NONCARDIAC CHEST PAIN

1. NONCARDIAC CHEST PAIN A nontraditional approach to diagnosis and management. Michael S. Morelli, MD

2. OBJECTIVES 1.)For the listener to have a generalized understanding of different esophageal testing methods for NCCP. 2.)To obtain a general overview of the evidence supporting the use of such testing methods-their usefulness and limitations. 3.)To gain an appreciation of potential tx methods for patients we encounter with NCCP. 4.)To create an evidence based algorithm for the work up and treatment of NCCP.

3. CLINICAL CASE HPI • 49 y/o wm to ed with ss cp radiating down his left arm. Intermittent x 6 mo- rest or exertion. Bad episode morning of presentation- admitted to card for evaluation. MEDS-hctz 25mg qd ALL-nkda SOC HX-1ppd for 25 yrs, occ etoh, no drug use FAM HX-father MI age 65 ROS- no f/n/v/c or weight loss, dysphagia, or heartburn

4. CLINICAL CASE PE • VITALS-afebrile with pulse 78 and bp 148/95 • HEENT-unremarkable • RESP-bilaterally clear • CV-rrr with NL S1 and S2 no m/g/r • ABD-nt/nd/good bs/no organomegaly • EXTRE-no edema • CHEST-no reproducible cp with chest palpation

5. CLINICAL CASE • LABS • Trop I < 0.1, ck 76, lytes and cbs wnl, cxr c/w copd. • Ekg lvh that was mild but otherwise wnl • HOSPITAL COURSE • Pt ruled out for myocardial infarction. • Since cp at rest pt had cath-showed patent arteries. • Cp continued but pt discharged home since cath was nl. • He was to be followed up as an outpatient by his pcp.

6. Introduction • Cp-one of most frequent complaints causing visits to MD. • >500,000 caths done yearly with 15k nl or unimpressive. • Esophagus implicated as etiology in 18-51% of cases. • Despite reassurance pts continue to have cp and visit ed and clinics putting large burden on health care costs. • It is important that NCCP be worked up efficiently.

7. Introduction • Much controversy about the proper fashion to identify etiology of NCCP and treat it appropriately. • Many different thoughts on what is the best initial diagnostic test. • Upper endoscopy, manometry, provocative testing, 24 hour pH probe, and empiric tx of GER all proposed.

8. Pathophysiology • Esoph-muscular 24 cm connecting stomach and pharynx. • Outer longitudinal and inner circular layers comprised of striated(upper 1/3), smooth(lower 1/3), and mixed(middle). • Innervated via para/sympathetic nervous systems through plexi(Auerbach between longitudinal/circular layers and Meissner’s- submucosal).

10. Pathophysiology • Plexi thought to have temperature/mechano/chemo receptors. • Stimulation of these receptors postulated to cause cp originating from esophagus. • Theory of irritable esophagus with low threshold for pain.

11. Esophageal Testing Methods • Edrophonium/ergonovine Test- iv edro or erg infused into esoph with goal of producing esoph contractions to reproduce cp. Cost is $90 greater than manometry alone. • Berstein’s Test- HCL infused into esoph with goal of proving GER is causing cp. Cost NCBH $170. • Manometry- catheter assembly introduced into esoph. Contraction, pressure, amplitude measured in resting state and after swallows looking for etx of cp. Cost is $477.

14. Esophageal Testing Methods • 24 hour pH Probe- probe connected to transducer inserted into esoph. pH measuered. GER dx established when % total time of esoph pH < 4 is > 4.2%. A + test for GER induced cp is when the pH is < 4 for > 20 secs and correlates with cp by diary. Cost=$534 at NCBH. • Esophagoduodenoscopy-A scope is placed into the esoph, stomach, and duod looking for signs of inflammation or PUD that may be causing cp. Prof fee at NCBH is $534 with biopsies adding roughly $200 to bill.

15. Diagnostic Modalities For NCCP • Endoscopy-Introduction • Felt to be best initial test by many. • Goal is to find evidence of esophageal inflammation or PUD that may be causing NCCP. • If macroscopic appearance nl, biopsies may be done searching for evidence of microscopic inflammation.

16. Upper Endoscopy in Pts with Nl Coronary Arteries-Endoscopy 1995. • Methods • Prospective study of 49 pts with cp and nl caths. • EF> 50%, no valve disease or cor spasm. • 22 pts served as controls for 24 pH monitoring. • All pts completed a sx quest and graded sx intensity. • All pts underwent egd with bx by blinded endoscopists. • Reflux index(% time with pH<4) calculated.

17. Upper Endoscopy in Pts with Nl Coronary Arteries-Endoscopy 1995. • Results • 5 of 49 had major GER sxs and 14 had slight sxs. • 15 pts (31%) macro esoph/11(25%) micro dz/3 PUD. • Median reflux index was 1.3 in pt group and 2.1 in control group(p=0.49) and didn’t differ in those with esophagitis vs those with nl egd. • Little overlap between egd findings/reflux sxs/reflux index.

18. Macro- and/or Microscopic Esophagitis 15 2 1 2 1 1 Reflux Symptoms Reflux Index >7.2%

19. Upper Endoscopy in Pts with Nl Coronary Arteries-Endoscopy 1995. • Conclusion • In this pt population there was a poor correlation between symptoms and pH monitoring. Egd revealed few abnormalities and its routine use is of limited value.

20. Upper Endoscopy in Pts with Nl Coronary Arteries-Endoscopy 1995. • Evaluation of study • Prospect study with blinding of endoscopists to pt sxs. • Techniques well-explained and easily reproducible. • Results are applicable. • 18 of 49 pt showed evidence of esophagitis which is underwhelming and an overestimation at best as causality is still an issue. • Deficiencies include small number of patients in study.

21. Diagnostic Modalities For NCCP • Endoscopy-Summary • Studies demonstrate that egd will identify potential etiology of NCCP in 50% of patients. • At best this is an overestimation as cause and effect relationship questionable. • This remains an inefficient and invasive way to work up NCCP.

22. Diagnostic Modalities For NCCP • Manometry/Prov. Test/24 Hour pH-Introduction • Some propose the use of these tests as initial diagnostic approach to NCCP. • Goal is to identify contraction abnormalities or GER as source of NCCP by observing their occurrence during episodes of pain.

23. Esophageal Testing of Pts with NCCP or Dysphagia-Annals of IM 1987. • Methods • Retrospect study of 1161 pts with NCCP or dysphagia. • 80% had nl caths and the rest nl non invasive studies. • Pts had egd or UGI to r/o structural lesions as etx of cp. • All pts had baseline manometry followed by Berstein’s/edrophonium testing.

24. Esophageal Testing of Pts with NCCP or Dysphagia-Annals of IM 1987. • Results • 910 pts had cp and 251 pts had dysphagia as main complaint. • 28% had esoph motility d/o with NE most common. • 53% of pts with dysphagia had esoph motility d/o • 6.5% had cp during Bernst test and 23% during edroph. • Cp during manometry was not mentioned. .

25. Manometry Provocative Test 4% 3% 28% 20% 52% 72% 21% Abnormal Manometry Abnormal Manometry Normal Normal Positive T & B Positive Bernstein Positive Tensilon

26. Esophageal Testing of Pts with NCCP or Dysphagia-Annals of IM 1987. • Conclusion • There is a low prevalence of motility d/o associated with NCCP with NE the most common one. • .Edrophonium has a high diagnostic yield and is safe. • Acid perfusion plus edrophonium testing will yield etx of NCCP in 29% of pts referred for evaluation.

27. Esophageal Testing of Pts with NCCP or Dysphagia-Annals of IM 1987. • Evaluation of study • Retrospective nature leads to bias. • Results are unimpressive and demonstrate poor sensitivity of these testing methods. • Establishing cause and effect is still problematic. • No f/u was done and true etiologies were never discovered, thus making comparisons of real and assigned diagnoses difficult.

28. 24 Hour Esoph. pH Monitoring: The Most Useful Test for Eval. NCCP-Am Jl Med 1991. • Methods • Prospect study of 100 pts(43M/57F) referred from card. • 66 pts nl cath, 16 nl stress test, 18 no other w/u. • 74 had prior GI w/u based on sxs with 38 having nl egd, 33 nl esophogography, and 3 erosive esophagitis. • All 100 had manom, Bernst, edroph, and pH probe. • Sx Index(# cp episodes when pH<4 divided by total # cp episodes x 100). Positive test >0 and was considered evidence that GER caused cp.

29. 24 Hour Esoph. pH Monitoring: The Most Useful Test for Eval. NCCP-Am Jl Med 1991. • Results • 33% had abnl mano/19% abnl Bern./19% abnl edroph. • Sens of Bern for GER 27% with spec 100%. • Of 83 pts with cp during probe, 37 had +/46 had - test. • Of the 37 pts with cp during the probe, 70% had + SI and 30% had - SI. • Of 46 pts with nl pH probe , 48% had - SI and 52% had + SI. Overall 50 of 100 pts had + SI.

30. 24 Hour Esoph. pH Monitoring: The Most Useful Test for Eval. NCCP-Am Jl Med 1991. • Conclusion • Manometry and provocative testing are insensitive ways to determine etiology NCCP while pH probe identified GER as etiology in 50% patients. • Those with + SI but - pH probe may have hypersensitive esophagus. • pH probe is single best test to evaluate NCCP.

31. 24 Hour Esoph. pH Monitoring: The Most Useful Test for Eval. NCCP-Am Jl Med 1991 • Evaluation of study • Prospective study with clearly defined methods. • Use of SI helps to establish cause/effect relationship but higher cut off would increase specificity • Results also based on diaries which are subject to bias.

32. Comparison of Esoph Manometry, Provocative Testing,… Dig Dis and Sci 1990. • Methods • Prospective study of 45 pts(24F/21M) with NCCP. • UGI/pan-endoscopy within normal limits in all pts. • All patientss underwent manometry- results compared to manometry of 95 healthy controls. • Bern and edrop done on all pts in single blind fashion with + test=reproduction of cp. • pH probe and manom done- pts kept diary of sxs.

33. Comparison of Esoph Manometry, Provocative Testing,… Dig Dis and Sci 1990. • Results • Manometry wnl in 56%/abnl 44%. 33% + Ber and 54% + edrophonium. • During amb monitoring 202 cp episodes recorded. • 31 occurred in 14 pts and were associated with GER. • 74% episodes occurred independently of pH or manometric abnormality.

34. Comparison of Esoph Manometry, Provocative Testing,… Dig Dis and Sci 1990. • Conclusion • Patients with normal manometry frequently have GER causing chest pain. • GER is the most common identifiable cause of esophageal chest pain while motility d/o are much less frequent causes of NCCP.

35. Comparison of Esoph Manometry, Provocative Testing,… Dig Dis and Sci 1990 • Evaluation of study • Protocol described clearly with strict criteria for tests to be considered positive. • Blinding was present. • Still difficult to establish cause and effect relationship although attempts are made. • The limited ability of these testing methods are again demonstrated.

36. Diagnostic Modalities For NCCP • Manometry/Prov. Test/24 Hour pH-Summary • These testing methods are insensitive, invasive, and costly. • Cause/effect relations are difficult to substantiate. • 24 Hour pH probe seems to be the best of these testing methods.

37. Diagnostic Modalities For NCCP • Empiric Tx of GER in Dx of NCCP-Introduction • Since GER is the most common condition associated with NCCP, empiric tx may be of use in both dx/tx. • Treatment of GER, if successful, helps strengthen cause and effect relationship between GER and NCCP.

38. The Clinical and Economical Value of a Short Course of Omeprazole-Gastro 1998. • Methods • 39 pts(38M/1F) referred for w/u of NNCP. • All pts underwent egd/pH probe and were assigned GER+/GER-. • Week one-pts had baseline symptom assessment. • Week 2- pts were randomized to either omeprazole 40mg am and 20mg pm or placebo for 7 d. • Week 3 was a washout period.

39. The Clinical and Economical Value of a Short Course of Omeprazole-Gastro 1998. • Methods-continued • Week 4- symptoms assessed again. • Week 5- pts were crossed over to the other tx arm. • Sx score was calculated based on diary entries. • Omeprazole test(ot) considered diagnostic of GER if cp score improved >50% after tx with omeprazole. • Placebo test considered + if score improved >50% while on placebo. • Economic analysis was performed.

41. The Clinical and Economical Value of a Short Course of Omeprazole-Gastro 1998. • Results • 2 of 39 pts excluded. • 23 pts classified as GER+ and 14 GER-. • 7 of 23(30%) had abnormal pH probe while 8 had only erosive esophagitis on egd. • 14 of 37 pts had nl results of both tests and called GER- • 74% of patients had symptoms of GER. • Sx intensity for cp in GER+ improved significantly during omeprazole tx vs placebo(p=0.0005)

42. The Clinical and Economical Value of a Short Course of Omeprazole-Gastro 1998. • Results-continued • 18 of 23 GER+ pts had a + ot with 12 pts having complete resolution of cp during tx and 6 at least 50% improvement. • 5 pts in placebo group reported>50% improvement. • Sens/spec of ot was 79%/86%(compared to gold standard of pH probe). • LR 5.6. • An ROC curve showed area 0.8587.

43. The Clinical and Economical Value of a Short Course of Omeprazole-Gastro 1998.

44. The Clinical and Economical Value of a Short Course of Omeprazole-Gastro 1998. • Results-continued • Using cutoff of 65% in cp reduction as accurate in predicting GER would result in sens/spec of 86% and 87% with PPV/NPV of 91% and 86%. • Economic analysis showed saving $573 per average NCCP through reduction of egd/pH probe.

45. The Clinical and Economical Value of a Short Course of Omeprazole-Gastro 1998. • Conclusion • The omeprazole test is an accurate and clinically practical method of diagnosing GER- related NCCP and its use may result in significant savings.

46. The Clinical and Economical Value of a Short Course of Omeprazole-Gastro 1998. • Evaluation of study • Well done, although small. • Randomized, double blinded, placebo controlled. • Comparison to gold standard was done. Testing methods described clearly and results are applicable. • Ot allows for tx of pts classified as GER- but still have acid-induced chest pain. • 74% GER+ pts had sxs of GER- hx taking is important. • Expanding results to females is questionable.

47. Diagnostic Modalities For NCCP • Empiric tx of GER in Dx of NCCP-Summary • Empiric tx of GER is an efficient, cost effective, and non invasive way to both dx the cause of and tx NCCP. • Sensitivity and specificity of ot is fairly good. • Test allows for tx of those who have GER induced cp but do not meet dxic criteria for GER by pH probe.

48. Treatment Options For NCCP • Introduction • If diagnostic testing or empiric tc fails to improve symptoms options remain for treatment. • CCB, nitrates, hydralazine, anti-depressants, and cognitive behavioral therapy have been studied.

49. Oral Nifedipine in Tx of NCCP in Pts with NE-Gastroenterology 1987. • Methods • Double blind placebo controlled trial of 20 pts(12M/8F) with NCCP x 28 mo. • All pts nl cardiac w/u(17 nl cath/3 nl stress test). • All pts had nl egd or UGI before randomization. • All pts had Bern testing (14 negative/4 heartburn/2 cp and heartburn) and all had manometry. • 18 pts had edrophonium testing- 7 reproduced cp.

50. Oral Nifedipine in Tx of NCCP in Pts with NE-Gastroenterology 1987. • Methods-continued • 6 pts unsuccessfully txed for GER in unspec manner. • 2 identical 6 wk periods of med intake separated by 2 wk washout period-pts took placebo in single blind fashion. • Pts received 10-30mg nifed tid based on SE/tolerability. • Pts seen every 2 wks to assess compliance. Diaries were kept recording frequency/severity cp. Cp index calculated