Diagnosis of Esophageal Motor Disorders

Esophageal motor disorders comprise a diverse group of diagnoses defined by an altered pattern and vigor of contractions and sphincter dysfunction. They commonly present with dysphagia or chest pain but also may be associated with heartburn, regurgitation, and globus sensation. The diagnosis of nonachalasic esophageal motor disorders requires normal endoscopy and esophageal biopsies followed by esophageal manometry.

Manometric testing previously lacked standardization, with variability between devices and protocols. The introduction of the Chicago Classification version 4.0 (CCv4.0), an international consensus, helped to improve the reproducibility of testing and establish diagnostic criteria for esophageal motility disorders identified on high-resolution manometry (HRM).¹

Although HRM is considered the gold standard for diagnosing esophageal motor disorders, other tests—including upper endoscopy, barium swallow, barium swallow with a tablet, timed barium esophagram (TBE), fluoroscopy, and endoscopic ultrasound—commonly are used for diagnostic support. Newly developed diagnostic tools, such as combined impedance/HRM and functional lumen imaging probe (FLIP) planimetry, allow for better assessment of esophageal body and sphincter function. New maneuvers that have been incorporated into the HRM protocol offer better diagnostic and prognostic information. Diagnostic testing for esophageal motor disorders remains an area of intense research due to the continued need for more accurate and simplified tools.

Basics of Esophageal Manometry

Manometric testing should be considered for any patient presenting with either dysphagia or chest pain and normal endoscopy (ie, the absence of ulceration, obstruction, or inflammation) and with unremarkable esophageal biopsies. When available, HRM is preferred over other diagnostic tests.¹ HRM is performed using an array of pressure sensors spaced approximately 1 to 2 cm apart. This approach allows for real-time, simultaneous measurements of pressures spanning the entire esophageal lumen and both sphincters. Older arrays used sensors spaced out at greater than 3-cm intervals, resulting in lower resolution and reduced diagnostic accuracy.

HRM pressure tracings are visualized using esophageal pressure topography, in which time is plotted in seconds along the x-axis and location within the esophagus is plotted in centimeters along the y-axis. Pressure is represented as a continuous color scale along the Cartesian coordinate system, with blue (“cool”) colors representing lower pressures and red (“hot”) colors higher pressures.

New to CCv4.0 is an updated standardized protocol for performing esophageal manometry. Patients should fast for at least 4 hours before testing, although small volumes of clear liquids are acceptable. The HRM catheter is placed into the esophageal lumen via nasal intubation, and testing is started with the patient in the supine position. On placement of the catheter, the patient is allowed 60 seconds for adaptation, after which the patient takes at least 3 deep inspirations to confirm catheter positioning. Baseline measurements are recorded for 30 seconds followed by 10 swallows of 5 mL of fluid (room temperature water, or saline if impedance measurements also are being performed). Swallows should be at least 30 seconds apart to prevent deglutitive inhibition. Supine testing concludes with a multiple rapid swallow (MRS) sequence of 5 liquid swallows, 2 mL each, administered using a 10-mL syringe, 2 to 3 seconds apart.^2,3 The protocol is repeated with the patient in the upright position, with 5 or more wet swallows followed by a rapid drink challenge (RDC) that involves swallowing 200 mL of fluid as quickly as possible through a straw instead of an MRS sequence.⁴

Diagnoses are based on manometric results from the 10 wet swallows in the primary testing position. The secondary testing position and provocative maneuvers are used to support or exclude the suspected diagnosis. If results from the secondary position differ from those obtained in the primary position, additional testing, such as a solid test meal (STM), pharmacologic provocation, TBE, or endoluminal FLIP, may be required.^5,6

Key manometric measures include integrated relaxation pressure (IRP), distal contractile integral (DCI), and distal latency. These metrics form the basis of the diagnostic criteria for esophageal motor disorders.

IRP reflects the adequacy of esophagogastric junction (EGJ) relaxation in response to swallowing. It is calculated by averaging the minimum EGJ pressure over 4 seconds of relaxation within 10 seconds of upper esophageal relaxation. The upper limit of normal IRP depends on patient positioning and which equipment is used. In the supine position, an abnormal IRP is at least 15 mm Hg (Medtronic) or at least 22 mm Hg (Laborie/Diversatek).⁷ In the upright position, an abnormal IRP is at least 12 mm Hg (Medtronic) or at least 15 mm Hg (Laborie/Diversatek).

DCI, a measure of esophageal contractile vigor, is an integrated value of the mean contractile amplitude, length, and time within the distal esophagus.^8,9 A normal DCI value is between 450 and 8,000 mm Hg•s•cm. Ineffective swallows include weak (100-450 mm Hg•s•cm), failed (<100 mm Hg•s•cm), and fragmented contractions. Fragmented contractions are represented by a break within the 20-mm Hg isobaric contour that is greater than 5 cm with a normal DCI.¹ A swallow is defined as hypercontractile if the DCI exceeds 8,000 mm Hg•s•cm.¹

Distal latency is measured as the time from upper esophageal sphincter relaxation to the contractile deceleration point (CDP), the transition point from the proximal rapid to distal slow esophageal contraction. This correlates anatomically with the beginning of the globular phrenic ampulla, a temporary structure formed by the elongated and elevated lower esophageal sphincter (LES).¹⁰ Physiologically, this represents the transition from peristaltic transport to ampullary emptying. Identifying the CDP can be challenging, but it can be pinpointed using the 30-mm Hg isobaric contour on esophageal pressure topographic plots. Two tangent lines are drawn: one along the slope of the initial, rapid contraction, and another extending proximally from EGJ along the slow contraction wave front. The intersection point of the 2 lines represents the CDP. Criteria dictate that the CDP should be within 3 cm of the EGJ proximal border.¹¹ The lower limit of normal for distal latency is 4.5 seconds, and in the setting of a normal DCI, distal latency less than 4.5 seconds is considered a premature contraction.⁹

Diagnosis of Esophageal Motor Disorders

HRM is considered the gold standard for the diagnosis of esophageal motor disorders. Before HRM is performed, endoscopy with possible esophageal biopsies should be considered to exclude any mechanical obstruction, mucosal ulceration, or inflammation that may otherwise explain a patient’s symptoms. In patients with suspected achalasia and those with esophageal dysphagia with a history of radiotherapy, caustic ingestion, or laryngeal surgery, barium swallow may be offered first.

Esophageal motor disorders are divided into 2 categories based on IRP: EGJ outflow abnormalities, suggested by an elevated median IRP, and peristaltic disorders, indicated by a normal IRP. Occasionally, HRM testing is inconclusive, with borderline measurements. A definitive diagnosis may require supportive testing in the form of pharmacologic provocation, TBE, or FLIP. Figure 1 demonstrates a diagnostic algorithm for esophageal motor disorders.

Figure 1. Diagnostic algorithm for esophageal motor disorders.

CCv4.0 Hierarchical Classification Scheme that defines the flow process of how the CCv4.0 diagnosis is generated within the constructs of the various phases of the protocol. In this conceptual model, the current protocol allows for some flexibility if the diagnosis is conclusive with 10 swallows in either the primary supine or upright position and allows for a sequenced progression of the protocol to help confirm or rule out the diagnosis. The flow diagram represents the optimal flow process, but exceptions will exist based on the fact that some cutoffs are arbitrary and the model assumes that a motility expert or a highly qualified motility technician or nurse is performing the protocol and analysis.

^a Patients previously defined absent contractility based on 10 swallows in the primary position may have achalasia if IRP is elevated in an alternate position with RDC and/or MRS. These cases should be considered inconclusive for type 1 or II achalasia as appropriate and evaluated further with TBE/FLIP.

^b Denote manometric patterns of unclear clinical relevance. A clinically relevant conclusive diagnosis requires additional information, which may include clinically relevant symptoms and/or supportive testing.

^c RDC, solid test swallows, and/or pharmacologic provocation can be instituted to assess for obstruction.

^d Patients with EGJ obstruction and peristaltic swallows would fulfill strict criteria for EGJOO and may have features suggestive of achalasia or other patterns of peristalsis.

^e If no evidence of a disorder of peristalsis or EGJ outflow in patients with high probability of missed EGJOO, STM can be added to rule out obstructive pattern; if abnormal, the possibility of mechanical obstruction should be readdressed. In patients with regurgitation or belching, postprandial high-resolution impedance monitoring can be used to assess for rumination/belching disorder.

DCI, distal contractile integral; EGJ, esophagogastric junction; EGJOO, esophagogastric outflow obstruction; FLIP, functional lumen imaging probe; IBP, Intrabolus pressurization; IRP, integrated relaxation pressure; LES, lower esophageal sphincter; MRS, multiple rapid swallow; PEP, panesophageal pressurization; RDC, rapid drink challenge; TBE, timed barium esophagram

Adapted from reference 1 with permission.

EGJ Outflow Abnormalities

The presence of an elevated median IRP suggests an EGJ outflow abnormality. Disorders of elevated IRP include achalasia and EGJ outflow obstruction (EGJOO). During HRM, an elevated median IRP should be observed in both the supine and upright positions.¹

Achalasia is classified into 3 subtypes, all of which are characterized by an elevated median IRP and the complete absence/failure of peristalsis. Type I achalasia (classic) is defined by an abnormal median IRP and absent contractility.^12-15 Type II achalasia has similar diagnostic requirements (increased IRP and 100% lack of peristalsis) but is distinguished by the presence of panesophageal pressurization in at least 20% of observed swallows.^12-15 Type III achalasia (spastic) is differentiated by the presence of esophageal spasm in at least 20% of swallows.^12-15 Type III achalasia has been shown to be associated with chronic opioid use; given this, testing should be performed with opioids held if possible.¹⁶ When the diagnosis for any type of achalasia is inconclusive, especially when the IRP is borderline or within normal range, additional testing with TBE and/or FLIP often is required.^5,6,17-20

In contrast to achalasia, EGJOO requires an abnormal median IRP in both the supine and upright positions. In addition, at least 20% of swallows should demonstrate elevated intrabolus pressures in the supine position with intact peristalsis.^21-25 Unlike achalasia, EGJOO can be a manometric finding without clinical significance. In addition, the diagnosis of EGJOO may be erroneous, with manometric findings representing developing achalasia or mechanical obstruction. For EGJOO to be deemed clinically relevant, dysphagia or chest pain must accompany manometric findings.^22,23,26,27 Further supportive testing, such as TBE or FLIP, also should be implemented to reinforce the presence of nonmechanical EGJ obstruction.^5,6,17,21 Because EGJOO may be a transient phenomenon, commonly due to medication use, some clinicians elect to repeat HRM after 6 months to ensure durability of the motility finding.²⁸

The importance of performing HRM in both the supine and upright positions is demonstrated in Figure 2. A patient is shown to have an abnormally elevated IRP in the supine position, which resolves with upright swallows.

Figure 2A. Abnormally elevated median IRP in the supine position during 10 wet swallows in a patient with dysphagia. Ten swallows in the supine position revealing an abnormally high IRP.

CFV, contractile front velocity; DCI, distal contractile interval; IRP, integrated relaxation pressure; LES, lower esophageal sphincter; UES, upper esophageal sphincter

Figure 2B. Normal IRP in upright position in same patient during a wet swallow. Representative of 1 of 5 upright wet swallows (all with normal IRP).

CFV, contractile front velocity; DCI, distal contractile interval; IRP, integrated relaxation pressure; LES, lower esophageal sphincter; UES, upper esophageal sphincter

Provocative testing and certain manometric observations can support the diagnosis of EGJOO. These include outflow obstruction and pressurization during RDC, outflow obstruction during STM swallow with accompanying clinical symptoms, and pharmacologic provocation with amyl nitrite revealing abnormal EGJ function.^4,29-33

When a diagnosis of EGJOO is made, the accompanying contractile pattern—for example, EGJOO with hypercontractility, EGJOO with absent peristalsis, EGJOO with normal peristalsis, or EGJOO with ineffective motility (IEM)—should be described because case series from various institutions have demonstrated that EGJOO can coexist with disorders of peristalsis.¹ The accompanying contractile pattern may indicate the treatments to which a patient will likely respond.³³

Peristaltic Disorders

Esophageal motor abnormalities with a normal IRP are categorized as disorders of peristalsis. These include distal esophageal spasm (DES), hypercontractile esophagus, absent contractility, and IEM. Patients may have overlapping features of multiple peristaltic disorders. When this is the case, a diagnostic hierarchy should be applied in the order of DES, hypercontractile esophagus, and finally IEM.¹

DES is defined as at least 20% of swallows with premature contractions in the context of normal IRP and DCI. Premature contractions are identified on HRM as a distal latency less than 4.5 seconds. Like EGJOO, DES can be observed on HRM but may lack clinical significance. Thus, for DES to be clinically relevant, manometric findings should correlate with symptoms of either chest pain or dysphagia.³⁴ An inconclusive diagnosis of DES occurs when at least 20% of the swallows are premature, but the DCI is less than 450 mm Hg•s•cm. When an inconclusive diagnosis is encountered, supportive testing can be considered. MRS support the diagnosis of DES when the absence of deglutitive inhibition is noted.³⁵ DES also should be suspected when barium esophagram reveals a corkscrew, or rosary bead–shaped esophagus.^36,37 Finally, DES is considered when FLIP demonstrates persistent obstructing contractions or cyclic retrograde contractions in the esophageal body during esophageal distention.¹⁸

Per the hierarchal order, the next peristaltic disorder to consider is hypercontractile esophagus. This disorder is defined as at least 20% of swallows with a DCI greater than 8,000 mm Hg•s•cm.^38-40 IRP must be normal and mechanical obstruction should be excluded via index endoscopy. The exclusion of mechanical obstruction is crucial, because obstruction may provoke a hypercontractile response. Similar to DES, one should distinguish between clinically relevant and irrelevant hypercontractile esophagus based on the presence of typical symptoms (chest pain and dysphagia).^41,42 Hypercontractile esophagus is further divided into 3 subgroups: single-peaked hypercontractile swallows, jackhammer with repetitive prolonged contractions, and hypercontractile swallows with vigorous LES after-contraction.⁴³ Although differentiating between the hypercontractile subtypes is outside the scope of this review, jackhammer tends be of greater clinical interest because it is associated with higher DCI values and greater symptom severity.⁴⁴

Absent contractility is defined as 100% failed peristalsis (DCI <100 mm Hg•s•cm) in the setting of a normal IRP in both the supine and upright positions.¹ Ensuring a normal median IRP in both positions is crucial because it is the only feature differentiating hypercontractile esophagus from type I achalasia. If IRP values are borderline elevated and the predominant symptom is dysphagia, type I achalasia should be included in the differential diagnosis. Confirmatory testing with TBE and/or FLIP should be performed.

The final diagnosis under peristaltic disorders is IEM. Previous versions of the Chicago Classification listed IEM and fragmented peristalsis as “minor disorders.” With CCv4.0, fragmented peristalsis has been incorporated into IEM, and the distinction between major and minor peristaltic disorders has been removed. The criterion for diagnosing IEM requires at least 70% ineffective swallows, defined as a DCI between 100 and 450 mm Hg•s•cm, or at least 50% failed swallows, defined as a DCI less than 100 mm Hg•s•cm.^45-48

Supportive Testing

Occasionally, manometric testing may return inconclusive or equivocal results, such as conflicting measurements in the supine versus seated positions, measurements inconsistent with clinical presentation, or indications of an EGJOO that does not fully meet the criteria for achalasia. Under these circumstances, supportive testing can assist with further delineation of esophageal motor patterns while supporting or challenging a specific diagnosis. Various HRM maneuvers and diagnostic tools have been proposed as supportive tests. A summary of supportive tests endorsed by CCv4.0 can be reviewed in Table 1.

Table. Supportive Maneuvers and Testing to High-Resolution Esophageal Manometry in Patients Suspected of Esophageal Motor Abnormality
Test		Description	Normal Response	Utility
Multiple rapid swallows		While supine, the patient performs 5 liquid swallows, 2 mL each, at 2- to 3-s intervals	Absent esophageal contractions and deglutitive inhibition of the LES, with an augmented peristaltic after-contraction at end of sequence	Evaluates peristaltic reserve; predicts dysphagia in patients who have undergone antireflux surgery; diminished after-contraction supports diagnosis of ineffective motility
Rapid drink challenge		While upright, the patient drinks 200 mL of fluid quickly through a straw	Absent esophageal contractions and inhibition of the LES, without any significant motility abnormalities observed after completion; an augmented after-contraction does not need to be present	Acts as a “stress test” of the EGJ; associated with outflow obstruction and may predict which patients with EGJOO will respond to therapy; elevated IRP or panesophageal pressurization during RDC supports the diagnosis of outflow obstruction
Solid test swallows		The patient performs 10 swallows of soft, solid foods (bread, boiled rice, marshmallows) each approximately 1 cubic cm in size	20% pharyngeal swallows followed by an effective peristaltic contraction (DCI >1,000 mm Hg•s•cm) and no breaks within the 20-mm Hg isobaric contour >5 cm	May be superior to water swallows in identifying patients with clinically relevant EGJOO who will respond to therapy
Solid test meals		The patient consumes 200 g of a soft, solid meal at a comfortable pace within 8 min	>20% pharyngeal swallows followed by an effective peristaltic contraction (DCI >1,000 mm Hg•s•cm) and no breaks within the 20-mm Hg isobaric contour >5 cm; patient should finish meal within 8 min	Elevated IRP or panesophageal pressurization supports diagnosis of outflow obstruction
Postprandial meal		Continued manometric recording for at least 10 min after completion of a meal (solid test or otherwise)	=4 transient LES relaxations during first 10 min and no regurgitation or rumination	Identification of rumination or belching disorder
	Amyl nitrite	While recumbent, the patient performs 4-5 sniffs of amyl nitrite	Significant relaxation of distal esophagus and LES; amyl nitrite–induced IRP should be similar to deglutitive IRP	Can differentiate LES dysfunction from mechanical obstruction/stricture; also distinguishes opioid-induced type III achalasia from idiopathic etiologies; may identify EGJOO patients who may respond to LES ablative therapies; supports diagnosis of EGJOO
	Cholecystokinin	While recumbent, patient receives a 40-ng/kg infusion	Esophageal shortening (typically <2 cm) after infusion, followed by partial EGJ relaxation	Distinguishes between opioid-induced type III achalasia and idiopathic etiologies; can differentiate absent esophageal contractility from type I achalasia when IRP measurement is borderline abnormal; supports diagnosis of EGJOO
Timed barium esophagram		Patient swallows 100-250 mL of barium sulphate with radiographs obtained at times 1, 3, and 5 min; an optional barium tablet may be combined with the liquid barium.	Complete emptying of barium within 5 min	Can assess response to therapy after pneumatic dilation in achalasia and idiopathic EGJOO; can differentiate EGJOO from type I achalasia; supportive test for diagnosing clinically relevant EGJOO
Functional luminal impedance		FLIP catheter is placed into the esophagus during endoscopy and a balloon inflated to measure esophageal compliance and distensibility	EGJ-DI >2.8 mm2/mm Hg, distensibility plateau >18 mm, and antegrade contractions in repetitive pattern	Reduced EGJ-DI, decreased maximal EGJ diameter, absent peristalsis during esophageal distension all support diagnosis of achalasia; can predict response to achalasia-type therapy in EGJOO patients; supportive test for diagnosing clinically relevant EGJOO
DCI, distal contractile integral; EGJ, esophagogastric junction; EGJ-DI, esophagogastric junction distensibility index; EGJOO, esophagogastric outflow obstruction; FLIP, functional lumen imaging probe; IRP, integrated relaxation pressure; LES, lower esophageal sphincter; RDC, rapid drink challenge Adapted from reference 1 with permission.

Multiple Rapid Swallows

MRS are included as part of the standardized HRM protocol. An MRS sequence is executed at the end of supine testing, with the patient asked to perform 5 liquid swallows of 2 mL each administered at 2- to 3-second intervals.^2,3 A normal response is the absence of esophageal contractions (DCI <100 mm Hg•s•cm) and complete deglutitive inhibition of the LES during the MRS sequence, with an augmented peristaltic after-contraction at the end of the sequence. The augmented contraction should have a DCI greater than the mean DCI of a single swallow.^3,49-51 For MRS function to be normal, the inhibitory and excitatory neural pathways within the esophagus, as well as the integrity of the esophageal muscle, must be intact.

Studies have demonstrated that MRS reflects the peristaltic motor reserve of patients with esophageal symptoms and hypotensive peristalsis.⁵² This has various applications, such as supporting the diagnosis of DES when deglutitive inhibition is absent.³⁵ MRS also can suggest a diagnosis of EGJOO when an upright IRP greater than 12 mm Hg is observed during rapid swallows.⁵¹ Rapid swallows also can have prognostic utility; the absence of an augmented contraction at the end of an MRS sequence is predictive of late postoperative dysphagia after antireflux surgery.³ Finally, the vigor of the MRS after-contraction has been shown to be inversely correlated with acid exposure time in patients with nonerosive reflux disease or IEM.^50,53 In light of the above-mentioned evidence, the lack of peristaltic reserve during MRS supports the diagnosis of IEM.¹

Rapid Drink Challenge

Like MRS, the RDC also is part of the standardized HRM protocol. It is performed at the end of upright testing and entails having the patient drink 200 mL of fluid quickly through a straw. A normal response is complete deglutitive inhibition of peristalsis (DCI <100 mm Hg•s•cm) and the LES during the RDC, without any significant motility abnormalities after completion.¹ Unlike in MRS, during RDC an augmented after-contraction is less readily assessed and may be absent in healthy controls. However, a greater esophagogastric pressure gradient is generated, allowing for better evaluation of esophageal outflow resistance.⁴⁹ Therefore, the focus of MRS is primarily the vigor of the after-contraction, whereas the focus of RDC is the IRP.

RDC has been shown to act as a “stress test” for the EGJ. The mean IRP during an RDC is predictive of radiographically confirmed outflow obstruction (sensitivity of 100% and specificity of 85.5% in untreated patients) and correlates with the Eckardt symptom score in patients with achalasia.^4,51 A study comparing healthy controls with patients with dysphagia and reflux symptoms established an elevated RDC-IRP as an accurate measure of outflow obstruction, with a sensitivity and specificity greater than 90%.⁵⁴ In addition to IRP measurements, stereotypical pressurization patterns have been observed during RDC, which may help identify motor disorders in patients with otherwise normal manometry.⁵⁵ More recently, RDC has been shown to be superior to standard 5-mL water swallows in identifying patients with clinically relevant EGJOO who are likely to respond to therapy.²⁹ Overall, an upright IRP greater than 12 mm Hg, or panesophageal pressurization greater than 20 mm Hg (measurement cutoffs based on Medtronic HRM catheter), during RDC support the presence of outflow obstruction.

Solid Test Swallows and Meals

Solid test swallows and meals have been introduced as an adjunct to the fluid swallows in the standardized HRM protocol. Solid test swallows comprise 10 swallows of soft, solid foods, such as bread, boiled rice, or marshmallows, each approximately 1 cm³ in volume. An STM is analogous to an RDC, with the patient consuming 200 g of a soft, solid meal at a comfortable pace. The test is stopped once the patient has completed the meal or 8 minutes have elapsed, whichever comes first. A normal response for both solid test swallows and meal is greater than 20% pharyngeal swallows followed by an effective peristaltic contraction with DCI greater than 1,000 mm Hg•s•cm and no breaks within the 20-mm Hg isobaric contour greater than 5 cm. For the STM, any symptoms that arise should be recorded, and an inability to finish the meal in 8 minutes is considered abnormal and should be noted.¹

Clinicians may elect to perform postprandial meal measurements, continuing manometric recording for at least 10 minutes after completion of an STM or other solid meal. A normal response is considered the absence of symptoms or abnormal motility. No more than 4 transient LES relaxations should be observed during the first 10 minutes, and no regurgitation or rumination should be seen.¹ The use of postprandial HRM immediately after an STM is the best diagnostic approach to identify rumination or belching disorder.

Solid test swallows, similar to RDC, were noted to be superior to water swallows in identifying patients with clinically relevant EGJOO who were likely to respond to therapy.²⁹ The utility of STM in increasing the diagnostic sensitivity of HRM was established by a large cohort study of 750 patients presenting with esophageal symptoms. STM was found to identify esophageal motor disorders among patients with a primary complaint of dysphagia.³⁰ Further evidence for the diagnostic utility of STM was demonstrated in a study evaluating HRM with STM results in healthy volunteers and patients with major motility disorders.³¹ Patients with motility disorders ate slower than healthy controls, and pathologic contractile patterns were reproduced readily. STM is considered a supportive test for the diagnosis of outflow obstruction by revealing an IRP greater than 25 mm Hg and/or panesophageal pressurization greater than 20 mm Hg (measurement cutoffs based on Medtronic HRM catheter).¹

Esophageal Impedance Monitoring

Impedance refers to the measurement of electrical resistance between closely arranged electrodes mounted on an intraluminal catheter. The directional movement of an intraluminal bolus and its contents can be determined during impedance monitoring. Air has a high impedance, whereas liquid (swallowed or refluxed) has a low impedance. A limitation of impedance monitoring is the inability to determine the volume of an intraluminal bolus.⁵⁶

Impedance monitoring has been shown to support the diagnosis of IEM. A study comparing 33 patients with IEM and 44 patients with normal motility testing demonstrated that a decreased bolus clearance percent is associated with IEM.⁵⁷ The utility of impedance monitoring for identifying impaired bolus transit has been further supported by studies showing agreement between abnormal impedance and impaired clearance on barium swallow.⁵⁸ Consequently, poor bolus transit observed during impedance monitoring supports the diagnosis of IEM.

Pharmacologic Provocation

Pharmacologic provocation refers to the use of compounds to stimulate the esophagus during HRM. Commonly used agents include amyl nitrite and cholecystokinin.

Amyl nitrite provocation is performed by having the patient inhale 0.3 mL of the compound in the recumbent position.⁵⁹ A normal response is significant relaxation of the distal esophagus and LES. In a healthy individual, the IRP is comparable to the deglutitive IRP after amyl nitrite inhalation, but patients with outflow obstruction secondary to LES dysfunction experience a profound drop in the IRP compared with the deglutitive IRP, with a difference of 10 mm Hg or greater. Patients with mechanical obstruction or stricture experience an IRP difference less than 10 mm Hg.¹

Cholecystokinin provocation is performed during HRM by infusing 40 ng/kg intravenously while the patient is in the recumbent position. A normal response is esophageal shortening followed by partial EGJ relaxation. In patients with achalasia and inhibitory dysfunction, cholecystokinin infusion results in a paradoxical contraction of the LES greater than 50 mm Hg.¹

A proposed use of pharmacologic esophageal stimulation during HRM is to distinguish between opioid-induced type III achalasia and idiopathic type III achalasia. After amyl nitrite inhalation, patients with opioid-induced type III achalasia demonstrate diminished esophageal contraction pressures. When cholecystokinin is administered, patients with opioid-induced type III achalasia exhibit an attenuated paradoxical contraction of the EGJ. Furthermore, patients with opioid-induced type III achalasia have 100% relaxation during the second phase of cholecystokinin response, as opposed to 26% relaxation for patients with idiopathic type III achalasia.⁵⁹

Another suggested use of pharmacologic provocation is to differentiate between absent contractility and type I achalasia among patients with borderline IRP measurements.⁶⁰ The use of amyl nitrite inhalation also may provide useful prognostic information by identifying EGJOO patients who may respond to LES ablative therapies. A study of 49 patients with true EGJOO revealed that only half demonstrate impaired LES relaxation during amyl nitrite inhalation. Patients with a drop in IRP that is greater than 10 mm Hg were hypothesized to respond better to LES-targeted therapies.³²

Timed Barium Esophagram

TBE can assist in identifying esophageal outlet obstruction. A patient swallows 100 to 250 mL of barium sulfate, and radiographs are obtained at set time intervals. The height and width of the retained barium column is measured to assess esophageal emptying.⁶¹ A small barium tablet (approximately 13 mm in diameter) sometimes is used in combination with liquid barium to better isolate delayed emptying and areas of retention.⁶² A healthy adult should show complete emptying of barium within 5 minutes.

Another potential application of TBE is differentiating between achalasia and nonachalasia dysphagia. Barium height of greater than 2 cm at 5 minutes has a sensitivity of 85% and specificity of 86% for achalasia. Combining TBE with a radiopaque tablet increases diagnostic yield for achalasia to 100%.¹⁷ TBE also has been used to assess response to therapy, such as pneumatic dilation in achalasia and idiopathic EGJOO.^63,64 In certain patients with clinical features of achalasia and normal IRP, impaired LES relaxation may be identified only during TBE.⁶⁵ Despite its many uses, TBE is limited by its inability to distinguish between anatomic obstruction and functional EGJOO.⁵

TBE has been shown to support the diagnosis of both EGJOO and achalasia. Esophageal contrast retention or delayed tablet transit suggests achalasia. TBE also is recommended for supportive testing in patients who have an inconclusive diagnosis of achalasia and a primary symptom of dysphagia. Lastly, TBE (in addition to FLIP) is considered a supportive test for diagnosing clinically relevant EGJOO.¹

Endoluminal FLIP

FLIP is a newer technology that measures the mechanical forces of the esophagus by using impedance planimetry during controlled luminal distention. The resultant luminal cross-sectional area and pressure measurements can be used to assess various mechanical properties of the esophagus, including its compliance and distensibility. In addition to providing novel planimetric measurements, FLIP testing can be performed during the index esophageal endoscopy.

Although the full application of FLIP continues to be explored, various uses have been investigated. A reduction in the EGJ distensibility index, decreased maximal EGJ diameter, and absence of peristalsis with esophageal distention all support the diagnosis of achalasia.¹⁸ Furthermore, FLIP can be used in patients with EGJOO to predict who may respond to achalasia-directed therapy. A low EGJ distensibility index predicts a better response to interventions used in achalasia, whereas patients with a normal EGJ distensibility index respond better to conservative management.⁶ Finally, FLIP has shown that a certain subset of patients with clinical and radiographic features of achalasia, but normal IRP on HRM and reduced EGJ distensibility index, are likely to respond positively to achalasia treatment.¹⁹ FLIP, as with TBE, is considered a supportive test for the diagnosis of achalasia and clinically relevant EGJOO.

Conclusion

HRM is considered the main diagnostic tool for esophageal motor disorders, supported by tests such as TBE and FLIP. Novel diagnostic maneuvers have been incorporated into the current HRM protocol. These help to better identify esophageal motor abnormalities in symptomatic patients, primarily those with dysphagia and chest pain. In addition, they help to elicit motor abnormalities in symptomatic patients who appear to have normal or nonspecific changes on HRM that do not explain their symptoms. The addition of new diagnostic maneuvers to the current protocol of HRM significantly prolongs the test, but they are essential for diagnostic accuracy and could prevent unnecessary treatment. It also is important to recognize that some of the diagnosed esophageal motor disorders are transient, commonly due to medication use, and thus repeat testing after several months may be needed to demonstrate durability. Furthermore, the importance of TBE and FLIP as supportive tests for establishing or ruling out the diagnosis of esophageal outlet obstruction has been recognized and incorporated into the diagnostic workup of esophageal motor disorders such as achalasia and EGJOO.

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Dr Ronnie Fass reported financial relationships with AstraZeneca, Clexio Biosciences, Daewoong, Diversitek, Eisai, GerdCare, Johnson & Johnson, Medtronic, Neurogastrx, Phathom and Takeda. Dr Ofer Fass reported no relevant financial disclosures.

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Diagnosis of Esophageal Motor Disorders

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