High-resolution manometry (HRM) allows nuanced evaluation of esophageal motor function, and more accurate evaluation of lower esophageal sphincter (LES) function, in comparison with conventional manometry. Pathophysiologic correlates of gastroesophageal reflux disease (GERD) and esophageal peristaltic performance are well addressed by this technique. HRM may alter the surgical decision by assessment of esophageal peristaltic function and exclusion of esophageal outflow obstruction before antireflux surgery. Provocative testing during HRM may assess esophageal smooth muscle peristaltic reserve and help predict the likelihood of transit symptoms following antireflux surgery. HRM represents a continuously evolving new technology that compliments the evaluation and management of GERD.
Key points
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High-resolution manometry (HRM) is an effective tool to study pathophysiologic motor events in gastroesophageal reflux disease (GERD).
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HRM has clinical utility in excluding esophageal outflow obstruction mimicking GERD.
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Preoperative esophageal HRM can alter surgical decisions and is of clinical value before antireflux surgery.
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Provocative testing during HRM may assess esophageal smooth muscle peristaltic reserve.
Introduction
High-resolution manometry (HRM) marks a major advance in the clinical evaluation of esophageal motor disorders. HRM topographic contour plots, known as Clouse plots, are more intuitive than conventional manometry waveform recordings, allowing for pattern recognition and utilization of software tools for interrogation, thereby reducing interobserver variance in interpretation. This article discusses the use of HRM in evaluating patients with GERD symptoms in terms of both manometric correlates of GERD and motor findings useful in preoperative assessment for antireflux surgery.
Introduction
High-resolution manometry (HRM) marks a major advance in the clinical evaluation of esophageal motor disorders. HRM topographic contour plots, known as Clouse plots, are more intuitive than conventional manometry waveform recordings, allowing for pattern recognition and utilization of software tools for interrogation, thereby reducing interobserver variance in interpretation. This article discusses the use of HRM in evaluating patients with GERD symptoms in terms of both manometric correlates of GERD and motor findings useful in preoperative assessment for antireflux surgery.
Advances in esophageal manometry
Manometry systems are designed to measure the timing and amplitude of pressure events in the esophagus and its sphincters via a linear array of pressure sensors on a catheter. Assimilation, integration, and display systems convert these pressure recordings into electrical signals that can be displayed as pressure waveforms or topographic pressure plots. The roots of HRM began in the mid-1970s when the first high-fidelity manometry system was developed by Jerry Dodds and Ron Arndorfer. This initial system was composed of water-perfused catheters, a pneumohydraulic pump, pressure transducers, and a strip-chart recorder with side holes spaced at 3- to 5-cm intervals. The apparatus was later modified by replacement of the strip-chart recordings with digital-analog converters and a video display on computer screens. Manometry subsequently evolved to the use of solid-state catheters, allowing for circumferential pressure averaging and finer evaluation of the pharynx and upper esophageal sphincter (UES) because of a faster frequency response that was better at sensing striated muscle contraction. Critical to the evaluation of the esophagogastric junction (EGJ), a 6-cm perfused sensor called the Dent sleeve was developed in 1976, which increased the ability of the manometry catheter to remain within the LES during esophageal movement, thereby increasing accuracy in LES assessment.
A major step forward occurred in the 1990s when Ray E. Clouse envisioned and developed HRM. This advance involved a vast increase in sensors on the esophageal manometry catheter, generating pressure data that could be displayed as a spatiotemporal plot using color contours to designate pressures ( Fig. 1 ). Modern HRM systems use circumferential solid-state sensors 1 cm apart, as well as custom assimilation and display software that allows intuitive interpretation using software tools. Because pressure phenomena from the entire esophagus can be visualized at once, sphincters can be easily identified, thus rendering the stationary pull-through maneuver obsolete. Identification of LES relaxation errors improved, and achalasia is now diagnosed with better accuracy. The technique also provided new insights into gastroesophageal reflux disease (GERD) by refining manometric correlates for the condition, both static (LES basal pressures, hiatus hernia) and dynamic (esophageal peristaltic performance), thereby serving as a useful tool in preoperative evaluation before antireflux surgery. In recent years, the Chicago Classification created new standards by which researchers and clinicians analyze Clouse plots to better describe esophageal motor phenomena. However, the Chicago Classification remains fluid and evolving, and new parameters continue to be designed that better evaluate pressure phenomena in the context of GERD.
Pathophysiologic correlates of GERD on HRM
By the Montreal definition, GERD develops when the reflux of stomach contents causes troublesome symptoms and/or complications. The disease is common worldwide and reduces the quality of life. Proton-pump inhibitors (PPIs) are the mainstay of GERD management, working by binding to the H + ,K + -ATPase enzyme in the gastric parietal cell to decrease the production of gastric acid. Although this medication class is excellent at suppressing acid production, 30% to 40% of GERD patients continue to have symptoms because the medication does not reverse the pathophysiology of GERD, since transient lower esophageal sphincter relaxations (TLESRs), thought to be the critical motor event leading to GERD, are not affected by PPIs. Though physiologically useful in allowing uncomfortable gas release from the stomach, TLESRs are pathologic when gastric contents escape into the lower esophagus, leading to symptoms and mucosal injury.
Transient Lower Esophageal Sphincter Relaxations
Early manometric studies demonstrated a higher proportion of TLESRs accompanied by acid reflux in GERD patients in comparison with controls. Holloway and colleagues defined objective conventional manometric criteria for detecting TLESRs, which included the following: absence of swallow, rate of relaxation, nadir LES pressure, duration of LES relaxation, crural diaphragm inhibition, and prominent LES aftercontraction. These criteria, though initially developed for conventional manometry, have also been used to determine the ability of HRM to detect TLESRs. The manometric signature of a reflux event is the common cavity, defined as a simultaneous intraesophageal pressure increase to gastric pressure levels. pH and pH-impedance studies segregate common cavity events occurring with and without reflux of gastric content. These comparative studies show that HRM is at least equal to, if not superior to conventional manometry in evaluating TLESRs, particularly those accompanied by true reflux. Sensitivity for detecting TLESRs associated with reflux is reported to be 96% for HRM and 86% for conventional manometry. The advantage of HRM consists of higher interobserver concordance than conventional manometry (72% vs 25%). Further, HRM also demonstrates that postprandial TLESRs are associated with acid reflux more often than those during fasting, particularly in GERD patients, with increased intragastric pressures during and in the 3 minutes before a TLESR.
Therefore, HRM can replace conventional manometry in the evaluation of TLESRs. However, in clinical evaluation of GERD patients the frequency of TLESRs during a time-limited recording may have less predictive value for patient management than the assessment of the consequence of TLESRs; that is, abnormal pH or reflux parameters on ambulatory pH or pH-impedance monitoring. Therefore, enumeration and evaluation of TLESRs is mostly used in the research setting. Newer motility systems show promise in long-term ambulatory recordings over several hours or even a full day, which may provide overall better understanding of reflux mechanisms.
Barrier Function of the Esophagogastric Junction
EGJ opening with reflux events
HRM has provided a more complete understanding of physiologic EGJ opening and barrier function critical for reflux prevention. Using a combination of HRM, pH probe, endoscopic clips placed at the squamocolumnar junction and 10 cm proximal to the junction, and fluoroscopic examination in the postprandial state, Pandolfino and colleagues demonstrated profound diaphragmatic crural inhibition during TLESRs with reflux, 60% of which occurred during inspiration rather than expiration. Longitudinal muscle contraction in the distal esophagus resulted in esophageal shortening visualized on both manometry and fluoroscopy, and the squamocolumnar junction moved proximal to the crural diaphragm in most instances. LES relaxation was halted by secondary peristalsis (56%), isolated contractions at the distal esophagus (17%), or primary peristalsis (27%). Few reflux episodes fulfilling manometric criteria were confirmed by the pH electrode placed 5 cm above the EGJ, supporting previous observations of the low yield of pH studies in detecting short-segment distal esophageal reflux events. Moreover, crural diaphragm function was reduced in patients with objective evidence of GERD when compared with controls and patients without objective evidence of reflux, and that reduced inspiratory EGJ pressure augmentation was an independent predictor of GERD. When the threshold value for inspiratory augmentation was 10 mm Hg, the sensitivity of predicting EGD or pH-positive GERD was 57% while specificity was 79%.
In these studies, fluoroscopy is used to localize the squamocolumnar junction following endoscopic clip placement. A new technique using an endoscopically placed magnetic clip at the squamocolumnar junction and a nasally placed probe alongside the HRM catheter continuously follows the location of the squamocolumnar junction during physiologic and pathologic LES events. This technique works through the Hall effect, using voltage changes on a semiconductor around the magnetic field generated by the magnetized clip to generate a digital signal that can be superimposed on the HRM Clouse plot. These and other studies show that both LES (and consequently EGJ) basal pressure and the crural diaphragm contribute to the EGJ barrier function. With TLESRs, in addition to LES opening, distal esophageal shortening from longitudinal muscle contraction and a gastroesophageal pressure gradient are essential for reflux to occur. HRM provides an intuitive image-based paradigm in the evaluation of these pathophysiologic correlates of GERD. It complements other contemporary techniques, including fluoroscopy, pH and pH-impedance monitoring, and high-frequency ultrasonography in the study of TLESRs and the LES-diaphragmatic relationship as a barrier function.
Pressure inversion point and hiatus hernia
A disrupted barrier can consist of low LES pressures as well as a separation between LES and the crural diaphragm. Both of these entities are well recognized on clinical HRM studies. The crural diaphragm is visually identified by the pressure signature of inspiratory crural contraction. The plane of pressure inversion between the intrathoracic and intra-abdominal cavities is identified by following color contours generated by intraluminal pressures between swallows in the esophageal and gastric lumens during respiration. Finally, a pressure inversion point (PIP) tool is used to interrogate the respiratory pressure inversion point, which can be moved across the LES high-pressure zone and EGJ to identify the precise plane where pressure inverses. Based on the degree of separation between the LES and the diaphragmatic crura as well as the location of the PIP, Pandolfino and colleagues characterize the EGJ findings with respiration into 4 categories ( Fig. 2 ). It is currently unclear as to whether these designations affect management decisions in GERD.
HRM allows better understanding of the dynamic nature of the relationship between the LES and the diaphragmatic crura, with spontaneous formation and reduction of hiatal hernias as measured by the separation between the LES diaphragmatic crura. Furthermore, HRM may be more accurate than endoscopy in recording the presence of a hiatus hernia. A study assessing endoscopic and HRM diagnosis of axial hiatus hernias greater than 2 cm in size in comparison with diagnosis at surgery documents that despite comparable sensitivity, HRM has higher specificity than endoscopy, with fewer false positives (5% vs 32%; P = .01). This study also describes that HRM has good value in both ruling in and ruling out the presence of an axial hiatus hernia.
In the presence of a large hiatus hernia, the tip of the manometry catheter may coil up within the hiatus hernia and not traverse the diaphragmatic crura. Despite this situation occurring about half the time in hiatus hernias longer than 5 cm, interrogation of the esophageal body motor pattern and the LES remains possible, and this is not considered a critical imperfection of the study. The distribution of esophageal body motor disorders in this setting is no different from that observed in patients without a hiatus hernia. However, an important point is to clarify that the pressure within the hiatus hernia is not elevated above the gastric baseline. Because the integrated relaxation pressure (IRP) is measured above the gastric baseline, elevated intrahernia pressures with pressure trapping within hiatus hernia will falsely lower the IRP if the gastric baseline is measured within the hiatus hernia. In these instances, placement of the catheter under endoscopic guidance may be warranted.
LES hypotension
A low LES end expiratory pressure is seen more often in GERD patients with regurgitation, those with medically refractory heartburn, and those being evaluated for antireflux surgery ( Fig. 3 ). The end-expiratory pressure is chosen as the metric for assessing resting LES pressure, recorded when diaphragmatic crura are relaxed and not contributing to the recorded pressure. A period of quiet rest and normal respiration is used for recording basal sphincter parameters at the beginning of the HRM study, making sure no TLESRs, dry swallows, or other artifacts occur within 30 seconds of the landmark recording period. In a large cohort of subjects referred for preoperative HRM before antireflux surgery, Chan and colleagues reported that the proportion of patients with end-expiratory LES pressure of 5 mm Hg or less was 34.1% in the setting of an abnormal ambulatory pH study, and 13.5% when the pH study was normal. The overall likelihood of LES hypotension in the surgical GERD population was 47.1%.
Esophageal Clearance
Esophageal hypomotility is a motor phenomenon evident on esophageal manometry in the setting of GERD, which, when present, may affect clearance of the refluxate and prolong acid contact with esophageal mucosa. Several terms have been used to describe this phenomenon, including ineffective esophageal motility (IEM) with conventional manometry, and descriptive breaks in the peristaltic contour with HRM. Mechanistically, GERD may lead to hypomotility through direct gastric acid exposure, causing esophageal injury and hypomotility. In turn, hypomotility can exacerbate GERD and predispose to erosive disease through decreased clearance of refluxed acidic contents from the distal esophagus. Peristalsis of weak contraction amplitude, typically less than 30 mm Hg in the distal esophagus, is designated IEM in the esophageal body with conventional manometry. In addition, proportions of failed sequences are reported in this context (see Fig. 3 ).
HRM provides a more detailed topographic map of smooth muscle contraction. Two smooth muscle contraction segments are identified: the proximal (segment 2) with predominantly cholinergic influences, and the distal (segment 3) with predominantly inhibitory influences. Several correlates of esophageal hypomotility are identifiable on an HRM study. The first of these are transition-zone defects (see Fig. 3 ). Though also present in normal subjects, transition-zone defects (intersegmental troughs) between striated and smooth muscle contraction segments are identified in hypomotility states including GERD. These defects are abnormal or visible breaks in the peristalsis contour between these contraction segments. As much as 93% of subjects evaluated had at least 1 identifiable transition-zone defect, so the mere presence of these defects does not imply hypomotility. However, extended transition-zone defects larger than 3 cm were reported more often in GERD patients (45%) than in normal controls and patients without GERD (27%), indicating that extended defects may represent hypomotility. This finding may result from poor formation of adjacent contraction segments, particularly the second segment. Timing of initiation of the second segment measured from initiation of the first segment (termed proximal latency) was delayed longer than 4 seconds in 36% of GERD patients, compared with 20% of healthy controls and 19% of patients without GERD. This result supports the fact that extended transition-zone defects may be associated with delayed onset of smooth muscle contraction, and may represent a hypomotility feature seen more often in the setting of GERD.
Another HRM characteristic of esophageal hypomotility is fragmentation of the smooth muscle contraction pattern, resulting in prominent troughs (breaks) between smooth muscle contraction segments (see Fig. 3 ; Table 1 ). Sometimes one of the contraction segments, particularly the second segment, may fail to form, resulting in large breaks in the peristaltic contour. When both segments fail to form, the sequence is designated as failed. Within the Chicago Classification algorithm, a threshold of 20 mm Hg is used to designate failure of peristalsis, because HRM studies combined with stationary impedance demonstrated that bolus transit may be facilitated by sequences that can generate 20 mm Hg of pressure in the esophageal body. Breaks in the peristaltic contour of less than 2 cm at 20 mm Hg and less than 3 cm at 30 mm Hg were found not to affect esophageal bolus clearance. Although failure of contraction has been characterized with conventional manometry in GERD, fragmentation of the peristaltic contour has only been recognized with the use of HRM.
| Category | Parameter or Metric |
|---|---|
| Clinical | |
| Anatomic | Esophageal length |
| Size of hiatus hernia | |
| LES length | |
| Length of intra-abdominal LES | |
| LES | End-expiratory LES pressure |
| Postswallow residual pressure (IRP) | |
| Esophageal body | Contraction amplitudes |
| Distal contractile integral (DCI) | |
| Transition zone defect, breaks, fragmentation | |
| Degree of hypomotility a | |
| Response to multiple rapid swallows (MRS) | |
| Research | |
| LES | Transient lower esophageal sphincter relaxations (TLESRs) |
| LES pressure integral, EGJ contractile integral | |
| 3-Dimensional structure of the LES | |
| Esophageal body | Response to provocative maneuvers |
a See Table 2 .
Comparison of the frequency of fragmentation of smooth muscle contraction segments demonstrated that patients with documented GERD, particularly those with Barrett esophagus, were more likely to demonstrate fragmented sequences when compared with controls and those without GERD, similar to the gradient in failed sequences. Patients with GERD also demonstrated lower peak and averaged contraction amplitudes in the esophageal body in comparison with controls and those without GERD. Whereas 8% of controls demonstrated fragmented sequences, 18% of GERD patients and 25% of those with Barrett esophagus demonstrated this finding. A combination of 30% failed or fragmented sequences could segregate GERD patients from controls (34% GERD patients, 8.4% controls; P = .04); 70% of those with Barrett esophagus met this threshold. When fragmented, the second esophageal segment was more likely than the third segment to be compromised (diminished or absent in 82%). These findings support the identification of fragmented and failed sequences as markers of esophageal hypomotility ( Fig. 4 ).
