The prevalence of abnormal esophageal test results in patients with cardiovascular disease and unexplained chest pain.

The purpose of our study was to assess the prevalence of esophageal test abnormalities in patients with known cardiovascular disease and persistent chest pain. We performed a retrospective review of symptoms, manometry, and provocative test results performed on patients with undiagnosed chest pain. The 220 patients with angiographically determined cardiac disease and persistent chest pain were divided into three groups: coronary artery disease (125 patients), mitral valve prolapse (38 patients), and coronary bypass/angioplasty (57 patients). A comparison group consisted of 159 patients with noncardiac chest pain. All patients underwent esophageal manometry and placebo-controlled provocative testing (acid perfusion test and edrophonium chloride test). The prevalence of esophageal motility disorders in the noncardiac chest pain group (27%) was similar to that in the coronary artery disease (24%), mitral valve prolapse (37%), and coronary bypass/angioplasty (30%) groups. The frequency of nutcracker esophagus (11% to 16%) and diffuse esophageal spasm (2% to 7%) was remarkably constant. The prevalence of any positive provocative result in the noncardiac chest pain group (27%) was similar to that in the coronary artery disease (19%), mitral valve prolapse (32%), and coronary bypass/angioplasty (20%) groups. Furthermore, completely negative results of esophageal investigation occurred in 55%, 62%, 42%, and 59% of the respective patient groups.

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.

Gastric acid secretory capacity falls after repeated within-day pentagastrin testing in fed subjects.

Between-day pentagastrin testing yields highly reproducible stimulated gastric acid output values, but little is known of the reproducibility of repeated within-day pentagastrin tests. We have performed three pentagastrin tests within the 1 day in nine healthy subjects. Within-day tests were 6 hours apart; the first followed an overnight fast and the second and third were both 4 hours after a substantial meal. A further test was performed the following morning, again after an overnight fast, which allowed comparison of within-day and between-day testing. In the second and third within-day tests there was a marked decrease of stimulated gastric acid output, with both maximal and peak acid output decreased to approximately half of the value of the first test (P less than 0.01). By contrast there were no significant differences in the acid output values obtained in between-day tests (both following an overnight fast). Possible mechanisms for the decreased output on repeated within-day testing include alterations in the sensitivity of the gastrin receptor, or some neurohumoral influence secondary to the preceding meal. Future studies of the duration of action of drugs affecting acid secretion may need to take account of these findings.

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)

Acid perfusion test and 24-hour esophageal pH monitoring with symptom index. Comparison of tests for esophageal acid sensitivity.

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.

The Newcastle hepatitis B outbreak. Observations on cause, management and prevention.

During December 1983 and January 1984, an outbreak of hepatitis B occurred among health care workers in the Newcastle area. The probable source was the victim of a motor-bicycle accident who was incubating the illness at the time of his accident. The outbreak led to an extensive contact tracing and immunization programme and suggested that ambulance and police officers were at increased risk of contracting hepatitis B.

The contribution of gastroesophageal reflux to chest pain in patients with coronary artery disease.

OBJECTIVE: To describe the effectiveness of investigating and treating the cause of refractory chest pain in patients with coronary artery disease who are receiving optimal antianginal therapy. DESIGN: Cohort study. SETTING: Tertiary referral center. PATIENTS: Between January 1988 and December 1989, 34 patients were identified as having angiographically proven coronary artery disease and atypical chest pain symptoms despite their having received aggressive medical or surgical antianginal therapy, or both. INTERVENTION: Patients with confirmed acid-related symptoms were treated with high-dose histamine-2 (H2) blockers or omeprazole for 8 weeks in an open-label study. MEASUREMENTS: Esophageal manometry and simultaneous 24-hour pH and Holter studies; global improvement in or disappearance of chest pain. RESULTS: Of the 34 patients, 30 (88%) experienced their identical chest pain symptoms during the study. A total of 164 pain episodes was recorded: 38 (23.2%) correlated with acid reflux; 6 (3.7%) were related to cardiac ischemia; and the remaining 120 (73.2%) had no identifiable cause. Of these 30 patients, 20 (67%) had some of their episodes of chest pain (range, 14% to 100%) secondary to acid reflux. After 8 weeks of vigorous acid suppression, 13 of these 20 patients had marked improvement or resolution of chest pain. Four other patients had ischemia-related episodes of chest pain that responded to more aggressive antianginal therapy. No episodes of acid reflux were clearly followed by ischemic chest pain. One patient had both acid- and ischemic-related episodes of chest pain that were indistinguishable. Overall, 24 of 34 (71%) patients had a definite cause of chest pain identified by combined pH and Holter monitoring. CONCLUSIONS: Gastroesophageal reflux disease is a common, treatable cause of chest pain in patients with coronary artery disease who have atypical symptoms and remain symptomatic despite aggressive antianginal therapy. Combined Holter and 24-hour esophageal pH studies are complementary investigations for elucidating the cause of chest pain in these patients.

Edrophonium provocative test in noncardiac chest pain. Evaluation of testing techniques.

Edrophonium chloride is used frequently as a provocative agent in the assessment of noncardiac chest pain (NCCP). However, the optimum dose and most appropriate method of interpreting test results is controversial. We studied 150 consecutive NCCP patients and 50 age-matched controls who alternately received either 80 micrograms/kg or 10 mg intravenous bolus doses of edrophonium preceded by saline placebo injections. Distal esophageal pressures were measured before and after drug injection in response to ten 5-cc wet swallows. Following 10 mg of edrophonium, 33% of patients and 4% of controls reported chest pain, while 29% of patients and no controls receiving the 80 micrograms/kg dose complained of chest pain. Amplitude changes after either dose were not significantly different for all comparisons, but the duration of response did distinguish the two doses in patients with chest pain. A significantly greater (P = 0.01) increase in distal contraction duration occurred after 10 mg (74 +/- 12%; +/- SE) compared to 80 micrograms/kg dose (43 +/- 6%). However, individual responses to the two doses overlapped considerably. If a positive test is redefined to include both chest pain and manometric changes that are significantly different from controls, the positivity rate changes drastically; 33% to 9% in the 10-mg group and 30% to 3% in the 80-micrograms/kg group. Side effects were similar between doses, but there was a significant (P = 0.02) linear relationship between intensity of side effects and the edrophonium dose per kilogram of body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Diffuse esophageal spasm. A rare motility disorder not characterized by high-amplitude contractions.

Diffuse esophageal spasm (DES) has frequently been described as a motility disorder characterized by simultaneous, high-amplitude contractions. We reviewed the results of esophageal manometry testing on a total of 1480 patients referred to our lab over 36 months. Lower esophageal sphincter (LES) pressure was determined by a mean of four station pull-through. Esophageal body motility was assessed following 10 wet swallows. In our lab a diagnosis of DES is made when greater than 10% but less than 100% of contractions are simultaneous. Manometric findings of DES were rare, with an overall prevalence of 4% (56/1480). Of the 56 patients with a manometric diagnosis of DES, high-amplitude (mean greater than or equal to 180 mm Hg) peristaltic contractions were found in only two (4%). No simultaneous contractions with amplitude greater than or equal to 180 mm Hg were seen. Pressures of simultaneous contractions were consistently lower than peristaltic contractions. A hypertensive LES pressure (greater than or equal to 45 mm Hg) was present in 5/56 DES patients (9%). Poor LES relaxation was found in 7/56 DES patients (13%). We conclude that DES is a rare manometric finding, regardless of the reason for referral, and that the occurrence of high-amplitude contractions in DES is equally rare.

Acid perfusion test: does it have a role in the assessment of non cardiac chest pain?

Using 24 hour pH monitoring as a reference standard, the usefulness of the acid perfusion (AP) test in predicting gastro-oesophageal reflux disease (GORD) was assessed in 71 non-cardiac chest pain (NCCP) patients and 23 endoscopic oesophagitis patients. Of the 71 NCCP patients, 35 had a positive AP test (of whom 20 had an abnormal 24 hour pH) and 36 had a negative AP test (of whom 14 had an abnormal 24 hour pH study). Thus, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the AP test in this group was 59%, 59%, 57%, and 61%, respectively. The corresponding values in the oesophagitis group were 85%, 67%, 94%, and 40%. In the NCCP group when heartburn alone was used as the positive criterion the PPV rose to 74%. When chest pain with or without heartburn was used, however, the PPV dropped to 38%. A 'symptom index' was used to define the number of chest pain episodes that were caused by acid reflux. Only 48% of AP test positive patients had demonstrable acid mediated chest pain. In the NCCP population with a normal oesophageal examination (1) AP test reproduction of chest pain is poorly predictive of GORD; (2) AP test reproduction of heartburn is more predictive of GORD but does not ensure that the chest pain is caused by GORD; (3) a negative AP test does not exclude GORD and (4) only 48% of AP test positive patients have demonstrable acid mediated chest pain. The ambulatory 24 hour pH test may have rendered the AP test obsolete in the assessment of GORD as the cause of NCCP.

Manometry and radiology. Complementary studies in the assessment of esophageal motility disorders.

The relationship between radiological and manometric findings in esophageal motility disorders is poorly understood. Therefore, 20 subjects (4 normal; 13 diffuse spasm; 3 other motility disorders) were studied using synchronous manometry and videofluoroscopy with alternate 5-ml and 10-ml barium swallows. A total of 181 swallows were analyzed. Concordance between manometry and fluoroscopy was excellent for individual swallows (98%), groups of 5 swallows (97%), and final diagnoses (90%). Contraction onset intervals less than 0.8 s apart over 5 cm (velocity greater than 6.25 cm/s) were critical in determining abnormal bolus transit (98% sensitivity and positive predictive value). Radiologically, segmental tertiary activity (complete luminal obliteration) was always associated with disrupted primary peristalsis, but nonsegmental tertiary activity was often seen with normal bolus transit and did not have a specific manometric correlate. Four patterns of interrupted peristalsis radiologically were found--segmental tertiary contractions, a generalized esophageal contraction, absence of motor activity, or discoordinated "to-and-fro" movement. Surprisingly, nearly complete barium clearance occurred by the first two mechanisms in two thirds of swallows. Thus, the authors believe radiology and manometry are both excellent studies for identifying abnormal esophageal peristalsis. In difficult cases, these tests give complementary information because radiology assesses bolus movement while manometry provides quantitative pressure data.

Effect of 'weekend therapy' with omeprazole on basal and stimulated acid secretion and fasting plasma gastrin in duodenal ulcer patients.

The effect of intermittent dosage with omeprazole on basal and pentagastrin stimulated gastric acid secretion and fasting plasma gastrin was assessed in eight duodenal ulcer subjects who were in remission. Omeprazole (20 mg daily) was given for a three day 'weekend' each week for two months. Twenty four hours after the first and eighth weekend, basal and peak acid output were still markedly suppressed (greater than 50%) compared with pretreatment. After the treatment free four days, however (just before the eighth weekend), peak acid output had returned to pretreatment values; basal acid output was still somewhat reduced (mean 3.6 mmol/l) but the difference from baseline was not statistically significant. Fasting plasma gastrin concentration increased slightly but significantly, from a baseline median of 17 pmol/l to 25 and 31 pmol/l respectively, 24 hours after the first and eighth weekends. All but two values (of 16) remained within the reference range. Before the fourth and eighth weekends, and again at 12 days and three months after treatment, gastrin values were not significantly different from baseline. Thus a 'weekend therapy' regimen with this long acting antisecretory compound produces substantial acid suppression, but for only part of the week, with modest and reversible changes in fasting plasma gastrin. It should therefore be suitable for efficacy testing for prevention of recurrence of peptic ulcer or reflux oesophagitis.

Esophageal motility: assessment with synchronous video tape fluoroscopy and manometry.

Synchronous video tape fluoroscopy and manometry of the esophagus was performed in 11 subjects (seven men and four women; mean age, 49 years). Four had normal and seven had abnormal esophageal motility (diffuse esophageal spasm, n = 4; nonspecific esophageal motility disorder, n = 3) that was shown by previous manometry. A digital timer appeared on the video tape recording and marked the manometric tracing synchronously. Alternate 5-mL and 10-mL barium boluses were recorded for a total of 10 swallows per patient. Video tape examinations were reviewed prospectively, and the status of primary peristalsis and presence and severity of tertiary activity were noted. A total of 98 swallows (58 normal, 40 abnormal) were correlated, and a 96% agreement was found in assessing primary peristalsis. Overall results of fluoroscopic examinations of each subject during all swallows showed complete agreement with those of manometry; segregating the swallows into groups of five showed 92% concordance. Severe tertiary activity was invariably seen with abnormal primary peristalsis at fluoroscopy.

Diffuse esophageal spasm: radiographic and manometric correlation.

Diffuse esophageal spasm (DES) is characterized by substernal chest pain, dysphagia, and a manometric pattern of frequent simultaneous contractions with intermittently normal peristalsis. The authors correlated the radiographic and manometric findings in 17 patients with DES to better clarify the role of radiography in the evaluation of this uncommon motility disorder. Incomplete or absent primary peristalsis was observed on radiographs in 13 patients (76%), and mild to severe tertiary activity was seen in 12 patients (71%). The mean estimated thickness of the esophageal wall in patients with DES was 2.6 mm compared with 2.5 mm in an age-matched control group of 17 patients with normal esophageal manometric findings (P greater than .05). The authors conclude that most patients with DES show abnormal esophageal motility on radiographs, although the findings were nonspecific and required clinical and manometric correlation. Esophageal wall thickness was normal in patients with DES and appears to be an overemphasized sign in differentiating DES from other esophageal motility disorders.