1. Dr Charles Panackel Consultant Gastroenterologist Medical Trust Kochi

2. Introduction 25% of general population experience chest pain at some point of life Of these only 11 -39% have cardiac pain

3. Definition Noncardiac Chest pain can be defined as recurrent angina-like or substernal chest pain believed to be unrelated to the heart after reasonable cardiac evaluation. What is reasonable ??? Unexplained Chest Pain (UCP)

4. Epidemiology The mean annual prevalence of NCCP in the general population is approximately 23-33% NCCP accounts for approximately 2% to 5% of all presentations to hospital emergency Both sexes equally affected Women seek medical attention more commonly

5. Epidemiology Prevalence of NCCP decrease with increasing age. Patients with NCCP are Younger, Consume greater amounts of alcohol, Smoke more, Suffer from anxiety than their counterparts with ischemic heart disease.

6. Natural History The long-term mortality of NCCP is low with reported rates of 1% at 10 yr Morbidity is high At one year after diagnosis, it is seen that 47% limited their activities, 51% were unable to work and 44% still believed they had CAD. NCCP patients have continued high rates healthcare use

7. Differential Diagnosis NCCP Miscellaneous 16% Musculoskeletal 36% Panic disorder 7.5% Esophageal 19% Pulmonary pericardial 5% Gastric/Biliary Pancreatic

8. Chest pain of Esophageal origin Osler in 1892 first suggested that esophagus may be source for Unexplained chest pain 23–80% of Patients with Unexplained chest pain have esophageal abnormalities

9. Differential Diagnosis Esophageal Esophageal dymotility 15-18% GERD 50-60% Functional chest pain of esophageal origin 32 -35% Psychological comorbidity

10. Pathophysiology Chest pain of esophageal origin could be caused by Noxious event in the esophagus, Acid reflux Nonacid reflux Esophageal distension Disturbed motility Abnormal mechanophysical properties of esophagus Sustained contractions of longitudinal muscles Visceral hypersensitivity Decrease in the esophageal nociceptive sensory receptor threshold, Disorder in the nociceptive pathway in the peripheral or central nervous system Autonomic dysregulation Altered central processing of pain stimuli Somatoform disorders

11. GERD and NCCP

12. GERD is by far the most common cause for NCCP

13. Esophageal Dysmotility and NCCP 28% of patients with Non GERD related NCCP No correlation between symptoms and abnormality on Manometry Response to muscle relaxants poor

14. Functional chest pain of presumed esophageal origin Recurrent episodes of substernal chest pain of visceral quality with no apparent explanation. GERD and esophageal dysmotility should be ruled out. Up to 80% of the patients with functional chest pain exhibit other functional disorders Visceral and somatic hypersensitivity

15. Approach to Non Cardiac Chest Pain Cardiac source reasonably ruled out. Other causes ruled out

16. Approach to Noncardiac Chest Pain A careful, thorough history looking for cardiac risk factors, 12-lead ECG, chest radiograph, Serial measurements of cardiac enzymes, If the patient is stable and the etiology is still unclear, echocardiography and TMT Coronary angiogram

17. What should be done next? Endoscopy Ambulatory pH monitoring Combined Impedance-pH testing Esophageal manometry Acid suppression therapy or PPI test.

18. Endoscopy Variable diagnostic yield (10-44%) in NCCP patients Not likely to change management Reserved for patients with NCCP and alarm symptoms (Anemia, Dysphagia, GI Bleed, Persistent Vomiting, Weight loss)

19. Ambulatory 24 hr pH TESTING

20. Sensitivity has ranged from 79% to 96% and specificity from 85% to 100% Can be done on or off PPIs. Diary allows correlation between symptoms and acid reflux.

21. Ambulatory 24 hr pH TESTING Invasive- greater pt discomfort ( occ chest pain) Can miss up to 25% of cases of reflux-not due to “acid” Value in patients with NCCP in whom objective evidence is required Patients who do not respond to PPI

22. Impedance-pH monitoring Has added sensor for impedance. It detects any bolus that enters the esophagus- acid, bile or other. Increases the sensitivity of the probe Same disadvantages as pH probe The gold standard for diagnosis of GERD-related NCCP.

23. Impedance-pH monitoring

25. Esophageal Manometry A thin probe is inserted intranasally and advanced into distal esophagus. Measurements are recorded as the pt is asked to swallow sips of water. Goal is to rule out motility disorders of the esophagus as cause for chest pain.

26. Esophageal Manometry Esophageal motility disorder is seen in approximately one third of NCCP patients. However, the relationship between these motility disorders and chest pain is unclear Considered in patients with a negative work-up for GERD-related NCCP. Role of manometry in NCCP is limited to diagnosis of achalasia cardia

27. Proton pump inhibitor test Empiric trial of double dose PPI therapy for 4 weeks. Readily available Cheap Noninvasive Well tolerated with few if any side effects. Both diagnostic and therapeutic advantages

28. Proton Pump Inhibitor test Two meta-analyses combining 14 studies have validated the PPI test. Sensitivity and specificity of 75-80%. Positive predictive value of ~90%. One study, using a decision analysis model, found the “treat first” approach to be better 11% more diagnostic accuracy 43% reduction in invasive procedures $454 saving per patient as compared to proceeding with endoscopy and pH monitoring.

29. NCCP Esophageal Origin Alarm Symptoms PPI Test Endoscopy Impedence pH Monitoring Esophageal Manometry GERD Other spastic disorders Functional esophageal pain Achalasia Yes No Response No Response Normal Reflux Psychological evaluation

30. Treatment of NCCP of esophageal origin

31. GERD-related NCCP Life style modification Elevation of the head of the bed, Weight loss, Smoking cessation, Avoidance of alcohol, coffee, fresh citrus juice, Medications that can exacerbate reflux such as narcotics, benzodiazepines, and calcium-channel blockers.

32. GERD-related NCCP The efficacy of histamine-2 receptor antagonists (H2 RAs) in GERD related NCCP range from 42% to 52% The efficacy of PPI in controlling symptoms in patients with GERD related NCCP range from 57.1% to 87%

33. GERD-related NCCP PPIs reduce the number of chest pain episodes, emergency department visits, and hospitalizations owing to chest pain Patients with GERD-related NCCP should be treated with at least double the standard dose of PPI until symptoms remit Long-term maintenance PPI treatment has been shown to be highly effective.

34. GERD-related NCCP Lap Fundoplication In carefully selected patients lap fundoplication results symptom improvement in 48 % to 90% of patients with NCCP.

35. NON GERD related NCCP Visceral hyperalgesia is the primary mechanism of pain in patients with non-GERD-related NCCP NCCP patients with spastic esophageal motor disorders respond better to pain modulators than to muscle relaxants. Patients with spastic esophageal disorders should receive a trial of PPI Patients with achalasia respond to muscle relaxants, balloon dilatation, botox injection or heller’s myotomy

36. NON GERD related NCCP Pain Modulators Tricyclic antidepressants (TCAs) Selective serotonin reuptake inhibitors Theophylline Trazodone.

37. NON GERD related NCCP TCA Central neuromodulatory effect Peripheral visceral analgesic effects Calcium channels blocker TCA are started in low dose and titrated to a maximum based on symptom improvement and development of side effects. Because of their anticholinergic side effects, TCAs are commonly administered at nighttime.

38. NON GERD related NCCP Benzodiazepine Alprazolam and clonazepam ameliorate chest pain in patients with NCCP and panic disorder Addiction

39. Psychological evaluation Between 17 and 43% of the patients with NCCP have some type of psychological abnormality. Psychological co-morbidity can lead to Visceral Hypersensitivity. Psychotherapy is useful in patients with NCCP and hypochondriasis, anxiety, or panic disorder.

40. NCCP Esophageal Origin PPI Test Impedance pH Monitoring PPI for 2-4 months Esophageal Manometry Achalasia Increase dose of PPI Other spastic disorders Functional esophageal pain Maintenance PPI Pain Modulators Psychotherapy Relaxants Balloon dilatation Hellers myotomy Response No Response GERD No GERD Normal

41. Summary NCCP is a very common problem with high cost to the healthcare system and significant morbidity to the patient. The most common cause of NCCP is GERD. An empiric trial of high dose PPI therapy is the single most effective approach to dealing with NCCP.

42. Summary Endoscopy is reserved for patients with alarm signs Impedence pH monitoring and Esophageal manometry, has a limited role in NCCP

43. TREATMENT

44. Summary GERD related NCCP is treated with double dose PPI Non GERD related NCCP – the main stay of treatment is Pain Modulators Psychotherapy for patients with psychological comorbidity.

49. Typical angina (80-90% likelihood of obstructive CAD), Atypical angina (40-80% likelihood) Noncardiac (20%-70% likelihood). Typical angina is characterized by the following three characteristics: Retrosternal chest discomfort experienced as pressure or heaviness; Duration of 5-15 min Induced by stress or exertion, a large meal, or exposure to cold and relieved by rest or nitroglycerin.

50. Mechanical distention, acid exposure, temperature, and osmolality-related stimuli can all induce esophageal pain. Esophageal dysmotility may also induce symptoms of heartburn and chest pain. Visceral hypersensitivity has been implicated in the pathogenesis of esophageal pain. Psychiatric disease plays a role in heartburn and chest pain.

51. The entity of noncardiac chest pain (NCCP) was first described during the American Civil War when a Philadelphia physician, Jacob Mendez Da Costa, NCCP

52. NCCP Esophageal Origin Alarm symptoms NoPPI Test Response present No response Impedence pH Measurement GERDNo GERD Esophageal Manom etry Motility disorder Normal Yes E ndoscopy Psychological Evaluation