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  • 1. Chest pain of unknown origin (CPUO): role of the esophagus Richard I. Rothstein, MD Chief, Section of Gastroenterology and Hepatology Dartmouth Hitchcock Medical Center Professor of Medicine Dartmouth Medical School
  • 2. Chest Pain of Unknown Origin
  • 3. Prognosis for angina-like pain with normal coronary anatomy Chambers, Prog Cardiovasc Dis 1990 Kemp, Am J Med 1973
  • 4. Functional Status – normal coronary anatomy Ockene N Engl J Med 1980
  • 5. Reflux common in pts with coronary disease Singh, Ann Intern Med,1992; 117:824-30 n = 30, 164 chest pain episodes
  • 6. Abnormal esophageal motility (n = 910) (n = 255) Katz, Ann Intern Med, 1987; 106:593-7
  • 7. Edrophonium Testing 80 mcg/Kg IV
  • 8. Diagnostic Yield of Esophageal Testing Katz, Ann Intern Med, 1987; 106:593-7
  • 9. Intraesophageal Balloon Inflation: Esophageal Hypersensitivity n = 30 NCCP, 30 controls Richter, Gastroenterol, 1986; 91:845-52
  • 10. Provocative Testing Barrish, Dig Dis Sci, 1986; 31:1292-8
  • 11. Subgroups of Patients With Chest Pain With Esophageal Symptoms Isolated Chest Pain Anxiety/Somatization Neurosis
  • 12. Subgroups of Patients With Chest Pain
    • Rare for esophageal pathology
    • Question the “non-cardiac”
    • Reassurance, tincture of time
    Isolated Chest Pain
  • 13. Subgroups of Patients With Chest Pain
    • Heartburn
    • Regurgitation
    • Dysphagia
    • Water brash
    • Nausea
    • Vomiting
    Evaluate or treat for recognized esophageal disorders With Esophageal Symptoms
  • 14. Detection of Esophageal Disorders Potentially Responsible for Symptoms Endoscopy
    • Reflux esophagitis
    • Infectious esophagitis
    • Pill esophagitis
    • Esophageal cancer
    • Esophageal stricture/web
    pH
    • EGD-negative GERD
    Barium swallow ± manometry
    • Esophageal stricture/web
    • Achalasia
    • Esophageal spasm
  • 15. pH testing - Conventional
    • Catheter Based:
    • Patient Intolerance
      • Uncomfortable
      • Pharyngeal and Throat Discomfort
      • Runny Nose
    • Artifact Prone
      • Alters Regular Diet and Activity
                             
  • 16. Bravo pH System™
    • Catheter-Free pH Monitoring System
    • pH Capsule attached to the esophageal wall transmits data to pager-sized Receiver
    • Eliminates uncomfortable 24-hr trans-nasal catheter
    • Allows normal activities, showering and does not interfere with sleeping
  • 17. Bravo pH Capsule with Delivery System pH Capsule Catheter Handle
  • 18. Step 1 Position Bravo Capsule Step 2 Apply Suction Step 3 Advance Pin Step 5 Begin pH Recording Step 4 Release Capsule Capsule Attachment
  • 19. Bravo pH Receiver
    • pH Capsule transmits data to pager-sized Receiver
    pH Capsule Receiver
  • 20. Digital Radio-Telemetry
    • Use Digital Radio-Telemetry
    • Capsule measures pH every 6 sec and transmits data to receiver every 12 sec
    • Keep the receiver within 1m to prevent data loss (range up to 3m)
  • 21.  
  • 22.  
  • 23. Esophageal Testing in 123 Patients with Chest Pain and Normal Coronary Arteriograms
    • Test % Abnormal
    • Ambulatory pH monitoring 82
    • Esophageal motility 29
    • Bernstein Test 10
    • Edrophonium 6
    • Endoscopy 5
    • Balloon distention 4
    • Treadmill with pH monitor 4
    Chenan P, et al Dis Esophagus 1995; 8:129
  • 24. Atypical presentations of GERD
    • Pulmonary
    • Asthma
    • Bronchitis
    • Aspiration pneumonia
    • Apnea
    • Atelectasis
    • Pulmonary fibrosis
    • ENT
    • Hoarseness
    • Cough
    • Globus
    • Halitosis
    • Vocal cord granuloma
    • Laryngeal stenosis
    • Laryngeal cancer
    • Loss of dental enamel
    • Sinusitis, otitis
    Chest Pain
  • 25. Esophageal Chest Pain Work-Up
    • Traditionally
      • Endoscopy
      • pH probe
      • Manometry
      • Provocative testing
    • Emerging role for up-front empiricism
  • 26. PPI Trial in GERD Patients With Non-Cardiac Chest Pain
    • 37 patients with daily chest pain and negative cardiologic evaluation
    • Categorized as GERD+ or GERD- by EGD and pH study
    • Randomized to omeprazole (40 mg q AM and 20 mg q PM for 7 days) or placebo then crossed over after washout
    • 50% reduction in symptoms constituted positive response
    Fass et al. Gastroenterology . 1998;115:42-49.
    • GERD-Positive
    • n=23
    • 78% response
    • GERD-Negative
    • n=14
    • 14% response
  • 27. Characteristics of the Patients
    • Patients with NCCP
    • GERD-positive GERD-negative
    Fass R, et al Gastroenterol 1998; 115:42-9 Subjects 23 14 Age (yr) 58.2± 2.3 61.6± 2.8 Range (yr) 35-76 47-83 Sex (M / F) 22 / 1 14 / 0 Upper endoscopy results Normal (grade 0-1) 7 14 Erosive esophagitis (grade 2-5) 16 Ambulatory 24-h esophageal pH monitoring (%)* Mean 9.6± 1.8 1.2± 0.3 Range 0.5-29.1 0.0-2.9 *% total time pH<4
  • 28. Enrollment Upper endoscopy & Ambulatory 24-hour esophageal pH monitoring GERD + GERD - Baseline symptom assessment Randomization Placebo Omeprazole (40 mg AM + 20 mg PM) Washout period Baseline symptom assessment Omeprazole Placebo (40 mg AM + 20 mg PM) Week 1 Week 2 Week 3 Week 4 Week 5 Fass R, et al Gastroenterol 1998; 115:42-9
  • 29. Omeprazole Test in NCCP
    • 18/23 GERD-positive (78%)
    • 2/14 GERD-negative (14%)
    • Sensitivity 78.3%
    • Sensitivity 85.7%
    • 59% reduction in number of diagnostic procedures
      • ($573 savings per patient evaluation)
    Fass R, et al Gastroenterol 1998; 115:42-9 Positive OT
  • 30. Results of Economic Analysis
    • Conventional
    • work-up OT Difference % Change
    Cost ($) 2025 1452 573 28 Reduction No. of endoscopies/ 1000 patients 1000 190 810 81 Reduction No. of ambulatory 24-hr pH tests/ 1000 patients 650 140 510 79 Reduction No. of esophageal motility tests / 1000 patients 310 470 -160 52 Increase Total no. of diagnostic procedures / 1000 patients 1960 800 1160 59 Reduction Fass R, et al Gastroenterol 1998; 115:42-9
  • 31. Omeprazole Test in NCCP
    • Generalizability?
      • Male, veteran population
      • High % esophagitis, GERD symptoms
      • Pain pattern of frequent chest pain (≥ 3x/wk)
      • Small numbers, short course treatment
    • Medication dosing, strength
    • Role of endoscopy
      • Reassurance factor
      • Once-in-a-lifetime Barrett’s check
    Issues
  • 32.  
  • 33. Los Angeles (LA) Grade Classification of Erosive Esophagitis LA Grade C LA Grade D One or more mucosal breaks no longer than 5mm, not bridging the tops of mucosal folds One or more mucosal breaks bridging the tops of mucosal folds involving <75% of the circumference One or more mucosal breaks bridging the tops of mucosal folds involving >75% of the circumference One or more mucosal breaks longer than 5mm, not bridging the tops of mucosal folds LA Grade B LA Grade A Lundell et al. Gut. 1999;45:172-180.
  • 34. The spectrum of heartburn frequency and severity is similar in GERD patients with and without esophagitis Severe Moderate Mild Severity of heartburn Smout 1997 Patients without esophagitis Patients with esophagitis
  • 35. GERD Therapeutic Options Prokinetics OTC or prescription H2RAs “ First - aid” : Life-style modifications and antacids Endoscopic techniques (plication, RF, implant) Surgery (Lap Nissen fundoplication) OTC or prescription PPIs Treatments
  • 36. Life-style Modifications Reduce weight Elevate head of bed Stop smoking Eat small meals, no late meals, reduce fat Consider alternatives to reflux-promoting drugs e.g., theophilline, anticholinergics
    • Avoid reflux-promoting agents e.g, alcohol, coffee; some foods
    • Not evidence-based
    Modifications
  • 37.  
  • 38. POSITION AND REFLUX Right side down Left side down pH pH 0 0 4 4 8 8 (Katz,LC. Et al, J Clin Gastro 1994;18(4):280-3
  • 39. GERD HEALING AND ACID CONTROL (Bell et al. Digestion. 1992;51(suppl 1):59-67.) Patients Healed (%) Duration Intragastric pH >4.0 (Hours) 100 80 60 40 20 0 2 4 6 8 10 12 14 16 18 20 22
  • 40. Medical Rx Outcomes (with H2RAs)
    • Relief of symptoms 50%
    • Healing esophagitis <50%
    • Prevent complications ---
    • Remission 25%
  • 41. Medical Rx Outcomes (PPIs)
    • Relief of symptoms 85-95%
    • Healing esophagitis 85-95%
    • Prevent complications 80%
    • Remission 90%
  • 42. GERD: Endoscopic Therapies
    • Endoscopic suturing – i.e., Endocinch (this leads to partial thickness plication)
    • Full thickness plication – i.e., NDO
    • Radiofrequency ablation – i.e., Stretta
    • Injection therapy with augmentation of LES – i.e., Enteryx
    • Bulking procedures with augmentation of LES – i.e., Gatekeeper
  • 43. BARD EndoCinch Suction of tissue just beneath z-line Needle with pre-loaded suture advanced Cinching/cutting catheter advanced to tissue Final appearance of plication in cardia
  • 44. NDO Plicator™ Plicator and gastroscope retroflexed Arms opened, tissue retractor advanced Gastric wall retracted, arms closed. Single, pre-tied implant deployed. Full-thickness plication completed 1 2 3 4 5
  • 45. Antegrade technique Balloon inflation Needle deployment 1 cm above z-line
  • 46. Injection at the Z-Line
  • 47. Gatekeeper™ System Stabilize site Expansion Deliver prosthesis Create pocket Access pocket
  • 48. MAINTENANCE THERAPY OF GERD Omeprazole vs surgery (Lundel et al: J Am Col Surg, 192:172, 2001)
  • 49. Outcomes of Atypical GERD Symptoms Treated by LNF
    • 150 consecutive laparoscopic antireflux surgery patients
    • 35 treated primarily for atypical symptoms
    So et al. Surgery . 1998;124:28-32.
    • Pulmonary Sx
    • Asthma
    • Chronic cough
    • n=16
    • n=12
    • Pharyngo/laryngeal Sx
    • Hoarseness
    • Globus
    • Halitosis/Dental
    • Sore throat
    • n=9
    • Independent observer assessment
    • GERD by EGD, ambulatory pH, or free reflux on x-ray (n=2)
    • 86% used OTC GERD meds; not dominant symptom in any
    • ENT/cardiological evaluation excluded other causes
    Atypical chest pain or epigastric pain
  • 50. Outcomes of Atypical GERD Symptoms Treated by LNF Symptom Score So et al. Surgery . 1998;124:28-32. Typical Symptoms (n=115) Improvement 6.2 points Atypical Symptoms (n=35) Improvement 4.4 points
    • Atypical Sx Improvement
    • Overall 58% of patients
      • Pulmonary 48%
      • Atypical chest pain 58%
      • Pharyngo/ laryngeal 76%
    Preoperative Postoperative
  • 51. Esophageal Chest Pain
    • GERD related
    • Motility related
    • Esophageal hyperalgesia
  • 52. Esophageal Hyperalgesia
    • “ Irritable esophagus”
    • Abnormal nociception
    • Lower threshold for pain
  • 53. Esophageal Hyperalgesia
    • Noxious stimulus in esophagus
    • Decrease in nociceptor threshold
    • Disorder of CNS nociceptive pathway
  • 54. Chest Pain - Imipramine
    • 50 mg nightly for 3 wks
    • 52% reduction in chest pain episodes
    • Suggested visceral analgesic effect
        • Cannon R, et al. N Engl J Med 1994; 330:1411-7
    • 15 healthy male volunteers
    • Balloon inflation volume at pain threshold higher on imipramine
        • Peghini PL, et al. Gut 1998; 42:807-13
  • 55. NCCP Non-GERD Esophageal Therapies
    • Calcium channel blockers
    • Anticholinergics
    • Nitrates
    • Botox
    • Antidepressants (Imipramine, Trazodone)
    • Octreotide
    • Bougienage
    • 5 HT 3 antagonists
  • 56. Initial Perception Threshold (S1) Before and 40 Minutes after Octreotide Injection Base 40 min 0 10 20 30 >30 CC p < 0.02 Johnson BT, et al Am J Gastroenterol 1999; 94:65-70
  • 57. Maximally Tolerated Pain Threshold (S2) Before and 40 Minutes after Octreotide Injection Base 40 min 0 10 20 30 >30 CC Johnson BT, et al Am J Gastroenterol 1999; 94:65-70
  • 58. Overlap Syndrome of Altered Pain Sensitivity
  • 59. Approach to the NCCP Patient
    • Take a history
    • Exclude coronary / cardiac disease
    • Check for musculoskeletal disease
    • Look for GERD
    • Check for dysmotility
    • Consider esophageal hyperalgesia
    • Collaborative management