The characteristic endoscopic signs of reflux oesophagitis are shown in Table 1.1 and Figure 1.1. As mentioned above, there is only a weak correlation between the severity of oesophageal acidification and the degree of peptic oesophagitis. On the other hand, it is clear that more severe grades of esophagitis are more difficult to heal. Oesophagitis should never be diagnosed based on anything short of mucosal erosion and never should be based on erythema of the distal oesophagus. The diagnostic endoscopic examination is always carried as far as the first part of the duodenum looking for incidental pathology. The finding of a chronic duodenal ulcer is significant as this may be the underlying cause of gastro-oesophageal reflux symptoms (see Ch 5).

Table 1.1 Classification of reflux at endoscopy (Los Angeles—LA—System)

Grade	Feature
Grade A	At least one mucosal break (erosion) each ≤ 5 mm
Grade B	At least one mucosal break > 5 mm but not continuous between the tops of two mucosal folds
Grade C	At least one mucosal break that is continuous between the tops of 2 mucosal folds, but which is not circumferential (< 75%)
Grade D	Circumferential mucosal break (≥ 75%)

Figure 1.1 Endoscopic view of linear erosive peptic oesophagitis (Grade D) of the distal oesophagus.

From plate 20-4 of the online edition of the Merck Manual, with permission from Dr D Martin.

Oesophageal biopsy at upper gastrointestinal endoscopy

Biopsy of a normal-appearing oesophagus was once suggested to aid in the diagnosis of GORD, but is not advocated by most experts in adult GORD. Microscopic changes suggestive of GORD include:

• relative increase in papillary height;

• relative increase in thickness of the basal layer of the epithelium;

• the presence of intraepithelial neutrophils and eosinophils.

These microscopic findings can be relatively difficult to quantify on routine biopsy specimens and the diagnostic value of these findings continues to be disputed, so biopsy is not recommended routinely. Recently, some experts have suggested obtaining midoesophageal biopsies in patients with any unexplained oesophageal symptom (especially dysphagia) to search for histological evidence of eosinophilic oesophagitis (Ch 2).

Upper gastrointestinal radiology

Before the establishment of flexible upper gastrointestinal endoscopy, upper gastrointestinal contrast radiology with barium was the initial investigation for dyspepsia and reflux symptoms. It has been downgraded to a second-line investigation, mainly because it is not a sensitive detector of oesophageal mucosal damage. It does, however, offer complementary information, which is sometimes useful. Some advocate routine radiological testing in any patient with dysphagia. It also allows better definition of the presence and size of a hiatus hernia, which may be important if surgery for reflux is contemplated. The demonstration of barium refluxing into the oesophagus is neither specific nor sensitive for the presence of pathological acid reflux.

Ambulatory reflux monitoring

Episodes of gastro-oesophageal reflux result in acidification of the distal oesophagus. Neutral pH is restored by oesophageal peristalsis. These episodes can be monitored and recorded by placement of a pH microelectrode in the distal oesophagus. In the past this test required prolonged nasal intubation, which is unpleasant. That discomfort can now be avoided by attaching the pH electrode to the lower oesophageal mucosa endoscopically. The pH recording then occurs by telemetry. The electrode subsequently detaches and passes spontaneously. Summation of the duration of episodes over an extended period, usually 24–48 hours, gives a measure of the underlying pathophysiological process, which can be used to score the severity of the disease. Further, a correlation between symptoms and episodes of oesophageal acidification can be established (see Fig 1.2). The test is not required for diagnosis in the majority of patients with typical symptoms of reflux in whom the diagnosis can be made either endoscopically or, if there is no oesophagitis, on the basis of a successful therapeutic trial with a course of antisecretory treatment.

Figure 1.2 24-hour oesophageal pH testing (pH probe 5 cm above lower oesophageal sphincter) A: Pathological upright reflux. The lines indicate the times at which the patient had reflux symptoms. These events all coincide with a decrease in pH to below pH 4. The symptoms of this patient are clearly caused by reflux.B: Pathological reflux during sleep. During sleep, in particular, the oesophageal pH persists longer at a low value due to disordered oesophageal clearance. A symptom index over 50% ([no. of symptoms with pH under 4 ÷ total no. symptoms] × 100%) is considered significant. The symptom-associated probability (SAP) is a more optimal method to estimate if acid reflux episodes are linked to symptoms. The 24-hour recording is divided into 2-min periods, and the 2-min periods before onset of symptoms identified for evidence of reflux (pH under 4.0). The probability (P) that events are unrelated is calculated (using Fisher’s exact test). SAP = (1.0 – P) × 100%

From Smout AJPM, Akkermans LMA. Normal and disturbed motility of the gastrointestinal tract. Petersfield: Wrightson Biomedical Publishing; 1972, with permission.

Recently, another technology has been developed that has the potential to measure not only acid reflux, but also the reflux of other substances with a more neutral pH. This technology takes advantage of the conductivity of refluxed liquid and is measured with a specially designed catheter that not only measures the movement of that fluid using impedance, but also measures pH (acid reflux). The exact role of this testing remains to be completely defined, but has been suggested to be of particular benefit in patients requiring testing while on acid suppression.

When contemplating performing an ambulatory reflux test, two questions must be answered: should the test be done on or off acid-supression therapy and should impedance monitoring be included? Off-therapy testing is the best way to determine if the patient has pathological gastro-oesophageal reflux. This testing can be performed with either a tube-based or tubeless system. If, on the other hand, the question is of ongoing reflux on therapy, some experts advocate a combined impedance pH test. An alternative, especially in the patient with either no or a modest response to therapy, is to stop medications and do a pH test off therapy. The application of the concept of pretest probability is important in that decision-making process. If the patient is believed to have reflux and a non-acid contribution to symptoms is to be excluded, on-therapy, impedance pH testing makes sense. If on the other hand, the patient is not believed to have reflux (often the case when there is a minimal response to therapy), stopping therapy and doing an off-therapy test is most reasonable. A negative off-therapy pH test and a failed therapeutic trial provide the best evidence that reflux is not the cause of an individual patient’s symptoms.

Bernstein testing

Bernstein testing is a test of mucosal sensitivity that is of mostly historical interest, although it may be available in a few referral centres. It involves transnasal oesophageal intubation and perfusion of the distal oesophageal mucosa with dilute (0.1 M) hydrochloric acid alternating with placebo (normal saline). The test is considered positive if the acid produces the patient’s symptoms and the saline does not. It can be complementary to pH monitoring in patients whose atypical symptoms, particularly chest pain, are infrequent and do not occur during a pH-monitoring study.

Oesophageal manometry

This test has no routine diagnostic role in the evaluation of symptoms of GORD unless antireflux surgery is being considered, where manometry is used to exclude achalasia and to tailor the tightness of the repair. It may sometimes be useful in the evaluation of patients with symptoms of dysphagia in addition to those of heartburn and regurgitation, where a barium swallow and endoscopy have been normal and the dysphagia remains unexplained (see Ch 2).

Treatment

Clinical management of heartburn and regurgitation

The intensity of reflux symptoms varies from a mild, occasional discomfort, for which the patient may want little more than antacid and reassurance, to a daily, incapacitating pain that prevents normal activity. Management needs to be commensurate with the magnitude of the clinical problem. Unlike duodenal ulceration, GORD is usually a persistent condition without exacerbations and remissions. Drug therapy has a hierarchy (see Box 1.1). Oesophagitis indicates a need for therapy to heal the mucosa and maintain healing; virtually all patients with severe oesophagitis (LA grade C and D oesophagitis; see Table 1.1) will relapse if medical therapy is stopped, as will most (80%) with milder oesophagitis. A review of the clinical management principles for patients with gastro-oesophageal reflux is presented in Table 1.2.

Box 1.1 Effectiveness of drugs for gastro-oesophageal reflux

Twice-daily proton pump inhibitors
Once-daily proton pump inhibitor combined with H₂-receptor antagonist
Once-daily proton pump inhibitors
Standard-dose H₂-receptor antagonists
Antacids

Table 1.2 Features of clinical management of gastro-oesophageal reflux

Patient-directed treatment	Doctor-directed treatment
Weight loss, if overweight Avoidance of large meals Postural advice such as elevation of bed head at night Avoidance of foodstuffs that precipitate reflux On-demand antacids or H₂-receptor antagonists for breakthrough symptoms

Continue lifestyle measures of low-level

Regular or on-demand full-dose H₂-receptor antagonist or proton pump inhibitor

High-dose proton pump inhibitor

Endoscopic or laparoscopic antireflux therapy

Patient-directed therapy

For most of the population who have occasional, mild symptoms of reflux, intermittent, patient-directed treatment is all that is required. Such treatment involves lifestyle changes including:

• weight loss, if overweight or in the face of recent weight gain;

• avoidance of large meals, particularly before retiring to bed at night;

• postural advice including elevation of the head of the bed by insertion of 20 cm blocks under the bed head and avoidance of bending;

• avoiding drugs, cigarettes, alcohol and foodstuffs that might precipitate reflux.

A foodstuff checklist includes spicy foods, alcohol, fatty foods, chocolates, nuts, tomatoes, as well as many others. Rather than prohibit ‘everything’ and risk losing patient compliance, it is wiser to establish with the patient which foodstuffs they recognise as triggers, ask them to avoid these, go through the checklist to identify triggers that the patient might not have previously considered and recognised, and then ask the patient to establish relationships between symptoms and triggers so that they might be avoided in the future. In addition, some aspects of the ‘reflux diet’ such as lower volume, lower fat and weight loss will provide added health benefits beyond the improvement in reflux symptoms.

Of these various lifestyle changes, only weight reduction has the potential to change the natural history of the disease. Thus, some patients can clearly identify a critical weight above which they experience symptoms and below which they are free of symptoms. It makes good sense to encourage these patients to stay below their critical weight. Interestingly, even patients of normal weight may develop reflux symptoms when they gain weight but do not become overweight or obese. Additionally, patients on low-level treatment may benefit from intermittent medication for symptoms. The medication could be antacids if short-term (about 30 minutes) relief is required, or an H₂-receptor antagonist or proton pump inhibitor if relief for several hours is required.

Doctor-directed treatment

When patients present to a physician, they often have tried the above manoeuvres. In some, it may be reasonable to simply emphasise the above and see if they can manage their symptoms on their own. On the other hand, most patients will be treated with a prescription medication.

The end point of therapy should be complete or near-complete resolution of symptoms. H₂-receptor antagonists have an onset of action that is rapid, but rate of symptom relief is about 50% when standard doses are taken twice daily. There is no evidence that greater than standard doses provide additional benefit. Proton pump inhibitors taken once daily provide a higher rate of symptom relief (60–80%) and endoscopic healing (80–90%), but have a somewhat slower onset of action. Once symptom relief is achieved an attempt to step down the dose or change to an ‘as needed’ approach is reasonable. If the patients relapse at that point, they are likely to need long-term treatment. While a prokinetic would seem to be a rational approach to GORD, there are no available, safe and effective agents in this category, leaving acid suppression as essentially the only medical therapy for GORD.

Some patients will have symptoms and/or oesophagitis that do not respond to standard doses of proton pump inhibitors. A common approach is to increase the dose to twice daily (before meals) for an additional 4–8 weeks to see if the disease is brought under control. This approach has not been tested in well-designed trials and it is not clear what proportion of patients will respond. An additional nocturnal dose of H₂-receptor antagonists may be of assistance, but benefits often wear off if given continuously. An alternative is to study the patient using ambulatory reflux testing to either confirm control of acid (on therapy testing) or to determine if they actually have the disease (off-therapy testing or perhaps combined impedance/pH testing). The addition of a prokinetic agent is an attractive concept, but none of the currently available agents have been proven to be effective as either mono or ‘add-on’ therapy in this situation. There are several agents in development that may inhibit transient LES relaxation. Some of the possibilities to be considered when a patient is ‘failing’ proton pump inhibitor therapy are outlined in Table 1.3.

Table 1.3 Failure of proton pump inhibitor therapy to control gastro-oesophageal reflux symptoms: management approach

Mechanism to consider	Management
Misdiagnosis	Review history and investigations.
Not taken before meals	Advise taking 30 minutes prior to a meal.
Inadequate dosing	Trial twice-daily therapy.
Nocturnal acid breakthrough	Twice-daily proton pump inhibitor; if that fails, H₂-receptor antagonist before bed as needed; consider surgery.
Acid hypersecretion	Exclude Zollinger-Ellison syndrome.
Drug resistance	Very rare; switch to H₂-receptor antagonist or consider surgery.
Oesophageal hypersensitivity	Add a low-dose tricyclic antidepressant.

Patients for whom medical therapy results in incomplete resolution of symptoms (especially regurgitation) can achieve that end point with antireflux surgery. Nevertheless, the majority of patients presenting for surgery present because they are keen to achieve long-term cure, without need for continuing medical therapy and follow-up. Most report the loss of reflux symptoms without the need to take medication from the day of surgery. There is complete control in up to 90% of patients with typical symptoms that responded to acid suppression in the hands of an experienced surgeon. However, in some studies up to 50% of cases eventually will have reintroduction of acid suppression therapy over the long term. The risk of postoperative sequelae has limited the more widespread utilisation of antireflux surgery. The more troublesome of these are painful abdominal distension (gas bloat), persistent dysphagia and, less commonly, persistent diarrhoea.

The surgical approach for most will be laparoscopic. This conveys the advantages of less postoperative pain and early return to full activity. The procedure involves an initial restoration of normal anatomical relationships by reduction of the commonly associated sliding hiatus hernia (see Fig 1.3A) and then wrapping of the lower oesophageal sphincter region with the gastric fundus (see Fig 1.3B). There is still debate as to whether the fundoplication should be complete as shown in Figure 1.3B, or whether the wrap should be incomplete—surrounding less than the 360° circumference of the lower oesophageal sphincter. Current data suggest that patients having the so-called incomplete fundoplication are more satisfied with the outcome because of an apparent reduction in sequelae, even though the long-term control of reflux might not be quite as good as with complete fundoplication. Endoscopic therapies to treat gastro-oesophageal reflux, including radiofrequency therapy, injection of biopolymer and endoscopic sewing around the lower oesophageal sphincter, have been studied. Of these, the systems that place sutures to form a ‘plication’ at the LOS are the only currently available options, while most of the others have been removed because of lack of efficacy, unacceptable side effects or both.

Figure 1.3A Schematic representation of a sliding hiatus hernia (left) and a paraoesophageal hernia (right).

Figure 1.3B Schematic representation of the Nissen fundoplication operation.

From Smout AJPM, Akkermans LMA. Normal and disturbed motility of the gastrointestinal tract. Petersfield: Wrightson Biomedical Publishing; 1972, with permission.

Maintenance therapy

Once a patient’s symptoms are controlled, they can be entered into a program of ‘maintenance’ in order to keep those symptoms under control. Some patients can be ‘stepped down’ to less complete acid suppression (from high dose proton pump inhibitor to standard dose or from standard dose proton pump inhibitor to H2-receptor antagonist or antacid therapy) and a few can discontinue treatment altogether, especially if they adhere to lifestyle changes. On the other hand, many patients require the same therapy that they needed to achieve remission in order to maintain that remission.

Risks of long-term acid suppression

When they were first introduced, the use of proton pump inhibitors was limited to a short period of time. Subsequently, concerns over the potential adverse effects of proton pump inhibitor-induced hypergastrinaemia were discounted and long-term therapy was approved. Acid suppressants have been very safe, but recently a few concerns have arisen. In addition to aiding digestion, gastric acid helps to eliminate ingested bacteria. Infections that have a small increased incidence in proton pump inhibitor-treated patients include Clostridiumdifficile,community-acquired pneumonia and perhaps traveller’s diarrhoea. Acid aids in the absorption of several nutrients (iron, calcium and vitamin B12), although clinically significant insufficiencies are very rare. Recent studies have found a very small increase in hip fractures in proton pump inhibitor-treated patients. Finally, there is no direct cardiovascular risk with acid suppression, although a negative interaction between proton pump inhibitors and the antiplatelet drug clopidogrel has been suggested.

Clinical management of dysphagia associated with reflux symptoms

Dysphagia is a ‘warning’ symptom (’red flag’) in the patient with reflux and must be respected as such. The possibilities include:

• a benign distal oesophageal stricture secondary to GORD;

• a benign distal oesophageal stricture secondary to GORD associated with a motility disorder (either primary or perhaps associated with a rheumatological condition such as scleroderma)

• a malignant stenosis in a patient with GORD;

• dysphagia due to another problem not related to reflux (misdiagnosed achalasia or eosinophilic oesophagitis, for example).

It is often helpful to define the presence and site of stenosis radiologically. Subsequently, the presence or absence of an oesophageal malignancy must be established or disproved by upper gastrointestinal endoscopy and biopsy of the stenosis and any mucosal irregularity. Once malignancy is excluded, oesophageal dilatation may be performed to relieve dysphagia. The dilatation may need to be staged if the stenosis is very narrow and additional care must be taken if the oesophagus has the typical ringed appearance associated with eosinophilic esophagitis. Assuming the patient has symptoms or endoscopy suggestive of GORD, they should start a proton pump inhibitor to achieve symptom control and healing. With this therapy, restenosis is less common. Antireflux surgery should be considered for those who require repeated dilatations or have poor control of heartburn and regurgitation. These patients are sometimes unsuitable for a laparoscopic operation, as oesophageal fibrosis may render the oesophagus short as well as narrow. Some surgeons will perform a Collis gastroplasty (oesophageal lengthening procedure) combined with a Nissen fundoplication in that situation.

Patients with oesophageal involvement from scleroderma are usually readily identifiable by the characteristic appearance of their hands and face. These patients have a hypomotile oesophageal body in addition to a failure of the lower oesophageal sphincter. Aggressive high-level medical therapy is to be preferred over surgical therapy. Oesophageal dysmotility is not isolated to scleroderma and may occur with many other rheumatologic and non-rheumatological conditions (long-standing diabetes, for example).

Hiatus hernia

A hiatus hernia is a protrusion of intraabdominal contents through the oesophageal hiatus in the diaphragm. Two main types of hiatus hernia are recognised radiologically (see Fig 1.3A).

Routine (sliding or fixed) hiatus hernia

This type of hernia is extremely common (in 10–15% of the population) and often asymptomatic. Its prevalence increases with age. It occurs as a result of circumferential telescoping of the segment of stomach that lies just distal to the lower oesophageal sphincter through the oesophageal hiatus. This type of hernia is not prone to obstruction or strangulation, so specific surgical treatment of the hernia is not required; when it is found incidentally in association with GORD, attention should be directed at treatment of the reflux disease. Herniae are more common in more severe grades of esophagitis and are almost universally present in patients with Barrett’s oesophagus.

Paraesophageal (rolling) hernia

This type of hernia is less common. It can range in size from just a small knuckle of fundus protruding alongside the non-displaced lower oesophageal sphincter to the whole stomach twisted and rotated within the posterior mediastinum. With larger herniae, there is a tendency for the lower oesophageal sphincter to be displaced proximally with the stomach. Such herniae should not be thought of as mixed herniae as the main component is usually the paraesophageal component. These herniae can cause dysphagia and uncommonly retrosternal pain due to ischaemia of the entrapped portion of stomach. There may be associated vomiting due to obstruction at either the lower oesophagus or at the gastric outlet. Early satiety and weight loss form part of a milder obstructive syndrome. Large herniae can cause dyspnoea by occupying part of the thoracic cavity, which would otherwise be available for expansion of the lungs. The only effective treatment is surgical repair of the hernia, but this is currently recommended only for patients with symptoms or complications from the hernia. There seems to be a higher than expected recurrence of herniae after repair of the paraesophageal type.

Barrett’s oesophagus

One of the consequences of long-term gastro-oesophageal reflux is a metaplastic transformation of the stratified squamous epithelium of the distal oesophagus to a columnar type epithelium. The affected oesophagus is termed Barrett’s or columnar-lined oesophagus. The significance of Barrett’s oesophagus is its predisposition to malignant change. Clinically, much effort is expended to identify and treat such patients before they present clinically with an adenocarcinoma of the distal oesophagus (Fig 1.4), when the outlook is likely to be poor (Ch 17). It has been suggested that patients with the following characteristics are at greatest risk of developing Barrett’s oesophagus and subsequently oesophageal adenocarcinoma: long-term reflux symptoms, male sex, Caucasian race and positive family history. Despite that, some patients will have reflux symptoms that are so minor that an endoscopy is not likely to be performed on clinical grounds. As a consequence, many patients remain unaware that they carry this malignant predisposition and present at a more advanced stage.

Figure 1.4 Adenocarcinoma of the distal oesophagus (arising in Barrett’s mucosa) on barium swallow.

The columnar lining of Barrett’s oesophagus is salmon pink in colour and has a matt surface texture, distinguishing it from stratified squamous epithelium, which is pearly pink in colour and shiny in texture. Histological confirmation is necessary and specialised intestinal metaplasia in the oesophagus is the hallmark finding.

Development of adenocarcinoma in Barrett’s oesophagus is a staged process that occurs over several years. The precursors of invasive carcinoma (low-grade and high-grade dysplasia) can be detected reliably only by histological examination of multiple samples of the columnar epithelium. There are no reliable serological markers or even endoscopic appearances, although advances in endoscopic imaging may change that in the next few years. There is no evidence that control of continuing reflux, after the metaplastic epithelial change has occurred, stops progression down the dysplastic pathway, even though this is appropriate for control of reflux symptoms. Preliminary data suggest that aspirin may slow the progression of Barrett’s oesophagus to dysplasia and is safe when combined with a proton pump inhibitor.

The aim of the management strategy of patients with Barrett’s oesophagus is to identify patients with high-grade dysplasia. These patients are very likely to proceed in the near future to invasive adenocarcinoma. In patients with non-dysplastic Barrett’s, it is recommended that endoscopic surveillance be conducted every 2–3 years, with biopsies (in each quadrant at 2-cm intervals) along the length of the Barrett’s mucosa. If low-grade dysplasia is identified, the interval should be shortened to at least yearly with a more intensive biopsy pattern (each quadrant every 1 cm). If high-grade dysphagia is found and confirmed, there is a high risk of underlying adenocarcinoma and removal of the Barrett’s epithelium is generally recommended. The traditional approach has been surgical resection of the oesophagus. If performed, as much of the oesophagus as possible should be removed to prevent recurrence of Barrett’s in the residual segment. Recently, endoscopic ablative techniques have been developed and are becoming a recognised alternative in patients with dysplastic Barrett’s epithelium.

Non-cardiac Chest Pain

Non-cardiac chest pain is a diagnosis reached by excluding myocardial ischaemia as the cause of pain by a combination of history taking, physical examination and one or more investigations. Historically, cardiac pain due to ischaemia is primarily retrosternal in position. It may radiate to the neck and jaw, and/or down one or both arms. It is pain that is severe in intensity, crushing in nature and usually not prolonged in duration. It is commonly precipitated by exercise and causes the patient to stop exercising. Patients with cardiac pain are more likely to have evidence of arterial disease in the lower limbs and cerebral arteries, and cardiac risk factors such as hypertension, diabetes mellitus, obesity, hypercholesterolaemia and tobacco use. Severe retrosternal chest pain that radiates through to the back should lead to consideration of dissection of a thoracic aortic aneurysm.

Chest pain of oesophageal origin is more likely to be prolonged, to radiate through to the back, to be precipitated by eating, and to be associated with dysphagia, heartburn and regurgitation. In spite of these differences, chest pain of oesophageal origin cannot be distinguished from cardiac chest pain with any degree of certainty on the basis of history alone. Further, physical examination is rarely of any significant help in separating the two. Signs of heart disease such as cardiac murmurs and cardiac failure, or manifestations of peripheral vascular disease such as bruits and absent pulses, increase the likelihood that the pain is cardiac in origin.

When there is any doubt investigation is initially focused on the heart. All patients should have an electrocardiogram (ECG) and cardiac enzymes measured if they are examined while they are having pain. Those without pain at the time of interview and normal resting ECG should have an exercise stress ECG performed. The extent of further cardiac investigation will depend on clinical judgment. This might include echocardiography, radionuclide studies and coronary angiography. Although coronary angiography remains the gold standard, its performance is sometimes delayed because of its invasive nature and slight risk of complications. The inconvenience and risk obviously need to be weighed against the likelihood that coronary disease will be uncovered and the likelihood that the findings will change the clinical management. One of the advantages of performing coronary angiography that reveals normal coronary arteries is that both patient and doctor can be reassured that sudden death becomes very much less likely. Once the patient is determined to not have occlusive disease of the coronary arteries, several other conditions (below) need to be considered.

Microvascular angina

Microvascular angina is a cause of ischaemic chest pain in the presence of normal coronary arteries; abnormalities may be found on non-invasive cardiac function testing (e.g. radionuclide ventriculography or thallium exercise scintigraphy). It appears these patients have survival rates similar to controls and the pain will, at times, respond to nitrates and/or calcium channel blockers.

Musculoskeletal conditions

Early in the clinical evaluation, before invasive cardiac investigations are performed, the possibility that the chest pain is musculoskeletal in origin should be considered. A history of chest wall injury might indicate a sternal fracture. Palpation of the anterior chest wall may reveal focal tenderness suggestive of costochondritis.

Panic attacks

Panic attacks can cause chest pain. They result in discrete periods of intense fear that occur abruptly with at least four of the following symptoms: chest pain, palpitations, sweating, trembling, shortness of breath, choking, nausea, dizziness, feelings of unreality or detachment, fear of losing control, fear of dying, paraesthesia and flushes or chills.

Oesophageal conditions

Oesophageal conditions that can cause non-cardiac chest pain, in order of importance, include:

• GORD (most common);

• non-specific motility disorder or hypertensive lower oesophageal sphincter (uncertain significance);

• high pressure ‘nutcracker’ oesophagus (uncertain significance);

• diffuse oesophageal spasm (rare); and

• achalasia (rare).

These conditions can be diagnosed either by endoscopy and pH monitoring in the case of GORD, and by oesophageal manometry in the remainder. Unfortunately it is often difficult to be sure that the oesophageal condition diagnosed is indeed the cause of the pain, as will be discussed below.

The program of investigation for patients deemed to have non-cardiac chest pain that might be oesophageal in origin will depend on how significant the symptoms are in terms of both their severity and frequency. Some patients will do well if reassured that their heart is not the cause of their symptoms. GORD should be the first consideration for the aetiology of oesophageal pain. If the patient has co-existing heartburn or regurgitation, a reflux aetiology is more likely. The diagnostic option is to either perform an ambulatory reflux test or offer a trial of proton pump inhibitor (PPI). The so called ‘PPI-test’ is a short-term (7–14 day) trial of a twice daily proton pump inhibitor that seems to have a reasonable sensitivity and specificity when compared to ambulatory pH testing. An ambulatory reflux test should be considered ‘positive’ if there is excess reflux or if symptoms occur in correlation with episodes of reflux. If proton pump inhibitor treatment is effective, it should obviously continue. The role of endoscopy in patients without typical symptoms in unclear, but the finding of erosive oesophagitis may clinch the diagnosis.

If the patient fails a treatment trial or if the symptoms are clearly related to swallowing, an oesophageal motility test may be of benefit although the minority of patients will have a clearly definable motility disturbance. The manometric characteristics of motor disorders that may cause non-cardiac chest pain are shown in Table 1.4. Unfortunately, manometry has significant limitations in this clinical setting as it is performed in a laboratory over a short time frame (which is standard) and the chance that the abnormal manometric findings will be observed, except in the case of achalasia, is low. This likelihood can be increased by using provocative agents, such as edrophonium, or extending the period of observation utilising a portable ambulatory manometry system. Effective therapy for diffuse oesophageal spasm, nutcracker oesophagus, non-specific motility disorder and hypertensive lower oesophageal sphincter is currently not available. Therapeutic trials of nitrates or a calcium channel blocker are worthwhile, but should be discontinued if there is no apparent response.

Table 1.4 Manometric features of oesophageal motility disorders that may be associated with non-cardiac chest pain

Disorder	Features
Achalasia (see Ch 2)	• Incomplete relaxation of the lower oesophageal sphincter • Aperistalsis of the oesophageal body

Diffuse oesophageal spasm

• Simultaneous contractions (> 10%)

• High-amplitude contractions (> 180 mmHg)

• Repetitive synchronous oesophageal body contractions (> 2 peaks)

• Prolonged oesophageal body contractions (> 6 s)

Nutcracker oesophagus

• High-amplitude peristaltic contractions (> 180 mmHg)

• Prolonged oesophageal body contractions (> 6 s)

Hypertensive lower oesophageal sphincter Elevated lower oesophageal sphincter pressure (> 45 mmHg) Non-specific motility disorder One or more of the following:

• non-transmitted contractions (> 20%);

• repetitive oesophageal body contractions (> 2 peaks);

• prolonged oesophageal body contractions (> 6 s);

• low-amplitude peristalsis (< 30 mmHg);

• frequent spontaneous contractions.

A group of patients will remain for whom no diagnosis will be achieved after all investigations have been completed and therapeutic trials undertaken. These patients probably have visceral hypersensitivity, a variant of irritable bowel syndrome. For the sufferer of chest pain, there is likely to be a significant degree of anxiety because of the fear of possible sudden death. Clearly, these patients need to be reassured sympathetically that it is very unlikely that their condition, although distressing, will be progressive or fatal and that continued observation is quite appropriate. Some of these patients will benefit from antidepressant therapy (e.g. low-dose tricyclic antidepressant).