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

GASTROENTEROLOGY 1986;90:1978-84

W-Hour Recording of Esophageal Pressure and pH iti Patients With Noncardiac Chest Pain JOZEF JANSSENS, GASTON VANTRAPPEN, GILBERT

and

GHILLEBERT

Division of Gastroenterology, Departments of Internal Medicine and Medical Research, University of Leuven, Leuven, Belgium

Sixty patients with anginalike chest pain of noncardiac origin were studied to determine the diagnostic value of 24-h ambulatory esophageal pH and pressure mpnitoring. The results of these 24-h studwith those obtained by estabies were compared lished methods, including x-rays, endoscopy with biopsy, cqnventional 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 The 24-h recordings, be likely in 27% of the patients.

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. Although the esophagus is frequently suspected to be the cause of pain in patients with anginalike chest pa@ of poncardiac origin, objective evidence that the esophagus is indeed the source of the pain is obtained in only a minority of cases (l-9).To improve the diagnostic yield, attempts have been made to pharmqcologically provoke esophageal motility Received February 11, 1985. Accepted December 16, 1985. Address requests for reprints to: G. Vantrappen, M.D., Agg. H.O., Head, Department of Medicine and Division of Gastroenterology, University Hospital, St. Rafael-Gasthuisberg, University of Leuven, Leuven, Belgium. This work was supported by grants of the FGWO and of the “Geconcerteerde Onderzoeksactie” of the University of Leuven. The authors thank Jan Servaes and Toon De Greef for their expert technical assistance. 0 1986 by the American Gastroenterological Association 0016-5085/86/$3.50

abnormalities and symptoms (10-23). Edrophonium was reported to yield a definitive diagnosis of chest pain in 20%-30% of the patients (21,22). The aim of this study was to investigate whether the diagnostic accuracy can be improved by prolonged (24 h) intraesophageal

pH and pressure

measurements.

Materials and Methods Sixty patients (26 men and 34 women) with a mean age of 50.6 yr (range, 31-76 yr), were studied (Table 1). The protocol for this study was approved by the Ethical Com-

mittee of the Medical Faculty of the University of Leuven. The inclusion criterium was the presence of severe anginalike chest pain that was diagnosed to be not of cardiac origin. This decision was made by the cardiologist after all the technical cardiological examinations that he judged necessary had been performed. The pain was exerciserelated in 21 patients; cardiological examination, which included coronarography, thallium scan, and ergonovine provocation test, excluded cardiac ischemia in 16 of them. The 5 remaining patients (patients 17, 27, 30, 46, and 49) also had negative coronarography and ergonovine provocation, but some minor abnormalities were found on thallium scan, which provided insufficient evidence that the pain was of cardiac origin. These patients were included in the study because of accompanying symptoms of reflux and dysphagia. The pain was not related to exercise in 39 patients; they all had negative exercise electrocardiogram tests and the consulting cardiologist considered further cardiological examination unwarranted. Twenty-one patients had daily episodes of their chest pain and 30 patients experienced their familiar chest pain two to three times per week; in the remaining 9 patients the pain

occurred more rarely (less than once a week). Qn repeated and carefully selected questioning, several patients had a history of heartburn (14 of 60) and several had some (mostly minimal) degree of dysphagia (30 of 60 patients). Radiologic and endoscopic examination of the upper gastrointestinal tract was carried out in order to exclude severe gastritis, ulcer, or carcinoma as potential causes of the pain. At radiologic examination, particular attention

Table

Patient

I.

No.

1. V.H.A 2. H.J. 3. V.M. 4. A.M. 5. F.M. 6. M.M. 7. CM. 8. F.G. 9. S.P. 10. F.R. 11. V.M. 12. C.M. 13. D.M. 14. D.J. 15. P.J. 16. F.M. 17. V.Y. 18. V.J. 19. V.A. 20. W.M. 21. D.J. 22. V.W.M. 23. P.W. 24. B.J. 25. H.J. 26. D.K. 27. T.E. 28. V.E. 29. G.M. 30. CF. 31. O.A. 32. L.L. 33. D.R. 34. M.R. 35. M.E. 36. B.E. 37. E.J. 38. V.M. 39. W.V. 40. D.C. 41. D.A. 42. V.G.A. 43. P.R. 44. S.H. 45. L.S. 46. D.A. 47. B.M. 48. V.L. 49. J.R. 50. L.M. 51. B.A. 52. D.L. 53. S.M. 54. D.M. 55. S.G. 56. A.E. 57. W.P. 58. J.A. 59. H.W. 60. M.M.

Patient

sex M M F F F F F M M M F F F M F F F F F F M F M M F M M M F M M M M M F M M M F M F F M F F F F F M F F M M F F M F F F F

Data

Age (yrl 48 52 52 65 47 55 49 41 44 46 56 64 55 46 75 54 45 58 58 42 58 48 57 53 50 32 53 35 76 49 45 34 41 45 48 39 63 67 37 33 60 66 31 41 63 42 53 38 45 60 53 49 43 53 48 62 44 58 53 59

Frequency of chest pain FW FW D R FW FW R D R D D D FW R D FW D FW R FW FW FW FW D D D FW FW R FW FW R D D FW D FW FW FW FW FW FW FW FW D D FW D FW D D D R D D FW FW FW FW R

Esophagogram MA

_ _ _ _ _ _ _ _ + _ _ _ _ _ _ + _ _ _ _ _ _ _ _ _ _ + + + _ _ _ _ _ _ + + + + + _ _ + _ + + _ _ + +

Reflux

_ _ _ _ _ _ _ _ _ _ + _ _ _ + + _ _ _ _ _ + _ + + _ _ _ _ _ + _ _ _ _ _ _ _ _ _ _ + _ _ _ _ _ + _ _ + + +

Endoscopy biopsy

Manometry MA

_ _ _ + + + + + + + + + + -

_ _ _ _ _ _ _ _ _ _ _ _

+ + + _ _ + _ + _

-(a) _ _

_ _ _ _ _ _ - (4 +@I +Vl (4 +(3) +(2) +(31 +(21 +(l) +(l) +(I) +(2) _ _ _ _ _ +(2) +(2) +(2) +(I) -t(2) +(21 +(21 -(a) _

+(3) +(2) +(21 (al -(a) _ _ +(21 f(21 +(2) +(2) +(2) (al

Bernstein test

_ _ _ _ _ _ _ _ + _ _ + _ _ _ + _ + + _ _ _ _ _ _ _ _ _ _ _ _ _ + _ + _ _ + _ _ + _ _ _ +R +R +R +R +R +R +R +R +R +R +R +R +R +R +R +R

24-h pH

Trigger on pain

_ _ _ _ _ _ _ _ _ _ _ _ _ _ ._ _ _ _ _ _ _ _ _ _ _ _ _ +(I) +c21 +(I) +(31 +(I1 +(l) +(1) +(2) +(I) +(I1 +(11 +(I) +(l) +(3) +(I1 -t(2) +(l) +(2) +(I1

(2) (3) (3) (3)

(31 (3)

(2)

+(ll *(31 _ _ _ _ _ _ _ _

Frequency of chest pain episodes (history]: D, daily; FW, a few times a week; R, only rarely, less than once a week. Manometry: MA, motor abnormalities; (l), achalasia; (21, multiple nonperistaltic contractions (diffuse spasm); (3), high-amplitude (>200 mmHg] contractions; (a), lower esophageal sphincter pressure
GASTROENTEROLOGY Vol. 90, No. 6

1980 JANSSENS ET AL.

was paid to the presence or absence of motor abnormalities (tertiary contractions) or reflux (the return of barium from the stomach into the thorax to a height equal to one-third or more of the length of the gullet). The diagnosis of esophagitis was based on the presence of erosions or ulcerations on endoscopy or on the presence of a polymorphonuclear cell infiltrate of the mucosa on biopsy. Manometric examination was performed with a catheter assembly consisting of seven polyvinyl chloride catheters (0.8 mm ID, 1.5 mm OD), connected to external transducers (E 0333E-E 154E; Siemens, Elema, Sweden). Pressures were recorded on an eight-channel polygraph (Mingograph 82; Siemens). All catheters were continuously perfused with distilled water via a low-compliance capillary tube infusion pump (Arndorfer Medical Specialists, Greendale, Wis.) at a rate of 0.6 mlimin. The four distal recording orifices were located at the same level but were oriented in four different radial directions, 90” apart. The three other catheters were spaced at 5-cm intervals. Lower esophageal sphincter (LES) pressure was measured by a stationary pull-through technique. The highest mean pressure of the four radially oriented orifices was taken as the LES pressure. Esophageal body motility was evaluated in the resting state and after wet swallows using the same stationary pull-through technique, with one or two wet swallows at each level. Severe motor disturbances such as diffuse spasm and achalasia were defined as previously described (2425). The presence of high-amplitude contractions in the lower esophagus (peak pressures >200 mm Hg) was also considered abnormal. [A mean pressure of >120 mmHg, as suggested by Benjamin et al. (6) to define high-amplitude contractions, could not be used because of the stationary pull-through recording technique.] Acid perfusion tests were performed according to the method of Bernstein and Baker (26). The test was called positiverelated if acid perfusion induced the familiar anginalike chest pain. When the acid perfusion provoked only substernal burning without the familiar chest pain, the test was called positive-unrelated. Twenty-four-hour pH and pressure measurements were performed with a portable recording system (Imcomed, Brussels, Belgium) (27) (Figure 1). The probe consisted of a pH glass-electrode, an intraluminal reference electrode, and three solid state pressure transducers. The probe was passed via the nose and was positioned under manometric control so that pressures were measured at 3, 10, and 17 cm and pH at 5 cm above the LES. The external diameter of the probe was 5 mm and its length was 120 cm. Pressures and pH were recorded on a four-track magnetic tape of a cassette recorder that consisted of pH and pressure amplifiers, a system for pulse-width modulation of the pH and for frequency modulation of the pressure signals. The magnetic tape of a commercial minicassette was sufficiently long to allow a 24-h registration period. Time multiplexing was used to record several signals on one track, i.e., the pH signal, the event marker, an automatic calibration, and a quartz clock. These signals were sampled with a frequency of eight per second. The sensitivity of the pH recording was 0.15 pH units. The three intraluminal pressures were registered on the three remaining tracks. The recording system allowed a correct

Figure 1. Twenty-four-hour pH and pressure recording system.

registration of intraluminal pressure variations up to 10 Hz. The size of the recorder was 15.5 x 9.5 x 4.5 cm, and its weight was low enough (815 g) to be easily portable during the 24 h of the patient’s daily routine. The patient was asked to indicate in a diary the periods of meals and sleep and to use a push button on the recorder in case of chest pain. The replay system of the recorder constructed, via a computer program, a 24-h pH plot and a numerical analysis of several pH parameters including the number of pH drops below 4, the number of pH drops below 4 that lasted longer than 5 min, and the percentage of time that the pH was below 4. The mean values determined in 15 control subjects (unpublished previous study) were 7.23 -C 7.53, 0.95 * 1.61, and 1.20 -C 1.82, respectively (mean -C SD). The value was considered abnormal if it exceeded the mean +2 SD. The replay system could also drive a polygraph (Mingograph 82) using the pain marker as a trigger. The recorder reproduced at normal paper speed (5 mm/s] both the pH and pressure tracings, starting 10 min before and lasting for 15 min after the trigger. In this way, parts of the 24-h recording of special interest could be studied in detail. However, for the purpose of this study the entire 24-h recording was replayed on paper, so that all episodes of motor disorders and of reflux could be evaluated.

Results The results of these investigations were analyzed step-wise in the following sequence: (a) barium esophagogram and esophagoscopy with biopsy, (b) conventional manometry, (c) acid perfusion test, (d) 24-h pH measurement, and (e) 24-h pH and pressure measurement. A summary of the results obtained in the 60 individual patients is shown in Table 1. Barium Esophagogram With Biopsy

and

Esophagoscopy

Esophageal origin of the anginalike chest pain was suspected if radiologic examination showed reflux or severe motor abnormalities, or both, or if

June 1986

INTRAESOPHAGEAL

J----

24-H pH & PRESSURE

2. Replay of a short period of a 24-h pH and pressure recording triggered on pain (event marker). High, simultaneous pressure peaks develop in the esophagus in the absence of reflux during the occurrence of chest pain. pH: intraesophageal pH at 5 cm above lower esophageal sphincter. Pressure tracings at 3, 10, and 17 sphincter. cm above lower esophageal

endoscopy with biopsy revealed signs of esophagitis (erosions, ulcerations, polymorphonuclear cell infiltration of the mucosa). Reflux or esophagitis, or both, were observed in 22 patients. Tertiary contractions were visualized radiologically in 15 patients, 5 of whom also had reflux or esophagitis, or both. Conventional

Manometry

Conventional manometric examination revealed severe motor disturbances in 25 patients. Four patients had achalasia (patients 28, 29, 30, and 41). Eighteen patients had frequent (>30% of the deglutitive waves) nonperistaltic contraction waves 15 of these 18 patients had a after deglutition; normal or high LES pressure-in 3 patients, the LES pressure was low (200 mmHg. No patient experienced his familiar chest pain during the manometric examination. In these 25 patients the esophagus was considered to be a probable cause of the anginalike chest pain. Acid Perfusion

1981

the mean value $2 SD) in 13 patients. As the mere presence of pathological reflux does not prove that this reflux is indeed the cause of the anginalike chest pain, it was accepted that a positive 24-h pH measurement would implicate that the esophagus was suspected to be the cause of the chest pain. 24-Hour pH and Pressure

Figure

RECORDINGS

Measurement

As the final step, the pH and pressure changes accompanying episodes of anginalike chest pain (as indicated by the patient on the recording by means of the push button] were analyzed. When a pain episode was correlated in time with severe motor abnormalities that were not present in other parts of the recording (Figure 2) or with a pH drop below 4 (Figure 3), or with both, esophageal origin of the chest pain was considered to be likely. A positive correlation was present in 21 patients. Of these 21 patients, 9 had a history of daily chest pain, 11 patients experienced the familiar pain two to three times a week, and 1 of the 21 patients belonged to the group of patients who had chest pain only rarely. To determine whether 24-h pH and pressure measurements improved the diagnostic yield or merely confirmed the results of conventional examinations, the probability that the esophagus was the cause of the chest pain was determined after the successive combination of examinations. The diagnostic score first was determined after radiology and endoscopy with biopsy, and then after adding successively the results of conventional manometry, the acid perfusion test, the 24-h pH plot with numerical analysis, and the replay of the pH and pressure recordings triggered by the pain marker. Based on well-defined criteria (see results a to e), and “likely” the terms “suspected, ” “probable,” were used to indicate the increasing degree of probability of an esophageal origin of the chest pain. This cumulative diagnostic score is shown in Figure 4.

Test

The acid perfusion test was positive-related in patients. Because the test provoked the familiar anginalike chest pain in these 16 patients, esophageal origin of the chest pain was considered to be likely. In 9 other patients, the acid perfusion test was positive-unrelated. In these patients, esophageal origin of the anginalike chest pain was, at most, suspected. 16

Figure

24-Hour pH Measurement Twenty-four-hour pH measurements yielded abnormal results (at least one parameter exceeding

3. Replay of a short period of a 24-h pH and pressure recording triggered on pain (event marker). Chest pain occurred during a period of reflux in the absence of motor abnormalities. pH: intraesophageal pH at 5 cm above lower esophageal sphincter. Pressure tracings at 3, 10, and 17 cm above lower esophageal sphincter.

1982

GASTROENTEROLOGY Vol. 90, No. 6

JANSSENS ET AL.

DIAGNOSTIC START

SCORE +

RX END0

+

BERNSTEIN

24hpH

+ TRIGGER PAIN

Figure 4. Diagnostic score calculated first after x-rays and endoscopy with biopsy, and then after adding successively the results of manometry, Bernstein test, 24-h pH analysis, and 24-h combined pH and pressure recording triggered on pain. 32

cl

=SUSPECTED

ESOPHAGEAL

After esophageal x-ray examinations and esoph_ _ agoscopy with biopsy, the esophagus was suspected of being the cause of the chest pain in 32 of the 60 patients (Figure 4, row 2). After adding the results of conventional manometry, the esophagus was shown to be the probable cause of the pain in 25 patients, including 16 from the previous group of 32 patients (Figure 4, row 3). In the 16 patients with a positive-related acid perfusion test, the esophagus was considered to be the likely cause of the anginalike chest pain, Of these 16 patients, 4 patients were from the group in which an esophageal origin was “suspected,” and 8 were from the group in which an esophageal origin was “probable”; in the other 4 patients all previous examinations (x-rays, esophagoscopy, manometry) were negative. Of the 9 patients with a positiveunrelated test, only 3 had normal findings before that examination. When the results of the acid perfusion test were added to the previous results, the esophageal origin of the pain was “suspected” in 15 patients, “probable” in 17 patients, and “likely” in 16 patients (Figure 4, row 4). The 24-h pH record was abnormal in 13 patients; in only 3 of them had esophageal origin remained unsuspected on the basis of the results of preceding examinations. The test

= PROBABLE

ORIGIN

OF

= LIKELY

PAIN

did not change the score in the other 10 patients (Figure 4, row 5). In the 21 patients in whom the chest pain was accompanied by reflux or severe motor abnormalities that were not present in other parts of the recording, or both, the esophagus was considered to be the likely cause of the pain. In 8 of these 21, this score had already been reached because of a positive-related acid infusion test. In i’of the remaining 13 patients the esophageal origin was only probable up until then, and in 4 it was merely suspected; in 2 of the 13 patients all tests had been normal up until then. The final diagnostic score in the 60 patients was as follows: the esophagus was “suspected” to be the cause of the pain in 14 patients; it was a “probable” cause of the pain in 10 patients, and it was a “likely” cause in 29 patients. In the 7 remaining patients the esophagus seemed not to be implied (Figure 4, row 61.

Discussion With the increasing use of coronary arteriography, it has become evident that some patients with a clinical history of coronary artery disease have

June1986

normal coronary arteries both anatomically and functionally. It seems likely that esophageal disorders are the cause of chest pain in some of these patients. The frequency with which various studies implicate the esophagus as the cause of the pain depends on the criteria set forth to prove the esophageal origin of the pain (25,7-g). According to Brand et al. (3), a definitive statement can ,be made only when the patient has a familiar attack of chest pain during manometry or pH-metry; if a characteristic and reproducible motor pattern appears on manometry or if the patient has pH-probe-proven reflux at the time of pain, a clear-cut case can be made for an esophageal origin of the pain. Unfortunately, this incidence is very low because of the intermittent nature of the pain and because of the limited duration of the conventional pH-probe and manometric examinations. To improve the diagnostic accuracy of the examinations, pharmacologic provocation tests have been proposed. Bethanechol, pentagastrin, edrophonium, and ergonovine have all been used with variable success (12-22). Bethanechol and pentagastrin were reported to induce chest pain in 6% and 3% of the patients, respectively (21).Ergonovine will induce chest pain and associated esophageal motor abnormalities in 22%-60% of patients, but the cardiac risks of this drug limit its use as a diagnostic test (14-16,18-20). Edrophonium may yield equivalent results and is much safer to use (16):-2O%-30% of patients with noncardiac chest pain will have a change in their manometric tracing simultaneously with chest pain provoked by the intravenous injec(21,22).Retion of 80-200 pg/kg of edrophonium cently, Richter et al. (23)used balloon distention in the lower esophagus as a provocative test; chest pain occurred in 56% of the patients and in only 20% of the controls. The present study aimed at determining whether the diagnostic accuracy could be increased by using prolonged (24-h) intraesophageal pH and pressure measurements in ambulatory patients. The pH and pressure monitoring was performed by means of a newly developed sensing, recording, and analyzing technique (27). The study also compared the results of these prolonged measurements to those of more conventional examinations such as radiology, esophagoscopy with biopsy, conventional manometry, and the acid-perfusion test. The patients selected for this study had severe complaints of anginalike chest pain of noncardiac origin. The anginalike chest pain was exerciserelated in 21 patients. Coronary arteriography with ergonovine testing and thallium scintigraphy were normal in 16 of these 21 patients; the remaining 5 patients (patients 17,27, 30,46, and 49) had some

INTRAESOPHAGEAL24-H

pH i? PRESSURE RECORDINGS

1983

minor abnormalities on thallium scan with negative coronarography and negative ergonovine provocation, insufficient to consider a cardiac origin of the pain; moreover, accompanying symptoms of reflux and dysphagia suggested a possible esophageal origin of the pain in these 5 patients. As a repeated and carefully selected questioning revealed some (often minor) degree of heartburn in 14 patients and dysphagia in 30 patients, the prevalence of esophageal disorders can be expected to be fairly high in this group of 60 patients and may be higher than in a less select group of patients with “noncardiac” chest pain seen in routine practice. The pathophysiologic basis of anginalike chest pain of esophageal origin remains unknown. Most investigators (1,3,28) believe that severe motor abnormalities or reflux, or both, are the cause of the pain in the majority of cases, although other still unknown mechanisms may be involved as well (232930). In this study, the esophagus was taken to be the likely cause of the anginalike chest pain if the familiar pain sensation could be reproduced by acid perfusion into the esophagus (positive-related acid infusion test) or if the pain occurred during a reflux episode or during a period of severe motor abnormalities (or both) on the 24-h pH and pressure recording. The other criteria used in the diagnostic score system are somewhat arbitrary but, nevertheless, logical. Severe motor abnormalities on routine manometry made esophageal origin of the chest pain probable. The mere presence of retlux or of tertiary contractions on barium esophagogram was considered to be of less importance for the scoring (esophageal origin suspected). Using these criteria we were able to demonstrate that the esophagus was indeed the likely cause of the anginalike chest pain in 29 of the 60 patients, whereas more routine examinations, including manometry and acid perfusion test, revealed the diagnosis in only 16 patients. Therefore, 24-h pH and pressure recording by means of a portable cassette recorder, which is well accepted and tolerated by the patients, is a major contribution to the exploration of patients with anginalike chest pain of noncardiac origin. As can be expected, a positive correlation between pain and a pH drop or severe motility disturbances on the 24-h recording was more frequently found in patients with a history of daily chest pain (positive 24-h testing in 43%) or with a few pain episodes a week (positive 24-h testing in 3%) than in patients who only rarely experienced chest pain (positive 24-h testing in 11%).The finding of a positive-related acid infusion test in 16 of the 60 patients, however, points to the importance of this simple technical examination in the exploration of these patients. Obviously, the diagnostic value of the

1984

JANSSENS

GASTROENTEROLOGY

ET AL.

24-h pH and pressure recording needs also to be compared with that of other provocation tests. Some interesting case findings merit special attention. A negative 24-h pH plot (no abnormal numerical parameters) does not exclude reflux as a possible cause of the chest pain as shown in patients 34,36, 43, 45, 48, and 52. Only 2 of 16 patients with a positive-related (producing anginalike chest pain) acid perfusion test but 5 of the 9 patients with a positive-unrelated (causing heartburn) test also had a positive 24-h pH recording. Only 8 of the 16 patients with a positive-related acid perfusion test developed severe motor abnormalities during reflux episodes on the 24-h recording. A positive acid perfusion test may be observed in patients who have severe motor disturbances during pain attacks but who have neither reflux on the 24-h pH plot nor esophagitis on endoscopy with biopsy, as illustrated in patients 50 and 51. When conventional exploration for esophageal disorders (esophagogram, endoscopy with biopsy, manometry, acid perfusion test) reveals no abnormalities, the esophagus may still be the cause of the chest pain as shown in patients 32 and 34. The finding of esophagitis on endoscopy or biopsy in patients with anginalike chest pain is strongly suggestive of the esophageal origin of the pain, as it was shown that the esophagus was the “likely” cause of their pain in 9 of the 15 patients with esophagitis and the “probable” cause in 4 of the 15 patients.

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