Diltiazem therapy for symptoms associated with nutcracker esophagus.

UNLABELLED: A randomized double-blind, cross-over prospective trial in 22 patients was designed to evaluate possible effect of an oral calcium channel blocker, diltiazem, on symptoms of chest pain and/or dysphagia in patients with nutcracker esophagus. We studied 22 consecutive patients referred to an esophageal diagnostic center for evaluation of noncardiac chest pain or dysphagia having high amplitude esophageal contractions, 14 of whom completed the study. Diltiazem (60-90 mg qid) was compared with placebo, each being administered for 8 wk. Patients were evaluated with esophageal motility pre- and posttreatment periods and with regular symptom assessment throughout each 8-wk treatment. Active diltiazem therapy resulted in significantly lower (p less than 0.05) mean distal esophageal peristaltic pressure (128 +/- 20 mm Hg; +/- SE) than placebo (158 +/- 16 mm Hg). Mean chest pains scores were significantly (p less than 0.05) lower with diltiazem therapy than with placebo. Only nine of the 14 patients fulfilled presently acceptable criteria for diagnosing nutcracker esophagus, and the diltiazem effect was similar, although not significant, because of the smaller sample. CONCLUSIONS: In this preliminary study involving 14 patients, the oral calcium channel blocker, diltiazem, appeared to improve noncardiac chest pain associated with strong esophageal contraction, the nutcracker esophagus. These improved symptoms were associated with significant decreases in contraction pressure.

Esophageal acid sensitivity in Barrett's esophagus.

Esophageal acid sensitivity was evaluated in 15 patients with Barrett's esophagus and in 15 patients with reflux esophagitis uncomplicated by Barrett's. Patients with Barrett's esophagus had sensitivity to esophageal acid perfusion less frequently than those with uncomplicated reflux esophagitis (66 vs. 100%; p less than 0.05). Moreover, patients with Barrett's esophagus with acid sensitivity took longer to develop pain during acid perfusion (p less than 0.05), and overall, experienced less severe symptoms (p less than 0.01) than those with reflux esophagitis. Over a 2-week period, as judged by diary, the Barrett's group had less frequent (p less than 0.01) and less severe (p less than 0.01) heartburn symptoms than the other patients. These results indicate that patients with Barrett's esophagus have significantly reduced esophageal acid sensitivity and, as a consequence, have an impaired ability to recognize acid reflux.

Barrett's esophagus. A prevalent, occult complication of gastroesophageal reflux disease.

A prospective study of patients with symptoms of gastroesophageal reflux was undertaken to determine the prevalence of Barrett's esophagus and reevaluate the diagnostic approach necessary to detect this complication. Endoscopy with mucosal biopsy was performed in 97 subjects. Twelve (12.4%) were found to have Barrett's esophagus. The sensitivity and specificity of the endoscopic and radiologic examinations for Barrett's esophagus were prospectively evaluated. Endoscopy (92%) was significantly more sensitive than radiology (24%) in detecting Barrett's esophagus (p less than 0.001). The frequency and severity of reflux symptoms among patients determined to have Barrett's esophagus, reflux esophagitis, or normal esophageal biopsies were quantitatively similar in all three groups, except for significantly greater daytime heartburn in those with reflux esophagitis (p less than 0.01). These data indicate that Barrett's esophagus complicates gastroesophageal reflux more often than previously believed.

Solid-phase gastric emptying in patients with Barrett's esophagus.

Delayed gastric emptying as a pathophysiologic factor in patients with gastroesophageal reflux (GER) is controversial. In order to further evaluate this question, we studied a population with severe reflux, specifically, patients with Barrett's esophagus. Solid-phase gastric emptying was measured in 17 patients and in 17 healthy volunteers using radionuclide imaging. Gastric emptying was variable among these patients with 70% normal, 18% rapid, and only 12% slow studies. From these observations, we conclude that delayed gastric emptying is unlikely to be a major factor in the pathogenesis of Barrett's esophagus.

Effects of oral calcium blocker, diltiazem, on esophageal contractions. Studies in volunteers and patients with nutcracker esophagus.

Animal studies have shown that calcium blocking drugs decrease lower esophageal sphincter pressure and inhibit peristaltic amplitude and duration. In a single-dose acute study, we compared the effects of a new oral calcium blocker, diltiazem (90, 120, 150 mg) with placebo in five volunteers and 10 patients with chest pain/dysphagia and high amplitude peristaltic contractions in the distal esophagus--nutcracker esophagus. In volunteers, diltiazem had no effect on esophageal contractions when compared to baseline values or placebo. In contrast, most doses of diltiazem significantly (less than 0.05) decreased amplitude and duration of peristaltic contractions in patients with nutcracker esophagus. Despite adequate blood levels, interstudy analysis was not statistically significant because placebo also decreased these parameters. During an eight-week open-labeled study, diltiazem 90 mg QID significantly (P less than 0.01) improved symptoms of chest pain and dysphagia. Side effects were minimal. Although oral diltiazem has minimal effect on baseline esophageal contractions, our chronic study suggests it may modify transient increases in neuromuscular tone associated with esophageal chest pain. These observations warrant further placebo-controlled studies.