1. ADVANCING PATIENTS ALONG THE REFLUX CARE CONTINUUM REDEFINING REFLUX CARE A PROACTIVE APPROACH TO MANAGING GERD AND BARRETT’S ESOPHAGUS PRESENTED BY LEVEL 1 NAME LEVEL 2

2. 2 Advancing Patients Along the Reflux Care Continuum | March 18, 2016 GERD MACRO TRENDS 1.Vaezi M, Zehrai A, Yuksel E. Testing for refractory gastroesophageal reflux disease. ASGE Leading Edge. 2012;2(2):1-13. American Society Gastroenterology Endoscopy, Pages 1-4. 2.Shaheen N, Hansen R, Morgan D, Gangarosa L, Ringel Y, Thiny M, et al. The burden of gastrointestinal and liver diseases. American Journal of Gastroenterology. 2006;101:2128-2138. 3.Nimish V. Prescribing proton pump inhibitors: Is it time to pause and rethink? Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison WI. Drugs. 2012;72:437-445. Gastroesophageal reflux disease (GERD) affects up to 40% of the U.S. population in their lifetime 1 $10 billion per year is spent on proton pump inhibitors 2 PPIs have been associated with several complications, including osteoporosis, bone fracture, hypomagnesaemia and pneumonia 3 About 30% of GERD patients fail to respond symptomatically to standard dose PPIs 1 GERD may lead to serious health consequences, including esophagitis, strictures, ulcers and Barrett’s esophagus 1 GERD has a serious effect on healthcare—in terms of both patient outcomes and economic burden

3. 3 GERD PUBLIC HEALTH TRENDS  Symptoms of GERD are heterogeneous, making diagnosis difficult 1  Annual spending on PPIs is a large public health burden 2  Prescribing PPIs without a diagnosis further exacerbates spending 3  Reflux testing is a reimbursed procedure that helps definitively diagnose GERD 4  Insights gained from reflux testing help the physician choose the right therapeutic option or stop unnecessary therapy 4 1.Richter J, Pandolfino J, Vela M, et al. Utilization of wireless pH monitoring technologies: a summary of the proceedings from the Esophageal Diagnostic working Group. Disease of the Esophagus, 2012 August 7. 2.Shaheen N, Hansen R, Morgan D, Gangarosa L, Ringel Y, Thiny M, et al. The burden of gastrointestinal and liver diseases. American Journal of Gastroenterology. 2006;101:2128-2138. 3.Vakil N. Prescribing Proton Pump Inhibitors: Is it Time To Pause and Rethink? Drugs. 2012;72:437-445. 4.Gawron A, Pandolfino JE. Ambulatory reflux monitoring in GERD: Which test should be performed and should therapy be stopped? Curr Gastrenterol Rep. 2013;15:316. Advancing Patients Along the Reflux Care Continuum | March 18, 2016

4. 4 THE PATIENT JOURNEY Advancing Patients Along the Reflux Care Continuum | March 18, 2016

5. 5 CLINICAL RECOMMENDATIONS UTILIZATION OF WIRELESS PH MONITORING TECHNOLOGIES 1 “The optimal work-up for patients being evaluated for GERD symptoms without previous objective evidence of abnormal pathologic acid reflux is ambulatory pH monitoring done ‘OFF’ medication”  Patients who continue to have symptoms when on double dose PPI therapy should be tested “OFF” PPI therapy to help determine which patients do not have pathologic acid gastroesophageal reflux and should stop using PPIs; which patients should be referred for treatment focused on non-GERD etiologies; and which patients may require further testing for optimizing GERD management  Wireless ambulatory pH monitoring should be performed for at least 48 hours, in order to increase the diagnostic yield and reduce false negative studies  pH impedance monitoring can be utilized as an adjunct diagnostic test to support management decisions in patients with objective evidence of GERD Advancing Patients Along the Reflux Care Continuum | March 18, 2016 1.Richter J, Pandolfino J, Vela M, Kahrilas P, Lacy B, Ganz R, et al. Utilization of wireless pH monitoring technologies: a summary of the proceedings from the Esophageal Diagnostic Working Group. Disease of the Esophagus. 2013;26:755-765

6. 6 CLINICAL RECOMMENDATIONS GUIDELINES FOR THE DIAGNOSIS AND MANAGEMENT OF GASTROESOPHAGEAL REFLUX DISEASE 1 “Patients with refractory GERD and negative evaluation by endoscopy or evaluation by ENT, pulmonary, and allergy specialists should undergo ambulatory reflux monitoring”  It has been estimated that failure to control symptoms occurs in up to 40% of patients treated with a PPI  The vast majority of patients with heartburn and regurgitation will not have erosions limiting upper endoscopy as an initial diagnostic test in patients with suspected GERD  In a patient with a negative test “OFF” therapy, PPIs can be stopped and the diagnostic effort should be steered toward non-GERD etiologies  Telemetry capsule pH monitoring offers increased patient tolerability and the option to extend the monitoring period to 48 or perhaps to 96 hours  Catheter-based monitoring allows for the addition of impedance and detection of weakly acidic or non-acid reflux Advancing Patients Along the Reflux Care Continuum | March 18, 2016 1.Katz P, Gerson B, Vela M. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013 Mar;(3):308-28.

7. 7 CLINICAL RECOMMENDATIONS USE OF MOTILITY TESTING IN PATIENTS WITH REFRACTORY GERD HIGH RESOLUTION ESOPHAGEAL MANOMETRY  Manometry is indicated to establish the diagnosis of dysphagia in instances in which a mechanical obstruction (e.g., stricture) cannot be found, especially in cases where a diagnosis of achalasia is suspected 1  Manometry is recommended to evaluate patients with a suspected esophageal GERD syndrome who have not responded to an empirical trial of twice-daily PPI therapy and have normal findings on endoscopy 2  All patients with suspected achalasia who do not have evidence of a mechanical obstruction on endoscopy or esophagram should undergo esophageal motility testing before a diagnosis of achalasia can be confirmed 3  Esophageal manometry is recommended for preoperative evaluation—all patients should undergo preoperative manometry to rule out achalasia or scleroderma-like esophagus 4 Advancing Patients Along the Reflux Care Continuum | March 18, 2016 1.Pandolfino JE, Kahrilas PJ. AGA medical position statement. Clinical use of esophageal manometry. Gastroenterology. 2005;128:207-208. 2.Hiltz SW, et al. AGA medical position statement on management of GERD. Gastroenterology. 2008; 135:1383-1391. 3.Vaezi MF, et al. ACG clinical guideline: diagnosis and management of achalasia. Am J Gastro. 2013;108(8):1238-49. 4.Katz PO, et al. Guidelines for the diagnosis and management of GERD. Am J Gastro. 2013;108:308-328.

8. 8 THE DIAGNOSTIC PATHWAY Reflux testing aids in effective patient management 1  Evaluate patients with normal EGD who are refractory to PPI therapy  Discontinue PPI therapy if GERD is ruled out  Refer patients for assessment of non-GERD causes of symptoms 1.Richter J, Pandolfino J, Vela M, Kahrilas P, Lacy B, Ganz R, et al. Utilization of wireless pH monitoring technologies: a summary of the proceedings from the Esophageal Diagnostic Working Group. Disease of the Esophagus. 2013;26:755-765 Advancing Patients Along the Reflux Care Continuum | March 18, 2016

9. 9 RECOMMENDED APPROACH TO DIAGNOSIS 1,2 Advancing Patients Along the Reflux Care Continuum | March 18, 2016 1.Kleiman DA, Beninato BP, et al. Early referral for esophageal pH monitoring is more cost-effective than prolonged empiric trial of proton pump inhibitors for suspected gastroesophageal reflux disease. J Gastrointest Surg. 2014;26-33. 2.Gawron A, Pandolfino J. Ambulatory reflux monitoring in GERD – Which test should be performed and should therapy be stopped? Published online: 9 March 2013.

10. 10 A SERIOUS DISEASE PROGRESSION Advancing Patients Along the Reflux Care Continuum | March 18, 2016 Timely diagnosis and treatment of GERD is essential, as it is part of a serious disease progression that can lead to Barrett’s esophagus and esophageal adenocarcinoma 1 Dysplastic Barrett’s esophagus Esophageal adenocarcinoma Esophagus damaged by prolonged acid exposure Barrett’s esophagus tissue Normal, healthy esophagus 1.“Complications of Heartburn and GERD.” WebMD. N.p., 2016. Web. 15 Feb. 2016.

11. 11 Advancing Patients Along the Reflux Care Continuum | March 18, 2016 TREATING BARRETT’S ESOPHAGUS SURVEILLANCE VS. RADIOFREQUENCY (RFA) ABLATION A study of patients with confirmed low-grade dysplasia (LGD) Barrett’s esophagus compared the efficacy of surveillance vs. radiofrequency ablation for reducing progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) 1 1.Phoa KN, van Vilsteren FG, Weusten BL, Bisschops R, Schoon EJ, Ragunath K, et al. Radiofrequency ablation vs. endoscopic surveillance for patients with Barrett’s esophagus and low-grade dysplasia: a randomized clinical trial. JAMA. 2014;311(12):1208-1217.

12. 12 Advancing Patients Along the Reflux Care Continuum | March 18, 2016 TREATING BARRETT’S ESOPHAGUS SURVEILLANCE VS. RADIOFREQUENCY ABLATION 1.Phoa KN, van Vilsteren FG, Weusten BL, Bisschops R, Schoon EJ, Ragunath K, et al. Radiofrequency ablation vs. endoscopic surveillance for patients with Barrett’s esophagus and low-grade dysplasia: a randomized clinical trial. JAMA. 2014;311(12):1208-1217. A study of patients with confirmed low-grade dysplasia (LGD) Barrett’s esophagus compared the efficacy of surveillance vs. radiofrequency ablation for reducing progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) 1

13. 13 Advancing Patients Along the Reflux Care Continuum | March 18, 2016 TREATING BARRETT’S ESOPHAGUS SURVEILLANCE VS. RADIOFREQUENCY ABLATION 1.Phoa KN, van Vilsteren FG, Weusten BL, Bisschops R, Schoon EJ, Ragunath K, et al. Radiofrequency ablation vs. endoscopic surveillance for patients with Barrett’s esophagus and low-grade dysplasia: a randomized clinical trial. JAMA. 2014;311(12):1208-1217. The Barrx ™ radiofrequency ablation system reduced progression of low- grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) by 94% 1

14. 14 INNOVATIVE SOLUTIONS BRAVO ™ REFLUX TESTING SYSTEM  Capsule-based pH monitoring system transmits pH data to recorder  96 hours of pH recording increases the identification of both symptoms and acid reflux episodes 1  Allows physicians to document relationships between symptoms and acid reflux events  Catheter-free design is less invasive and allows patients to resume regular activities Advancing Patients Along the Reflux Care Continuum | March 18, 2016 1.Garrean CP, Zhang Q, Gonsalves N, Hirano I. Acid reflux detection and symptom-reflux association using 4-day wireless pH recording combining 48-hour periods off and on PPI therapy. Am J Gastroenterol. 2008;103:1631-1637. Page 1636, Col 2.

15. 15 INNOVATIVE SOLUTIONS DIGITRAPPER ™ PH AND IMPEDANCE TESTING SYSTEM  Helps to correlate extra-esophageal symptoms with reflux and differentiates between acid and non- acid reflux to better identify the root cause of symptoms 1  Improves accuracy of ruling out weakly acidic NERD in order to diagnose functional heartburn 2  Provides confirmation of efficacy of PPI therapy, helping to maximize appropriate treatment 3  Helps identify patients who are likely to benefit from anti-reflux surgery 4 Advancing Patients Along the Reflux Care Continuum | March 18, 2016 1.Sifrim D, Castell D, Dent J, Kahrilas PJ. Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux. Gut. 2004;53(7):1024-1031. Page 1030. 2.Mainie I, Tutuian R, Shay S, et al. Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: a multicentre study using combined ambulatory impedance-pH monitoring. Gut. 2006;55(10):1398-1402. 3.Gawron AJ, Pandolfino JE. Ambulatory reflux monitoring in GERD: which test should be performed and should therapy be stopped? Curr Gastroenterol Rep. 2013;15(4):316 Page 7. 4.Hershcovici T, Fass R. Step-by-step management of refractory gastro-oesophageal reflux disease. Diseases of the Esophagus. 2012, Page 7.

16. 16 INNOVATIVE SOLUTIONS MANOSCAN ™ ESOPHAGEAL MANOMETRY SYSTEM  Provides additional motor correlates for esophageal hypermotility and GERD 1  Enables complete physiological mapping of motor function from pharynx to stomach 2  Helps distinguish patterns of esophageal pressurization to aid in the diagnosis of multiple subtypes of achalasia 3  Esophageal manometry offers useful clinical information before anti-reflux surgery and provides insights that may alter surgical decisions 1 Advancing Patients Along the Reflux Care Continuum | March 18, 2016 1.Mello M, Gyawali C. Esophageal Manometry in Gastroesophageal Reflux Disease. Gastroenterology Clinics of North America. 2014;43(1):83. 2.Kahrilas P. Esophageal Motor Disorders in Terms of High-Resolution Esophageal Topography: What Has Changed? Am J Gastroenterology. 2010;105: 981-987. 3.Bansal A, et al. Has high-resolution manometry changed the approach to esophageal motility disorders? Curr Opin Gastroenterol. 2010;26;344-351.

17. 17 INNOVATIVE SOLUTIONS BARRX ™ RADIOFREQUENCY ABLATION SYSTEM  Patients with low-grade dysplasia have a substantial progression risk 1  The Barrx ™ radiofrequency ablation system is proven to reduce the risk of low-grade dysplasia progressing to high-grade dysplasia or esophageal adenocarcinoma by 94% 1  Endoscopic ablation will move the standard of care of Barrett’s esophagus from surveillance to a cancer prevention strategy 2  Comprehensive results for RFA have been presented in more than 90 peer- reviewed publications 1,3 Advancing Patients Along the Reflux Care Continuum | March 18, 2016 1.Phoa KN, van Vilsteren FG, Weusten BL, Bisschops R, Schoon EJ, Ragunath K, et al. Radiofrequency ablation vs. endoscopic surveillance for patients with Barrett’s esophagus and low-grade dysplasia: a randomizedclinical trial. JAMA. 2014;311(12):1208-1217. 2.El-Serag HB, Graham DY. Routine polypectomy for colorectal polyps and ablation for Barrett’s esophagus are intellectually the same. Gastroenterology. 2011;140:386-388. 3.Shaheen NJ et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med. 2009;360(22):2277-88.

18. 18 THANK YOU Replace this box with Doctor/Practice/Hospital logo Advancing Patients Along the Reflux Care Continuum | March 18, 2016

19. 19 Advancing Patients Along the Reflux Care Continuum | March 18, 2016 RISK INFORMATION Caution: Federal law restricts this device to sale by or on the order of a licensed healthcare practitioner. Rx only. Risk Information: The risks of the Bravo ™ reflux testing system include premature detachment, discomfort, failure to detach, failure to attach, capsule aspiration, capsule retention, tears in the mucosa, bleeding, and perforation. Endoscopic placement may present additional risks. Medical, endoscopic, or surgical intervention may be necessary to address any of these complications, should they occur. Because the capsule contains a small magnet, patients should not have an MRI study within 30 days of undergoing the Bravo ™ reflux test. Please refer to the product user manual or medtronic.com/gi for detailed information.medtronic.com/gi The risks of catheter insertion into the nasal passage associated with the Digitrapper ™ pH and impedance testing system include: discomfort, nasal pain, minor bleeding, runny nose, throat discomfort, irregular heartbeat with dizziness, and perforation. In rare instances, the catheter may be misdirected into the trachea causing coughing or choking, or the catheter may shift up or down causing false results. Medical, endoscopic, or surgical intervention may be necessary to address any of these complications, should they occur. The system is not compatible for use in an MRI magnetic field. Please refer to the product user manual or medtronic.com/gi for detailed information.medtronic.com/gi

20. 20 Advancing Patients Along the Reflux Care Continuum | March 18, 2016 RISK INFORMATION The risks of catheter insertion into the nasal passage associated with the ManoScan ™ ESO high resolution manometry system include: discomfort, nasal pain, minor bleeding, runny nose, throat discomfort, irregular heartbeat with dizziness, and perforation. In rare instances, the catheter may be misdirected into the trachea causing coughing or choking, or the catheter may shift up or down causing false results. Medical, endoscopic, or surgical intervention may be necessary to address any of these complications, should they occur. These systems are not compatible for use in an MRI magnetic field. Please refer to the product user manual or medtronic.com/gi for detailed information.medtronic.com/gi The following are transient side effects that may be expected after treatment: chest pain, difficulty swallowing, painful swallowing, throat pain and/or fever. Complications observed at a very low frequency include: mucosal laceration, minor and major acute bleeding, stricture, perforation, cardiac arrhythmia, pleural effusion, aspiration, and infection. Potential complications that have not been observed include: death. Please refer to the product user manual or medtronic.com/gi for detailed information.medtronic.com/gi US160354 © 2016 Medtronic. All rights reserved. Medtronic, Medtronic logo and Further, Together are trademarks of Medtronic. All other brands are trademarks of a Medtronic company.