# Evaluation and Management of Patients with Noncardiac Chest Pain

Authors: C. Shekhar; P. J. Whorwell
Journal: Gastroenterology Research and Practice
 (2008)

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## Abstract

Up to a third of patients undergoing coronary angiography for angina-like chest pain are found to have normal coronary arteries and a substantial proportion of these individuals continue to consult and even attend emergency departments. Initially, these patients are usually seen by cardiologists but with accumulating evidence that the pain might have a gastrointestinal origin, it may be more appropriate for them to be cared for by the gastroenterologist once a cardiological cause has been excluded. This review covers the assessment and management of this challenging condition, which includes a combination of education, reassurance, and pharmacotherapy. For the more refractory cases, behavioral treatments, such as cognitive behavioral therapy or hypnotherapy, may have to be considered.


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## Body

## 1. Introduction

Noncardiac chest pain (NCCP) is defined as the presence of pain resembling
angina in the absence of evidence of any coronary artery disease [1, 2]. The
pain, which may be relieved by glyceryl trinitrate (GTN), can radiate to the
arms or neck although it can be very difficult to separate NCCP from true cardiac
pain [3]. However, a distinguishing feature which can be useful is the radiation
of the pain to the back which is not so common in angina [4]. It is important
that cardiac disease is excluded at least by an exercise stress test and, in
many cases, it may be necessary to undertake an angiogram. The latter is
especially useful in refractory cases so that physicians can be secure about
their reassurance as well as being confident in their therapeutic approach.
Nothing undermines management more than endlessly repeating the cardiogram “just
in case.”


## 2. Assessment

Because of its close relationship to the heart, the esophagus is often incriminated
in NCCP but this may not always be the case. Gastroesophageal reflux disease
(GERD) is probably the commonest cause of pain arising from the esophagus and
this can be assessed by pH monitoring although there has been a recent trend to
replace this with a therapeutic trial of a proton pump inhibitor (PPI) [5].
Gastroscopy is also worthwhile [6] and perhaps we should be considering
esophageal biopsy more frequently in the light of the increasing number of
reports of eosinophilic esophagitis [7], as we know little about the contribution
of this problem to chest pain. Routine blood tests are unlikely to be helpful
although barium studies of the esophagus may raise the suspicion of a motility problem.
It is possible to record the motility of the esophagus or its sensitivity to
either mechanical or chemical (e.g., acidic) stimuli [8, 9] and although useful
for research purposes, this approach has not found a great deal of utility in the
routine investigation of NCCP. With respect to motility recording, a number of
different contraction abnormalities of the esophagus have been described, such
as the nutcracker esophagus, although the temporal relationship of these events
to symptoms has not always been clear cut. More recently, there has been increasing
interest in the phenomenon of nonacid esophageal reflux [10] but its role in
NCCP has not yet been defined. This problem can be identified by esophageal
impedance monitoring [11] although at present this technique tends to be confined
to research centers.Another important concept, especially from a therapeutic point of view, that is
common to all functional gastrointestinal disorders, is the notion that the
central processing of noxious stimuli from the gut is disturbed [12]. Thus,
how the patient perceives and reacts to their pain is critical and there is some
evidence that this may be a problem in patients with NCCP [13–16]. These patients
also exhibit a higher prevalence of psychopathology than those with angina and
a simple assessment by an instrument such as the hospital anxiety depression
scale (HAD) [17] can be very useful. A dietary evaluation is also worthwhile as
certain foods or drinks may exacerbate the pain and it has been shown that
alcohol and nicotine can affect lower esophageal sphincter function [18, 19].
Furthermore, it should be remembered that a range of medications might exacerbate
gastrointestinal symptoms in general as well as esophageal symptoms in particular,
so a drug history is helpful.


## 3. Management

Once a cardiological cause for the pain has been ruled out, an assessment
along the lines already described should be undertaken. Reassurance is crucial
but these patients are notoriously resistant to this because of the lethal
connotations of chest pain and the fear that something might have been overlooked.A trial of a PPI should be the first pharmacological step and these may be
required at high doses such as omeprazole 40 mg twice a day or equivalent. If the
patient responds, then GERD-related chest pain is the most likely diagnosis and
maintenance treatment may be required. Failure to respond to a PPI suggests that
acid reflux is not the problem although obviously this does not exclude nonacid
reflux. In the absence of reflux, it is usually assumed that the problem may be
due to a disorder of motility or sensation. On the assumption that esophageal contractions
may be contributing to the pain, a variety of treatments aiming at relieving
spasm have been evaluated. Drugs such as GTN, long acting nitrates, and a variety
of calcium channel blockers have been tried with variable results and some
problems with side effects [20, 21]. Nifedipine has probably received the
most attention, probably because of the demonstration of an effect on esophageal
motility [22, 23] and this drug is sometimes worth a trial although there is no
convincing evidence of efficacy.There is a general consensus that antidepressants, particularly of the
tricyclic variety, are valuable in irritable bowel syndrome although the data
supporting this view are rather old [24, 25]. Not surprisingly, therefore, a
variety of tricyclic agents have been tried in NCCP although, as with the IBS
studies, these studies are somewhat dated. However, the results have been
consistently positive suggesting that these drugs have a definite role in
managing the condition [26–28]. It is a usual practice in functional gastrointestinal
disorders to use relatively low doses of tricyclic antidepressants starting with
amitriptyline 10 mg daily or equivalent. There is evidence that selective
serotonin reuptake inhibition can reduce chemical and mechanical sensitivity
of the esophagus [29] although there has only been one study assessing the effect
of this class of drug in NCCP, but this was encouraging [30]. Benzodiazepines
have also been shown to possibly be beneficial [31, 32]. This is probably
because of their anxiolytic properties as patients with NCCP have been shown to
be prone to panic disorder [33–36]. Unfortunately, this group of drugs is out of
favor at present because of their addictive potential. However, if patients can
be trusted to take them on an “as necessary basis” when the pain is especially
severe, we find that they have a role in NCCP and other functional gastrointestinal
disorders, as long as they are used with caution. There has been recent interest
in the possibility that theophylline might have a role in the treatment of
NCCP [37], especially as it appears to increase the threshold to balloon
distension-induced pain in the esophagus. In the one trial so far reported,
the drug appeared to significantly relieve symptoms in a relatively small group
of patients [38]. There have also been some reports that the injection of Botox
might help spastic disorders of the esophagus [39] although there have been no
formal controlled trials.Behavioral treatments are being increasingly used in functional gastrointestinal
disorders and NCCP is no exception to this rule. There have been five studies of
cognitive behavioral therapy (CBT) in this condition all of which have been
positive [40–44]. Whether this form of treatment has a long lasting effect is not
so certain although one of these trials suggested benefit may be sustained [38].
Another form of treatment that is gaining some acceptability in FGD’s is
hypnotherapy [45, 46] and we have recently reported a trial of this modality in
a small group of highly selected patients with NCCP [47].
These results were very encouraging and we have subsequently shown
that the beneficial effects appear to be long lasting [44, 48].Thus, in summary, it is mandatory to exclude a cardiac cause for chest pain
before undertaking appropriate gastrointestinal investigation and making a confident
diagnosis of NCCP. Once this has been established, a trial of a PPI should be
the next step. Subsequent investigation should be kept to a minimum and a variety
of other medications can be tried although the tricyclic antidepressants are
probably the most effective. If pharmacological approaches fail, behavioral
treatments can be of value depending on their availability.



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