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Keywords:

  • high-resolution manometry;
  • hypercontractile;
  • nutcracker esophagus

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Original Definition Using Conventional Manometry
  5. Characterization of Hypertensive Peristaltic Contractions with HRM
  6. Definition of Hypertensive Peristaltic Disorders with HRM
  7. Conclusion
  8. Conflict of Interest
  9. Author Contributions
  10. References

Background  Esophageal motility abnormalities include a series of manometric findings that differ to a significant degree from findings in normal, asymptomatic volunteers.

Methods  Current review summarizes conventional and high-resolution esophageal manometry criteria used to define and characterize esophageal hypertensive motility abnormalities.

Key Results  In the conventional esophageal manometry classification scheme hypertensive esophageal motility abnormalities include nutcracker esophagus (average distal contraction amplitude >180mmHg), hypertensive lower esophageal sphincter (average resting LES pressure >45mmHg) and poorly relaxing lower esophageal sphincter (average LES residual pressure >8mmHg). The new, high resolution esophageal manometry scheme includes in the group of hypertensive peristaltic disorders hypertensive peristalsis (“nutcracker esophagus”: mean DCI >5000 mmHg*sec*cm) and hypercontractile esophagus (“jackhammer esophagus”: at least one contraction with DCI > 8,000 mmHg*sec*cm) and defines a separate group for disorders with impaired esophageal-gastric junction relaxation (mean integrated residual (LES) pressure >15mmHg).

Conclusions & Inferences  Hypertensive motility disorders represent a heterogeneous condition subdivided into hypercontractile esophagus and hypertensive peristalsis. Further studies are required to determine the clinical relevance of this new classification.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Original Definition Using Conventional Manometry
  5. Characterization of Hypertensive Peristaltic Contractions with HRM
  6. Definition of Hypertensive Peristaltic Disorders with HRM
  7. Conclusion
  8. Conflict of Interest
  9. Author Contributions
  10. References

Esophageal motility abnormalities are, with the exception of achalasia and scleroderma esophagus, esophageal manometry findings that differ to a significant degree from findings in normal individuals. Hypertensive esophageal peristalsis also known as ‘nutcracker esophagus’ has been reported in association with dysphagia, non-cardiac chest pain,1 and heartburn.2 Their physiopathology remains unclear and different hypotheses have been suggested. A primary neuromuscular disorder was suspected. Contrary to esophageal spasm which is associated with impaired deglutitive inhibition,3 central, and inhibitory mechanisms induced by repetitive swallows are preserved in nutcracker esophagus.4 Vigorous esophageal contractions may be related to excessive excitation or myocyte hypertrophy.5 Using concomitant esophageal manometry and high frequency intraluminal ultrasound examination, increased esophageal muscle thickness was observed in patients with hypertensive contractions. Asynchrony between the circular and longitudinal muscularis propria contractions was also observed in these patients.6 Finally this asynchrony might be reversed by atropine.7 Therefore, these findings support the concept that excessive cholinergic drive could be an important pathophysiological component of hypertensive motility disorders. However, these disorders might also be a reactive process. Gastro-esophageal reflux disease was associated with chest pain and hypertensive esophageal contractions.8 Hypertensive contractions were observed in case of esophago-gastric junction (EGJ) obstruction. Thus, experimental EGJ obstruction led to esophageal muscle hypertrophy and hyper-excitability in cats.9 In humans hypertensive contractions were noticed in presence of mechanical obstruction induced by fundoplication or gastric lap band.10 Anderson et al.11 documented a statistically significant increase in esophageal contraction amplitudes in both healthy volunteers and patients with non-cardiac chest pain while being exposed to acute stressors (intermittent bursts of white noise and difficult cognitive tasks).

The initial description of hypertensive motility disorders was realized with conventional manometry.12 The term ‘nutcracker esophagus’ was coined to illustrate the vigor of the contractions and the fluoroscopic pattern. However, the clinical relevance of these hypertensive disorders was debated as hypertensive contractions were encountered in asymptomatic patients.13 Moreover, hypertensive contractions might persist although patients’ symptoms were alleviated. Thus, the relationship between observed hypercontractility and symptoms is not clear. Evaluating bolus transit in patients with various esophageal motility abnormalities Tutuian et al.14 found that 97% of patients with nutcracker esophagus had a complete bolus transit assessed by impedance. These data raised the question of an overestimation of hypertensive motility disorders. Therefore, a revision of criteria for diagnosis of hypertensive peristalsis was suggested to improve clinical relevance.1

In the era of high-resolution manometry, a new metric (Distal Contractile Integral, DCI) is used to assess contractile vigor.15 It reflects not only the amplitude of the contraction but also integrates the duration and the length of the contractile segment. Moreover, as pressure variations are displayed as esophageal pressure topography (EPT) or Clouse plots, contractions pattern might be described more accurately with HRM than with conventional manometry.

The aims of this overview on hypertensive peristaltic disorders were (i) to describe the original definition of hypertensive disorders with conventional manometry, (ii) to characterize these disorders with HRM metrics and Clouse plots patterns, and (iii) to propose a definition of hypertensive peristaltic disorders in high-resolution manometry.

Original Definition Using Conventional Manometry

  1. Top of page
  2. Abstract
  3. Introduction
  4. Original Definition Using Conventional Manometry
  5. Characterization of Hypertensive Peristaltic Contractions with HRM
  6. Definition of Hypertensive Peristaltic Disorders with HRM
  7. Conclusion
  8. Conflict of Interest
  9. Author Contributions
  10. References

Nutcracker esophagus was defined by Castell and colleagues as a condition in which patients with unexplained chest pain and/or dysphagia exhibit peristaltic contractions in the distal esophagus with mean amplitudes exceeding normal values by more than two DS.12 In the classification of esophageal motility abnormalities proposed by Spechler and Castell,16 hypertensive peristalsis was defined as a mean distal esophageal peristaltic wave amplitude >180 mmHg. This mean amplitude was measured as the average amplitude of 10 swallows at two recording sites positioned 3 and 8 cm above the lower esophageal sphincter (LES). This disorder occurs in a context of normal EGJ relaxation and normal contraction propagation. Even if many patients with nutcracker esophagus exhibited peristaltic contractions with duration exceeding 6 s, this criterion was not required to diagnose hypertensive motility disorders with conventional manometry. Resting LES pressure was usually normal but might be elevated in patients having nutcracker esophagus with hypertensive LES.

Subsequently, the defining peristaltic amplitude has been debated and more recent work suggests that the amplitude threshold should be increased to 260 mmHg (mean amplitude exceeding normal values by four DS), a value which might have a greater clinical relevance.1 This revision is based on findings according to which patients with distal esophageal amplitude >260 mmHg presented more frequently chest pain and dysphagia and less frequently abnormal esophageal acid exposure than patients with distal esophageal amplitude between 180 and 260 mmHg. As this criterion might be too stringent, Agrawal et al.1 proposed to include possible patients with a mean distal esophageal amplitude of more than 220 mmHg to define nutcracker esophagus.

Hypertensive contractions might also occur in the context of incomplete LES relaxation or distal esophageal spasm. In case of incomplete LES relaxation, esophageal motility disorder was classified as achalasia. In case of simultaneous contraction and normal LES relaxation, the esophageal motility disorder was classified as distal esophageal spasm.

Finally isolated hypertensive LES was defined as a mean resting LES pressure of >45 mmHg measured in mid respiration using the station pull through technique.16 This abnormality has normal LES relaxation (defined as LES residual pressure <8 mmHg) and was classified into the group of esophageal hypercontraction as hypertensive lower esophageal sphincter (LES). The physiologic and clinical implications of the hypertensive LES are also not free of debate. Hypertensive LES has been associated with gastroesophageal reflux even though at first this association appears paradoxical because of the original association of GERD and decreased LES pressures.17 Other investigators reported an increased intrabolus pressure and impaired bolus transit in patients with hypertensive LES suggesting that this motility abnormality might be a form of outflow obstruction.18

In clinical practice it is not uncommon to find a combination of the above-mentioned abnormalities. For example a patient may have high esophageal contractions amplitudes (i.e. nutcracker esophagus) in combination with a high lower esophageal sphincter pressure (i.e. hypertensive LES) and even a high LES residual pressure (poorly relaxing LES).

Characterization of Hypertensive Peristaltic Contractions with HRM

  1. Top of page
  2. Abstract
  3. Introduction
  4. Original Definition Using Conventional Manometry
  5. Characterization of Hypertensive Peristaltic Contractions with HRM
  6. Definition of Hypertensive Peristaltic Disorders with HRM
  7. Conclusion
  8. Conflict of Interest
  9. Author Contributions
  10. References

The introduction of HRM and Clouse plots allow further stratification of hypertensive peristalsis to account for both excessive vigor and abnormal morphology of the peristaltic contraction. The summary metric for contractile vigor in the entire distal segment is the distal contractile integral (DCI). The hypertensive contraction pattern is also easily described with HRM: repetitive pattern and location of the hypertensive segment might be clinically relevant.

Distal contractile integral

The distal contractile integral corresponds to the volume of the distal contraction in dimensions of amplitude, time, and length between the proximal and the distal troughs using the 20-mmHg isobaric contour at the base (Fig. 1). It is calculated by multiplying the integral of the contraction amplitude in the distal esophagus (mmHg) times the duration of contraction (s) times the length of the distal esophageal segment (cm).15 It is expressed as mmHg*sec*cm. Pressures lower than 20 mmHg were excluded from the DCI calculation to eliminate intra-bolus pressure.15

image

Figure 1.  The distal contractile integral (DCI) corresponds to the entire volume (amplitude x time x length) of the distal contraction spanning from the proximal (P) to the distal (D) troughs (white box) above 20 mmHg. The DCI is calculated by multiplying the integral of amplitude x the duration x the length of the contractile segment contained in the white box.

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In 75 controls, the median (IQR) DCI was 2416 (1967–2963) mmHg*sec*cm.19 A value of 5000 mmHg*sec*cm being the 95th percentile of normal was considered as abnormal. A value >8000 mmHg*sec*cm was never encountered in control subjects. These thresholds have been suggested to define hypertensive peristaltic disorders in HRM.19

Contraction pattern

Clouse plots allow easy pattern recognition of motility disorders. It might facilitate studies review and improve diagnostic yield of this examination.20 A more physiological characterization is also possible and may provide a better understanding of motility disorders.

Multipeaked pattern might be a characteristic of hypertensive contraction (Fig. 2). Clouse21 was the first to hypothesize that double-peaked contractions occurred as a consequence of the overlap and imperfect coordination between the adjacent second and third contractile segments. Further he described multipeaked pattern in symptomatic patients.22 The main symptom associated with this pattern was unexplained chest pain. The second peak was a typically short, simultaneous or retrograde pressure event in the distal esophagus. Multipeaked contractions tended to be associated with greater maximal amplitude in the third segment compared to single peak contractions. Recently Roman et al.23 observed that multipeaked contractions were encountered in 82% of patients with at least one esophageal high amplitude contraction (DCI > 8000 mmHg*sec*cm) in a context of normal propagation and normal EGJ relaxation. To compare, the multipeaked pattern was observed in only 3% of control subjects. On the other hand, double-peaked contractions are observed in healthy volunteers24 relativating their clinical importance in the patients with esophageal symptoms. However, Sampath et al.25 proposed that multipeaked contractions might be an artifact. As the distal esophagus and diaphragm are attached at the EGJ, they move in unison during respiration. These respiratory oscillations could cause the appearance of a multipeaked pattern attributable to movement of the contracting esophagus relative to the sensor recording that contraction. Suspended breathing and hyperventilation modified the esophageal contraction waveform morphology accordingly. It is important to note that only three patients of nine included in the study of Sampath presented a hypertensive motility disorder. Thus, even if the respiratory oscillation hypothesis may explain a multipeaked contraction at the spatial margins of the contractile segment in some instances, this explanation seems insufficient to explain the extreme oscillations spanning the entire contractile segment as illustrated in Fig. 2. Finally Roman et al.23 systematically explored the synchrony between multipeaked contractions and respiration in patients with at least one contraction with a DCI > 8000 mmHg*sec*cm in a context of normal propagation and normal EGJ relaxation. Multipeaked contractions were synchronized with respiration in about half of the patients whereas in the other half they were not. There was no apparent clinical difference between these subsets.

image

Figure 2.  Extremely abnormal contraction (DCI > 8000 mmHg*sec*cm) in a patient with a hypercontractile esophagus. The esophago-gastric junction relaxation is normal (integrated relaxation pressure IRP = 5 mmHg) and the distal latency (DL > 4.5 s). This swallow is associated with repetitive prolonged contractions evoking the action of the jackhammer.

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Hypertensive contractions might also be characterized with the location of maximal amplitude. Indeed Clouse21 showed that nutcracker esophagus primarily affected the distal segment in the smooth muscle body. Gyawali26 suggested that the location of maximal amplitude segment might be used to differentiate primary from secondary motility disorders. Indeed in patients with impaired EGJ relaxation and preserved esophageal peristalsis location of maximal amplitude varied according to the etiology of EGJ outflow obstruction. Mechanical obstruction was associated with higher pressure volume in the second segment and lower pressure volume in the third segment compared to controls. On the other hand, functional obstruction was associated with the reverse change, higher pressure volume in the third segment and lower in the second. It remains to be determined if the location of maximal amplitude segment might be also predictive of the etiology of hypercontractility in absence of EGJ outflow obstruction. Finally in the same study Gyawali26 noticed that some patients with EGJ functional obstruction also exhibited multipeaked contractions and prolonged contraction duration. This supports the hypothesis that hypertensive peristalsis might be reactive to EGJ outflow obstruction in some instances.

Definition of Hypertensive Peristaltic Disorders with HRM

  1. Top of page
  2. Abstract
  3. Introduction
  4. Original Definition Using Conventional Manometry
  5. Characterization of Hypertensive Peristaltic Contractions with HRM
  6. Definition of Hypertensive Peristaltic Disorders with HRM
  7. Conclusion
  8. Conflict of Interest
  9. Author Contributions
  10. References

Conventional manometry and HRM have not been directly compared to diagnose hypertensive motility disorders. One of the major differences with the two techniques is that hypercontractility is defined only on the amplitude of the contraction in conventional manometry whereas it is defined by amplitude, duration, and length of contraction in HRM. In the first versions of the Chicago classification for esophageal motility disorders in EPT, hypertensive peristalsis definition was proposed by analogy with the classification of Spechler and Castell in conventional manometry. Thus, the diagnosis of hypertensive peristalsis was based on an elevated mean contractile vigor. As the metric used in HRM to measure the vigor of the contraction is the DCI rather than the amplitude, hypertensive peristalsis was defined using a mean DCI of 10 swallows.19,27 In the context of normal EGJ relaxation and normal propagation, hypertensive peristalsis was defined as a mean DCI > 5000 mmHg*sec*cm. Based on this definition, hypertensive peristalsis was diagnosed in 9% of a 400 patient series.27 As hypertensive peristalsis presented a substantial heterogeneity, it was subsequently divided into ‘Nutcracker esophagus’ if the mean DCI was within the 5000–8000 range and into ‘Spastic nutcracker’ if the mean DCI was >8000. As previously mentioned, the threshold value of 8000 mmHg*sec*cm was chosen because this value was never encountered in healthy volunteers. It was also uniformly associated with dysphagia or chest pain.27 The presence of repetitive high-amplitude contractions was noticed in patients with spastic nutcracker but was not required for the positive diagnosis. A sub classification according to the location of hypertensive segment was also proposed in the first version of the Chicago classification.27 The segmental nutcracker corresponded to the presence of only one segmental focus of hypertensive contraction (>180 mmHg) and the nutcracker LES to the focus of hypertensive contraction (>180 mmHg) limited to the LES-after contraction. Finally hypertensive peristalsis was associated with hypertensive LES (>35 mmHg) in 19%.27

The Chicago Classification of esophageal motility disorders continually evolves through the workings of an international group. A general process is to re-define motility disorders based on individual swallows classification. Thus, new criteria have been proposed for achalasia,28 distal esophageal spasm,29 weak and frequent failed peristalsis.30 This process of re-definition was also applied to hypertensive peristalsis.

Thus the classification is now based on the evaluation of the individual swallows. A contraction is characterized as hypercontractile if DCI > 8000 mmHg*sec*cm in the context of normal propagation.31 Thus a swallow may be classified as hypercontractile only if the distal latency is normal. If the distal latency is reduced (<4.5 s), the swallow is classified as premature whatever the DCI.29 Once again, this pattern represents an extreme phenotype never encountered in control subjects. Hypercontractile contractions are further sub typed as single peaked or multipeaked contraction synchronized or not with respiration. They might occur in a context of normal or impaired EGJ relaxation.

The current iteration of the Chicago classification of esophageal motility disorders defines a hypercontractile esophagus (‘Jackhammer esophagus’) by the presence of at least one hypercontractile contraction (DCI > 8000 mmHg*sec*cm) in the context of normal EGJ relaxation. This motility disorder is rare (4.1% of a 2000 patient series).31 It is constantly associated with esophageal symptoms (dysphagia, reflux, chest pain). However, the clinical presentation remains diverse and hypercontractile esophagus may be attributable not only to primary esophageal muscle hypercontractility but also secondary to reflux disease or mechanical EGJ obstruction.23 As similar characteristics and similar outcomes have been observed in patients with single peak and multipeaked contractions synchronized or with respiration, the distinction between different subtypes does not seem relevant. Finally it is proposed to nickname this extreme phenotype of hypercontractile esophagus ‘Jackhammer esophagus’ (rather than spastic nutcracker) to fit better with the contractile morphology and to avoid confusion with spasm which occurs in a context of reduced distal latency.

Hypertensive peristalsis known as ‘nutcracker esophagus’ is reserved for patients with mean DCI > 5000 mmHg*sec*cm and without any contraction with DCI > 8000 mmHg*sec*cm (criteria for hypercontractile esophagus). The current separation between hypercontractile esophagus and hypertensive peristalsis is a good starting point for future studies aimed at refining (high resolution) manometric criteria according to symptoms and treatment outcome. First results suggest that an average DCI > 8000 mmHg*sec*cm is more likely associated with chest pain.32 However, direct relationship between the occurrence of hypercontractile swallow and symptom has not yet been proved. It remains also to be determined if treatment of hypercontractility is associated with reduction of symptoms.

Conclusion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Original Definition Using Conventional Manometry
  5. Characterization of Hypertensive Peristaltic Contractions with HRM
  6. Definition of Hypertensive Peristaltic Disorders with HRM
  7. Conclusion
  8. Conflict of Interest
  9. Author Contributions
  10. References

Hypertensive motility disorders represent a heterogeneous condition which may be attributable to primary muscle hyperexcitability but also to a reactive process to reflux disease or EGJ outflow obstruction. Diagnosis of hypertensive peristaltic disorders is retained only if the disorder occurs in a context a normal EGJ relaxation (Fig. 3). Using high-resolution manometry and Clouse plots, hypertensive peristaltic disorders are subdivided into hypercontractile esophagus (‘Jackhammer esophagus’: at least one swallow with a DCI > 8000 mmHg*sec*cm) and hypertensive peristalsis (‘Nutcracker esophagus’: mean DCI > 5000 mmHg*sec*cm without any swallow with DCI > 8000 mmHg*sec*cm). Although hypercontractile swallows are often characterized by a multipeaked pattern, no specific pattern has been so far identified as being associated with a homogeneous population and clinical presentation potentially amenable to specific pharmacological treatment. Furthermore studies are required to precisely examine the clinical relevance of this new classification.

image

Figure 3.  Algorithm for the diagnosis of hypertensive peristaltic disorders. Panel A: conventional manometry criteria, Panel B: high-resolution manometry (Chicago) criteria. Legend: DEA – distal esophageal amplitude, LESP – lower esophageal sphincter pressure (resting), LESRP – lower esophageal sphincter residual pressure.

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References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Original Definition Using Conventional Manometry
  5. Characterization of Hypertensive Peristaltic Contractions with HRM
  6. Definition of Hypertensive Peristaltic Disorders with HRM
  7. Conclusion
  8. Conflict of Interest
  9. Author Contributions
  10. References
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