Comparison of esophageal manometry,provocative testing,and ambulatory monitoring in patients with unexplained chest pain

Prolonged ambulatory esophageal pH and pressure monitors are being developed to evaluate noncardiac chest pain. This new technology needs comparison with conventional esophageal tests before determining which studies are most useful in diagnosing and treating esophageal chest pain. Therefore, we studied 45 patients with esophageal manometry, acid perfusion and edrophonium tests, and 24 hr pH and pressure monitoring. Manometry was abnormal in 20 patients (44%) with nutcracker esophagus, the most common motility disorder. Fifteen (33%) had positive acid perfusion test and 24 (55%) positive edrophonium test. During ambulatory monitoring, all patients experienced chest pain with a total of 202 individual events: 32 events (15%) secondary to acid reflux, 15 (7%) secondary to motility abnormalities, 7 (3%) to both pH and pressure changes, and 149 events (74%) occurred in the absence of any abnormal pH or motility changes. Patients with normal manometry were significantly (P less than 0.01) more likely to have acid reflux chest pain events than did nutcracker patients, who had an equal frequency of pH and motility events. A positive acid perfusion test was significantly associated with abnormal pressure events (P = 0.02; odds ratio 5.95), while a positive edrophonium test more likely predicted acid reflux chest pain during 24-hr monitoring (P = 0.007; odds ratio 7.25). Therefore, abnormal manometry and positive provocative tests point to the esophagus as the likely source of chest pain. However, ambulatory pH and pressure monitoring are required to accurately define the relationship between chest pain and acid reflux or motility disorders.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spontaneous noncardiac chest pain: Value of ambulatory esophageal pH and motility monitoring

We performed esophageal investigations in 20 patients suffering from noncardiac chest pain in order to assess the diagnostic value of short- versus long-term manometric and pH studies. Patients had baseline esophageal manometry with two provocative tests: a Bernstein test and an intravenous injection of edrophonium. On a separate occasion they had a 24-hr ambulatory esophageal pH and motility recording. The Bernstein test provoked chest pain in two patients, while edrophonium injection did not elicit pain in any of the patients. The ambulatory pH study helped to establish the esophagus as the likely source of pain in one patient, and the ambulatory motility one in another. In our experience, ambulatory pH and motility recordings have a low diagnostic yield in the evaluation of patients with noncardiac chest pain.     

Noncardiac Chest Pain: Is the Esophagus Really a Frequent Source?

The occurrence of esophagus-related noncardiac chest pain was investigated in 22 unselected consecutive patients referred by local cardiologists. The investigations included endoscopy, standard manometry, esophageal scintigraphy, a double-blind placebo-controlled edrophonium provocation test on two occasions (during manometry and scintigraphy), an acid perfusion test, and 24-h ambulatory esophageal pH-monitoring. Nine patients had reflux symptoms; none had dysphagia. Abnormal test results were found in 11 patients. In only three of them was a definite relation between chest pain and the esophagus established: the acid perfusion test was positive in these three, as was 24-h pH-monitoring in two of them. All three had symptomatic reflux. The absence of patient selection and, possibly, the exclusion of biasing during the edrophonium tests are considered to be the most important factors for the finding of only few patients with definite esophagus-related noncardiac chest pain in this study. A prudent approach towards patients with noncardiac chest pain, with regard to the evaluation of an esophageal cause, is recommended.     

How Long Should a Long-Term Esophageal Motility Study Be?

It was the aim of this study to analyze whether a shorter measuring period would render the same diagnostic information on esophageal motility as a circadian measuring period in ambulatory esophageal manometry. In an investigation on normal volunteers (n = 10), patients with gastroesophageal reflux disease without esophageal motility disorders (n = 13), and patients with esophageal motility disorders (n = 14), a comparison was performed between a 5-hr and a 24-hr motility study. An analysis was performed on inter- and intraindividual reproducibility of time periods, prandial phases, and motility sequences (Wilcoxon and Spearman test). There was no significant difference between the two analyzed measuring periods in all three groups with regard to the diagnostic information on esophageal motility in 44 of 45 comparisons for intraindividual variability. A measuring period restricted to 5 hr offers the same diagnostic information on esophageal peristaltic activity as a 24-hr motility study.     

Combined 24-hour recording of esophageal pH and pressure

Twenty-four-hour ambulatory recording of esophageal pH and pressure is a newly developed technique that has the potential of proving that a patient's noncardiac chest pain is of esophageal origin (esophageal reflux or motor abnormality). Until now four groups described their experiences with application of the technique in the work-up of noncardiac chest pain. It is now clear that the diagnostic yield of the technique in this syndrome is rather limited, especially when the incidence of pain episodes is low. Reflux appears to be a more common cause of chest pain than esophageal motor disorders. Complete quantitative analysis of the 24-hr motility data by hand is very time-consuming, so that automated, computerized data analysis is a prerequisite for more widespread clinical use of the technique.     

The cost-effectiveness of the omeprazole test in patients with noncardiac chest pain.

PURPOSE: Recent evidence suggests that an empiric trial of omeprazole (the "omeprazole test") is sensitive and specific for diagnosing gastroesophageal reflux disease (GERD) as the cause of noncardiac chest pain. Our objective was to examine the clinical, economic, and policy implications of alternative diagnostic strategies for patients with noncardiac chest pain. METHODS: Decision analysis was used to evaluate the clinical and economic outcomes of two diagnostic strategies that begin with the omeprazole test (60 mg daily for 7 days) followed sequentially by invasive testing utilizing endoscopy, ambulatory 24-hour esophageal pH monitoring, and esophageal manometry as necessary, compared with two traditional strategies involving sequential invasive diagnostic tests. Cost estimates were based on Medicare reimbursement and the Red Book of average wholesale drug prices. Probability estimates were derived from a systematic review of the medical literature. RESULTS: The average cost per patient for the four diagnostic strategies varied from $1,859 to $2,313. Strategies utilizing the initial omeprazole test resulted in 84% of patients being symptom free at 1 year, compared with 73% to 74% for the strategies that began with invasive tests. The strategy of the omeprazole test, followed if necessary by ambulatory pH monitoring, then manometry, and then endoscopy, was both most effective and least expensive. It led to an 11% improvement in diagnostic accuracy and a 43% reduction in the use of invasive diagnostic tests, thus yielding an average cost savings of $454 per patient, compared with the strategy of beginning with endoscopy, then pH monitoring, and then manometry. CONCLUSIONS: Among patients with noncardiac chest pain, diagnostic strategies that begin with the omeprazole test result in reduced costs, improved diagnostic certainty, and a greater proportion of symptom-free patients at 1 year than do traditional strategies that begin with invasive diagnostic tests.     

REVIEW: Ambulatory Esophageal pH Monitoring: Technique, Interpretations, and Clinical Indications

Gastroesophageal reflux disease (GERD) is the most common esophageal disorder and perhaps among the most prevalent conditions seen in the primary care setting. The clinical manifestations of GERD, typical or atypical, such as noncardiac chest pain, respiratory or ear, nose, and throat symptoms, result from the reflux of gastric contents into the esophagus. Thus the clinical spectrum is wide and requires accurate diagnosis. Ambulatory 24-hr esophageal pH monitoring is not useful in all patients suspected to have GERD. This review describes the technique of ambulatory 24-hr esophageal pH monitoring, the interpretation of findings, and clinical applications of this test.     

Noncardiac chest pain: is the esophagus really a frequent source?

The occurrence of esophagus-related noncardiac chest pain was investigated in 22 unselected consecutive patients referred by local cardiologists. The investigations included endoscopy, standard manometry, esophageal scintigraphy, a double-blind placebo-controlled edrophonium provocation test on two occasions (during manometry and scintigraphy), an acid perfusion test, and 24-h ambulatory esophageal pH-monitoring. Nine patients had reflux symptoms; none had dysphagia. Abnormal test results were found in 11 patients. In only three of them was a definite relation between chest pain and the esophagus established: the acid perfusion test was positive in these three, as was 24-h pH-monitoring in two of them. All three had symptomatic reflux. The absence of patient selection and, possibly, the exclusion of biasing during the edrophonium tests are considered to be the most important factors for the finding of only few patients with definite esophagus-related noncardiac chest pain in this study. A prudent approach towards patients with noncardiac chest pain, with regard to the evaluation of an esophageal cause, is recommended.     

Twenty-four-hour esophageal pH monitoring: the most useful test for evaluating noncardiac chest pain

STUDY OBJECTIVE: To compare the diagnostic capabilities of traditional esophageal tests (manometry and provocative testing with acid and edrophonium) and 24-hour esophageal pH monitoring in identifying an esophageal cause of chest pain. DESIGN: A prospective study of 100 consecutive patients referred by cardiologists to the esophageal laboratory for evaluation of esophageal causes of chest pain. SETTING: Tertiary-referral university hospital. METHODS: Esophageal manometry performed with 10 wet swallows of water. Acid perfusion (0.1 N hydrochloric acid) and edrophonium (80 micrograms/kg intravenously) tests were placebo-controlled with a positive study defined as replication of typical chest pain. Esophageal pH monitoring identified (1) abnormal acid exposure times in the upright, supine, or combined position, and (2) correlation between symptoms and acid reflux, i.e., symptom index. The esophagus was identified as "probably" contributing to chest pain only if the acid or edrophonium test was positive or if there was a positive correlation between symptoms and acid reflux during pH monitoring. RESULTS: Esophageal manometry was abnormal in 32 patients (32%), but patients were asymptomatic during the study. The acid perfusion test was positive in 18 of 95 patients (19%), and the edrophonium test was positive in 15 of 78 patients (19%). Abnormal acid exposure times were found in 48 patients (48%). Of the 83 patients with spontaneous chest pain during 24-hour pH testing, 37 patients (46%) had abnormal reflux parameters and 50 patients (60%) had a positive symptom index (mean positive score 56%, range 6% to 100%). CONCLUSIONS: Acid reflux is a common and potentially treatable cause of noncardiac chest pain. Traditional esophageal tests usually miss this diagnosis. Twenty-four-hour esophageal pH monitoring with symptom correlation is the single best test for evaluating patients with noncardiac chest pain.     

Acid perfusion and edrophonium provocation tests in patients with chest pain of undetermined etiology

During the last five years, 672 patients were referred to our esophageal investigation unit; 110 patients (16.3%) of these presented with chest pain of undetermined etiology (CPUE) alone. Since the nature of this pain is intermittent and rarely present during the diagnostic study, acid perfusion and intravenous edrophonium tests were added as provocative tests after baseline esophageal manometry. Following completion of the motility studies, 24-hr pH study was performed to detect gastroesophageal reflux (GER). Twenty-nine patients (26.4%) had positive acid perfusion (APT) test whereas 26 patients (23.6%) had positive edrophonium test (ET). In the group of patients with positive acid perfusion test, 12/29 (41.3%) had GER, 8/29 (27.5%) had both motility disorder and GER, 2/29 (6.8%) had motility disorder, and 7/29 (24.1%) had normal esophageal motility and 24-hr pH studies. In the other group, 13/26 (50%) had motility disorder and 13/26 (50%) had both motility disorder and GER. There were no significant differences between the two tests as far as reproducibility of symptoms was concerned. We conclude that ATP and ET showed the esophageal origin of CPUE in half of our patients and therefore in a substantial percentage of patients the esophageal origin of chest pain will remain very diffcult to prove.Presented at the British Society of Gastroenterology (Gut 30:A1482, 1989).     

Ambulatory esophageal manometry,pH-metry,and holter ECG monitoring in patients with atypical chest pain

Standard Holter electrocardiographic (ECG) monitoring was combined with ambulatory esophageal manometry and pH-metry in 25 patients with atypical chest pain in order to determine whether an association could be found between spontaneous pain episodes and ischemic ECG changes or esophageal dysfunction. Results of ambulatory testing were compared to those obtained with standard esophaeal manometry and provocative testing. Twenty-two of the 25 patients experienced a total of 88 pain episodes during ambulatory testing. Although 15 of the 22 patients (68%) experiencing pain during testing had at least one pain episode that corelated temporally with gastroesophageal reflux, esophageal dysmotility or ischemic ECG changes, 65% of all pain episodes were unrelated to abnormal esophageal events or ECG changes. Seventeen percent of pain episodes were associated with gastroesophageal reflux, 15% with esophageal dysmotility,and 2% with a combined acid reflux and esophageal dysmotility event. Only one pain episode was associated with ischemic ECG changes. Twelve of the 15 patients with chest pain episodes associated with reflux or esophageal dysmotility had othe identical pain episodes in which there was no correlation. Reproduction of a patient's pain during standard manometry with provocative testing did not predict a strong correlation between the patient's spontaneous pain episodes and esophageal dysfunction during ambulatory recordings. In summary, patients with atypical chest pain have relatively few spontaneous pain episodes that correlate with gastroesophageal reflux, esophageal dysmotility, or ischemic ECG changes. It appears that different stimuli can trigger identical episodes of chest pain, which suggests that many of these patients may have dysfunction of their visceral pain sensory mechanisms.     

What is the optimal time window in symptom analysis of 24-hour esophageal pressure and pH data?

Since noncardiac chest pain is the only well-established indication for 24-hr esophageal pH and pressure recording, the analysis of the association between chest pain episodes and esophageal motility abnormalities or reflux is the most important part of data analysis in 24-hr monitoring. Until now, different time windows have arbitrarily been used by various research groups. The aim of this study was to determine the optimal time window for symptom analysis in 24-hr esophageal pH and pressure monitoring. For this purpose repetitive symptom association analysis was carried out, using time windows of various onsets and durations. For each time window, the symptom indices for reflux and dysmotility were calculated. The symptom index for both reflux and dysmotility showed a gradual increase for windows with increasingly early onset, following a pattern that would be predicted on the basis of Poisson's theory. However, both indices had a relatively sharp cutoff point at 2 min before the onset of pain. Both indices only showed a predictable gradual increase when the time window starting at –2 min was extended beyond the moment of pain onset. It is concluded that the optimal time window for symptom analysis in 24-hr esophageal pH and pressure recording begins at 2 min before the onset of pain and ends at the onset of pain.     

Analysis of 24-hour esophageal pressure and pH data in unselected patients with noncardiac chest pain

Fourty-four unselected patients with noncardiac chest pain were studied using conventional manometry with additional edrophonium provocation and 24-hour ambulatory esophageal pH and pressure recording with a system developed by our group. New, fully automated techniques of statistical analysis of the complete set of esophageal pressure and pH signals were used to examine the temporal relation between pain, esophageal motility disturbances, and gastroesophageal reflux. The analysis used the 97.5th percentile of amplitude and duration of all esophageal contractions in each patient as well as a chi 2 test of the distribution of contraction types to determine whether a pain episode was related to abnormal motility or not. The edrophonium test results were positive in 2 patients. Only 25 patients (56.8%) had at least one pain episode (total, 111 episodes) during 24-hour recording. Thirty-three percent of the pain episodes were related to reflux and 23.4% to abnormal motility, and 43.2% were not related to an esophageal function disturbance. In the patient-oriented analysis in this study, it was required for a positive correlation that the symptom index (percentage of related pain episodes) was higher than 75%. It was found that the pain was related to reflux in 2 patients (4.6%), to reflux and motor abnormalities in 4 (9.2%), and to motor abnormalities in 2 patients (4.6%). In 36 patients (81.8%), no relation with an esophageal abnormality could be established, either because the patients had no pain during the 24-hour study, or because the pain seemed unrelated to reflux or abnormal motility.     

Acid perfusion test and 24-hour esophageal pH monitoring with symptom index

The acid perfusion (Bernstein) test and esophageal pH monitoring are the two most popular tests for identifying esophageal acid sensitivity in difficult cases of reflux disease. Therefore, we prospectively compared these test results in 75 consecutive noncardiac chest pain patients who had both an acid perfusion test and chest pain during 24-hr pH testing. A positive acid perfusion test was defined by the replication of the patient's typical chest pain twice by the acid infusion. Esophageal pH testing identified abnormal amounts of acid reflux and correlated symptoms with acid reflux-the symptom index. Fifteen patients (20%) had a positive acid perfusion test while 45 patients (59%) had a positive symptom index (range 6–100%). Only 9/34 (26%) patients with abnormal reflux had a positive acid perfusion test. Although it had excellent specificity (83–94%), the acid perfusion test had poor sensitivity (32–46%) when compared to the symptom index regardless of the percent positive cutoff level. The best positive predictive value for the acid perfusion test was 87%, but this occurred when the test sensitivity was 32%. Modifying the end point of a positive acid perfusion test to include heartburn improves the sensitivity (52–67%) while markedly compromising specificity and positive predictive value. Thus, esophageal pH monitoring correlating symptoms with acid reflux is superior to the acid perfusion test for identifying an acid sensitive esophagus in patients with noncardiac chest pain.     

Approach to the patient with unexplained chest pain

Patients with unexplained or noncardiac chest pain continue to present a difficult challenge to the gastroenterologist. Cardiac disease must be ruled out first as the history will not distinguish between coronary artery disease and other causes of substernal chest pain. A systematic approach to evaluation should include reassurance that the heart is normal and attempts to confirm an esophageal etiology. Gastroesophageal reflux disease is the most common esophageal abnormality associated with unexplained chest pain and may be identified by an aggressive trial of anti-reflux therapy or an abnormal prolonged ambulatory pH monitoring study. Endoscopy is almost always normal and of less use in this population than in those with heartburn as the presenting symptom. Judicious use of manometry with provocative testing to evaluate for esophageal motility abnormalities or esophageal sensitivity allows for optimal evaluation of those who do not have gastroesophageal reflux disease. This article reviews the clinical presentation, differential diagnosis, and approach to evaluation and therapy of this complex group of patients.     

Esophageal testing of patients with noncardiac chest pain or dysphagia. Results of three years' experience with 1161 patients

Records from 910 patients referred to our clinical esophageal manometry laboratory for evaluation of noncardiac chest pain between January 1983 and December 1985 were reviewed and compared with records from 251 patients referred for dysphagia. Evaluation included baseline esophageal manometry, acid perfusion test, and edrophonium provocation. In the chest-pain group, 655 patients (72%) had normal esophageal motility and 255 (28%) had abnormal motility. Nutcracker esophagus was present in 48% of abnormal tracings, suggesting that it is a manometric marker for noncardiac chest pain. Of the total chest-pain group, 243 patients (27%) had their pain reproduced during provocative testing ("definite" esophageal pain); 192 patients (21%) had baseline manometric abnormalities but no pain during provocative testing ("probable" esophageal chest pain). The highest percentage of positive provocative responses (34%) occurred in patients with nutcracker esophagus on baseline manometry. Manometric abnormalities were statistically commoner (p less than 0.001) in patients with dysphagia, occurring in 53%. Achalasia (36%) and nonspecific esophageal motility disorders (38%) were the commonest abnormalities in this group, with nutcracker esophagus being infrequent (10%).     

24-hour recording of esophageal pressure and pH in patients with noncardiac chest pain

Sixty patients with anginalike chest pain of noncardiac origin were studied to determine the diagnostic value of 24-h ambulatory esophageal pH and pressure monitoring. The results of these 24-h studies were compared with those obtained by established methods, including x-rays, endoscopy with biopsy, conventional esophageal manometry, and acid perfusion test. Esophageal origin of the chest pain was considered to be likely if the familiar pain sensation was reproduced by the acid perfusion test, or if the pain occurred during an episode of gastroesophageal reflux, severe motor disorders, or both. When the results of established methods were combined and interpreted according to predetermined criteria, esophageal origin of the pain was shown to be likely in 27% of the patients. The 24-h recordings, alone, showed the esophagus to be the likely cause of the pain in 35% of the patients. Combination of all conventional examinations and of 24-h recordings made esophageal origin of the pain likely in 48% of the patients.     

Comparison of the Esophageal Manometric Characteristics of Idiopathic and Reflux-Associated Esophageal Spasm: Evaluation by 24-Hour Ambulatory Esophageal Motility and pH Monitoring

Diffuse esophageal spasm (DES) is a typical esophageal dysfunction, but its cause is unknown. DES has been classified into reflux-associated esophageal spasm (RDES), caused by acid exposure, and idiopathic esophageal spasm (IDES), of unknown causes. The differences in esophageal motility pattern between the RDES and IDES are clues to elucidating the pathogenesis of DES. Although 24-hr ambulatory esophageal motility and pH monitoring is considered a feasible method for evaluating gastroesophageal reflux and esophageal function, most researchers previously defined the RDES as DES accompanied by esophagitis and heartburn using standard manometry over a short time frame. To clarify the pathogenesis of RDES, we did this research using 24-hr ambulatory esophageal motility and pH monitoring. The investigation included 25 normal controls and 116 patients with upper digestive symptoms. Among the 116 patients, 45 had DES (11 RDES, 30 IDES, and DES-GERD coexistence). Patients with RDES showed a significantly higher frequency of simultaneous contractions than did patients with IDES. Heartburn has been said to be peculiar to RDES, but also occurred in 12.5% of IDES. No significant differences in the mean pH of the esophagus during acid reflux were found between the RDES and IDES patients. Based on the results, we have proposed a refined definition of RDES.     

Ambulatory esophageal manometry/pH-metry discriminates between patients with different esophageal symptoms

Ambulatory esophageal manometry/pH-metry has been used primarily in patients with chest pain of presumed esophageal origin, and it is unclear whether the discriminating power of this test applies to other esophageal symptoms. In the present study, prolonged ambulatory manometry/pH recordings were compared in 17 healthy controls, 12 patients with atypical chest pain, and 11 patients with chest pain and nonstructural dysphagia using the Synectics microdigitrapper system. Chest pain patients tended to have higher values for all the pH variables, but their esophageal motility parameters were no different than controls. On the other hand, the chest pain plus dysphagia group was characterized by a significantly lower proportion of propagated contractions between 10 and 5 cm above the lower esophageal sphincter. This group also tended to have a higher frequency of high-amplitude or prolonged-duration contractions. In comparison to the results of standard stationary esophageal manometry, the prolonged ambulatory recordings were more sensitive in detecting esophageal motor dysfunction in the two patient groups. This study suggests that quantitative analysis of ambulatory pH/motility recordings is a sensitive method of evaluating patients with suspected esophageal dysfunction.Supported in part by grants from Janssen Pharmaceutica (Canada) and the MRC of Canada (grant MA9978). Dr. Paterson was supported by a Career Scientist Award from the Ontario Ministry of Health.     

Effect of hiatal hernia on esophageal manometry and pH-metry in gastroesophageal reflux disease

An increased frequency of reflux events and a prolonged acid clearance have been shown in gastroesophageal reflux (GER) patients with a hiatal hernia as compared to those without. The objective of the present study was to further investigate esophageal motility and patterns of reflux in GER patients, in relation to the presence or absence of hiatal hernia. Esophageal manometry and ambulatory 24-hr esophageal pH-metry were used in 42 patients with GER and 18 controls. Eighteen of the patients were considered to have a nonreducing hiatal hernia on endoscopy. Hiatal hernia patients showed a higher extent of reflux (total composite score,P=0.016; total reflux time,P=0.008, reflux time in supine position,P=0.024; reflux time in upright position,P=0.008), a lower frequency of reflux events (P=0.005), a more severe esophagitis on endoscopy (P<0.01) and a lower amplitude of peristalsis at 5 cm proximal to LES (P=0.0009) as compared to patients without hiatal hernia. The amplitude of peristalsis at the distal esophagus was inversely related to the extent of reflux (P=0.024). Acid clearance was also significantly prolonged in the hernia subgroup (P=0.011). Although LES resting pressure did not differ significantly between the two subgroups of patients, it was inversely related to the extent of reflux in the patients with hiatal hernia (P=0.0005). It is concluded, that GER patients with hiatal hernia present with an increased amount of reflux and more severe esophagitis, which results in more severely impaired esophageal peristalsis as compared to patients without hernia. Prolonged acid clearance and impaired esophageal emptying observed in patients with hiatal hernia could be the result of both the presence of the hernia itself and the reduced peristaltic activity of the esophagus.