Analysis of Intersegmental Trough and Proximal Latency of Smooth Muscle Contraction Using High-resolution Esophageal Manometry Nitin Kumar, MD, Ryan F. Porter, MD, Jake M. Chanin, MD, and C. Prakash Gyawali, MD, MRCP Background and Aims: Intersegmental troughs (ISTs) between striated and smooth muscle contraction segments on high- resolution manometry (HRM) have been linked to hypomotility disorders. We investigated the relationship between ISTs, latency of initiation of smooth muscle contraction, and motor patterns in symptomatic patients and normal controls. Methods: HRM Clouse plots were analyzed in 199 participants (47.2 ± 1.2 y, 112F/87M), categorized into 110 participants with gastroesophageal reflux disease (GERD), 74 symptomatic partic- ipants without GERD, and 15 healthy controls. IST length was measured in centimeters and percentage esophageal length, desig- nated extended when Z20% esophageal length on >30% swallows. Proximal latency was measured as the time interval between onset of skeletal and smooth muscle contraction segments, and designated prolonged when Z4s in Z50% of swallows. Results: ISTs of any length were noted in 74.6% swallows and in 92.5% of participants, with a similar frequency across the 3 groups. ISTs and proximal latency were both longer in the GERD group, especially when Barrett esophagus was present, compared with non- GERD patients or controls (Pr0.03 across groups); extended IST and prolonged proximal latency followed similar trends. On multivariate logistic regression, extended IST predicted GERD [odds ratio (OR), 2.30; 95% confidence intervals (CI) 1.18-4.47], as did lower esophageal sphincter pressure <5 mm Hg (OR, 3.79-3.96; 95% CI 1.77-8.49), after controlling for age and sex; prolonged proximal latency predicted both GERD (OR, 2.03; 95% CI 1.01-4.12) and Barrett esophagus (OR 1.91, 95% CI 1.24-2.94). Conclusions: Measurement of IST and proximal latency add value to HRM analysis, and may be markers of esophageal hypomotility. Key Words: high-resolution manometry, esophageal hypomotility, intersegmental trough, latency (J Clin Gastroenterol 2012;46:375–381) H igh-resolution manometry (HRM) consists of multiple high fidelity pressure recordings displayed using dedi- cated computer software as topographic color-coded contour plots (Clouse plots) of pressure events. 1–5 With esophageal HRM, the 2 sphincters, the upper esophageal sphincter (UES) and the lower esophageal sphincter (LES), are easily identified as pressure bands anchoring the upper and lower extents of the Clouse plot (Fig. 1A). Esophageal peristalsis is visualized as a chain of peristaltic events occurring in sequence, starting with UES relaxation triggered by a wet swallow. This is closely followed by contraction of the skeletal muscle segment in the proximal esophagus, termed segment 1. Peristalsis is then handed off to the smooth muscle peristaltic segments, of which there are 2 in the esophageal body (segments 2 and 3). The LES relaxes preceding arrival of the peristaltic wave, followed thereafter by LES after contraction. HRM is thus an optimal tool to evaluate the functional integrity of esophageal sphincters and segmental characteristics of esophageal peristalsis. 3,6 As the recognition of contraction segments on Clouse plots, aberrations in individual contraction segments and adjacent troughs have been indentified and studied. Atten- tion has focused on the pressure trough between the skeletal and smooth muscle contraction segments, which may be associated with abnormal bolus transit when extended. This has previously been termed “transition zone” and “low esophageal pressure zone,” and is hypothesized to reflect the spatiotemporal hand-off of the contraction wave originating in the striated muscle of the upper esophagus to the con- traction wave propagating distally along the smooth muscle segments. 6–9 When abnormal or visible as a break in the peristaltic contour, the term “intersegmental trough” (IST) has been applied. A related measurement, the time lag between skeletal (segment 1) and smooth muscle (segment 2) contraction segments, has also been recognized as part of the spatiotemporal aberrations in an abnormal IST. 8 This time lag is termed latency of smooth muscle contraction; in recognition of the recently described “distal latency” metric representing the time lag between UES relaxation and the contractile deceleration point, 10 we have chosen to use the term “proximal latency” to describe the time lag between segments 1 and 2. In this study, we used HRM to evaluate the prevalence of ISTs and abnormal proximal latency in symptomatic patients and asymptomatic healthy volunteers. We hy- pothesized that extended ISTs and prolonged proximal Received for publication May 27, 2011; accepted October 14, 2011. From the Division of Gastroenterology, Washington University School of Medicine, St Louis, MO. Presented in preliminary form at the Annual Joint International Meeting of the American Neurogastroenterology and Motility Society Chicago, Illinois, August 2009 and the Annual Meeting of the American Gastroenterological Association New Orleans, Louisiana, May 2010. C. Prakash Gyawali has received research support and speaking fees from Sierra Scientific, Inc. No conflicts of interest exist for Nitin Kumar, Ryan Porter, and Jake Chanin. Sierra Scientific had no role in this study or in manuscript preparation. This study was not funded by Sierra Scientific. Funded in part by a Mentors in Medicine grant (Nitin Kumar) from the Department of Medicine, Washington University School of Medicine. No writing assistance was obtained. Author roles: Nitin Kumar: study design, data collection and analysis, manuscript preparation; Ryan Porter: data collection and analysis, manuscript preparation and review; Jake Chanin: data collection and analysis; C. Prakash Gyawali: study concept and design, data analysis, critical review and manuscript preparation. Reprints: C. Prakash Gyawali, MD, MRCP, Division of Gastro- enterology, 660 S. Euclid Avenue, Campus Box 8124, St Louis, MO 63110 (e-mail: cprakash@wustl.edu). Copyright r 2012 by Lippincott Williams & Wilkins ORIGINAL ARTICLE J Clin Gastroenterol  Volume 46, Number 5, May/June 2012 www.jcge.com | 375