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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. References

Aims:

To test the usefulness of upper gastrointestinal investigations and quality of life assessment in Chinese patients with non-cardiac chest pain.

Methods:

Seventy-eight consecutive patients with non-cardiac chest pain underwent upper endoscopy. Eight patients had upper gastrointestinal pathology (10%). The remaining 70 patients received acid perfusion test, oesophageal manometry and 24-h ambulatory oesophageal pH (n=65)/manometry (n=61), and the results were compared with those of healthy controls (n=20). Symptoms and quality of life (SF-36) were assessed by standard validated questionnaire.

Results:

Significant acid reflux symptoms were present in five (5/70, 7%) patients. Abnormal 24-h oesophageal pH, indicating gastro-oesophageal reflux, was found in 19 (19/65, 29%) patients. The percentage of simultaneous contractions was higher and the percentage peristalsis was lower in patients with non-cardiac chest pain when compared with normal subjects by 24-h ambulatory manometry. Patients with non-cardiac chest pain had a lower SF-36 score when compared to controls.

Conclusions:

Typical acid reflux symptoms are uncommon in Chinese patients with non-cardiac chest pain, but abnormal 24-h pH results, indicating gastro-oesophageal reflux, were found in 29% of patients. Ineffective contractions were more frequently found in patients with non-cardiac chest pain by 24-h ambulatory manometry, which may have a bearing on the impaired quality of life in such patients. Upper gastrointestinal investigations are useful for the evaluation of Chinese patients with non-cardiac chest pain.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. References

Non-cardiac chest pain (NCCP) is defined by recurrent episodes of retrosternal pain in patients lacking a cardiac abnormality after reasonable evaluation: angiography remains the gold standard. After a normal coronary angiogram, upper gastrointestinal investigations are the most commonly used tests to evaluate these patients. The diagnostic tests available include upper endoscopy, 24-h oesophageal pH monitoring, oesophageal manometry and combinations of the above, with provocative testing in an attempt to correlate symptoms with diagnostic abnormalities. Upper endoscopy in the absence of dysphagia has not been shown to be useful in the initial evaluation of NCCP.1, 2 However, 24-h pH monitoring, together with a positive symptoms index, was able to identify the oesophagus as the probable cause of NCCP in 50% of patients,3 while baseline manometry plus provocative testing with Tensilon and Bernstein tests identified the oesophagus as the probable cause of NCCP in 28% of patients.3 We have shown previously that 24-h ambulatory pH monitoring and baseline oesophageal manometry are abnormal in 28.7% and 19.4%, respectively, of Chinese patients with NCCP (normal exercise electrocardiogram or cardiac catheterization);4 however, upper endoscopy was not performed and Helicobacter pylori status was not determined in that study. On the other hand, 24-h ambulatory manometry has also been shown to be useful in the evaluation of patients with NCCP.5–10 The prevalence of gastro-oesophageal reflux disease in patients with normal upper endoscopy and NCCP, and the most useful diagnostic test, remain to be defined in our locality. We performed the present study to examine the usefulness of upper endoscopy, Bernstein test, 24-h oesophageal pH monitoring and ambulatory oesophageal manometry for the evaluation of Chinese patients with NCCP. Furthermore, the impact of NCCP on the quality of life of these patients was assessed by a validated Chinese translation of SF-36. 11

METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. References

Patient population

Consecutive Chinese patients with chest pain for at least 12 weeks in the preceding 12 months, who were referred to the Cardiology Division of Queen Mary Hospital for evaluation by cardiac catheterization from November 1998 to February 2000, were assessed for their suitability to enter the study. Patients were included if they had a normal coronary angiogram. They were excluded if they had mitral valve prolapse, left ventricular hypertrophy or abnormal left ventricular function, a past history of gastrointestinal surgery or peptic ulcer disease, connective tissue disorder or had taken H2 receptor blockers, bismuth or proton pump inhibitors in the preceding 4 weeks. Informed written consent was obtained from all patients participating in the study. All patients received an upper endoscopy. During endoscopy, two antral biopsies and one corpus biopsy were taken. One antral biopsy was used for CLO test and the rest were sent for histological examination of H. pylori status by haematoxylin and eosin stains and Giemsa stain if necessary. Specimens were read by experienced pathologists who were blind to all clinical information, including the CLO test results. The definition of H. pylori infection required both tests to be positive. Patients with normal endoscopy then received baseline manometry followed by ambulatory 24-h pH/manometry. Each patient was investigated using a local validated questionnaire to assess symptoms of chest pain, heartburn, acid reflux, dysphagia and dyspepsia; the questionnaire consisted of 14 items graded on a five-point scale as follows: 1 (none), no symptoms; 2 (mild), symptoms can be easily ignored; 3 (moderate), awareness of symptoms but easily tolerated; 4 (severe), symptoms sufficient to cause interference with normal activities; 5 (incapacitating), incapacitating symptoms with an inability to perform daily activities and/or requiring days off work.12 Quality of life was assessed by a locally validated version of the SF-36 questionnaire.11 The SF-36 consisted of 11 items measuring eight aspects of psychological general well-being (physical functioning, role functioning–physical, bodily pain, general health, vitality, social functioning, role functioning–emotional and mental health). Twenty healthy subjects with no upper gastrointestinal symptoms were recruited by advertisement as normal controls; they underwent quality of life assessment, upper endoscopy, baseline oesophageal manometry and 24-h ambulatory pH/manometry. This study was approved by the local ethics committee.

Oesophageal manometry

Oesophageal manometry was performed after an overnight fast with patients in a supine position. Stationary oesophageal motility was determined using an eight-lumen silicone catheter with a distal sleeve (length, 6 cm) for lower oesophageal sphincter measurement (external diameter, 4.7 mm; internal diameter, 0.74 mm) (Dentsleeve Pty Ltd, Belair, Australia). The catheter was passed transnasally into the stomach. Each lumen was continuously perfused with degassed water at a rate of 0.5 mL/min from a low-compliance, pneumohydraulic capillary infusion system (Dentsleeve Pty Ltd, Belair, Australia). After a 5-min rest, the lower oesophageal sphincter was located using the station pull-through technique. The catheter was connected to external transducers with output to an analogue-to-digital converter (Synectics Inc., Stockholm, Sweden). The pressure recordings were stored on disk for off-line analysis using an IBM-compatible computer and commercially available software (Polygram 2.05 for Windows, Medtronic Inc., 1997). Two experienced observers who were blind to the clinical details of the patients interpreted the results. Standard definitions of dysmotility were used.13

Bernstein test

The Bernstein test was performed with patients in a supine position after the manometry study. Normal saline was infused at 3 mL/min for 5 min, followed by 0.1 M hydrochloric acid infused at a similar rate for 15 min. The acid infusion was stopped if patients developed chest pain. The test was performed in duplicate. A test was defined as positive if the patient's usual chest pain was reproduced by acid but not by saline.

Twenty-four-hour ambulatory pH/manometry

Twenty-four-hour ambulatory oesophageal pH/manometry was performed on an out-patient basis directly after stationary manometry. Before each procedure, the pH electrode was calibrated using buffers of pH 1.0 and 7.0. The pH electrode was passed transnasally and positioned 5 cm above the proximal border of the manometrically identified lower oesophageal sphincter. Gastric acidity was confirmed in all patients by passing the probe into the stomach before its final placement above the lower oesophageal sphincter. Patients were asked to take their usual diet, but to avoid alcohol and food or beverages with a pH below 5.0. A diary card and an event recorder button were used to record the time of symptoms during the 24-h ambulatory period. The manometry catheter contained three solid-state pressure microtransducers positioned 5 cm apart and radially offset by 120° (Synectics Medical, Stockholm, Sweden). The transducers were calibrated before each procedure and re-calibrated after the procedure to look for drift. Both the pH and manometry catheters were tied together and passed through the nose into the oesophagus. Their recording ends were connected to an ambulatory recording device (Synectics Medical, Stockholm, Sweden), which sampled pH and motor activity at a rate of 4 Hz. On completion, data were transferred from the recorder to an IBM-compatible personal computer for graphical display and numerical analyses using commercially available software (Multigram 6.31, Gastrosoft Inc.). All recordings were checked visually for technical quality to exclude artefacts. A reflux episode was defined as any fall in distal gastro-oesophageal pH below a threshold of pH 4.0 for more than 10 s. Abnormal gastro-oesophageal reflux was defined by the presence of any of the following: (i) total oesophageal pH < 4 for more than 4.6% of the 24-h period; (ii) total upright oesophageal pH < 4 for more than 7.0% of the total upright period; (iii) total supine oesophageal pH < 4 for more than 4.5% of the total supine period; (iv) total number of reflux episodes > 73; (v) duration of the longest episode > 11.2 min; (vi) number of long reflux episodes (> 5 min) > 4. These figures were the 95th percentile values obtained from 20 asymptomatic volunteers (see below). The percentage peristalsis (percentage of peristalsis in each channel) on 24-h manometry was defined by examining the coordination between the contractions on each channel. Contractions were considered to be coordinated if they occurred in successive channels, one after the other, within a short period of time. The minimal amplitudes used to define effective peristalsis at 15 cm, 10 cm and 5 cm above the lower oesophageal sphincter were 20 mmHg, 25 mmHg and 30 mmHg, respectively, and the maximum time interval allowed for a peristaltic contraction was 5 s. The percentage of simultaneous contractions was defined as the percentage of contractions in each channel which occurred simultaneously with a contraction on another channel. The maximum time interval allowed for simultaneous contractions was 0.3 s.

Statistical analysis

The statistics used included chi-squared test, Fisher's exact test and Student's t-test; the Mann–Whitney U-test was used for data with a skewed distribution. A P value of 0.05 or less was considered to be statistically significant.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. References

Two hundred consecutive patients with NCCP were screened. Ten patients were excluded because of the presence of structural heart diseases. Seventy-eight patients agreed to participate in the study. Upper endoscopy was normal in 70 (90%) patients. For the remaining eight patients, three had duodenal ulcer, three had gastric ulcer and two had endoscopic oesophagitis. The demographic data of the 70 NCCP patients with normal upper endoscopy and the 20 healthy controls are given in Table 1. NCCP patients were significantly older (P < 0.001) than the healthy controls and there were more females in the NCCP group (P=0.019) when compared with the controls. Other parameters, including smoking history, use of alcohol, body mass index and H. pylori positivity, were similar between the two groups.

Table 1.  . Demographic data of 70 patients with non-cardiac chest pain (NCCP) and 20 control subjects Thumbnail image of

Symptoms of heartburn ≥ once per month, acid regurgitation ≥ once per month and dysphagia were present in two (2.9%), three (4.3%) and six (8.6%) patients, respectively. Forty-six (66%) patients reported mild chest pain, 21 (30%) reported chest pain of moderate severity and three (4%) reported severe chest pain.

Oesophageal manometry and Bernstein test

None of the 70 patients with NCCP and normal upper endoscopy had abnormal manometry findings during the baseline motility study, and the Bernstein test was negative in all patients.

Twenty-four-hour ambulatory oesophageal pH study

Five patients had a total recording time of less than 10 h and were excluded from further analysis. Complete 24-h pH data were available in 65 NCCP patients and 20 control subjects. Abnormal gastro-oesophageal reflux was found in 19 patients (19/65, 29%). Only one of the 19 patients (5%) complained of typical reflux symptoms ≥ once per month. Overall 24-h ambulatory pH data were similar between patients with NCCP and controls (Table 2). No patient complained of chest pain during the 24-h recording period.

Table 2.  . Results of 24-h ambulatory oesophageal pH study in 65 patients with non-cardiac chest pain (NCCP) and 20 control subjects. All data presented are mean values ± s.d. Thumbnail image of

Twenty-four-hour ambulatory oesophageal manometry

Complete 24-h manometry data were available in 61 NCCP patients and 18 control subjects (Table 3). The mean number of contractions per minute was insignificantly higher in NCCP patients when compared to controls. There were a significantly higher number of simultaneous contractions in NCCP patients when compared to controls and the difference occurred in all three channels (15 cm, P=0.004; 10 cm, P < 0.001; 5 cm, P=0.02). The mean amplitude of contractions (P=0.04) and the number of contractions per hour greater than 180 mmHg (P < 0.037) were higher 5 cm above the lower oesophageal sphincter in control subjects. The percentage peristalsis was higher in controls than in NCCP patients, with statistical significance (P=0.001) in the proximal channel (15 cm above the lower oesophageal sphincter). No patient complained of chest pain during the 24-h recording period.

Table 3.  . Results of 24-h ambulatory oesophageal manometry in 61 patients with non-cardiac chest pain (NCCP) and 18 control subjects. All data presented are mean values ± s.d. Manometry channels are indicated by the respective distances above the lower oesophageal sphincter Thumbnail image of

Quality of life assessment

Quality of life assessments were available in 68 NCCP patients and 13 control subjects. There was a trend for healthy controls to have higher scores in all domains of the SF-36 quality of life assessment, with statistical significance in physical functioning (P=0.003), role functioning–physical domain (P=0.002) and general health domain (P=0.001). The results are tabulated in Table 4.

Table 4.  . SF-36 questionnaire of 68 patients with non-cardiac chest pain (NCCP) and 13 controls. All data presented are mean values ± s.d. Thumbnail image of

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. References

Upper gastrointestinal pathology was present in 10% of patients with NCCP by upper endoscopy. For the 70 patients with normal upper endoscopy, typical acid reflux symptoms or abnormal gastro-oesophageal reflux on 24-h pH monitoring identified gastro-oesophageal reflux disease as the probable cause of NCCP in five patients and 19 patients, respectively. The majority of patients (18/19, 95%) with abnormal gastro-oesophageal reflux on 24-h pH monitoring did not complain of typical acid reflux symptoms. Simultaneous contractions were more frequent in NCCP patients than in healthy controls.

The usefulness of upper gastrointestinal investigations for the evaluation of patients with NCCP has been questioned previously.14 However, patients with chest pain and a normal coronary angiogram are still commonly referred for oesophageal testing,1, 15–22 and gastro-oesophageal reflux disease remains the most common abnormality found.15 Although upper endoscopy identified upper gastrointestinal pathology in only 10% of patients in our study, we still regard upper endoscopy as a useful screening test, in which specific therapy can be tailored to each individual. It also allows the direct visualization of mucosal injury, as well as guidance to treatment.

Oesophageal manometry combined with provocative testing has been reported to identify oesophageal abnormality in 25–30% of patients with NCCP in Western populations.23 However, the combination of manometry and Bernstein test did not identify any significant motility disorder in our study. Another study performed in Asian patients also reported a low yield for oesophageal manometry in the evaluation of patients with NCCP.24 It has been shown previously that motility abnormalities are more common in patients with chest pain and dysphagia, while patients with chest pain alone have oesophageal motility parameters little different from those of healthy controls.9 The low percentage (9%) of patients with dysphagia may potentially account for the low yield of oesophageal manometry in our study.

Twenty-four-hour ambulatory oesophageal pH monitoring identified 19 NCCP patients (19/65, 29%) with a diagnosis of gastro-oesophageal reflux disease as the probable cause of chest pain, which may respond to acid suppression therapy. Typical acid reflux symptoms were present in only one of the 19 patients with abnormal gastro-oesophageal reflux. This may be due to the difficulty in reporting burning retrosternal discomfort in Chinese patients. There is no direct Chinese translation of the word `heartburn'. Thus the use of typical reflux symptoms to identify gastro-oesophageal reflux disease may result in an underestimation of this condition in Chinese patients. The pathogenesis of NCCP remains unknown, but altered motility of the oesophagus, altered sensitivity of the oesophagus and psychological factors, including anxiety, have been implicated.25, 26 A significantly higher percentage of simultaneous contractions and a lower percentage of effective peristalsis were found in NCCP patients when compared with controls in our study, suggesting that abnormal motility may be important in the pathogenesis of NCCP. The reason why the mean amplitude and the proportion of contractions per hour greater than 180 mmHg were significantly greater 5 cm above the lower oesophageal sphincter channel in control subjects is unclear, but the magnitudes were similar to Western data.

NCCP patients have been shown to have a high proportion of psychiatric disorders, including anxiety, somatization, depression and panic disorder,27 and psychiatric, oesophageal and cardiac disorders may overlap in NCCP patients.28 Quality of life assessment generally revealed lower scores in NCCP patients when compared with healthy controls in our study, indicating an adverse effect of this condition on psychological parameters. Future intervention studies in Chinese patients with NCCP should include an evaluation of the psychosocial aspects of patients by quality of life assessment.

There are two limitations in our study. Firstly, the NCCP patients and control subjects were not totally identical in terms of age and sex distribution. Secondly, it is not possible to attribute the cause of chest pain directly to the presence of oesophageal pH and manometric abnormalities, as no direct symptom correlation was demonstrated during the 24-h recording period in these patients.

In conclusion, typical acid reflux symptoms are infrequently reported in Chinese patients with NCCP. Upper gastrointestinal investigations, including upper endoscopy, 24-h oesophageal pH monitoring and 24-h oesophageal manometry, are useful for the evaluation of Chinese patients with NCCP.

ACKNOWLEDGEMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. References

The authors thank Nurse Specialist Ms M. Chong, Endoscopy Nurse Ms K. W. Wong, Vera S. Y. Tang, Doris M. Y. Lee and Diana K. K. Chang for assistance. This study was supported by the Simon K. Y. Lee Gastroenterology Research Fund and Peptic Ulcer Research Fund, University of Hong Kong.

Footnotes
  1. *Contributed equally to this work.

References

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. METHODS
  5. RESULTS
  6. DISCUSSION
  7. ACKNOWLEDGEMENTS
  8. References
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