Abnormal esophagocardiac reflex in patients with non-cardiac chest pain

As the mechanoreceptor stimulation of the esophagus activates an esophagocardiac inhibitory reflex, with possible cardiac hypokinetic arrhythmias, we investigated whether patients with non-cardiac chest pain have this reflex, which could represent a source of risk in predisposed individuals during the intraesophageal balloon distension test. Electrocardiogram readings were recorded in nine patients with non-cardiac chest pain (group A), the esophageal origin of which was diagnosed with cardiac and esophageal examinations, in 10 patients with hyperkinetic esophageal motor disorders without chest pain (group B), and in eight normal subjects used as controls (group C), after swallowing solid boluses and during intraesophageal balloon inflation at 100 mmHg for 10 s. The percent variation of the R-R interval from its mean basal value to its highest value observed after stimulation was calculated. Solid swallows induced an increase in heart rate followed by a decrease that was significantly higher in group B than group C, while group A was not significantly different from group C. Balloon inflation induced a significant decrease in heart rate in all groups, but in group A the degree of decrease was significantly lower than in groups B and C. In conclusion, esophageal wall distension, either as a result of solid bolus or balloon inflation, elicits an inhibitory esophagocardiac reflex that is higher than normal in patients with hyperkinetic esophageal motor disorders without pain and lower than normal in patients with non-cardiac chest pain of esophageal origin, who, consequently, have nothing to fear from this procedure.     

Long-term outcome of patients with non-cardiac chest pain.

OBJECTIVE: To assess long-term outcome for patients with chest pain in our environment, to estimate direct resource use, and to evaluate the influence of patient views regarding pain origin on outcome. PATIENTS AND METHODS: All patients referred to our Department between 1994 and 1998 to undergo pH-metry as a result of chest pain were identified. Those detected were subjected to a structured direct interview on the telephone. RESULTS: 104 patients with a follow-up period (since pH-metry) of 3.76 years were evaluated. Thirty nine percent of patients were free from pain (37.5%), and one had died from a seemingly unrelated cause (1%), whereas the rest still suffered from pain. The mean number of visits per patient during the last year was 2.83 to their general practitioner, 1.04 to an specialist, and 0.99 to an Emergency Unit; hospitalisations were 0.26, and ICU admissions 0.09. Patients who trusted medical diagnoses showed better outcomes than those who did not trust or understand them, in association with lower resource use, particularly Emergency Unit use. CONCLUSION: Patients with chest pain had a favourable life prognosis, but 60% still suffer from pain after nearly 4 years of follow-up, which entails a relevant use of health-care resources. Trust in medical diagnosis seemingly influences outcome, and the use of diagnostic procedures to determine pain origin is thus likely beneficial for patient.     

Central sensitization in patients with non-cardiac chest pain: A clinical experimental study

Objective. Patients with non-cardiac chest pain (NNCP) suffer from unexplained and often intractable pain which can pose a major clinical problem. The aim of this study was to investigate nociceptive processing in NNCP patients and their response to experimentally acid-induced oesophageal hyperalgesia using a multimodal stimulation protocol. Material and methods. Ten highly selected patients with NCCP (mean age 43?years, 1?M) were compared with an age- and gender-matched group of 20 healthy subjects. After preconditioning, the distal oesophagus was painfully distended with a balloon using “impedance planimetry”. This method assesses the luminal cross-sectional area of the oesophagus based on the electrical impedance of the fluid inside the balloon. The baseline distensions were done before and after pharmacological relaxation of the smooth muscle with 20?mg butylscopolamine. After baseline distensions, a series of up to 10 mechanical stimuli was performed (temporal summation). The stimulations were repeated after sensitization of the oesophagus induced by acid perfusion. The sensory intensities were assessed during the stimulations and the referred pain area was mapped. Results. At baseline distensions, no differences were seen between patients and controls before and after relaxation of the smooth muscles. The patients tolerated fewer repeated distensions than controls (4.8±0.5 versus 9.1±0.9; p=0.04) and had an increased size of the referred pain areas to the mechanical stimulations (32.9±6.2 versus 64.9±18.3?cm²; p=0.01). After sensitization with acid, the patients developed hyperalgesia (p<0.001), whereas no significant changes were seen in controls. Conclusions. NCCP patients showed facilitated central pain mechanisms (temporal summation and visceral hyperalgesia after sensitization). This could be used in the diagnosis and understanding of the symptoms in these patients.     

The pathophysiology of non-cardiac chest pain

Abstract:   Various underlying mechanisms have been described in patients with non-cardiac chest pain (NCCP). By far, gastroesophageal reflux disease (GERD) is the most common cause and thus requires initial attention when patients with NCCP are managed. Esophageal dysmotility can be demonstrated in 30% of the NCCP patients, but appears to play a very limited role in symptom generation. A significant number of patients with NCCP lack any evidence of GERD and have been consistently shown to have reduced perception thresholds for pain. Peripheral and/or central sensitization have been suggested to be responsible for visceral hypersensivity in NCCP patients. Further understanding of the underlying mechanisms for pain in patients with NCCP will likely improve our current therapeutic approach.     

Cardiac autonomic function and oesophageal acid sensitivity in patients with non-cardiac chest pain

BACKGROUND: Acid reflux can elicit non-cardiac chest pain (NCCP), possibly through altered visceral sensory or autonomic function. The interactions between symptoms, autonomic function, and acid exposure are poorly understood. AIM: To examine autonomic function in NCCP patients during exposure to oesophageal acid infusion. SUBJECTS AND METHODS: Autonomic activity was assessed using power spectral analysis of heart rate variability (PSHRV), before and during oesophageal acidification (0.1 N HCl), in 28 NCCP patients (40.5 (10) years; 13 females) and in 10 matched healthy controls. Measured PSHRV indices included high frequency (HF) (0.15-0.5 Hz) and low frequency (LF) (0.06-0.15 Hz) power to assess vagal and sympathetic activity, respectively. RESULTS: A total of 19/28 patients had angina-like symptoms elicited by acid. There were no significant manometric changes observed in either acid sensitive or insensitive patients. Acid sensitive patients had a higher baseline heart rate (82.9 (3.1) v 66.7 (3.5) beats/min; p<0.005) and lower baseline vagal activity (HF normalised area: 31.1 (1.9)% v 38.9 (2.3)%; p< 0.03) than acid insensitive patients. During acid infusion, vagal cardiac outflow increased (p<0.03) in acid sensitive but not in acid insensitive patients. CONCLUSIONS: Patients with angina-like pain during acid infusion have decreased resting vagal activity. The symptoms elicited by perception of acid are further associated with a simultaneous increase in vagal activity in keeping with a vagally mediated pseudoaffective response.     

Central sensitization in patients with non-cardiac chest pain: a clinical experimental study

OBJECTIVE: Patients with non-cardiac chest pain (NNCP) suffer from unexplained and often intractable pain which can pose a major clinical problem. The aim of this study was to investigate nociceptive processing in NNCP patients and their response to experimentally acid-induced oesophageal hyperalgesia using a multimodal stimulation protocol. MATERIAL AND METHODS: Ten highly selected patients with NCCP (mean age 43 years, 1 M) were compared with an age- and gender-matched group of 20 healthy subjects. After preconditioning, the distal oesophagus was painfully distended with a balloon using "impedance planimetry". This method assesses the luminal cross-sectional area of the oesophagus based on the electrical impedance of the fluid inside the balloon. The baseline distensions were done before and after pharmacological relaxation of the smooth muscle with 20 mg butylscopolamine. After baseline distensions, a series of up to 10 mechanical stimuli was performed (temporal summation). The stimulations were repeated after sensitization of the oesophagus induced by acid perfusion. The sensory intensities were assessed during the stimulations and the referred pain area was mapped. RESULTS: At baseline distensions, no differences were seen between patients and controls before and after relaxation of the smooth muscles. The patients tolerated fewer repeated distensions than controls (4.8+/-0.5 versus 9.1+/-0.9; p=0.04) and had an increased size of the referred pain areas to the mechanical stimulations (32.9+/-6.2 versus 64.9+/-18.3 cm2; p=0.01). After sensitization with acid, the patients developed hyperalgesia (p<0.001), whereas no significant changes were seen in controls. CONCLUSIONS: NCCP patients showed facilitated central pain mechanisms (temporal summation and visceral hyperalgesia after sensitization). This could be used in the diagnosis and understanding of the symptoms in these patients.     

Cerebral potentials evoked by oesophageal distension in patients with non-cardiac chest pain.

Cerebral evoked potential recording was used to study the oesophagus-brain axis in 10 controls and 10 patients with non-cardiac chest pain with a manometric diagnosis of either nutcracker oesophagus or diffuse spasm and a positive edrophonium test. A series of 50 inflations (10/minute; inflation rate of 170 ml/second) of an intraoesophageal balloon (5 cm proximal to the lower oesophageal sphincter) was performed in each subject. Three different inflation volumes were used and were individually determined to cause no sensation, slight sensation, and definite sensation, respectively (volume ranges: 2-8 ml, 5-18 ml, and 8-22 ml). All signals were coded and their quality was scored on a scale from 0 (no recognisable pattern) to 5 (well defined potential of good quality) by four 'blinded' observers. The evoked potential quality scores and amplitude of the major peaks increased significantly (p less than 0.01) with increasing sensation, both in patients and in controls. In the patients, quality score and amplitude of all four peaks of the evoked potentials were lower (p less than 0.05) and latencies of two of the four peaks were longer (p less than 0.02) than in the controls. The volumes of air required to produce the various sensations were lower in the patients (p less than 0.01). When divided by the balloon volume, amplitude and quality of the evoked potential were no longer significantly different between the groups. These results suggest that the increased perception of oesophageal distension in patients with non-cardiac chest pain is caused by altered central processing rather than (functionally) abnormal receptors in the oesophageal wall.     

Investigation and management of non-cardiac chest pain

Recurring substernal chest pain is an important clinical problem, causing anxiety for patients and their physicians because of the fear of possible cardiac disease. The differential diagnosis includes coronary artery disease, oesophageal disorders such as acid reflux disease and motility disturbances, musculoskeletal problems, psychological disorders including panic attacks, and a new 'fly in the ointment'--microvascular angina. History alone usually cannot distinguish cardiac from non-cardiac chest pain. After exclusion of significant coronary artery disease, attention must be turned to oesophageal disorders, which may be seen in as many as 50% of these patients. Oesophageal motility disorders, particularly the nutcracker oesophagus, are common, but the relationship between pain and abnormal contraction pressures is not well established. Provocative tests such as edrophonium (Tensilon) and balloon distension help to identify the oesophagus as the source of chest pain but do not direct therapy. Recent studies with ambulatory oesophageal monitoring suggest that gastro-oesophageal reflux may be a more common cause of chest pain than motility disorders. This is an important finding as acid reflux is a treatable problem, while therapies for motility disorders may only worsen reflux disease. The recent observation that oesophageal disorders are frequently associated and interact with psychological disorders such as anxiety, depression, somatization and panic attacks complicates the evaluation and understanding of chest pain. How these various abnormalities may be linked is an unresolved issue. Increased central nervous system stimulation and altered visceral and/or central pain sensitivity could be the common factors. It is hoped that further research into these areas will lead to new understandings of and possible solutions to the complex problem of non-cardiac chest pain.     

Manometric findings of esophageal motor disorders in 240 Brazilian patients with non-cardiac chest pain

Two hundred and forty Brazilian patients with chest pain and normal cardiac evaluation were submitted to computerized esophageal manometry. Endoscopic examination and/or swallow barium studies had excluded obstructive lesions. Motor disorders were found in 63% of patients; non-specific motors disorders and hypotensive lower esophageal sphincter were the most common. The finding of nutcracker esophagus in only 6% of the patients is a quite different rate from what has been previously described in the literature. Esophagitis was observed at endoscopy in 13.4% of the patients, hiatus hernia in 19.7% and peptic gastric or duodenal ulcer in 4.9%. It should be emphasized that after excluding pain as being of cardiac origin an abnormal manometry result points to the esophagus as the probable site of origin of the pain; esophageal investigation is important for establishing proper treatment for these patients.     

Clinically distinct characteristics in patients younger than 40 years old with non-cardiac chest pain

Background and Aim: Little is known about non‐cardiac chest pain (NCCP) in young patients. We aimed to examine the proportion of gastroesophageal reflux disease (GERD) in young patients with NCCP compared to the average‐aged NCCP patients and to evaluate their symptomatic characteristics and the clinical efficacy of a 2‐week proton pump inhibitor (PPI) trial. Methods: Ninety‐six patients with NCCP ≥ 1/week were classified into the young‐aged (≤ 40 years, n = 38) and the average‐aged groups (> 40 years, n = 58). Typical reflux symptoms were assessed. The patients were defined into a GERD group and non‐GERD group according to reflux esophagitis on esophagogastroduodenoscopy and/or pathologic acid exposure on 24‐h esophageal pH monitoring. Then the patients were treated with 30 mg of lansoprazole bid for 14 days. Results: Nine patients (23%) in the young‐aged group and 22 patients (38%) in average‐aged group were diagnosed with GERD‐related NCCP (P = 0.144). The proportion of typical reflux symptoms was higher in the GERD group compared with the non‐GERD group in both age groups. A PPI test improved symptoms in the GERD group irrespective of age, but this improvement was not observed in non‐GERD group. Conclusions: In young NCCP patients, the prevalence of GERD was relatively low compared to average‐aged NCCP, but the difference was insignificant. The PPI test was very effective in diagnosing GERD in the NCCP patients in both age groups. Therefore, in young NCCP patients, if there is a negative response to a 2‐week PPI trial, the possibility of extra‐esophageal disease origin needs to be considered.     

Study on the contraction pattern of esophageal body in 27 patients with non-cardiac chest pain

<正>Objective To analyze the differences in the contraction pattern of esophageal body in patients with different types of non-cardiac chest pain( NCCP).Methods From January 1,2019 to December 31,2020,46 NCCP patients visiting the First Affiliated Hospital of Zhejiang Chinese Medical University were selected.According to the Lyon consensus and Rome Ⅳ dignostic criteria,     

How do we define non-cardiac chest pain?

Abstract:   Noncardiac chest pain (NCCP) is a heterogeneous disorder associated with substantial health-care costs and resource utilization. NCCP is defined by recurrent episodes of substernal chest pain in patients lacking a cardiac cause after a comprehensive evaluation. The magnitude of the problem is quite high because of fear of serious or life-threatening heart diseases. Patients with chest pain who present for the first time to ambulatory care or to the emergency room, only 11% to 39% are ultimately diagnosed with coronary artery disease. The likely causes of NCCP are numerous and often overlap. Diagnosing NCCP is difficult because NCCP remains a diagnosis of exclusion that encompasses heterogeneous patient populations. First, cardiac ischemic must be excluded and coronary angiography remains the gold standard. Once cardiac causes have been ruled out, a diagnosis of NCCP is made. Mostly, the source for NCCP originates in essence from the esophagus. Gastroesophageal reflux disease (GERD) is the most common esophageal diseases present in patients with NCCP. An initial empiric trail of high-dose acid suppression is the most cost-effective measure in the management of these patients. When a diagnostic workup is chosen, it centers on upper gastrointestinal endoscopy, 24-hr esophageal pH monitoring and esophageal manometry.     

How do we define non-cardiac chest pain?

Abstract: Noncardiac chest pain (NCCP) is a heterogeneous disorder associated with substantial health-care costs and resource utilization. NCCP is defined by recurrent episodes of substernal chest pain in patients lacking a cardiac cause after a comprehensive evaluation. The magnitude of the problem is quite high because of fear of serious or life-threatening heart diseases. Patients with chest pain who present for the first time to ambulatory care or to the emergency room, only 11% to 39% are ultimately diagnosed with coronary artery disease. The likely causes of NCCP are numerous and often overlap. Diagnosing NCCP is difficult because NCCP remains a diagnosis of exclusion that encompasses heterogeneous patient populations. First, cardiac ischemic must be excluded and coronary angiography remains the gold standard. Once cardiac causes have been ruled out, a diagnosis of NCCP is made. Mostly, the source for NCCP originates in essence from the esophagus. Gastroesophageal reflux disease (GERD) is the most common esophageal diseases present in patients with NCCP. An initial empiric trail of high-dose acid suppression is the most cost-effective measure in the management of these patients. When a diagnostic workup is chosen, it centers on upper gastrointestinal endoscopy, 24-hr esophageal pH monitoring and esophageal manometry.     

Factors predictive of gastroesophageal reflux disease and esophageal motility disorders in patients with non-cardiac chest pain

Background: Patients with non-cardiac chest pain (NCCP) are referred for esophageal motility testing and pH monitoring since gastroesophageal reflux disease (GERD) and esophageal motility disorders are frequently encountered in these patients. Our aim was to determine the prevalence and distribution of these disorders and to identify predictors of abnormal esophageal function testing.

Methods: We performed a retrospective study of NCCP patients who presented after a negative cardiac evaluation and underwent esophageal manometry, esophageal pH monitoring and upper endoscopy from January 2010 to January 2017.

Key results: In a total of 177 patients, esophageal motility disorders were diagnosed in 31% and GERD in 35% of the patients. The most common diagnoses were ineffective esophageal motility (IEM) in 14.1%, jackhammer esophagus in 6.8%, diffuse esophageal spasm in 5.1% and achalasia in 2.3% patients. Older age [for every 5-year increment, odds ratio (OR) 1.2 (95% confidence intervals (CI) 1.00–1.3) p?=?.047] and dysphagia [OR 3.8 (95% CI, 1.9–7.5) p?p?=?.032] was predictive of GERD. Abnormal esophageal testing was associated with male gender [OR 2.2 (95% CI, 1.04–4.6) p?=?.039], older age [for every 5-year increment, OR 1.2 (95% CI, 1.03–1.3) p?=?.016] and Caucasian race [OR 3.1 (95% CI, 1.1–8.7) p?Conclusions: Approximately two thirds of patients presenting with NCCP have GERD or esophageal motility disorders. Esophageal function testing in NCCP should be considered in older patients, men, Caucasians and those presenting with dysphagia.     

Clinical usefulness of subgrouping of patients with non-cardiac chest pain according to characteristic symptoms in Korea

BACKGROUND: Non-cardiac chest pain (NCCP) is a heterogeneous disorder. There is controversy about the associations between symptoms and causes in NCCP patients. The purpose of the present study was to evaluate the clinical usefulness of subgrouping according to characteristic symptoms in NCCP patients. PATIENTS AND METHODS: Fifty-eight patients were classified into two groups, as patients with typical reflux symptoms (group I, n = 24) and those without typical reflux symptoms (group II, n = 34). They underwent upper endoscopy, manometry, and 24-h esophageal pH monitoring. RESULTS: Twenty-four (41%) of the patients were diagnosed with gastroesophageal reflux disease (GERD) at upper endoscopy or 24-h esophageal pH monitoring. Eleven (19%) were diagnosed with GERD-associated esophageal motility disorder and 13 (22%) were diagnosed with non-GERD-associated esophageal motility disorder. The two groups did not differ significantly in age, sex, weight, smoking history, history of chronic alcoholism, or the severity, duration and frequency of symptoms. The sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio of group I for GERD-related NCCP were significantly higher than those of group II. Group I had a higher proportion of patients with GERD-associated esophageal motility disorder (55%) than non-GERD-associated esophageal motility disorder (23%). CONCLUSION: Typical reflux symptoms can be used to distinguish patients with GERD-related NCCP from patients with NCCP, and subgrouping according to characteristic symptoms may assist the diagnosis of these patients in Korea.     

Comparison of one-week and two-week empirical trial with a high-dose rabeprazole in non-cardiac chest pain patients

Background:  In patients with non-cardiac chest pain (NCCP), the optimal duration of an empirical trial with a high-dose proton pump inhibitor (PPI) is unclear. We aimed to compare the efficacy of one-week and two-week PPI trial in patients with weekly or more than weekly NCCP and to determine its optimal duration for diagnosing gastroesophageal reflux disease (GERD)-related NCCP.
Methods:  Forty-two patients with at least weekly NCCP were enrolled. The baseline symptoms were assessed using a daily symptom diary for seven days. Also, esophago-gastro-duodenoscopy and 24 h esophageal pH monitoring were performed for the diagnosis of GERD. Then, patients were treated with rabeprazole 20 mg twice daily for 14 days. To assess NCCP improvement during the PPI trial, the first week and the second week symptom diary were kept for 1–7 and 8–14 days. The PPI test was considered positive if a symptom score improved (50% compared to the baseline.
Results:  There was no significant difference for a positive PPI test between GERD-related NCCP group ( n  = 8, 50%) and non GERD-related NCCP group ( n  = 6, 23%) during the first week of the PPI test. However, during the second week, GERD-related NCCP had a higher positive PPI test ( n  = 13, 81%) than non GERD-related NCCP ( n  = 7, 27%) ( P  = 0.001) with a sensitivity and specificity of 81% and 62%, respectively.
Conclusions:  The rabeprazole empirical trial was diagnostic for patients with GERD-related NCCP, and its optimal duration was determined to be at least two weeks.