Follow-up of patients with noncardiac chest pain

Noncardiac chest pain may be a debilitating symptom. The utility of esophageal testing to enhance patient quality of life has been inconclusive. The purpose of this study was to evaluate prospectively the impact of esophageal testing on patient well-being. Fifty-five patients undergoing esophageal testing were available for follow-up. Seventeen (31%) patients were classified in group 1: considered to have the esophagus as a likely etiology because of positive testing; 14 (25%) in group 2: possible contribution of the esophagus to symptoms; and 24 (44%) in group 3: unlikely esophageal etiology with negative testing. Thirty-four patients continued to be symptomatic at follow-up (median 112 days). The change in pain intensity from pretesting to follow-up was significant only for group 3 (P=0.001). There was a decline in hospital utilization in all three groups. (Emergency room visitsP=0.004 group 1, hospital admissionsP=0.02, group 3). Group 1 and 2 patients tended to miss less work, social functions, and activities. Group 3 continued to stay in bed and avoid normal functions. Nine of 34 (26%) patients who were symptomatic at follow-up identified the esophagus as the source of symptoms. In all, 42% of group 1, 29% of group 2, and 18% of group 3 patients considered the esophagus to be the source of their symptoms. We conclude that esophageal testing does not always prevent the persistence of symptoms and that patients have misperceptions about testing results on follow-up.This work was presented in part at the American Gastroenterological Association, New Orleans, Louisiana, May 1991.     

Neurophysiologic assessment of esophageal sensory processing in noncardiac chest pain

BACKGROUND & AIMS: Esophageal hypersensitivity is thought to be important in the generation and maintenance of symptoms in noncardiac chest pain (NCCP). In this study, we explored the neurophysiologic basis of esophageal hypersensitivity in a cohort of NCCP patients. METHODS: We studied 12 healthy controls (9 women; mean age, 37.1 +/- 8.7 y) and 32 NCCP patients (23 women; mean age, 47.2 +/- 10 y). All had esophageal manometry, esophageal evoked potentials to electrical stimulation, and NCCP patients had 24-hour ambulatory pH testing. RESULTS: The NCCP patients had reduced pain thresholds (PT) (72.1 +/- 19.4 vs 54.2 +/- 23.6, P = .02) and increased P1 latencies (P1 = 105.5 +/- 11.1 vs 118.1 +/- 23.4, P = .02). Subanalysis showed that the NCCP group could be divided into 3 distinct phenotypic classifications. Group 1 had reduced pain thresholds in conjunction with normal/reduced latency P1 latencies (n = 9). Group 2 had reduced pain thresholds in conjunction with increased (>2.5 SD) P1 latencies (n = 7), and group 3 had normal pain thresholds in conjunction with either normal (n = 10) or increased (>2.5 SD, n = 3) P1 latencies. CONCLUSIONS: Normal esophageal evoked potential latencies with reduced PT, as seen in group 1 patients, is indicative of enhanced afferent transmission and therefore increased esophageal afferent pathway sensitivity. Increased esophageal evoked potential latencies with reduced PT in group 2 patients implies normal afferent transmission to the cortex but heightened secondary cortical processing of this information, most likely owing to psychologic factors such as hypervigilance. This study shows that NCCP patients with esophageal hypersensitivity may be subclassified into distinct phenotypic subclasses based on sensory responsiveness and objective neurophysiologic profiles.     

Diagnosis of chest pain of esophageal origin

Committee members are: David L. Earnest, MD, Chairman; John S. Balint, MD; Stanley B. Benjamin, MD; Thomas H. Browning, MD; James N. Cooper, MD; Peter Cotton, MD; Haile T. Debas, MD; David E. Fleischer, MD; Emmanuel Friedman, MD; Stanley W. Goldberg, MD; Peter M. Loeb, MD; Mark McPhee, MD; Walter L. Peterson, MD; John R. Stroehlein, MD; Jane L. Todaro, MD; and John B. Wyman, MD.     

Utility of ambulatory 24-hour esophageal pH and motility monitoring in noncardiac chest pain: report of 90 patients and review of the literature

It is unclear whether prolonged motility monitoring improves the diagnostic yield of standard esophageal tests in patients with noncardiac chest pain. Our aim was to assess the diagnostic value of ambulatory 24-hr pH and pressure monitoring in patients with noncardiac chest pain. Stationary manometry, edrophonium testing, and ambulatory pH and motility studies were performed in 90 consecutive patients with recurrent chest pain and normal coronary angiograms. Normality limits of ambulatory 24-hr motility were established in 30 healthy controls. The diagnoses of specific esophageal motility disorders (nutcracker esophagus and diffuse esophageal spasm) by stationary and ambulatory manometry were discordant in 48% of the patients. Edrophonium testing was positive in 9 patients, but correlated poorly with esophageal diagnoses. During ambulatory studies, 144 chest pain events occurred in 42 patients, and 72 (50%) were related to esophageal dysfunction. Strict temporal associations of events with esophageal dysfunction in relation to ambulatory 24-hr pH'motility scores permitted four patient categorizations: true positives (event-related and abnormal tests), N = 15; true negatives (event-unrelated and abnormal tests), N = 10; reduced esophageal pain threshold (event-related and normal tests), N = 4; and indeterminate origin (event-unrelated and normal tests), N = 13. Overall, 19 patients (21%) had a probable esophageal cause for chest pain (14 esophageal motility disorder, 4 acid reflux, 1 both). In conclusion, ambulatory manometry increases the diagnostic yield of standard esophageal testing in noncardiac chest pain, but the gain is small. Causes of chest pain other than high esophageal pressures and acid reflux must still be sought in most patients with chest pain of unknown origin after a negative cardiac work-up.     

Congenital esophageal stenosis associated with esophageal atresia

Congenital esophageal stenosis (CES) is a rare clinical condition but is frequently associated with esophageal atresia (EA). The aim of this study is to report the diagnosis, management, and outcome of CES associated with EA. Medical charts of CES‐EA patients from Lille University Hospital, Sainte‐Justine Hospital, and Montreal Children's Hospital were retrospectively reviewed. Seventeen patients (13 boys) were included. The incidence of CES in patients with EA was 3.6%. Fifteen patients had a type C EA, one had a type A EA, and one had an isolated tracheoesophageal fistula. Seven patients had associated additional malformations. The mean age at diagnosis was 11.6 months. All but two patients had non‐specific symptoms such as regurgitations or dysphagia. One CES was diagnosed at the time of surgical repair of EA. In 12 patients, CES was suspected based on abnormal barium swallow. In the remaining four, the diagnostic was confirmed by esophagoscopy. Eleven patients were treated by dilation only (1–3 dilations/patient). Six patients underwent surgery (resection and anastomosis) because of failure of attempted dilations (1–7 dilations/patient). Esophageal perforation was encountered in three patients (18%). Three patients had histologically proven tracheobronchial remnants. CES associated with EA is frequent. A high index of suspicion for CES must remain in the presence of EA. Dilatation may be effective to treat some of them, but perforation is frequent. Surgery may be required, especially in CES secondary to ectopic tracheobronchial remnants.     

Noncardiac chest pain: diagnostic evaluation

Noncardiac chest pain (NCCP) is a common and challenging clinical problem. It is estimated that more than 70 million Americans (23% of the population) suffer from this condition yearly. Patients with NCCP represent a diagnostic dilemma. Their chest pain is often indistinguishable from cardiac pain leading to extensive and expensive evaluations. Once coronary artery disease and other cardiac and pulmonary sources of chest pain are excluded, patients are frequently referred to gastroenterologists to look primarily for esophageal sources of pain. A variety of diagnostic tests are available to the practicing clinician to identify the origin of pain, including ambulatory pH testing, esophageal motility, upper endoscopy, provocative testing and even therapeutic trials.     

Spectrum of esophageal disorders in children with chest pain

The charts of 83 children with chest pain who underwent esophageal manometry followed by esophagogastroscopy were reviewed. Forty-seven (57%) had normal esophageal histology and normal motility (group I). Esophagitis and normal motility were demonstrated in 15 children (group II), normal esophageal histology and esophageal dysmotility in 13 (group III), and both esophagitis and abnormal motility in 8 (group IV). Diffuse esophageal spasm and achalasia were the most common motility disorders identified (in seven and four patients, respectively). The presence and duration of symptoms, the age, and the gender were not different among the four patient groups. After six months of H₂-receptor blockade, 12 of 15 group II patients were asymptomatic, whereas a significantly smaller percentage (five of 18) of patients with abnormal esophageal motility responded to esophageal dilation or treatment with calcium channel blockade, H₂-receptor antagonist, and/or prokinetic agents (P<0.01). These data suggest that the evaluation of children with chest pain should include esophageal motility testing and esophagoscopy, even in the absence of other gastrointestinal-associated symptoms, and that while treatment of esophagitis results in resolution of symptoms, motility disorders were relatively refractory to therapy.     

Congenital esophageal stenosis

Esophageal stenosis is a rare congenital anomaly (1 per 25,000 live births), which usually presents during infancy (1). The stenosis is typically aperistaltic, and the onset of symptoms depends upon the degree of deformity. In severe stenosis, symptoms of vomiting or r'egurgitation occur at birth or with the introduction of solids (2, 3). In mild cases, patient adaptation may delay the diagnosis (1,4). We report an unusual case of congenital esophageal stenosis, where abnormal peristalsis was preserved within the stenotic segment and presentation as acute food impaction was delayed until adulthood. Endoscopic, radiographic, and esophageal manometric findings of congenital esophageal stenosis are described, and the therapeutic alternatives discussed.The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official policy or reflecting the views of the Army or the Department of Defense.     

Esophageal mucosal mast cell infiltration and changes in segmental smooth muscle contraction in noncardiac chest pain

Mast cells release potent mediators that alter enteric nerve and smooth muscle functions and may contribute to the pathogenesis of functional gastrointestinal disorders. The goal of this study was to determine if mucosal mast cell infiltration was associated with smooth muscle segmental changes in esophageal contraction. All patients with noncardiac chest pain (NCCP) were divided into two groups consisting of patients with non‐erosive reflux disease or functional chest pain (FCP) according to the results of ambulatory 24 hours esophageal pH monitoring and high‐resolution manometry. Pressure–volume (PV) was calculated by multiplying the length of the esophageal segment, duration of the contraction, and mean pressure over the entire space–time box (P mean). Quantification of mast cells was performed in five consecutive nonoverlapping immunostained sections. Spearman correlation analysis showed that the distal segment PV correlated with the mast cell count in all of the patients combined and in patients with FCP with correlation coefficients of 0.509 and 0.436, respectively (P = 0.004 and P = 0.042). Similar findings were observed for the segmental ratio of distal to proximal smooth muscle PV in all patients and in patients with FCP (correlation coefficients 0.566; P = 0.001 and correlation coefficients 0.525; P = 0.012, respectively). Mucosal mast cell infiltration was associated with distal esophageal contraction as a key pathophysiologic factor of NCCP.     

Role of upper esophageal reflex and belch reflex dysfunctions in noncardiac chest pain

Fifty-four patients examined for noncardiac chest pain (NCCP), showing no esophageal motor disorder or gastroesophageal reflux disease compatible with NCCP, were subjected to an intraesophageal balloon distension test and a study of the belching reflex provoked by intraesophageal air injection. Thirty-three control subjects were also studied, allowing us to define high-threshold belchers (group I) as those who belched during two of three 40-ml distensions and low-threshold belchers (group II) as those who did not. The balloon distension test induced NCCP in 64% of the patients in group I, and in 14% of the patients in group II (P<0.01). High-threshold belching was a factor favoring the positivity of the balloon distension test. This result supports the hypothesis that esophageal distension by air due to a belching disorder may be the mechanism responsible for NCCP in some patients with an abnormal sensitivity to balloon distension.     

Prevalence of esophageal disorders in patients with recurrent chest pain*

The objective of this study is to determine the prevalence of esophageal disorders (ED) associated with recurrent chest pain (RCP) and the utility of esophageal functional tests (EFT) in the study of these patients. The cross-sectional study was conducted at Hospital Clínico de La Frontera, Chile. One hundred and twenty-three patients with RCP were studied using esophageal manometry, edrophonium stimulation and 24-h pH monitoring. The performance of EFT was considered acceptable when they were capable of finding ED. To state the probability that RCP had an esophageal origin, patients were classified according to whether their pain had a probable, possible or unlikely esophageal origin. The prevalence of ED was determined according to diagnoses obtained after applying EFT and a multivariate analysis was performed to examine the association between the esophageal origin of RCP and ED. Rates of correct diagnosis of 65.9%, 56.9% and 31.7% was verified for 24-h pH monitoring, esophageal manometry and edrophonium stimulation, respectively. In 38.2% of patients with RCP, the pain was probably of esophageal origin, in 42.3% there was a possible esophageal origin and in 19.5% an unlikely esophageal origin. A 44.7% prevalence of GERD, 26.8% of GERD with secondary esophageal motor dysfunction and 8.9% of pure esophageal motor dysfunction were verified. The multivariate analysis allowed us to verify the association between the probability of esophageal origin of RCP, the variables RCP duration, esophagitis and dysphagia coexistence (P= 0.037, P= 0.030 and P= 0.024, respectively), and a statistically significant association between ED and dysphagia coexistence (P= 0.028). A high prevalence of ED was identified in patients with RCP.     

Prospective evaluation of high-dose bethanechol in investigation of esophageal chest pain

We compared the value of bethanechol 80 g/kg subcutaneously, acid infusion with a 0.1 normal hydrochloric acid, and edrophonium 80 g/kg intravenously as provocative agents to reproduce chest pain and manometric alterations in 72 patients with noncardiac chest pain. No patient developed typical chest pain and manometric alteration with acid infusion, while five (6.9%) patients developed these changes with edrophonium and four (5.6%) with bethanechol. Only one patient developed diagnostic changes exclusively with bethanechol. All patients tested with bethanechol developed some degree of local pain or significant cholinergic symptoms, with two patients requiring atropine for relief. Side effects from edrophonium were infrequent (28% of patients tested) and did not require atropine administration. We conclude that, using the parameters of typical chest pain and the development of manometric alterations as proof of the esophageal origin of chest pain, bethanechol at 80 g/kg adds little information beyond that obtainable with edrophonium. Further, the high incidence of bethanechol-related side effects at 80 g/kg suggests that this dose should not be generally recommended.     

Factors predictive of gastroesophageal reflux disease and esophageal motility disorders in patients with non-cardiac chest pain

Background: Patients with non-cardiac chest pain (NCCP) are referred for esophageal motility testing and pH monitoring since gastroesophageal reflux disease (GERD) and esophageal motility disorders are frequently encountered in these patients. Our aim was to determine the prevalence and distribution of these disorders and to identify predictors of abnormal esophageal function testing.

Methods: We performed a retrospective study of NCCP patients who presented after a negative cardiac evaluation and underwent esophageal manometry, esophageal pH monitoring and upper endoscopy from January 2010 to January 2017.

Key results: In a total of 177 patients, esophageal motility disorders were diagnosed in 31% and GERD in 35% of the patients. The most common diagnoses were ineffective esophageal motility (IEM) in 14.1%, jackhammer esophagus in 6.8%, diffuse esophageal spasm in 5.1% and achalasia in 2.3% patients. Older age [for every 5-year increment, odds ratio (OR) 1.2 (95% confidence intervals (CI) 1.00–1.3) p?=?.047] and dysphagia [OR 3.8 (95% CI, 1.9–7.5) p?p?=?.032] was predictive of GERD. Abnormal esophageal testing was associated with male gender [OR 2.2 (95% CI, 1.04–4.6) p?=?.039], older age [for every 5-year increment, OR 1.2 (95% CI, 1.03–1.3) p?=?.016] and Caucasian race [OR 3.1 (95% CI, 1.1–8.7) p?Conclusions: Approximately two thirds of patients presenting with NCCP have GERD or esophageal motility disorders. Esophageal function testing in NCCP should be considered in older patients, men, Caucasians and those presenting with dysphagia.     

The puzzle of normal coronary arteries in the patient with chest pain: What to do?

Over one million Americans undergo cardiac catheterization each year because of chest pain, with the expectation that coronary artery disease will be found. However, up to 30%—a subgroup that includes patients with both cardiac and noncardiac pathology—will have angiographically normal coronary arteries. While the prognosis of the group as a whole is excellent, successful management requires a clear understanding of the multiple and varied conditions that can cause this syndrome.     

Unexplained chest pain: When is it panic disorder?

Noncardiac chest pain is a common costly phenomenon in the cardiology setting. Recent research suggests that panic disorder, a highly distressful yet treatable anxiety disorder, occurs in a significant proportion of noncardiac chest pain patients. This article reviews research on the prevalence of panic disorder in patients seen in cardiology settings for unexplained chest pain. Financial, psychosocial, and historical aspects of noncardiac chest pain are described. Panic disorder and the potential consequences of its nonrecognition by physicians are examined. Current psychological and pharmacologic treatments are reviewed. Recommendations on the management of panic patients in the cardiology setting are provided.     

Comparison of central and intraesophageal factors between gastroesophageal reflux disease (GERD) patients and those with GERD‐related noncardiac chest pain

Gastroesophageal reflux disease (GERD) causes a wide range of symptoms. Some patients present with typical symptoms such as heartburn and regurgitation and others with atypical symptoms such as chest pain. The mechanism responsible for the varying clinical presentation of GERD is still not fully elucidated. The aim of this study was to prospectively evaluate differences in central and local intraesophageal factors between patients with typical GERD symptoms and those with noncardiac chest pain (NCCP). Patients presenting with typical and atypical symptoms suspicious of GERD underwent upper endoscopy and 24‐hour pH monitoring with four sensors, each positioned at a different esophageal level. All patients completed GERD symptom, Hospital Anxiety and Depression Scale, and Symptom Stress Rating questionnaires. From January 2006 to December 2009, 50 patients were recruited, 29 with typical symptoms, and 21 with NCCP. Patients with proven GERD and NCCP had higher proximal extension of acid during reflux episodes than patients with typical symptoms. They were found to be older, had a shorter history of symptom onset, worse anxiety scores, and more endoscopic findings compatible with gastritis. Proximal extension of acid during the reflux episodes in patients with GERD presenting with NCCP may play a role in symptom generation.     

Increasing pain sensation to repeated esophageal balloon distension in patients with chest pain of undetermined etiology

Previous studies have demonstrated lowered sensory thresholds to esophageal balloon distension in patients with chest pain of undetermined etiology. Whether this finding is specific to patients with chest pain or is simply related to an underlying esophageal motility disorder is unclear. In the present study, distension-induced pain-sensation scores and the effect of repeated balloon distension were compared in patients with chest pain, dysphagia secondary to esophageal dysmotility, and healthy controls. All subjects underwent standard esophageal manometry followed by mid-esophageal balloon distension. Volumes 2.5, 5, 7.5, and 10 ml (each volume repeated three times) were applied in random order in a single-blind fashion, and the pain-sensation score was recorded after each distension. Pain-sensation scores varied directly with balloon volume. Mean pain scores were significantly higher (P<0.001) in the chest pain group than in either the controls or dysphagia group. There was no significant difference between controls and the dysphagia group, and the motor response to distension was no different between groups. In the controls and dysphagia groups, painsensation score was not significantly different between the first, second, or third distension at a given volume. However, in the chest pain group, pain-sensation scores increased significantly with the second (P=0.004) or third (P=0.002) distension using the same balloon volume. These studies suggest that abnormal esophageal nociception in patients with chest pain of undetermined etiology is not simply related to underlying esophageal motor dysfunction. In addition, chest pain patients display a conditioning phenomenon, further supporting the presence of a visceral sensory abnormality.     

Stress induces alteration of esophageal pressures in healthy volunteers and non-cardiac chest pain patients

The present study was designed to explore the relationship between psychological stress and esophageal motility disorders. Nineteen non-cardiac chest pain patients (10 with the nutcracker esophagus and nine with normal baseline manometry) and 20 healthy control subjects were administered two acute stressors: intermittent bursts of white noise and difficult cognitive problems. The results indicated that the esophageal contraction amplitudes and levels of anxiety-related behaviors of non-cardiac chest pain patients and control subjects were significantly greater during the stressors than during baseline periods. All patients demonstrated significantly greater (P<0.01) increases in contraction amplitude and anxiety-related behavior during cognitive problems than during the noise stressor. The nutcracker esophagus patients showed a greater increase in contraction amplitude during the problems (23.50±9.42 mm Hg, ¯X ±SE) than control subjects (P<0.01), while the amplitude changes of chest pain patients with normal baseline manometry were not significantly greater than that of control subjects (9.00±1.91 mm Hg). The present results identified an increase in contraction amplitude as the primary esophageal response to stress. The possible interaction of esophageal contraction abnormalities, psychological stress, and the perception of chest pain is discussed.This work was supported by Public Health Services grant AM 34200-01AI from NIADDK.     

Recent advances in noncardiac chest pain in Korea

Gastroesophageal reflux disease (GERD) is the most common cause of noncardiac chest pain (NCCP) and is present in up to 60% of patients with NCCP in Western countries. In Korea, after a reasonable cardiac evaluation, GERD is reported to underlie 41% of NCCP cases. Typical reflux symptoms are frequent in Korean patients suffering from NCCP. Therefore, a careful history of the predominant symptoms, including heartburn and acid regurgitation, is relatively indicative of the GERD diagnosis in Korea. In Korea, in contrast to Western countries, patients aged 40 years and over who have been diagnosed with NCCP but who are without alarming features should undergo endoscopy to exclude gastric cancer or peptic ulcers because of the higher prevalence of peptic ulcer disease and gastric cancers in the region. In a primary care setting, in the absence of any alarming symptoms, a symptomatic response to a trial of a proton pump inhibitor (PPI) is sufficient for the presumptive diagnosis of GERD. In addition, the optimal duration of a PPI test may be at least 2 weeks, as GERD symptoms tend to be less frequent or atypical in Korean patients than in patients from Western countries. In patients diagnosed with GERD-related NCCP, long-term therapy (more than 2 months) with double the standard dose of a PPI is required to alleviate symptoms. Esophageal dysmotility is relatively uncommon, and pain modulators seem to offer significant improvement of chest pain control in non-GERD-related NCCP. Most traditionally available tricyclics or heterocyclics have many undesirable effects. Therefore, newer drugs with fewer side effects (for example, the serotonin - norepinephrine reuptake inhibitors) may be needed.     

非心源性胸痛患者心理异常与症状间的关系

目的调查非心源性胸痛（NCCP）患者的心理精神因素异常状况，探讨它们与症状程度间的关系。方法对87例NCCP患者和健康对照组90人进行问卷调查，内容包括Zung焦虑自评量表（SAS）、Zung抑郁自评量表（SDS）、症状评分表，进行分析比较。结果1、NCCP患者焦虑、抑郁的发生率明显高于健康对照组（P〈0．005），平均焦虑、抑郁程度高于对照组（P〈0．001）。2、NCCP患者的症状积分与焦虑评分、抑郁评分呈正相关（P〈0．001）。结论焦虑和抑郁在NCCP发病机制中具有重要地位。