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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. Chest Pain of Unknown Origin.

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chest pain of unknown origin cpuo role of the esophagus

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

prognosis for angina like pain with normal coronary anatomy
Prognosis for angina-like pain with normal coronary anatomy

Chambers, Prog Cardiovasc Dis 1990

Kemp, Am J Med 1973

reflux common in pts with coronary disease
Reflux common in pts with coronary disease

n = 30, 164 chest pain episodes

Singh, Ann Intern Med,1992; 117:824-30

abnormal esophageal motility
Abnormal esophageal motility

(n = 910)

(n = 255)

Katz, Ann Intern Med, 1987; 106:593-7

diagnostic yield of esophageal testing
Diagnostic Yield of Esophageal Testing

Katz, Ann Intern Med, 1987; 106:593-7

intraesophageal balloon inflation esophageal hypersensitivity
Intraesophageal Balloon Inflation:Esophageal Hypersensitivity

n = 30 NCCP, 30 controls

Richter, Gastroenterol, 1986; 91:845-52

provocative testing
Provocative Testing

Barrish, Dig Dis Sci, 1986; 31:1292-8

subgroups of patients with chest pain

Anxiety/Somatization

Neurosis

Subgroups of Patients With Chest Pain

With

Esophageal

Symptoms

Isolated

Chest

Pain

subgroups of patients with chest pain12
Subgroups of Patients With Chest Pain

Isolated

Chest

Pain

  • Rare for esophageal pathology
  • Question the “non-cardiac”
  • Reassurance, tincture of time
subgroups of patients with chest pain13
Subgroups of Patients With Chest Pain
  • Heartburn
  • Regurgitation
  • Dysphagia
  • Water brash
  • Nausea
  • Vomiting

With

Esophageal

Symptoms

Evaluate or treat for recognized esophageal disorders

detection of esophageal disorders potentially responsible for symptoms

Esophageal stricture/web

  • Achalasia
  • Esophageal spasm

Barium swallow ± manometry

pH

  • EGD-negative GERD
Detection of Esophageal Disorders Potentially Responsible for Symptoms
  • Reflux esophagitis
  • Infectious esophagitis
  • Pill esophagitis
  • Esophageal cancer
  • Esophageal stricture/web

Endoscopy

ph testing conventional
pH testing - Conventional

Catheter Based:

  • Patient Intolerance
    • Uncomfortable
    • Pharyngeal and Throat Discomfort
    • Runny Nose
  • Artifact Prone
    • Alters Regular Diet and Activity
bravo ph system
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
slide18

Capsule Attachment

Step 1

Position Bravo Capsule

Step 2

Apply Suction

Step 3

Advance Pin

Step 4

Release Capsule

Step 5

Begin pH Recording

bravo ph receiver
Bravo pH Receiver
  • pH Capsule transmits data to pager-sized Receiver

Receiver

pH Capsule

digital radio telemetry
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)
esophageal testing in 123 patients with chest pain and normal coronary arteriograms
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

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

Atypical presentations of GERD

Chest Pain

esophageal chest pain work up
Esophageal Chest Pain Work-Up
  • Traditionally
    • Endoscopy
    • pH probe
    • Manometry
    • Provocative testing
  • Emerging role for up-front empiricism
ppi trial in gerd patients with non cardiac chest pain
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
  • GERD-Positive
  • n=23
  • 78% response
  • GERD-Negative
  • n=14
  • 14% response

Fass et al. Gastroenterology. 1998;115:42-49.

characteristics of the patients
Characteristics of the Patients

Patients with NCCP

GERD-positive GERD-negative

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

Fass R, et al Gastroenterol 1998; 115:42-9

slide28

Enrollment

Upper endoscopy &

Ambulatory 24-hour esophageal pH monitoring

GERD + GERD -

Week 1

Baseline symptom assessment

Randomization

Week 2

Placebo Omeprazole

(40 mg AM + 20 mg PM)

Washout period

Week 3

Baseline symptom assessment

Week 4

Fass R, et al Gastroenterol 1998; 115:42-9

Week 5

Omeprazole Placebo

(40 mg AM + 20 mg PM)

omeprazole test in nccp
Omeprazole Test in NCCP

Positive OT

  • 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

results of economic analysis
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

omeprazole test in nccp31
Omeprazole Test in NCCP

Issues

  • 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
los angeles la grade classification of erosive esophagitis
Los Angeles (LA) Grade Classification of Erosive Esophagitis

LA Grade A

LA Grade B

One or more mucosal breaks no longer than 5mm, not bridging the tops of mucosal folds

One or more mucosal breaks longer than 5mm, not bridging the tops of mucosal folds

LA Grade C

LA Grade D

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

Lundell et al. Gut. 1999;45:172-180.

slide34

Patients with esophagitis

Patients without esophagitis

The spectrum of heartburn frequency and severity is similar in GERD patients with and without esophagitis

Severity ofheartburn

Severe

Moderate

Mild

Smout 1997

gerd therapeutic options
GERD Therapeutic Options

Prokinetics

“First - aid” : Life-style modifications and antacids

OTC or prescription H2RAs

Treatments

OTC or prescription PPIs

Surgery

(Lap Nissen fundoplication)

Endoscopic techniques

(plication, RF, implant)

life style modifications
Life-style Modifications

Reduce weight

Stop smoking

Elevate head of bed

Modifications

Avoid reflux-promoting agents e.g, alcohol, coffee; some foods

  • Not evidence-based

Consider alternatives to reflux-promoting drugs e.g., theophilline, anticholinergics

Eat small meals, no late meals, reduce fat

position and reflux
POSITION AND REFLUX

8

Right side

down

pH

4

0

8

Left side

down

pH

4

0

(Katz,LC. Et al, J Clin Gastro 1994;18(4):280-3

slide39

GERD HEALING AND ACID CONTROL

100

80

60

Patients Healed (%)

40

20

0

2

4

6

8

10

12

14

16

18

20

22

Duration Intragastric pH >4.0 (Hours)

(Bell et al. Digestion. 1992;51(suppl 1):59-67.)

medical rx outcomes with h2ras
Medical Rx Outcomes(with H2RAs)
  • Relief of symptoms 50%
  • Healing esophagitis <50%
  • Prevent complications ---
  • Remission 25%
medical rx outcomes ppis
Medical Rx Outcomes (PPIs)
  • Relief of symptoms 85-95%
  • Healing esophagitis 85-95%
  • Prevent complications 80%
  • Remission 90%
gerd endoscopic therapies
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
bard endocinch
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

ndo plicator
NDO Plicator™

1

2

3

Plicator and gastroscope retroflexed

Arms opened, tissue retractor advanced

Gastric wall retracted, arms closed.

4

5

Single, pre-tied implant deployed.

Full-thickness plication completed

gatekeeper system
Gatekeeper™ System

Create pocket

Stabilize site

Access pocket

Expansion

Deliver prosthesis

maintenance therapy of gerd omeprazole vs surgery
MAINTENANCE THERAPY OF GERDOmeprazole vs surgery

(Lundel et al: J Am Col Surg, 192:172, 2001)

outcomes of atypical gerd symptoms treated by lnf
Outcomes of Atypical GERD Symptoms Treated by LNF

Preoperative

Postoperative

  • Atypical Sx Improvement
  • Overall 58% of patients
    • Pulmonary 48%
    • Atypical chest pain 58%
    • Pharyngo/laryngeal 76%

Symptom Score

Typical Symptoms (n=115)Improvement 6.2 points

Atypical Symptoms (n=35) Improvement 4.4 points

So et al. Surgery. 1998;124:28-32.

esophageal chest pain
Esophageal Chest Pain
  • GERD related
  • Motility related
  • Esophageal hyperalgesia
esophageal hyperalgesia
Esophageal Hyperalgesia
  • “Irritable esophagus”
  • Abnormal nociception
  • Lower threshold for pain
esophageal hyperalgesia52
Esophageal Hyperalgesia
  • Noxious stimulus in esophagus
  • Decrease in nociceptor threshold
  • Disorder of CNS nociceptive pathway
chest pain imipramine
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
nccp non gerd esophageal therapies
NCCP Non-GERD Esophageal Therapies
  • Calcium channel blockers
  • Anticholinergics
  • Nitrates
  • Botox
  • Antidepressants (Imipramine, Trazodone)
  • Octreotide
  • Bougienage
  • 5 HT3 antagonists
initial perception threshold s1 before and 40 minutes after octreotide injection
Initial Perception Threshold (S1) Before and 40 Minutes after Octreotide Injection

>30

p < 0.02

30

20

CC

10

0

Base

40 min

Johnson BT, et al Am J Gastroenterol 1999; 94:65-70

maximally tolerated pain threshold s2 before and 40 minutes after octreotide injection
Maximally Tolerated Pain Threshold (S2) Before and 40 Minutes after Octreotide Injection

>30

30

20

CC

10

0

Base

40 min

Johnson BT, et al Am J Gastroenterol 1999; 94:65-70

approach to the nccp patient
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