Which Symptom is Not Consistent With Cardiac Related Chest Pain
Which Symptom is Not Consistent With Cardiac Related Chest Pain
J Neurogastroenterol Motil.
2011 Apr; 17(2): 110–123.
Noncardiac Chest Pain: Epidemiology, Natural Grade and Pathogenesis
Ronnie Fass
1Department of Gastroenterology, Section of Medicine, Southern Arizona VA Health Care System, Tucson, Arizona, USA.
Sami R Achem
2Mayo College of Medicine, Mayo Clinic, Jacksonville, Florida, USA.
Received 2011 February 11; Revised 2011 Mar 17; Accepted 2011 Mar 28.
Abstract
Noncardiac breast pain is defined equally recurrent chest pain that is indistinguishable from ischemic heart pain after a reasonable workup has excluded a cardiac crusade. Noncardiac chest hurting is a prevalent disorder resulting in high healthcare utilization and significant work absenteeism. However, despite its chronic nature, noncardiac chest pain has no impact on patients’ mortality. The main underlying mechanisms include gastroesophageal reflux, esophageal dysmotility and esophageal hypersensitivity. Gastroesophageal reflux disease is likely the near common cause of noncardiac breast pain. Esophageal dysmotility affects only the minority of noncardiac chest pain patients. Esophageal hypersensitivity may be present in non-GERD-related noncardiac chest pain patients regardless if esophageal dysmotility is present or absent. Psychological co-morbidities such as panic disorder, anxiety, and depression are as well common in noncardiac chest pain patients and often attune patients’ perception of illness severity.
Keywords:
Chest pain, Esophageal motility disorders, Esophagus, Heartburn
Introduction
Noncardiac breast pain (NCCP) is very common in the general population; nevertheless, a patient’s history and characteristics exercise not reliably distinguish betwixt cardiac and esophageal causes of breast pain.1
,
2
When it comes to chest pain, the cardiologist’s starting time priority is to exclude whatever acute life-threatening cardiovascular condition.3
These include acute coronary syndrome, aortic autopsy, pulmonary thromboembolism, and pericardial tamponade. If these acute conditions have been excluded, evaluation for chronic ischemic eye disease or pericardial disease must be pursued. Various tests can help determine the presence and severity of ischemia, left ventricular function, advent of the coronary arteries, and functional capacity. They include exercise examination electrocardiogram, echocardiography or nuclear unmarried photon emission computed tomography (SPECT) and, if patients are unable to practice, pharmacologic echocardiography, nuclear SPECT or cardiac MRI. The determination about which tests to pursue should be left to the discretion of the treating cardiologist.four
The heightened awareness about the potentially devastating ramifications of chest pain may drive patients to seek further medical attending despite a negative cardiac workup.5
Compared to patients with cardiac angina, those with NCCP are ordinarily younger, less likely to have typical symptoms, and more likely to take a normal resting electrocardiogram.6
Additionally, levels of feet of NCCP patients seen in a rapid access breast pain clinic significantly exceeded those of patients with cardiac angina and remained higher up community norms for at least 2 months later on clinic visit.7
NCCP patients view their condition as significantly less controllable and less understandable than those whose pain is of cardiac origin.8
NCCP may be the manifestation of gastrointestinal (GI) or not-GI-related disorders. An important step toward understanding the underlying mechanisms of NCCP was the recognition that gastroesophageal reflux disease (GERD) is the about common contributing factor for breast hurting. While breast pain has been considered an atypical manifestation of GERD, it is an integral part of the express repertoire of esophageal symptoms. In patients with non-GERD related NCCP, esophageal motility disorders, and functional chest pain (FCP) of presumed esophageal origin are the main underlying mechanisms for symptoms. The Rome Three Commission does not specifically accost NCCP but rather a subset of patients with NCCP termed “functional chest pain of presumed esophageal origin” to describe recurrent episodes of substernal breast pain of visceral quality with no apparent explanation. Equally with all other functional esophageal disorders, GERD and esophageal dysmotility should likewise be ruled out before the diagnosis is established.9
Even so, up to 20% of patients with FCP exhibit other functional disorders, primarily irritable bowel syndrome (27%) and intestinal bloating (22%).10
Definition
Noncardiac chest pain is defined as recurrent chest pain that is indistinguishable from ischemic heart hurting afterwards a reasonable workup has excluded a cardiac cause.
Patients with NCCP may written report squeezing or burning substernal chest hurting, which may radiate to the back, neck, arms and jaws, and is duplicate from cardiac related breast hurting. This is compounded by the fact that patients with history of coronary artery affliction (CAD) may also experience NCCP. Consequently, all NCCP patients should kickoff undergo evaluation by a cardiologist to exclude cardiac angina.11
,
12
Differentiating on a clinical basis only between cardiac angina and NCCP has been shown to exist a very difficult task.1
Furthermore, NCCP patients tend to report a higher rate of chest pain occurrence and greater pain intensity. They besides more apply unremarkably sensory and affective words than patients with ischemic heart disease.i
For the cardiologist, any two of the post-obit clinical characteristics are suggestive of atypical cardiac angina and just i or none of these characteristics is indicative of NCCP: (i) substernal breast discomfort, pressure or heaviness that lasts several minutes, (ii) hurting induced past exertion, emotion, exposure to common cold or a large meal and (three) hurting that is relieved by residual or nitroglycerine normally signify cardiac angina.3
When it comes to chest pain, the cardiologist’s start priority is to exclude any acute life threatening cardiovascular condition.3
These include astute myocardial infarction, unstable angina, aortic autopsy, pulmonary thromboembolism and pericardial tamponade. If an acute cardiac syndrome has been excluded, then evaluation for chronic ischemic centre affliction or pericardial disease should be pursued. Diverse tests tin aid decide the presence and severity of ischemia, left ventricular function, appearance of the coronary arteries and functional capacity. They include exercise electrocardiogram or exercise echocardiography, echocardiography or nuclear SPECT and, if patients are unable to practise, pharmacologic (dobutamine, persantine or adenosine) echocardiography, nuclear SPECT or cardiac MRI. The decision of which tests to pursue should be left to the discretion of the treating cardiologist.4
A recent, population-based cohort study with nested case-control analysis demonstrated that patients with chest hurting but without established ischemic centre disease had an increased risk of being diagnosed with ischemic heart disease (hazard ratio, 18.ii; 95% CI, 11.6 to 28.6) in the year afterwards the index event of chest hurting.13
We did non include frequency or severity of breast pain in our definition, because in that location is no clear spectrum or threshold of both clinical parameters in the literature. As a outcome, any endeavor to limit the frequency and/or severity of chest pain may exclude many true sufferers with NCCP.
There are many causes for NCCP, and they are not limited to the esophagus (Table 1). Thus, the term NCCP is more inclusive and includes musculoskeletal, pulmonary, cardiovascular, infectious, drug-related, psychological and other GI disorders.14
Our focus in these guidelines will exist but on esophageal-related mechanisms for NCCP. The Rome Criteria do non specifically address NCCP simply rather a subset of patients with NCCP termed FCP of presumed esophageal origin.9
These are patients with recurrent episodes of substernal chest pain of visceral quality with no apparent caption using currently available tests.
Table 1
Common Noncardiac, Nonesophageal Etiologies for Chest Pain
Epidemiology
Noncardiac chest pain is a prevalent disorder resulting in high healthcare resource utilization and significant piece of work absenteeism.
Information nigh the epidemiology of NCCP in the Usa and around the globe is relatively limited. Shortly, chest hurting is the second most common presentation to hospital emergency departments; even so, only 25% of individuals who experience chest pain actually present to a hospital.15
The mean annual prevalence of NCCP in six population-based studies was approximately 25%. Still, these studies differ in many aspects such as NCCP definition, geography, sample size, sampling gild and ethnic disparities.sixteen
A population-based survey in the United States assessed the prevalence of GERD in Olmsted County, Minnesota and reported an overall NCCP prevalence of 23%.17
Gender distribution amidst NCCP patients was like (24% among males and 22% among females). Using the Rome criteria for functional GI disorders, Drossman et al18
reported a prevalence of xiii.6% in 8,250 households in the U.s.a.. In this written report, FCP of presumed esophageal origin was diagnosed rather than NCCP. Eslick et alxix
,
20
recently evaluated the prevalence of NCCP in Australia by using a mailing of a validated Breast Hurting Questionnaire to 1,000 randomly selected individuals. The study demonstrated a prevalence rate of 33% with most equal gender distribution (32% in males versus 33% in females). This study as well showed that the population prevalence of NCCP decreases with increasing age.19
,
twenty
A nationwide population-based written report from South America found that the annual prevalence of NCCP was 23.5% and that NCCP has been equally reported by both sexes.21
In this study, frequent typical GERD symptoms (at least once a week) were significantly and independently associated with NCCP. Another recently published epidemiologic study demonstrated that the annual prevalence of NCCP in a Chinese population was nineteen%.22
Although females with NCCP tend to consult healthcare providers more than ofttimes than men, the disorder affects both sexes equally.17
,
19
,
21
Additionally, females are more probable to present to infirmary emergency departments with NCCP than males, merely there are no sex differences regarding chest pain intensity.23
Overall, women tend to use terms like “burning” and “frightening” more oftentimes than men.24
Epidemiologic studies study a decrease in the prevalence of NCCP with increasing age. Women nether 25 years of age and those between 45 and 55 years of age have the highest prevalence rates.twenty
Patients with NCCP are younger, eat greater amounts of alcohol and tobacco, and are more likely to suffer from anxiety than their counterparts with ischemic heart affliction. Patients with NCCP continue to seek handling on a regular basis after the diagnosis was established for both chest pain and other unrelated symptoms, but few are in contact with infirmary services.25
In 1 study, almost a fourth of individuals with NCCP had sought healthcare for chest pain inside the previous 12 months. None of the GI (heartburn, dysphagia and acid regurgitation) or psychological (anxiety, low and neuroticism) risk factors was significantly associated with pursuing consultation for NCCP.20
A contempo US-based survey revealed that cardiologists manage by themselves near half of the patients who are diagnosed with NCCP.26
Of those NCCP patients who were referred, 45.9% were sent back to the primary intendance physician (PCP), and only 29.three% to a gastroenterologist. In a survey of PCPs, Wong et al27
demonstrated that nigh NCCP patients were diagnosed and treated by PCPs (79.five%) without being referred to a gastroenterologist. The nigh preferred subspecialty for the initial diagnostic evaluation of a patient presenting with breast pain was cardiology (62%), followed by gastroenterology (17%). The mean percentage of such referrals was only 22%. The almost preferred subspecialty for further direction of NCCP was gastroenterology (76%), followed by cardiology (8%). The hateful percentage of the bodily referral charge per unit was 29.viii% for gastroenterologists and 14% for cardiologists.27
A study by Eslick and Talley28
reported that 78% of patients who presented to a hospital emergency department with acute breast pain had seen a healthcare provider in the last 12 months. The most mutual healthcare provider seen was a general practitioner (85%), followed by cardiologist (74%), gastroenterologist (30%), pulmonologist (14%), alternative therapist (viii%) and psychologist (10%).28
A multiple logistic regression analysis revealed that patients with chest hurting who are as well suffering from heartburn were 16 times more likely to see a general practitioner (OR, 16.40; 95% CI, 1.98-135.99) and 3 times more likely to consult a gastroenterologist (OR, three.10; 95% CI, 1.26-seven.62). Additionally, work absenteeism rates (29%) and interruptions to daily activities (63%) were high because of NCCP.
Many patients with NCCP study poor quality of life and admit taking cardiac medications despite lack of evidence for a cardiac crusade. Only a small fraction of patients experience reassured. Consequently, the economic brunt of the disease has been proposed to exist very high, although studies evaluating the cost impact of NCCP on the healthcare system are very scarce. In 1 study, the healthcare cost for NCCP was estimated to exist more than than $315 1000000 annually, primarily considering of multiple clinic visits, emergency room visits, hospitalizations and prescription medications.29
This toll estimate does not include indirect costs such equally lost days of piece of work or the impact of symptoms on patients’ quality of life, which take been demonstrated to exist more meaning when evaluating the economic burden of patients with functional bowel disorders. In Australia, the almanac cost associated with NCCP presentations to the Nepean Hospital amount to approximately a $ane.4 million.30
The researchers extrapolated these costs to the Australian healthcare system and conservatively estimated that NCCP accounts for at least a $30 million of the healthcare upkeep annually.
Natural Course
Noncardiac chest hurting is a chronic disorder that reduces patient’s quality of life but has no impact on mortality.
Thus far, very few studies accept evaluated the natural form of NCCP. Evidently, the main concern is the likelihood of these patients developing true ischemic center affliction if followed long term. One of the early studies by Wielgosz et al31
followed 821 patients with chest hurting and normal coronary arteries for a catamenia of 1-year. The authors demonstrated that only three (0.iii%) patients died, and all were due to nonischemic reasons.31
However, about of the patients (67%) continued to feel breast pain to some caste (39% less hurting, 26% the same pain and 2% more than severe hurting). In a written report that followed 46 NCCP patients over a catamenia of 11 years, but 2 (four.three%) of the subjects died from a cardiovascular-related consequence (stroke and ischemic heart disease). Again, as in the previous study, 74% of the surviving NCCP patients continued to report chest pain 11 years later, and of those 34% reported chest pain symptoms weekly.32
Other studies also documented a very limited long-term bloodshed in NCCP patients but with continuous debilitating symptoms, impaired functional condition, chronic use of drugs (GI, cardiac and psychiatric), repeated admissions to the hospital, and repeated cardiac and noncardiac procedures.25
,
33
–
37
In a survey study, 119 NCCP patients, of which 63 were diagnosed as having pain from the esophagus, were followed for a menses of 21.8-month.38
Patients with esophageal-related breast hurting usually continued to accept recurrent hurting. Interestingly, a specific diagnosis did not significantly increment the likelihood of pain resolution. However, patients who understood that the esophagus was the source of their pain were significantly less likely to feel disabled by their pain and therefore were less likely to require continued md evaluation. This written report was published prior to the proton pump inhibitor (PPI) era. Information technology is unlikely that patients with NCCP due to GERD volition keep to have symptoms long term if they are compliant with their antireflux treatment. In another study that compared long-term natural history between NCCP and GERD patients, the authors institute no significant difference in survival between the two groups (hazard ratio, 1.1; 95% CI, 0.8-ane.five). Interestingly, the diagnosis of NCCP disappeared from the electronic hospital record in 96% of the patients within 2 years of follow-up.39
In a contempo report that followed 355 NCCP patients, the authors demonstrated that 49% sought intendance in the emergency section, 42% underwent repeated cardiac workup, and only 15% were seen past a gastroenterologist.thirteen
Survival free of cardiac death in the subset with NCCP and a GI disorder was ninety.2% at 10 years and 84.8% at 20 years, compared to 93.seven% at 10 years and 88.1% at 20 years for those with NCCP of unknown origin.
Less than a handful of studies reported similar mortality between patients with NCCP and those with CAD.37
,
twoscore
A more recent study by Eslick and Talley41
followed 126 NCCP and 71 cardiac patients who were seen in the emergency room for a period of 4-twelvemonth. The majority of the NCCP (71%) and the CAD patients (81%) continued to have symptoms four years afterwards. The authors found no difference in the bloodshed rate between the 2 groups (CAD-11.0% vs NCCP-5.5%,
P
= 0.16). However, the study may suffer from type 2 error, and the results need to be confirmed in a larger accomplice of patients.
Overall, the aforementioned data support the overall determination that increased mortality is uncommon in NCCP patients. However, patients with NCCP demonstrate poor quality of life primarily due to continuation of symptoms many years after diagnosis.
Pathogenesis
Gastroesophageal Reflux Disease
Gastroesophageal reflux affliction is the most common esophageal cause for noncardiac breast pain in patients with and without coronary artery disease.
Many studies have shown an association betwixt GERD and NCCP. Withal, association does not confer causality. Resolution or comeback of breast hurting symptoms in response to treatment with antireflux medications provides the missing causal link.
Locke et al and colleagues17
have demonstrated that NCCP is more commonly reported by patients (37%) who experience heartburn symptoms at least weekly, equally compared with 30.7% of those who have infrequent heartburn (less than in one case a week) and vii.ix% of those without whatever GERD symptoms. In some other community-based study, the authors constitute that 53% of all patients with NCCP experienced heartburn and 58% acid regurgitation.xx
Stahl et al42
found in a pocket-size sample of NCCP patients that 61.five% had GERD-related symptoms. In 3 different studies evaluating the role of the PPI examination in patients with NCCP, the authors found GERD-related symptoms in 68%-90% of the patients.43
–
45
Convalescent 24 hour esophageal pH testing studies have demonstrated that about one-half of NCCP patients have an abnormal esophageal acid exposure. Stahl et al42
evaluated 13 sequent NCCP patients and establish that 69.two% had an abnormal pH test. Beedassy et al46
evaluated 104 patients with NCCP and documented that 48% of them had an abnormal pH test. It should be noted that only 21% of the 52 patients who reported breast hurting during the written report had a concomitant acrid reflux consequence. Interestingly, only 10 of the 52 subjects had a positive symptom alphabetize (> 50%). Similarly, DeMeester et al47
demonstrated that 46% of patients with chest pain had symptoms associated with an acid reflux result equally documented during pH testing. Pandak et al48
constitute an aberrant pH test in 42% of NCCP patients. In 3 dissimilar studies evaluating the role of the PPI examination, the authors institute abnormal pH examination in 37.5%-67% of the NCCP patients.43
–
45
In a study from Asia, 34.three% of the NCCP patients had at least i abnormal pH parameter.49
Even in patients with CAD who continued to have atypical chest pain symptoms, up to 67% had some of their painful episodes associated with acid reflux.l
The presence of esophageal mucosal abnormalities consistent with GERD appears to exist less common in NCCP patients than GERD symptoms or backlog esophageal acrid exposure. From different studies, the range has been betwixt ii.v%-75%.14
,
49
,
51
,
52
In three different studies evaluating the role of the PPI test in patients with NCCP, the authors found GERD-related endoscopic findings in 44%-75% of the NCCP patients.43
–
45
In all of these studies, low-grade erosive esophagitis was the main GERD-related endoscopic finding. A recent study by Dickman et al53
evaluated upper GI findings in patients with NCCP as compared with those having simply GERD-related symptoms using a large multicenter consortium. Of the NCCP grouping, 28.half-dozen% had hiatal hernia, 19.6% erosive esophagitis, 4.4% Barrett’s esophagus, and 3.6% esophageal stricture/stenosis (Table 2). The prevalence of these findings was significantly lower in the NCCP group when compared with the GERD group. From this study, information technology appears that GERD-related mucosal abnormalities are not uncommon in the esophagus of NCCP patients. Notwithstanding, the prevalence of these anatomical findings is lower than what has been observed in GERD patients. Chiefly, NCCP patients may also demonstrate Barrett’s esophagus, albeit uncommonly.
Table ii
The Value of Endoscopy in Noncardiac Breast Hurting Patients From a Large Multicenter Consortium
The mechanism past which gastroesophageal reflux causes NCCP remains poorly understood. It is even so unclear why esophageal exposure to gastric content in some patients causes heartburn and in others chest pain. This is compounded by the fact that some patients may experience chest hurting at 1 time and heartburn at other times.
Characteristics of the private reflux episodes (elapsing and pH level) take been proposed to influence patients’ symptoms. Smith et al54
studied 25 individuals with NCCP to determine the relation between the awareness of pain in GERD and pH of the refluxate. They found that all 25 patients had reproduction of their pain during intraesophageal infusion of solutions with pH 1 and 1.v. Reflux events resulting in hurting were significantly longer than those without pain and were more often associated with a recently preceding painful episode.
Different underlying mechanisms have been suggested to result in esophageal hypersensitivity in NCCP patients. These include peripheral sensitization of esophageal sensory afferents leading to heightened responses to physiologic and pathologic stimuli and modulation of afferent neural function at the level of the spinal dorsal root or the central nervous arrangement.55
In 1 written report,56
healthy subjects underwent perfusion of the distal esophagus with normal saline or 0.1 N hydrochloric acid. Perceptual responses to intraluminal esophageal balloon amplification were evaluated using electronic barostat. Every bit compared with saline, acid perfusion reduced the perception threshold (innocuous sensation) and tended to reduce the pain threshold (aversive awareness). This study demonstrated curt-term sensitization of mechanosensitive afferent pathways by transient exposure to acid. The authors suggested that in patients with NCCP, acid reflux induces sensitization of the esophagus, which may later on alter the way the esophagus perceives otherwise normal esophageal distentions. Sarkar et al57
recruited 19 healthy volunteers and vii patients with NCCP. Hydrochloric acid was infused into the distal esophagus over 30 minutes. Sensory responses to electric stimulation were monitored within the acrid-exposed distal esophagus and the not-exposed proximal esophagus earlier and later infusion. In the good for you subjects, acid infusion into the distal esophagus lowered the pain threshold in the upper esophagus. Patients with NCCP already had a lower resting esophageal pain threshold than salubrious subjects. After acrid perfusion, their pain threshold in the proximal esophagus fell further and for a longer duration than was the case for the healthy subjects. Additionally, in that location was a decrease in pain threshold after acid infusion in the anterior chest wall. This report demonstrated the development of secondary allodynia (visceral hypersensitivity to innocuous stimulus in normal tissue that is in proximity to the site of tissue injury) in the proximal esophagus by repeated acid exposure of the distal esophagus. The concurrent visceral and somatic pain hypersensitivity is almost probable caused by central sensitization (an increment in excitability of spinal string neurons induced past activation of nociceptive C-fibers in the area of tissue injury). The patients with NCCP demonstrated visceral hypersensitivity and amplified secondary allodynia in the esophagus.
Another explanation how GERD may cause chest pain was provided by studies using high-frequency, intraluminal ultrasonography. Balaban et al58
demonstrated a temporal correlation between sustained contractions of the esophageal longitudinal musculus and spontaneous as well as provoked esophageal chest pain. In a follow-upward report, the authors suggested that the duration of sustained esophageal contraction determines the type of symptom perceived past patients.59
Heartburn was associated with shorter duration contractions, whereas chest pain was associated with contractions of longer duration. In a recent study, the authors suggested that esophageal muscle thickness per se, in the absence of esophageal motion abnormality, can lead to chest pain symptoms.60
Studies have demonstrated that NCCP patients with testify of GERD (endoscopic findings and/or abnormal pH test) commonly respond to antireflux treatment. Betwixt 78%-92% of NCCP patients with objective evidence of GERD demonstrated symptoms improvement on antireflux treatment.43
,
45
,
48
,
49
In contrast, response to PPI treatment in NCCP patients without objective evidence of GERD ranged between 10% and fourteen%.43
–
45
It Kushnir et al61
have demonstrated that a positive symptom-association probability and elevated acid exposure time predicted response to PPI treatment in patients with NCCP. When used hierarchically, response to antireflux treatment was best predicted when GERD parameters (acid exposure time, symptom-clan probability and symptom alphabetize) were all abnormal and poorest when all normal. These information advise a causal relationship betwixt patients’ GERD and chest pain symptoms.
Esophageal Motility
Only the minority of patients with noncardiac chest hurting demonstrate esophageal motion abnormalities.
Several large studies demonstrated that approximately 30% of NCCP patients had aberrant esophageal manometry.62
–
64
In 1 written report that included 910 NCCP patients, the authors found that seventy% had normal esophageal move.62
Nutcracker esophagus (xiv.4%) was the most ordinarily documented esophageal motion abnormality, followed past nonspecific esophageal motor disorder (10.viii%). Diffuse esophageal spasm, achalasia and hypertensive lower esophageal sphincter were very uncommon in this NCCP group. In another study, Dekel et al63
evaluated 140 NCCP patients using the Clinical Outcomes Research Initiative database. Dissimilar the previous report that included patients from 1 major center with interest in esophageal motion, the study by Dekel et al63
included patients from more than threescore academic, Veteran Diplomacy, and individual centers from around the United States. The authors also constitute that seventy% of the subjects had a normal esophageal motion examination. Hypotensive lower esophageal sphincter (61%) was the nearly mutual motion abnormality diagnosed, followed by hypertensive lower esophageal sphincter, nonspecific esophageal motor disorder and nutcracker esophagus (10% each). In this study, achalasia and diffuse esophageal spasm were also very uncommon. The difference in the distribution of motility abnormalities between the ii studies reflects the different study designs. In the first study, only not-GERD-related NCCP patients were included, whereas all newcomers were enrolled into the 2d study. A recent study from Chile evaluated 100 newly diagnosed NCCP patients and plant that 8% of them had an abnormal esophageal manometry.65
In this study, 36% of patients had nutcracker esophagus, 28% hypotensive lower esophageal sphincter, and 16% nonspecific esophageal motor disorder. The reason for the discrepancy between the results of this study and the other 2 is unclear. It appears, nevertheless, that the loftier rate of esophageal motility abnormalities recorded in NCCP patients in this study may reflect a local referral bias.
The relationship betwixt NCCP and esophageal dysmotility remains an expanse of intense controversy because documentation of esophageal dysmotility during manometry is rarely associated with reports of breast pain symptoms.two
In addition, different GERD we are even so devoid of highly effective pharmacologic compounds that can eliminate esophageal dysmotility and thus can be used to demonstrate a causal relationship.66
Furthermore, in NCCP patients who underwent simultaneous esophageal manometry and pH testing, chest hurting was more commonly associated with acid reflux events than move abnormalities.64
,
67
Fifty-fifty the past usage of convalescent 24 hour esophageal manometry was unable to improve the sensitivity of the examination in NCCP. In fact, studies take demonstrated that 27%-43% of patients did not report any chest pain symptoms during the test.64
,
68
Moreover, the investigators were able to chronicle hurting episodes to recorded esophageal dysmotility in just thirteen%-24% of patients. Consequently, the routine usage of ambulatory 24 hour esophageal manometry has been questioned, and the technique is rarely performed in clinical practise. In 1 study, the authors were able to demonstrate improvement of NCCP symptoms in patients with nutcracker esophagus receiving antireflux handling but with no effect on esophageal motion.69
Some government have proposed using esophageal motility abnormalities in NCCP patients as a marker for an underlying motor disorder that may exist responsible for patients’ symptoms.70
Withal, information technology is plausible that our current evaluative techniques of the esophagus provide just crude data about esophageal motor part. Futurity tests will require providing a more comprehensive evaluation of anatomical structure and biomechanics of the esophagus and their relationship to pain.
Esophageal Hypersensitivity
Esophageal hypersensitivity has been demonstrated in virtually of the non-gastroesophageal reflux disease-related noncardiac chest pain patients, regardless if esophageal dysmotility is present or absent.
Studies have consistently documented alteration in pain perception regardless of whether dysmotility was nowadays or absent in patients with NCCP.
Visceral hypersensitivity is a phenomenon in which conscious perception of visceral stimulus is enhanced independently of the intensity of the stimulus.55
Peripheral and cardinal mechanisms have been proposed to be responsible for visceral hypersensitivity in patients with NCCP. Information technology has been hypothesized that peripheral sensitization of esophageal sensory afferents leads to after heightened responses to physiologic or pathologic stimuli of the esophageal mucosa.55
Additionally, central sensitization at the brain level or the dorsal horn of the spinal string may modulate afferent neural function and thus enhance perception of intraluminal stimuli.71
What causes peripheral or key sensitization remains to be determined. Studies accept shown that acute tissue irritation results in subsequent peripheral and central sensitization, which is manifested every bit increased groundwork activity of sensory neurons, lowering of nociceptive thresholds, changes in stimulus response curves and enlargement of receptive fields.72
Peripheral sensitization involves the reduction of esophageal pain threshold and increase in the transduction processes of master afferent neurons.73
Esophageal tissue injury, inflammation, spasm or repetitive mechanical stimuli tin all sensitize peripheral afferent nerves. The presence of esophageal hypersensitivity tin be later demonstrated long after the original stimulus is no longer present and the esophageal mucosa has healed. However, information technology is even so unclear what factors are pivotal for the persistence of such esophageal hypersensitivity.
Studies have demonstrated that patients with not-GERD-related NCCP accept lower perception thresholds for pain. Richter et al74
used balloon distension protocol in the distal esophagus and institute that 50% of patients with NCCP adult pain at volumes of 8 mL or less in comparison with 9 mL or more in healthy subjects who developed hurting. The authors found no divergence in the pressure-volume curve of the 2 groups as well as no difference in esophageal motility.74
When the balloon was inflated to 10 mL, patients with a history of NCCP were more likely to experience hurting (18/30) than the control subjects (6/30).73
Barish et al73
evaluated 50 patients with NCCP and 30 salubrious volunteers using graded balloon amplification protocol. Of the patients with NCCP, 56% (28/50) experienced their “typical” chest hurting during balloon distension as compared with 20% (six/30) of the normal controls.73
Of those with NCCP who experienced pain, 85% reported hurting at values below the usual sensory threshold (twenty cm H2O).75
There was no difference in esophageal tone betwixt the 2 groups.
Rao et al75
used impedance planimetry to evaluate 24 patients with NCCP and 12 healthy controls. Using airship distention, they demonstrated that those with NCCP had lower perception thresholds for first sensation, moderate discomfort and hurting in comparing to the healthy controls.75
Typical chest pain was reproduced in 83% of the NCCP patients.75
In addition, the reactivity of the esophagus to airship amplification was increased in those with NCCP, as was the pressure elastic modulus. Rao et al76
also performed graded balloon distensions of the esophagus using impedance planimetry in xvi consecutive patients with NCCP (normal esophageal evaluation) and thirteen healthy command subjects. Patients who experienced chest pain during balloon distension were subsequently restudied later receiving intravenous atropine. Balloon distensions reproduced chest pain at lower sensory thresholds in most NCCP patients as compared with controls. Similar findings were documented after atropine administration despite relaxed and more than deformable esophageal wall. Thus, the investigators ended that hyperalgesia, rather than motor dysfunction, is the predominant machinery for FCP.
Sarkar et al57
recruited 19 healthy volunteers and 7 patients with NCCP. Muriatic acid was infused into the distal esophagus during a period of 30-minute. Sensory responses to electrical stimulation were monitored inside the acid-exposed distal esophagus and the non-exposed proximal esophagus both before and after infusion. In the healthy subjects, acid infusion into the distal esophagus lowered the pain threshold in the upper esophagus. Patients with NCCP already had a lower resting esophageal pain threshold than salubrious subjects. Later on acid perfusion, their pain threshold in the proximal esophagus brutal further and for a longer duration than in healthy subjects. Additionally, at that place was a decrease in the hurting threshold of the inductive chest wall after acid infusion. This study demonstrated the development of secondary allodynia (visceral hypersensitivity to innocuous stimulus in normal tissue at proximity to site of tissue injury) in the proximal esophagus by repeated acid exposure of the distal esophagus. The concurrent visceral and somatic pain hypersensitivity is most probable caused by fundamental sensitization (increase in excitability of spinal cord neurons induced by activation of nociceptive C-fibers in the area of the tissue injury). The patients with NCCP demonstrated both visceral hypersensitivity and amplified secondary allodynia in the esophagus. However, it is unclear from the study what mechanism is responsible for the exaggerated secondary allodynia and what initiates central sensitization in patients with NCCP. It is interesting to notation that other studies in NCCP, using a like homo model of acute tissue irritation by acid infusion, showed no significant upshot on pain thresholds.77
Börjesson et al77
also demonstrated that patients with NCCP have reduced sensitivity to esophageal balloon distension during simultaneous transcutaneous electric nerve stimulation (TENS) as compared with healthy controls.78
This further supports the role of visceral hypersensitivity in NCCP and suggests that the phenomenon is probably due to fundamental sensitization.79
Mehta et al79
as well demonstrated that acid infusion into the distal esophagus reduces esophageal pain thresholds for balloon amplification in patients with NCCP not previously sensitive to balloon distension or acid infusion.
In ane written report, subjects underwent perfusion of the distal esophagus with either normal saline or 0.1 Due north muriatic acid.56
Perceptual responses to intraluminal esophageal balloon distension using electronic barostat were recorded. Perfusion with acid was associated with a reduced sensation threshold (innocuous perception) and tended to reduce the hurting threshold (aversive sensation). The report demonstrated short-term sensitization of mechanosensitive afferent pathways by transient exposure to acid. It was suggested that in patients with NCCP, acid reflux induces sensitization of the esophagus. This may later modify the way in which otherwise normal esophageal distensions are perceived.lxxx
Sarkar et al80
also evaluated fourteen patients with GERD-related NCCP and 8 healthy controls. All subjects underwent an esophageal electric stimulation protocol in the proximal esophagus, and those with NCCP demonstrated lower perception thresholds for hurting than normal controls.80
However, there was an increase in the perception thresholds for pain during electrical stimulation in the NCCP patients after a vi-week form of high-dose PPI (omeprazole 20 mg twice daily).80
This study demonstrated that patients with NCCP and show of GERD have a component of esophageal hypersensitivity that is responsive to high-dose PPI therapy.80
In another small study that enrolled 22 NCCP patients with documented nutcracker esophagus, the authors demonstrated that stepwise balloon distensions reproduced pain symptoms at a lower threshold in 90% of NCCP patients every bit compared with 20% of healthy controls.81
It was concluded that patients with NCCP and nutcracker esophagus likewise exhibit visceral hypersensitivity. Additionally, visceral hypersensitivity is the likely master underlying machinery for patients’ symptoms, rather than the presence of the high amplitude contractions (nutcracker esophagus). Unfortunately, the presence of GERD in these patients was not determined in this study.
In a contempo written report, 75% of patients with FCP who underwent impedance planimetry demonstrated esophageal hypersensitivity.82
These patients had larger cantankerous-sectional areas, decreased esophageal wall strain, distensibility, and lower thresholds for perception, discomfort, and pain as compared with FCP patients without esophageal hypersensitivity or healthy controls. Some other recent written report showed that pain evoked by bag distention in FCP patients is dependent primarily on stress and to a bottom degree on strain.83
The pain does not appear to be related to mucosal perfusion.
Psychological Comorbidity
Psychological co-morbidities, such as panic disorder, anxiety and depression are common in noncardiac breast pain patients.
Psychological comorbidity has been shown to exist mutual in NCCP and affects upwardly to 75% of patients.84
It has withal to be determined if the high level of psychological comorbidity may be related to referral bias to 3rd referral centers or if it is the result of long-term experience of pain. Regardless, studies reported a high prevalence (> l%) of panic disorder, anxiety and major depression in NCCP patients.20
,
84
–
97
Other psychological abnormalities accept also been reported including neuroticism, hypochondriac behavior, obsessive-compulsive disorder, phobic disorder, and somatization.20
,
89
–
92
,
98
–
102
In a minor study of 36 subjects with NCCP, the authors found that 58% had some type of psychological abnormality.103
Of those, feet, low and panic disorder were the virtually mutual. In a large population-based written report in Australia, the authors surveyed a random sample of ane,000 residents in the Sydney area.xx
Amidst those with NCCP, the prevalence of anxiety was 23% and depression vii%. In a telephone survey from Hong Kong that included two,209 subjects, the authors demonstrated that low and anxiety were significantly more than common in NCCP patients than those without NCCP.93
Amid all esophageal symptoms, breast pain was shown to closely correlate with psychometric abnormalities. In some patients, chest hurting is part of a host of symptoms that characterize panic assault. Panic attack is a common cause for emergency room visits due to chest pain. In a large study that encompassed 441 consecutive ambulatory patients presenting with breast pain to the emergency section of a eye middle, 25% were diagnosed as suffering from a panic attack.104
Whilst the reason for the observed association between NCCP and panic disorder remains to be fully elucidated, hyperventilation was demonstrated to precipitate chest pain in 15% of patients with NCCP.104
Additionally, it was demonstrated that hyperventilation could provoke reversible esophageal manometric abnormalities such as esophageal spasm (four%) and a nonspecific esophageal motor disorder (22%).105
Furthermore, studies have demonstrated that hyperventilation may precipitate a panic assail.
Anxiety and depression influence reports of pain and thus contribute to the pathophysiology of NCCP. Lantinga et al106
establish that patients with NCCP had college levels of neuroticism and psychiatric comorbidity before and later cardiac catheterization than did patients with CAD. This finding appears to have prognostic significance because these patients brandish less improvement in pain, more than frequent pain episodes, greater social maladjustment, and more anxiety at 1-year follow-up than individuals with relatively depression initial levels of psychosocial disturbances. In a large epidemiological study from England, a significant human relationship betwixt NCCP and psychiatric disorders was demonstrated in young adults.107
Two independent variables were associated with chest pain: parental illness and fatigue during childhood.
Studies have been inconsistent when the frequency of panic disorder, anxiety, and depression were compared between NCCP patients and those with CAD. Some studies reported increased panic disorder, anxiety, and depression in NCCP patients, while others found no significant departure in the prevalence of psychological disorders between the ii groups.100
,
108
–
110
In i written report of 199 participants, panic disorder was more common in NCCP as compared with those with CAD (41% vs 22%).108
However, other psychiatric disorders were highly prevalent (72%) merely without any deviation between the 2 groups. In contrast, Cormier et al111
demonstrated that 98 NCCP patients scored higher on measures of feet and negative life events and had a significantly greater prevalence of DSM III panic disorder (47% vs 6%), major depression (39% vs eight%) and ii or more than uncomplicated phobias (43% vs 12%) than did patients with CAD. In a recent multivariate analysis, the authors were able to develop a predictive model for distinguishing between NCCP and CAD that includes alexithymia (a condition in which patients are unable to express their feelings with words), quality of life and coping based on organized religion and seeking medical help (85.four% sensitivity and 80.0% specificity).112
NCCP patients with psychological disorders show diminished quality of life, more frequent chest hurting, and less treatment satisfaction than NCCP patients without psychological comorbidity.97
I written report suggested that NCCP patients with more than than 1 psychological disorder are more hard to treat than those with a unmarried psychological disorder.113
Cheng et al114
demonstrated that patients with NCCP, when compared to patients with rheumatism and healthy controls, tended to monitor more, utilise more problem-focused coping, display a coping pattern with a poorer strategy-situation fit and receive less emotional support in times of stress. Additionally, monitoring perceptual style and problem-focused coping were associated with higher levels of anxiety and low. Jerlock et al115
evaluated 231 NCCP patients and compared their psychosocial contour with 1,069 healthy subjects without NCCP. The authors found that NCCP patients had more sleep problems, mental strain at work, stress at dwelling house, and negative life events as compared with the salubrious grouping.
Gender differences related to psychological factors have likewise been observed in NCCP patients. Men reported less depression and trait feet than women.116
Conclusion
Our understanding of the epidemiology and natural course of NCCP remains relatively express. Overall, the disease appears to be very mutual, without any gender predilection, and be associated with a expert prognosis. More than has been learned over the years almost GERD, esophageal dysmotility, esophageal hypersensitivity and psychological comorbidity as important underlying mechanisms of NCCP. In patients with functional chest pain, the exact pathogenesis and the initial event or events that consequence in life-long chronic chest pain still remain poorly understood.
Footnotes
Financial support: None.
Conflicts of interest: None.
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Articles from
Journal of Neurogastroenterology and Movement
are provided hither courtesy of
The Korean Club of Neurogastroenterology and Motility
Which Symptom is Not Consistent With Cardiac Related Chest Pain
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093002/
