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

Twenty-Four-Hour Esophageal pH Monitoring: The Most Useful Test for Evaluating Noncardiac Chest Pain EDWARDG. HEWSON,M.D., JANEW. SINCLAIR,P.A.-c., CHRISTINEB. DALTON,P.A.-c., Winston-Salem, North Carolina, JOELE. RICHTER,M.D., Birmingham, Alabama

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 pg/hg 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 refhtx 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 24hour pH testing, 37 patients (46% ) had abnormal reflux parameters and 50 patients (60%) had a

From the Gastroenterology Division (EGH, JWS, CBD), Bowman Gray School of Medicine, Winston-Salem, North Carolina, and the Division of Gastroenterology (JER), University of Alabama at Birmingham, Birmingham, Alabama. Requests for reprints should be addressed to Joel E. Richter, M.D., Division of Gastroenterology, University of Alabama at Birmingham, UAB Station, Birmingham, Alabama 35294. Manuscript submitted August 23, 1990, and accepted in revised form February 5, 1991.

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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 noncardisc chest pain.

P

atients with recurrent chest pain who are found to be free of significant coronary artery disease account for 10% to 30% of patients undergoing coronary angiography [1,2]. Their symptoms are associated with a low mortality [3,4], but many patients remain physically and emotionally disabled [4]. Most patients still believe that they may have heart disease, possibly because they sense their physician’s uncertainty and inability to identify an alternative cause for their chest pain. The identification of a noncardiac source of pain, therefore, may be of considerable value to these patients in allaying their fears. Esophageal disorders are the most common cause of noncardiac chest pain, accounting for identifiable abnormalities in 18% to 58% of these individuals [5-81. Esophageal motility disorders and gastroesophageal reflux (GER) disease are the most frequent findings. However, few studies have assessed the prevalence of both disorders using stateof-the-art esophageal testing. We have studied 100 consecutive patients with angina-like chest pain referred by cardiologists to our esophageal laboratory after extensive evaluations did not identify a cardiac source for their chest pain. Patients underwent traditional esophageal testing (manometry and provocative testing with acid and edrophonium) for noncardiac chest pain [9], as well as outpatient ambulatory esophageal pH monitoring. The latter test is the best technique available for identifying and quantifying the presence of abnormal amounts of acid reflux [lo] and can be done in the home or work setting, thereby replicating the environment associated with these patients’ chest pains. Diary cards and event mark-

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ers allow accurate recording and correlation of multiple chest pain episodes with the presence or absence of acid reflux for periods of up to 24 hours. The size of our study population permitted us to directly compare the diagnostic capabilities of traditional esophageal tests and pH monitoring for identifying the esophagus as a probable cause of chest pain. Additionally, this large study may suggest common mechanisms for esophageal test abnormalities and a more streamlined diagnostic evaluation for this common problem.

PATIENTS AND METHODS Patients Over an l&month period, 100 consecutive patients with noncardiac chest pain were evaluated in our esophageal laboratory at the Bowman Gray School of Medicine with traditional esophageal tests (manometry, acid perfusion test, edrophonium test) and ambulatory 24-hour esophageal pH monitoring. This group was comprised of 43 men and 57 women, with a mean age of 50 years (range: 22 to 69 years). All patients had been directly referred to the laboratory by their university cardiologists after extensive work-ups failed to identify a cardiac source for their chest pain. All patients had electrocardiograms during their chest pain episodes, which did not show evidence of ischemic ST segment responses or arrhythmias. Sixty-six patients had undergone cardiac catheterization: normal coronary arteries were present in 48 patients and nonobstructive disease (less than 50% narrowing of coronary artery diameter) was found in 18 patients. Thirty-four patients did not have cardiac catheterization. Of this latter group, 16 patients had negative stress thallium studies, while the remaining 18 patients were not thought to have cardiac disease primarily based on normal electrocardiograms with pain, negative exercise stress tests, and normal echocardiograms. No patient had mitral valve prolapse. In this group, studies were not explicitly done to exclude microvascular angina since this was considered unlikely by the referring cardiologists based on the absence of ischemic changes during pain and/or normal left ventricular response to exercise during thallium testing [11,12]. Over the time of this study, 583 patients without evidence of prior cardiac disease had undergone cardiac catheterization for the evaluation of anginalike chest pain. From this group, 102 patients (17.4%) were found to have normal coronary arteries or nonobstructive disease. This was the group from which the 66 patients were referred to our esophageal laboratory. These patients were referred by nine different staff cardiologists, although

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76% came from four cardiologists who most commonly in the past had found our esophageal laboratory evaluation helpful. Patients were sent directly to the laboratory without prior consultation with a gastroenterologist. Whether these patients were screened by the cardiologists for esophageal symptoms prior to referral is unknown to the investigators. Detailed information about gastrointestinal symptoms was obtained from all patients. Patients were specifically questioned about symptoms or habits suggesting esophageal disease, especially GER disease: heartburn (greater than two episodes/ month), effortless regurgitation of acidic material, dysphagia for solids or liquids, odynophagia, or a history of antacid/Hz blocker use for peptic symptoms. Seventy-four patients had had prior esophageal evaluations for suspected GER disease: normal endoscopy was reported for 38 patients, unremarkable barium esophagram was documented in 33 patients [13], and three patients had had previous endoscopic evidence of erosive esophagitis. Twenty-six patients had no esophageal evaluation prior to referral to our laboratory for their chest pain. No patient had previous esophageal or ulcer surgery. Esophageal Tests ESOPHAGEAL MANOMETRY: Studies were done with an 8-lumen polyvinyl catheter (external diameter 4.5 mm; intraluminal diameter 0.8 mm; Arndorfer Specialities, Inc., Greendale, Wisconsin). The distal four openings were 1 cm apart at 90° angles, and the four proximal openings were spaced at 5-cm intervals. Each lumen was continuously perfused with distilled water at a rate of 0.5 mL/ minute from a low-compliance, pneumohydraulic capillary infusion system (Arndorfer Specialities Inc.). The catheter was connected to external transducers (model 4-327-C, Beckman Instruments, Inc., Norcross, Georgia) with output to a Beckman recorder (model R-612). Patients were studied in the supine position after an overnight fast. Medications known to affect esophageal contractions or acid secretion or to modulate pain were withheld for at least 24 hours and usually 48 hours before the study. After the catheter was introduced through the nose into the stomach, lower esophageal sphincter (LES) pressure was measured by the station pull-through technique. The four proximal catheter openings were next positioned in the esophageal body at 3, 8, 13, and 18 cm above the LES. Esophageal contractions were recorded from these openings in response to wet swallows (5 mL of water) given at 30-second intervals. The basal study consisted of 10 consecutive

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wet swallows over a 5minute period. Tracings were analyzed for mean distal amplitude and duration at the recording sites 3 and 8 cm above the LES. Contraction sequences were evaluated for the presence of peristalsis as well as simultaneous, nonconducted, retrograde, or triple-peaked contractions. Baseline esophageal motility disorders were classified as nutcracker esophagus, diffuse esophageal spasm, achalasia, hypertensive LES, or nonspecific esophageal motor disorder as defined in our laboratory from prior studies in 95 healthy control subjects PJ41. PROVOCATIVE TESTING: Immediately after manometry while still in the supine position, patients were administered acid and edrophonium chloride (Tensilon; Roche Laboratories, Nutley, New Jersey) in an attempt to provoke their typical chest pain. The acid perfusion test was done by first infusing normal saline into the distal esophagus at a rate of 7 ml/minute for 2 minutes [15]. Without the patient’s knowledge, the solution was then switched to 0.1 N hydrochloric acid and infused at a similar rate for 10 minutes. Lack of symptom reproduction after acid infusion constituted a negative test. If chest pain was reproduced after acid infusion, normal saline was again infused for 10 minutes or until symptoms eased, at which time the acid infusion was repeated. A positive test occurred when the patient’s typical chest pain was twice reproduced during acid infusion. Although heartburn symptoms were recorded, heartburn was not considered a positive endpoint for the purpose of this study. The edrophonium test was also placebo-controlled. A placebo (1 mL of 0.9% normal saline) and edrophonium chloride (80 pg/kg) were consecutively administered intravenously by rapid bolus infusion in an order unknown to the patients. Immediately after each injection, 10 wet (5 mL of water) swallows were given and the patients were asked about the similarity of symptoms to their typical chest pain. A positive edrophonium test was defined as the replication of the patient’s chest pain only after the edrophonium injection. Motility changes were not required for a positive edrophonium test [16]. Twenty-two patients did not receive edrophonium because they reported histories of bronchospasm (asthma, chronic obstructive lung disease) or cardiac arrhythmias. AMBULATORY24-HOURESOPHAGEALpHMONITORING: This study was performed on an outpatient

basis, usually immediately after the previous esophageal tests. One of two systems was employed: the Sandhill pH system (Sandhill, Littleton, Colorado), which uses an antimony electrode with a 3.0mm outer diameter, or the Synectics pH system 578

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(Synectics Medical Inc., Irving, Texas), which also uses an antimony electrode with a 2.1-mm outer diameter. Both systems utilize reference electrodes attached to the anterior chest. Before and after each procedure, the pH electrode was calibrated using buffers of pH 2 and 7. The pH electrode was passed nasally and positioned 5 cm above the proximal border of the manometrically identified LES. Patients were given a standard diet sheet and instructed to avoid food or drink with a pH less than 5. Alcohol and smoking were allowed. Patients were specifically encouraged to participate in activities that may have been associated with prior chest pain episodes. Meals and chest pain episodes were noted on a written diary card and recorded via an event marker on the pH monitor. All tracings were analyzed by computer and inspected by one of the authors to confirm the calculations and ensure the quality of the tracings. A drop of pH below 4 lasting greater than 20 seconds was considered evidence of GER [17]. The end of a reflux episode was defined as the point at which the pH had risen from below 4 and remained above that pH value for at least 6 seconds. Previous studies in our laboratory have suggested that the most reproducible 24-hour pH parameters are the percentages of upright, recumbent, and total acid exposure times [18]. Therefore, GER disease was deemed present if any of these three parameters exceeded the 95th percentile for normal values obtained by studying 48 healthy volunteers (24 men, 24 women, mean age 32 years, range 19 to 57 years): upright time greater than 6.7%, recumbent time greater than 2.4%, and total time greater than 4.7%. A subgroup of patients has recently been identified who, despite a normal 24-hour pH test, have chest pain episodes temporally associated with periods of acid reflux. A chest pain episode was defined as secondary to acid reflux if the esophageal pH dropped below 4 for longer than 20 seconds and occurred up to 5 minutes before the onset of chest pain. To assess the prevalence of reflux-mediated chest pain episodes, we calculated a “symptom index” in all patients with chest pain during the 24hour pH study [19]. This index used the following formula: number of chest pain episodes occurring when the pH was below 4 divided by the total number of chest pain episodes reported. This quotient was then multiplied by 100 to give the percentage of chest pain episodes associated with reflux. Thus,, a negative symptom index implies that no chest pains were acid-mediated, whereas a positive symptom index means at least one chest pain episode was associated with acid reflux. At this time, the appropriate percent cutoff for a positive symptom index is unknown but, for the purposes of this study, any

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positive association was considered evidence that GER disease was probably contributing to the patient’s complaints of chest pain. Statistical Analysis All data are reported as percentages or as mean f SE. x2 analysis (with Yates’ correction for cell sizes less than five when appropriate) was used to compare prevalences between groups. Frequency of chest pain episodes and positive symptom index scores between groups were compared using Student’s t-test for unpaired data. An esophageal test was defined as identifying the esophagus as a probable cause of chest pain only if provocative testing replicated the patient’s identical chest pain or the patient’s spontaneous chest pain correlated with at least one episode of acid reflux (positive symptom index) during 24-hour pH monitoring. This conservative definition was chosen because we believe that a definite diagnosis is only possible in these patients after an esophageal abnormality has been identified and the patients’ symptoms have improved with therapy specific for that esophageal disorder [20]. Otherwise, abnormal manometry or acid reflux parameters without associated chest

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RelationshipBetweenEsophagealTestAbnoYmalities and

Abnormal Manometry (n = 32)

Symptoms Heartburn Regurgitation Dyiphigia Odynophagia No symptoms

24 25 19 7 3

(75%)* (78%) (59%j (22%) (10%)

Provocative Tests (n = 28)

Positive

Both

GER (n = 22)

(n 2’24)

(GnE:!$

23 (82%) 21(75%) i4(5o%j 4(14%) 3(11%)

16 (73%) 14 (64%) lo (45%j 3(14%) 1(5%)

20 (83%) 16 (67%) 16 (67%j 2(8%) 2(8%)

19 (73%) 20 (79%) 13 (5o%j 4(15%) 4(15%)

i

GER = abnormal acid exposure time by Whour pH test; positive SI = positive symptom index by 24-hour pH test. * Number of patients with symptoms (percentage of patients with abnormal esophageal tests).

pain only suggested the esophagus as a possible cause of pain. McNemar’s test for matched samples [21] was used to compare the incidence of definite esophageal diagnoses after traditional esophageal tests and 24-hour esophageal pH monitoring.

RESULTS Esophageal Symptoms Esophageal symptoms were common in this consecutive group of patients with noncardiac chest

100 patients with NCCP 24 hour pH test I 83 patients CP during test /

\

Normal 24 hour pH

Abnormal 24 hour pH

46 patients

37 patients

22 patients

24 patients

26 patients

11patients

Figure 1. Results of ambulatory 24-hour esophageal pH monitoring in 100 consecutive patients referred by cardiologists for the evaluation of noncardiac chest pain (NCCP). Seventeen patients did not experience chest pain (CP) during the pH test. Of the remaining 83 patients, 55% had normal acid reflux parameters while 45% had abnormal reflux parameters. More than twice as many patients with abnormal reflux parameters had at least one of their chest pain episodes coincident with acid reflux, i.e., positive symptom index (9). Despite only physiologic amounts of acid reflux in the other group, 24 (52%) patients had a positive symptom index. Overall, 50 patients had at least one episode of their chest pain closely associated with gastroesophageal reflux.

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pain (heartburn [74%], regurgitation [67%], dysphagia [49%], and odynophagia [14%]). Despite the absence of esophageal symptoms in 11 patients, three (27%) had motility abnormalities, three (27%) had positive provocative tests, and seven (63%) had evidence of acid reflux by 24-hour pH testing. As shown in Table I, the abnormalities recorded by esophageal testing were equally distributed among the patients regardless of the presence or type of esophageal symptoms. Traditional Esophageal Tests Traditional esophageal tests were abnormal and/ or reproduced the chest pain in 52 patients. Esophageal manometry was abnormal in 32 of 100 patients (32%): nonspecific esophageal motor disorder (21), nutcracker esophagus (six), diffuse esophageal spasm (four), and hypertensive LES (one). However, no patient with these motility abnormalities had spontaneous chest pain. The acid perfusion test was positive in 18 of 95 patients (19%) and the edrophonium test was positive in 15 of 78 patients (19%). Evidence of GER disease (abnormal acid exposure and/or positive symptom index) by the 24hour pH test was no more frequent in the patients with abnormal manometry results (22 of 32 patients, 69%) than in those with normal baseline manometry (48 of 68 patients, 71%). Patients in whom the acid perfusion test was positive more commonly had evidence of reflux disease than did patients with negative acid perfusion results (18 of 18 patients [lOO%] versus 48 of 77 patients [62%]; p
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index had significantly (p O.lO, unpaired t-test) between the patients with a positive symptom index alone (58 f 5%) and those patients with a positive symptom index and abnormal reflux parameters (67 f 5%). Overall Diagnostic Yield Traditional esophageal tests identified the esophagus as probably contributing to chest pain in 28% of patients: positive acid perfusion test, 13%; positive edrophonium test, 10%; both tests positive, 5%. Additionally, 24% of patients had abnormal manometry results only, suggesting the esophagus as a possible cause of their chest pain. In contrast, a positive symptom index during the 24-hour pH test identified GER as probably contributing to chest pain in 50% of patients. Another 22% of patients (11 without chest pain, 11 with a negative symptom index) had abnormal acid exposure times, suggesting that GER may be a possible cause of their chest pain. These differences are particularly striking when the test results in individual patients are examined. Twenty-four-hour pH testing permitted a probable esophageal diagnosis in 31 patients when traditional tests were negative or inconclusive, but the converse was true in only nine patients. Therefore, 24-hour pH testing with symptom index was significantly superior (p
COMMENTS We report the largest study to date investigating patients with noncardiac chest pain with state-ofthe art esophageal testing including manometry, provocative tests, and 24-hour pH monitoring. All patients were directly referred by their cardiologists; therefore, the frequency of esophageal abnormalities found was not a selection bias introduced by the gastrointestinal investigators. The 52% prev-

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TABLEII RelationshipBetweenSymptomIndexand AbnormalAcid RefluxParameters SymptomIndex lZ5% 26%-50% 51%-75% >75%

Abnormal 11/33 2/8 lo/18 5/10 lo/14

Reflux Parameters patients patients patients patients patients

(33%) (25%) (56%) (50%) (71%)

alence rate of abnormal traditional esophageal tests is similar to previous studies from our laboratory [9] and others [6,7]. However, manometry and provocative testing only identified the esophagus as probably contributing to chest pain in 28% of patients: positive acid perfusion tests, 13%; positive edrophonium test, 10%; both tests positive, 5%. In contrast, outpatient 24-hour esophageal pH monitoring identified GER as probably contributing to chest pain in 50% of patients based upon their symptoms occurring coincident with acid reflux, i.e., a “positive symptom index.” An additional 22% had abnormal reflux parameters that could not be associated with their chest pain symptoms. Overall, 24-hour pH monitoring was significantly superior

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(p
Traditional Esophageal Tests

24 Hour pH Study Possible 24%

Possible 22%

Probable 20%

Probable 50%

Flgure 2. Comparison between the diagnostic yield of traditional esophageal tests (manometry and provocative testing with acid and edrophonium) and 24-hour esophageal pH monitoring in 100 consecutive patients with noncardiac chest pain. An esophageal test was defined as identifying the esophagus as a probable cause of chest pain only if provocative testing replicated the patient’s identical chest pain or the patient’s spontaneous chest pain correlated with at least one episode of acid reflux (positive symptom index) during 24-hour pH monitoring. Otherwise, abnormal manometry or acid reflux parameters without associated chest pain only suggested the esophagus as a possible cause of chest pain. Esophageal pH monitoring with symptom index was significantly superior (p
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shown that GER is two to three times more common a cause of chest pain than esophageal motility disorders. Our study confirms the high prevalence of GER disease in a population with noncardiac chest pain. Esophageal symptoms were common in our study but did not distinguish patients with GER disease from those with motility disorders or positive provocative tests. This may represent the common interaction between acid reflux and motility disturbances as well as the limited number of responses that the esophagus has to noxious stimuli. For example, spastic motility disorders may promote poor acid clearance, thereby producing symptoms of heartburn and regurgitation, whereas acid reflux can produce complaints of dysphagia from esophageal inflammation or secondary motility disturbances. However, the lack of esophageal symptoms does not preclude the presence of esophageal test abnormalities, especially GER. It appears that approximately 10% of patients will have no esophageal symptoms at the time they present with severe chest pain. GER disease may be the common link between most of the esophageal test abnormalities observed in patients with noncardiac chest pain. From a treatment standpoint, this would be very important since drug therapy for spastic motility disorders (nitrates, anticholinergics, calcium channel blockers) could exacerbate acid reflux [8]. The results of this study and others are tantalizing but inconclusive. Schofield et al [26] found that GER was significantly more common (p (0.01) in patients with esophageal motility disorders (19 of 26, 73%) than in patients with normal manometry (five of 26,19%). We could not confirm this observation. Abnormal 24-hour acid exposure times and/or positive symptom indexes were no more frequent in our patients with esophageal motility disorders (22 of 32, 69%) than in those patients with normal manometry (48 of 68, 71%). However, we did note a trend that nearly reached significance (p = 0.07) for GER to be more common in patients with a positive edrophonium test (13 of 15,87%) than in those patients with a negative test (39 of 63,52%). A similar overlap between positive edrophonium testing and GER has been reported by Schofield et al [26] and Vantrappen et al [27]. The patients with a positive symptom index, who account for 50% of the abnormalities identified by 24-hour pH testing, are an interesting group. Nearly half of these patients (49%) had normal acid reflux parameters, but their mean symptom index (58 f 5%) was not significantly different from that of patients with a positive symptom index and abnormal reflux parameters (67 f 5%). In agreement with our experience, Schofield and colleagues [23] found 582

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that 13 of 22 (59%) patients with a positive sympindex had normal 24-hour acid reflux parameters. However, two other reports [7,22] infrequently documented acid-related symptoms without associated abnormal reflux parameters. It is not known whether patients with a positive symptom index alone represent a group with hypersensitivity to physiologic episodes of acid reflux or patients in whom abnormal quantities of acid reflux were missed by the pH probe [28]. We also do not know if these acid-sensitive patients are as responsive to antireflux therapy as are patients with a positive symptom index and concomitant abnormal reflux parameters. The frequency of acid reflux-induced symptoms in patients with noncardiac chest pain is an important finding since excellent medical and surgical therapies are available for GER disease. However, does acid-induced chest pain respond as well as heartburn to vigorous antireflux measures? Only the study by DeMeester et al [22] addresses this issue, and it is not a controlled trial. Of the 12 patients they identified with documented acid reflux during chest pain episodes, eight had symptom relief following Nissen fundoplication and four improved with medical therapy (postural changes, antacids, cimetidine). The remaining 11 patients with abnormal reflux parameters but no correlation of their chest pain with reflux or no chest pain during monitoring did not achieve such good results. Two of three patients responded to antireflux surgery, but only three of eight medically treated patients were pain-free. This excellent response to antireflux surgery suggests that near total elimination of acid reflux may be required for relief of chest pain. Recommended doses of HZ blockers may not accomplish this goal [29,30], consistent with our observations that these patients frequently need higher doses (ranitidine 300 mg twice a day or famotidine 40 mg twice a day) for initial pain control. The substituted benzimidazole, omeprazole, which markedly suppresses gastric acid secretion by inhibiting the H-K-ATPase found on the parietal cell secretory surface, offers another exciting therapeutic option. Additionally, omeprazole may permit investigators to characterize the treatability of the various abnormal groups identified by esophageal pH testing. Unfortunately, the sensitivity and specificity of these tests for identifying an esophageal source of chest pain are not known because no “gold standard” exists for the diagnosis of esophageal chest pain. It is known that these tests are rarely positive in healthy individuals [10,12,16,18,unpublished data]. Furthermore, esophageal motility disorders have only been reported in 10% of patients with angina pectoris and significant coronary artery distom

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ease [26], but the prevalence of positive provocative tests and acid reflux has not been studied. In addition, the symptom index needs further refinement to exclude the possibility that some of the refluxassociated events may occur randomly. Nevertheless, similar limitations in sensitivity and specificity exist for the tests diagnosing microvascular angina [ll] and panic disorders [31], which are the “new” candidate diseases popularized as common causes of noncardiac chest pain. In the end, the only means to resolve these issues is the development of effective therapies for these pain problems. At this time, only acid reflux disease has effective medical and surgical therapy, which reinforces the need not to miss this diagnosis. Our results suggest that 24-hour esophageal pH monitoring is the single best test for evaluating patients with noncardiac chest pain. The 50% prevalence of acid-induced chest pain is important since these patients have a potentially treatable problem. Esophageal pH monitoring can be done on an outpatient basis with excellent diagnostic yield merely by encouraging activities previously known to exacerbate chest pain. Unfortunately, current accurate placement of the pH probe requires the LES to be located by esophageal manometry [32]. Future pH systems will need to include a pressure transducer in the pH probe to simplify this task. The evaluation of noncardiac chest pain could then be streamlined, with manometry and provocative testing reserved for patients with negative pH tests or those patients with positive tests who do not respond to vigorous antireflux regimens.

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11. Cannon RO, Watson RM, Rosing DR, Epstein SE. Angina caused by reduced vasodilator reserve of the small coronary arteries. J Am Coil Cardiol 1983; 1: 1359-73. 12. Cannon RO. Thegastroenterologist and microvascular angina. Gastroenterology 1990; 98: 1103-5. 13. Ott DJ. Chen YM, Gelfand DW, Wu WC. Analysis of the multiphasic radiographic examination for detecting reflux esophagitis. Gastrointest Radio1 1986; 11: 1-6. 14. Richter JE, Wu WC, Johns DN, et al. Esophageal manometry in 95 healthy adults: variability of pressures with age and frequency of “abnormal” contractions. Dig Dis Sci 1987; 32: 583-92. 15. RichterJE. Johns DN, Wu WC, Castell DO. Areesophageal motilityabnormalities produced during the intraesophageal acid perfusion test? JAMA 1985; 253: 1914-7. 16. Richter JE, Hackshaw BT, Wu WC, Castell DO. Edrophonium: a useful provocative test for esophageal chest pain. Ann Intern Med 1985; 103: 14-21. 17. Shaker R, Kahrilas PJ, Dodds WJ, Hogan WJ. Esophageal clearance of small amounts of acid [Abstract]. Gastroenterology 1986; 90: 1628A. 18. Wiener GJ, Morgan TM, Copper JB, et al. Ambulatory 24-hour esophageal monitoring. Reproducibility and variability of pH parameters. Dig Dis Sci 1988; 33: 1127-33. 19. Wiener GJ, Richter JE, Copper JB, Wu WC, Caste11 DO. The symptom index: a clinically important parameter of ambulatory 24hour esophageal pH monitoring. Am J Gastroenterol 1988; 83: 35861. 20. Richter JE. Selected summary: esophageal test for all seasons and all reasons but, how do they help the patient?? Gastroenterology 1990; 99: 1846-

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Q. Psychological statistics. New York: Wiley, 1955. 22. DeMeester TR, O’Sullivan GC, Bermudez G, Midell Al, Cimochowiski GE, O’Drobinak JO. Esophageal function in patients with angina-type chest pain and normal coronary angiograms. Ann Surg 1982; 196: 488-98. 23. Schofield PM, Bennett DH, Whorwell PJ, et al. Exertional gastro-oesophageal reflux: a mechanism for symptoms in patients with angina pectoris and normal coronary angiograms. Br Med J 1987; 294: 1459-61. 24. Janssen J, Vantrappen G, Ghillebert G. 24-hour recording of esophageal pressure and pH in patients with non-cardiac chest pain. Gastroenterology 1986; 90: 1978-84. 25. Peters LJ, Maas LC, Petty D, et al. Spontaneous non-cardiac chest pain: evaluation by 24-hour ambulatory esophageal motility and pH monitoring. Gastroenterology 1988; 94: 878-86. 26. Schofield PM, Whorwell PJ, Brooks NH, Bennett DH, Jones PE. Oesophageal function in patients with angina pectoris: a comparison of patients with normal coronary angiograms and patients with coronary artery disease Digestion 1989; 42: 70-8. 27. Vantrappen G, Janssen J, Ghillibert G. The irritable oesophagus: a frequent cause of angina-like chest pain. Lancet 1987; 1: 1232-4. 28. Murphy DW, Yuan T, Castell DO. Does the intraesophageal pH probe accurately detect acid reflux? Dig Dis Sci 1989; 34: 649-56. 29. Orr WC, Robinson MG. HumphriesTJ, Antonella J. Caglalio A. Dose response effect of famotidine on gastroesophageal reflux [Abstract]. Gastroenterology 1987; 92: 1562A. 30. Russell J, Orr WC, King JF, Finn AL. The effects of high doses of ranitidine on esophageal reflux and severity [Abstract]. Am J Gastroenterol 1988; 83: 1025A. 31. Beitman BD, Mukerji V, Lamberti JW, et al. Panic disorders in patients with chest pain and angiographically normal coronary arteries. Am J Cardiol 1989;

63: 1399-1403. 32. Walther B, DeMeester TR. Placement of the esophageal pH electrode for 24 hour esophageal pH monitoring. In: DeMeester TR, Skinner DB, eds. Esophageal disorders: pathophysiology and therapy. New York: Raven Press, 1985: 53941.

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