized into two groups: normal EGJ opening (NEO/BnEO) and abnormal EGJ opening (BrEO/REO). On HRM, elevated IRP was defined by both supine and upright IRP (≥22 and ≥15 mmHg, respectively) per CCv4.0 (Diversatek)5. A subgroup analysis of individuals who also underwent timed barium esophagram (TBE) was performed. Abnormal TBE was defined as >5 cm barium column at 5 minutes or >5 cm column at 1 minute with retention of 12.5 mm barium tablet.7 Study findings were compared between patients with normal (19-24.9 kg/m2) and elevated (≥25 kg/m2) BMI. (Supplementary Methods)
RESULTS
Ninety-three patients (64 female, age 60.9±14.6 years, BMI 28.1±6.0 kg/m2) were enrolled, including 38 (40.9%) with elevated IRP. The vast majority of patients presented for evaluation of dysphagia, with no significant differences in symptoms between BMI cohorts. (Table 1) Of 55 patients with normal IRP, those with elevated BMI had a higher rate of abnormal EGJ opening classifications (REO/BrEO) on FLIP than patients with normal BMI [22/36 (61.1%) vs 6/19 (31.6%), p=0.037] (Figure 1a). Moreover, the average BMI was higher among those with abnormal EGJ opening classifications in this group of patients with normal IRP (28.2±4.09 vs 25.0±4.57, p=0.016). On subgroup analyses among patients with normal IRP, compared to subjects with normal BMI, those with obesity (BMI ≥30 kg/m2) continued to have significantly higher rate of abnormal EGJ opening on FLIP [12/18 (66.7%) vs 6/19 (31.6%), p=0.033], while a trend was observed with the overweight subgroup (BMI 25-29.9 kg/m2) [10/18 (55.6%) vs 6/19 (31.6%), p=0.14]. A secondary analysis was also performed excluding patients with borderline EGJ classifications (BnEO/BrEO). In this subset of 25 patients with normal IRP, a similar trend of higher rate of REO on FLIP was found among patients with elevated BMI, although statistical significance was not reached, likely due to sample size [9/16 (56.3%) vs 3/9 (33.3%), p=0.27].
TABLE 1:
Characteristics of study cohort.
| Elevated BMI (≥25 kg/m2) N=62 | Normal BMI (19-24.9 kg/m2) N=31 | p-value | |
|---|---|---|---|
|
| |||
| Age, years ±SD | 59.0±14.7 | 59.9±16.8 | 0.78 |
|
| |||
| BMI, kg/m2 ±SD | 31.3±5.6 | 22.4±1.8 | <0.0001 |
| Overweight (25-29.9 kg/m2), n (%) | 33 (53.2%) | ||
| Obesity (≥30 kg/m2), n (%) | 29 (46.8%) | ||
|
| |||
| Female, n (%) | 44 (71.0%) | 20 (64.5%) | 0.69 |
|
| |||
| Race | |||
| White, n (%) | 51 (82.3%) | 19 (61.3%) | 0.054 |
|
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| Ethnicity | |||
| Hispanic, n (%) | 4 (6.5%) | 2 (6.5%) | 1.00 |
|
| |||
| Symptoms, n (%) | |||
| Dysphagia | 52 (83.9%) | 24 (77.4%) | 0.45 |
| Regurgitation | 6 (9.7%) | 0 (0%) | 0.16 |
| Heartburn | 6 (9.7%) | 3 (9.7%) | 0.99 |
| Chest pain | 2 (3.2%) | 4 (12.9%) | 0.07 |
| Nausea | 0 (0%) | 1 (3.2%) | 0.67 |
|
| |||
| IRP, mmHg ±SD | |||
| Supine | 19.5±14.2 | 20.6±13.0 | 0.70 |
| Upright | 19.7±16.9 | 19.3±14.6 | 0.93 |
| Elevated IRP (2 positions), n (%) | 26 (41.9%) | 12 (38.7%) | 0.94 |
| Gastric Baseline, mmHg ±SD | 8.37±3.81 | 5.45±3.39 | 0.0008 |
|
| |||
| Distal esophageal contractile function | |||
| %Failed | 45.0±40.8 | 42.5±43.2 | 0.79 |
| %Weak | 13.7±19.9 | 10.6±17.2 | 0.46 |
| %Normal | 34.5±36.1 | 42.8±40.1 | 0.31 |
| %Hypercontractile | 5.67±17.9 | 2.75±9.42 | 0.31 |
|
| |||
| Complete bolus transit (%) | 31.8±33.3 | 32.1±33.1 | 0.97 |
|
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| FLIP at 60 mL distention | |||
| EGJ Distensibility, mm /mmHg ±SD | 3.60±2.93 | 4.19±2.95 | 0.18 |
| EGJ Diameter, mm ±SD | 11.7±5.00 | 12.3±3.43 | 0.18 |
|
| |||
| FLIP EGJ Opening, n (%) | |||
| NEO | 11 (17.7%) | 8 (25.8%) | 0.16 |
| BnEO | 9 (14.5%) | 9 (29.0%) | |
| BrEO | 17 (27.4%) | 4 (12.9%) | |
| REO | 25 (40.3%) | 10 (32.3%) | |
|
| |||
| FLIP Topography, n (%) | |||
| RAC | 19 (30.6%) | 14 (45.2%) | 0.30 |
| RRC | 3 (4.8%) | 2 (6.5%) | |
| Absent Contraction | 40 (64.5%) | 15 (48.4%) | |
BMI: body mass index; IRP: integrated relaxation pressure; NEO: normal esophagogastric junction (EGJ) opening; BnEO: borderline normal EGJ opening; BrEO: borderline reduced EGJ opening; REO: reduced EGJ opending; RAC: repetitive antegrade contractions; RRC: repetitive retrograde contractions.
Figure 1:
(a) Frequency of esophagogastric junction (EGJ) opening classifications on impedance-planimetry (FLIP) in patients without evidence of outflow obstruction on high-resolution manometry (HRM); (b) Concordance between EGJ opening classifications on FLIP and integrated relaxation pressure (IRP) on HRM. Four categories of EGJ opening: normal EGJ opening (NEO), borderline normal EGJ opening (BnEO), borderline reduced EGJ opening (BrEO), and reduced EGJ opening (REO). Normal EGJ opening cohort includes patients with NEO and BnEO classifications and abnormal EGJ opening cohort includes those with BrEO and REO classifications on FLIP. *p<0.05 versus normal body mass index (BMI)
Eighty-two patients also completed TBE, with 9 (11.0%) meeting criteria for conclusive EGJOO per CCv4.0. Among 73 patients with no EGJOO, abnormal EGJ classifications on FLIP were again more common in those with elevated BMI than those with normal BMI [65.3% (32/49) vs 41.7% (10/24), p<0.05] (Figure 1a). Notably, TBE was normal in the majority (63.6%) of overweight patients with abnormal EGJ opening on FLIP but normal IRP.
When patients were classified by concordance between IRP on HRM and FLIP measures of EGJ (Table 2), the normal IRP/abnormal FLIP combination was the most common among patients with elevated BMI, while normal IRP/normal FLIP was the most common combination in the normal BMI group (p<0.05) (Figure 1b). Notably, the measured gastric baseline pressure on HRM, which may impact the calculated IRP, did not significantly differ between groups (Table 2). On multivariable analysis adjusting for age, sex, and IRP on HRM, elevated BMI remained an independent predictor for abnormal EGJ opening on FLIP (aOR 1.66, CI:1.03-2.67, p=0.038).
TABLE 2:
Characteristics of categories by esophagogastric junction (EGJ) opening classification on impedance-planimetry (FLIP) and integrated residual pressure (IRP) on high-resolution manometry (HRM).
| Normal EGJ Opening Normal IRP n=27 | Abnormal EGJ Opening Normal IRP n=28 | Normal EGJ Opening Abnormal IRP n=10 | Abnormal EGJ Opening Abnormal IRP n=28 | p-value | |
|---|---|---|---|---|---|
|
| |||||
| Age, years ±SD | 54.7±15.0# | 65.0±12.7* | 57.0±18.7 | 63.2±12.9 | 0.057 |
|
| |||||
| BMI, kg/m2 ±SD | 25.0±4.57# | 28.2±4.09* | 27.9±7.80 | 27.7±5.23 | 0.98 |
|
| |||||
| Female, n (%) | 19 (70.4%) | 18 (64.3%) | 6 (60%) | 21 (75%) | 0.7628 |
|
| |||||
| Symptoms, n (%) | |||||
| Dysphagia | 21 (70.8%) | 23 (82.1%) | 8 (80%) | 24 (85.7%) | 0.90 |
| Regurgitation | 1 (3.7%) | 4 (14.3%) | 0 (0%) | 1 (3.6%) | 0.23 |
| Heartburn | 4 (14.8%) | 4 (14.3%) | 0 (0%) | 1 (3.6%) | 0.29 |
| Chest pain | 3 (11.1%) | 1 (3.6%) | 0 (0%) | 2 (7.1%) | 0.90 |
| Nausea | 0 (0%) | 1 (3.6%) | 0 (0%) | 0 (0%) | 0.90 |
|
| |||||
| IRP, mmHg ±SD | |||||
| Supine | 10.4±5.64@% | 12.7±4.15@% | 38.7±10.6*#% | 30.3±11.5*#@ | <0.0001 |
| Upright | 7.36±6.31@% | 10.3±4.88@% | 39±4.08*# | 30.6±13.7*# | <0.0001 |
| Gastric Baseline, mmHg ±SD | 6.70±4.33 | 8.07±3.26 | 5.72±4.34 | 6.63±4.29 | 0.22 |
|
| |||||
| FLIP EGJ Opening, n (%) | |||||
| NEO | 13 | 0 | 6 | 0 | <0.0001 |
| BnEO | 14 | 0 | 4 | 0 | |
| BrEO | 0 | 16 | 0 | 5 | |
| REO | 0 | 12 | 0 | 23 | |
BMI: body mass index; IRP: integrated relaxation pressure; NEO: normal EGJ opening; BnEO: borderline normal EGJ opening; BrEO: borderline reduced EGJ opening; REO: reduced EGJ opening
p<0.05 vs Normal EGJ Opening/Normal IRP
p<0.05 vs Abnormal EGJ Opening/Normal IRP
p<0.05 vs Normal EGJ Opening/Abnormal IRP
p<0.05 vs Abnormal EGJ Opening/Abnormal IRP
DISCUSSION
FLIP is increasingly utilized to assess esophageal function, with the most evidence in evaluating EGJ distensibility/opening. However, data regarding the impact of specific patient characteristics such as different body compositions on FLIP findings remain limited. In this study, we showed that discordant findings for EGJ opening between FLIP and HRM were more common among patients with elevated BMI, driven by more frequent reduced EGJ opening classifications (REO/BrEO) on FLIP when IRP was normal or conclusive EGJOO was not met. Elevated BMI was also found to be an independent predictor for abnormal EGJ opening on FLIP, even after adjusting for IRP.
Changes in intraabdominal and transdiaphragmatic pressure associated with higher BMI may affect measurements of EGJ function. Prior studies found that IRP is generally higher when measured in the supine compared to upright position8. This difference appeared more pronounced in patients with obesity4, which may be related to higher intraabdominal and EGJ pressure exerted by increased abdominal fat due to gravity. Indeed, increased abdominal compression has been shown to correlate with impaired esophageal clearance9,10. Changing into an upright position may help redistribute abdominal fat and reduce compression, leading to improved bolus passage and lower IRP measured. FLIP is generally performed in a left lateral decubitus or supine position, where the effects of abdominal pressure may be greater due to abdominal fat distribution. This may explain the discrepant findings observed between FLIP and HRM, where both supine and upright increase in IRP are required for EGJOO per CCv4.0.
It is also possible that higher BMI/intraabdominal fat may impair EGJ opening that is more fully captured by FLIP than manometric IRP. Calculation of IRP is dependent on the gastric baseline pressure, with an inverse relationship between the two metrics. As gastric baseline pressure is higher among patients with elevated BMI, the resultant IRP may be falsely low, thereby contributing to the discrepancy between FLIP and HRM findings. However, in our cohort, the baseline gastric pressure on HRM did not significantly differ between those with concordant and discrepant FLIP and HRM findings. The IRP metric also depends on both the nadir lower esophageal sphincter pressure and intrabolus pressure through the EGJ during a primary swallow, while FLIP estimates EGJ opening using pressure and cross-sectional area data during passive distention of a water-filled balloon. FLIP may, therefore, provide a more direct measure of impairment in EGJ opening, whether from intrinsic sphincter abnormalities or extrinsic effects by abdominal pressure, that is independent of bolus flow.
Our study has some limitations. First, this was a retrospective study of patients presenting for evaluation of clinical symptoms, which may impact generalizability. However, the prevalence of reduced or borderline EGJ opening on FLIP was comparable to those found in prior studies1,6. Second, the sample size of this exploratory study precluded further stratification by severity of obesity. Finally, it is unclear if BMI is the optimal surrogate for abdominal pressure/adiposity.
In conclusion, elevated BMI is independently associated with reduced EGJ opening on FLIP, despite normal IRP on HRM. Further studies are needed to better understand the impact of body habitus on measures of esophageal biomechanical properties, and to determine if FLIP metrics should be adjusted based on body composition.
Supplementary Material
Funding:
BH is supported by the NIH/NIDDK award T32DK135449-01.
Footnotes
Potential Conflicts of Interest: WWC served on the advisory board for Phathom Pharmaceuticals, Sanofi Pharmaceuticals, and Regeneron Pharmaceuticals. No other authors have potential conflicts of interest to disclose.
Data Availability:
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
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Supplementary Materials
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.