Manometric Abnormalities in the Postural Orthostatic Tachycardia Syndrome: A Case Series
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- Huang, R.J., Chun, C.L., Friday, K. et al. Dig Dis Sci (2013) 58: 3207. doi:10.1007/s10620-013-2865-9
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Postural orthostatic tachycardia syndrome (POTS) is a rare disease that is believed to be mediated by dysautonomia. Gastrointestinal complaints in POTS patients are common and disturbing but not well characterized.
We hypothesized that gastrointestinal dysmotility may be contributory to these symptoms.
We studied 12 POTS patients who presented with gastrointestinal symptoms to a tertiary referral center. Gastrointestinal symptoms were quantified using a previously validated symptom questionnaire. All patients underwent gastroduodenal manometry (GDM); select patients also underwent further testing including esophageal manometry (EM), anorectal manometry (ARM), plain abdominal radiography (AXR), abdominal computed tomography (CT), gastric emptying studies (GES), and colonic transit time (CTT) studies.
The four most common symptoms were bloating, constipation, abdominal pain, and nausea/vomiting, all experienced by greater than 70 % of patients. On GDM testing, 93 % of patients demonstrated signs of neuropathy, and the most common abnormalities observed included bursts of uncoordinated phasic activity in both fasting (59 %) and post-prandial (42 %) states, low contractility in the post-prandial state (67 %), and lack of post-prandial pattern (42 %). A total of 67 % of patients undergoing EM and 86 % of those undergoing ARM demonstrated abnormalities consistent with dysmotility. On AXR or CT, 58 % demonstrated either dilated intestinal loops or air-fluid levels. On CTT 80 % demonstrated delayed colonic transit, while on GES 60 % demonstrated delayed gastric emptying.
In this cohort of POTS patients with gastrointestinal symptoms, there is a high prevalence of abnormal manometric and radiographic findings suggestive of dysmotility.
The postural orthostatic tachycardia syndrome (POTS) is a rare and incompletely understood pathophysiologic condition characterized by symptoms of orthostatic intolerance (such as lightheadedness, dizziness, visual blurring, and frank syncope) in response to postural stress, accompanied by a hallmark excessive increase in heart rate. First described in the early 1990s, POTS is believed to be a rare disease without epidemiologic description. The disease is usually diagnosed in otherwise healthy and younger individuals, with a typical presentation by the third to fourth decade of life [1, 2]. As with other syndromes of orthostasis, females are predominantly affected by a ratio of 4–5:1 . Although the etiology of POTS is unknown, it is believed to be mediated by autonomic dysregulation.
In addition to orthostatic intolerance, POTS often presents with clinically disturbing gastrointestinal complaints. In one large series, nausea, bloating, abdominal pain, constipation, and diarrhea were all variously described by anywhere between 15 and 40 % of POTS patients . Mechanisms underlying these gastrointestinal complaints are unknown, and have not been previously studied. As the orthostatic symptoms of POTS are believed to be mediated by autonomic dysfunction, we hypothesized that the gastrointestinal complaints of POTS may also be mediated by autonomic dysfunction, presenting as perturbed motility.
The aim of this series was to describe the clinical, manometric, and radiographic findings of 12 consecutive POTS patients with gastrointestinal symptoms referred to a tertiary medical center.
Following Stanford University Institutional Review Board for Human Subjects Research approval, we reviewed the medical records of all patients with the diagnosis of POTS referred to Stanford University Medical Center between January 1, 2008 and June 30, 2012. The diagnosis of POTS was made by a specialized cardiologist (KF) if a patient met the following criteria: (a) symptoms of orthostatic intolerance for more than 6 months, (b) baseline sinus rhythm without arrhythmia or known structural heart disease, (c) a sustained heart rate increase of greater than 30 beats per minute or an increase to 120 beats per minute or greater within the first 10 min of tilt table testing, and (d) absence of other overt cause of orthostatic symptoms or tachycardia. A total of 78 patients diagnosed with POTS were identified. Of these 78 patients, a total of 12 (15 %) with gastrointestinal complaints were referred to a gastroenterologist (GT) for further assessment. Based on their presenting symptoms, all of these patients received gastroduodenal manometry (GDM); a portion of the cohort also received esophageal manometry (EM), anorectal manometry (ARM), or other radiographic studies.
Data retrieved from the patients’ medical records included demographics, age at symptom onset, family history, underlying pathologies, presenting symptoms, the presence of any extra-intestinal manifestations, results of manometric studies, and results of radiographic studies.
Assessment of Symptoms
We semi-quantitatively assessed our patients’ symptoms in terms of frequency and severity, using a gastrointestinal questionnaire that was previously used and validated in our center [5, 6]. According to this scoring system, symptom frequency and severity range from 0 to 3, with 0 representing no occurrence, 1 representing mild symptoms <50 % of the time, 2 representing moderate symptoms 50–75 % of the time, and 3 representing severe symptoms 75–100 % of the time. We report the median score for each symptom in our patients.
Gastroduodenal manometry was conducted after an overnight fast. This study was carried out using an 8-lumen perfusion catheter introduced using combined endoscopic and fluoroscopic guidance. Briefly, a proximal enteroscopy was performed, and a super-stiff guide wire (Boston Scientific, Natick, MA) was placed into the proximal jejunum. The endoscope was then removed, and, under fluoroscopy, the motility catheter was thread over the guide wire to reach beyond the ligament of Treitz. The catheter extruding from the patient’s mouth was perfused with water at a rate of 0.1 mL min−1 by a pneumo-hydraulic pump and then connected to a transducer (Medtronic, Minneapolis, MN), which recorded pressure profiles from the distal antrum, pylorus, and the duodenal C-loop. Pressure activity was recorded continuously in each patient for 3 h before (fasting period) and 2 h after (fed period) ingestion of a mixed solid–liquid meal .
Myopathy was suggested by the presence of (1) low-amplitude contractions (<10 mm Hg in the small bowel) during phase II of the fasting state; (2) low-amplitude contractions during phase III of the fasting state; (3) low-amplitude waves in the antrum (<40 mm Hg) during the fed state; (4) low-amplitude waves in the small bowel (<10 mm Hg) during the fed state.
Enteric neuropathy was suggested in the fasting state by (1) bursts of phasic activity of abnormal duration (>2 min), amplitude (>20 mm Hg), and frequency (10–12/min) that are non-propagating and distinct from phase III; (2) sustained (>30 min) poorly coordinated phasic activity isolated to 1 or more segments; (3) lack of propagation, incomplete propagation, or retrograde propagation of phase III complexes; (4) prolonged (> 3 min) increase in basal tone (>30 mm Hg) during phase III activity. Enteric neuropathy was suggested in the fed state by (1) persistent fasting pattern after a meal; (2) bursts of non-propagating phasic contractions; (3) premature return of phase III within 90 min after a meal; (4) broad-based clusters of contractions occurring in the presence of increased tone.
Esophageal Manometry and Anorectal Manometry
Patients underwent radiographic studies based on clinical history and symptom presentation. Seven patients (58 %) underwent abdominal radiography (AXR), six patients (50 %) underwent abdominal CT (CT), five patients (42 %) underwent gastric emptying studies (GES), and five patients (42 %) underwent colonic transit time studies (CTT). Conventional methods, as reported in the literature, were used for all such studies.
Gastroduodenal manometric abnormalities in patients with postural orthostatic tachycardia syndrome (POTS) (N = 12)
Gastroduodenal manometric abnormalities
Bursts of uncoordinated phasic activity
Lack of postprandial pattern
Abnormal duration and/or propagation of phase III
Lack of propagation, incomplete or retrograde propagation of phase III of the MMC
Premature return of phase III after meal
Cluster of contractions of longer than 30 min
Increased tone during phase III
Nonpropagated clusters (minute) contractions
Patterns of gastroduodenal abnormalities in patients with postural orthostatic tachycardia syndrome (POTS) (N = 12)
Gastroduodenal abnormalities suggestive of
No. of patients
Neuropathy without evidence of myopathy
Neuropathy with evidence of myopathy
Normal without evidence of either neuroapthy or myopathy
Esophageal Manometry and Anorectal Manometry
Six patients underwent EM because of heartburn and dysphagia. Two (33 %) of these patients had normal patterns. Low, absent, or impaired esophageal peristalsis was the most common abnormal finding (observed in 50 % of patients), followed by hypotension of the lower esophageal sphincter (observed in 33 % of patients).
Anorectal manometric abnormalities in patients with postural orthostatic tachycardia syndrome (POTS) (N = 7)
Anorectal manometric abnormalities
Hypotensive internal sphincter
Hypotensive external sphincter
Absent anorectal inhibitory reflex
Impaired balloon sensation
Impaired balloon expulsion
Because of periumbilical abdominal pain, bloating and nausea/vomiting, 12 patients underwent either AXR or CT. Seven patients (58 %) demonstrated signs of pseudo-obstruction (dilated loops of bowel and/or air-fluid levels) on at least one imaging study. Of the five patients with postprandial nausea who underwent GES, three (60 %) demonstrated delayed gastric emptying. Of five patients with constipation who underwent CTT, four (80 %) demonstrated delayed colonic transit (colonic inertia).
Nearly two decades after its first description, POTS remains a rare and imprecisely understood disease affecting a predominantly young, female, and otherwise healthy population. It is increasingly apparent that POTS has a diverse set of manifestations outside of the cardiovascular system, including the gastrointestinal system. In this study, we evaluated the hypothesis that gastrointestinal complaints in POTS may be associated with abnormal motility patterns.
On GDM, 93 % of patients demonstrated at least one manometric abnormality, 75 % demonstrated at least two abnormalities, and 58 % demonstrated three or more abnormalities. As we lacked a contemporaneous control group, we employed previously published GDM data from studies of chronic dysmotility to characterize patterns of dysmotility [10, 11, 15]. In one large historical series of patients diagnosed with chronic dysmotility, abnormal patterns on GDM were found in 82 % of patients, similar to our series . As improvements in symptoms have also been associated with normalization on GDM testing, it is possible that POTS patients may demonstrate normalization in GDM testing with appropriate symptom control .
Abnormal patterns were also observed on EM and ARM. On EM, absent or impaired peristalsis and decreased lower esophageal tone have been described in studies of hereditary hollow visceral myopathy and chronic intestinal pseudo-obstruction [6, 17]. On ARM, absence or impairment of the inhibitory reflex in response to rectal distention is strongly suggestive of loss or impaired ganglionic control of the colon and neuropathy [18, 19]. Sphincter hypotension may also be a sign of perturbed neural regulation, as normal sphincter tone is maintained through a combination of sympathetic lumbar and parasympathetic sacral outflow and local nerve pathways in the gut wall .
On radiographic studies, 58 % of patients demonstrated dilated loops of gut and/or air-fluid levels on either AXR or CT. Although these radiographic findings are certainly suggestive, their absence does not exclude dysmotility. Previously, it has been shown that manometric abnormalities often precede radiographic evidence of dysmotility, and the appearance of dilated gut or air-fluid levels usually signifies a fairly advanced degree of disease . A total of 60 % of patients undergoing GES demonstrated delayed emptying, and 80 % of patients undergoing CTT demonstrated signs of colonic inertia. These data suggest that the perturbations in POTS involve multiple segments of the gut.
To our knowledge, this is the first observational study of the gastrointestinal manifestation of POTS, and combines clinical symptom assessment with objective manometric and radiographic data of a rare disease entity. A number of important limitations exist in this study. First and foremost, this study is limited by its inherent design as a retrospective, consecutive, case series without a control or comparison group. As such, the results are only observational in nature, and can provide only weak evidence of causality because they are particularly prone to bias and confounding. In our study, we attempted to address the lack of a control group by using previously published manometric data as reference, but this approach can only provide for limited analysis. Furthermore, the referral nature of recruitment makes the study vulnerable to referral bias, as only patients with symptoms severe enough to warrant seeking care from a gastroenterologist were studied. The sample size of 12 is also small, and does not provide for statistical analysis. Finally, the study does not include any description of management of symptoms, and it is unclear if improvement in symptoms would lead to normalization in manometric or radiographic testing.
In summary, we present a retrospective case series demonstrating a pattern of manometric and radiographic abnormalities in a cohort of symptomatic POTS patients.
Conflict of interest