With respect to reflux, quite a few of our patients had dyspeptic symptoms, but this reached statistical significance only in the case of dysphagia. Only one patient received omeprazole at study entry. We admit that patients with overt gastrointestinal symptoms were probably referred to a gastroenterologic center, but it is unlikely that patients with severe chest pain were not evaluated in the cardiac clinic and thus were not possible candidates for our study.

Because many variables can be extracted from 24-hour multiple-channel esophageal monitoring, it will always be possible to find single patients who exceed the mean ± 2 SDs of a control group in one or more variables. In this way, the more variables that are considered, the more patients can be expected to have an esophageal disorder. We wanted to overcome this by comparing groups. We also used patients as their own controls when comparing periods of pain with periods of no pain. To detect even the smallest sign of esophageal abnormalities, we amplified the signal from the pain periods by a time-weighted analysis. Still, nothing indicated the presence of esophageal abnormalities. Three of the 63 patients had a reflux index exceeding the mean ± 2 SDs of the controls. None of these 3 patients had an apparent concordance between reflux episodes and chest pain.

The excellent correlation between the diurnal distribution of patient reflux episodes and patient pain episodes was even better when we correlated reflux in the controls with episodes of patient pain. In our opinion, this finding emphasizes that one must be careful not to assume direct associations between variables that may incidentally peak at the same time.

Cause and effect relations may have been wrongly interpreted in many reports on the esophagus and chest pain [1]. Several studies [2, 3], including our own, strongly question such relations. No blinded, randomized trial in which drugs reduced the postulated esophageal abnormalities has yet documented an effect on symptoms. In our opinion, clinical esophageal investigations should therefore be performed only in patients with obvious gastrointestinal symptoms. New techniques must clarify how other mechanisms, such as pain perception [4], with or without the esophagus, may contribute to chest pain in these patients.

Our study was initiated on the basis of our previous findings of a high prevalence of esophageal abnormalities in patients with variant angina [5]. The criticism of being predetermined does not facilitate fruitful progress in this area.