Table 2

Summary of diagnostic accuracy of tests used in non-cardiac chest pain
Author, year
Evaluated test Reference standard Prevalence,% LR+ LR-
Symptoms
Kim et al. [24] NCCP with atypical GERD symptoms Endoscopy (LA classification) and/or 24 h pH-metry (>4%, pH <4 24 0.49 2.71
Kim et al. [24] NCCP with typical GERD symptoms Same 67 2.75 0.42
Mousavi et al. [27] NCCP with typical GERD symptoms GERD if two tests positive: endoscopy (Hentzel-Dent), Bernstein test, omeprazole trial 45 2.70 0.78
Mousavi et al. [27] NCCP relieved by antacid Same 45 0.51 3.51
Mousavi et al. [27] NCCP and heartburn in past history Same 45 2.15 0.74
Mousavi et al. [27] NCCP and regurgitation in past history Same 45 2.98 0.61
Hong et al. [25] NCCP Manometry (Specler 2001 criteria) and/or 24 h pH-metry (>4% pH <4) 43 0.83 1.13
Hong et al. [25] Control: dysphagia Same 45 1.27 0.97
Hong et al. [25] Control: GERD-typical symptoms Same 44 1.26 0.93
Netzer et al. [26] NCCP Manometry and/or 24 h pH-metry (>10.5% pH <4) 84 0.43 1.23
Netzer et al. [26] Control: GERD-typical symptoms Same 84 1.53 0.74
Netzer et al. [26] Control: dysphagia Same 84 1.16 0.97
Proton pump inhibitor (PPI) trial
Dickman et al. [31] Rabeprazole 20 mg twice a day for 1 week SIS ≥50% Endoscopy (Hentzel-Dent grades) and/or 24 h pH-metry (>4.2% pH <4) 46 7.13 0.28
Dickman et al. [31] Placebo for 1 week Same 46 0.89 1.03
Bautista et al. [32] Lansoprazole 60 mg AM, 30 mg PM for 1 week SIS ≥50% Endoscopy (Hentzel-Dent grades) and/or 24 h pH-metry (>4.2% pH <4) 45 8.56 0.24
Bautista et al. [32] Lansoprazole 60 mg AM, 30 mg PM for 1 week SIS ≥65% Same 45 18.33 0.17
Bautista et al. [32] Placebo for 1 week Same 45 0.61 1.22
Fass et al. [33] Omeprazole 40 mg AM, 20 mg PM for 1 week SIS ≥50% Endoscopy (Hentzel-Dent grades) and/or 24 h pH-metry (>4.2% pH <4) 62 5.48 0.25
Fass et al. [33] Placebo for 1 week Same 62 3.04 0.84
Pandak et al. [34] Omeprazole 40 mg twice a day for 2 weeks SIS ≥50% Endoscopy and/or 24 h pH-metry (>4.2% pH <4) 53 2.70 0.15
Pandak et al. [34] Placebo for 2 weeks SIS ≥50% Same 53 0.30 1.14
Kim et al. [35] NCCP rabeprazole for 1 week SIS ≥50% Endoscopy (LA classification) and/or 24 h pH-metry (>4.0 pH <4) 38 2.17 0.65
Kim et al. [35] NCCP rabeprazole for 2 weeks SIS ≥50% Same 38 3.02 0.26
Xia et al. [36] Lansoprazole 30 mg once a day for 4 weeks SIS ≥50% 24 h pH-metry (De Meester pH <4, 7.5 s) 33 2.75 0.13
Xia et al. [36] Placebo for 4 weeks SIS ≥50% Same 38 0.95 1.03
Kushnir et al. [37] High-degree response on PPI (not specified) 24 pH-metry (≥4%, pH <4) 53 1.97 0.38
Provocation test
Cooke et al. [39] NCCP during exertional pH-metry 24 h pH-metry (5.5% pH <4 for 10 s) 38 14.40 0.79
Cooke et al. [39] Control group: CVD with angina: exertional pH-metry Same 19 4.33 0.72
Bovero et al. [40] NCCP with normal ECG during exertional pH-metry 24 h pH-metry (De Meester criteria: >4.5% pH <4)) 69 7.76 0.66
Bovero et al. [40] NCCP at rest: NCCP with normal ECG during exertional pH-metry Same 74 3.88 0.74
Bovero et al. [40] NCCP exertion/mixed: NCCP with normal ECG during exertional pH-metry Same 57 10.00 0.50
Romand et al. [41] NCCP: pH <4 for 10 s during exertional pH-metry 24 h pH-metry (De Meester criteria: >4.5% pH <4)) 23 1.65 0.52
Abrahao et al. [42] NCCP reproducible during balloon distension Endoscopy (Savary-Miller) and/or manometry and/or pH-metry (De Meester criteria: >4.5% pH <4 88 2.00 0.75
Abrahao et al. [42] NCCP reproducible during Tensilon test Same 88 0.43 1.38
Abrahao et al. [42] NCCP reproducible during Bernstein test Same 88 1.29 0.93
Abrahao et al. [42] Tensilon and Bernstein Test and balloon distension (+ if 1 test +) Same 88 0.95 1.07
Ho et al. [29] NCCP reproducible during Bernstein test 24 h pH-metry (>4% pH <4, 4 s) 23 0.75 1.06
Musculoskeletal disorders
Stochkendahl et al. [44] ≥3 of 5 palpation findings: (1) sitting motion of end-play restriction in lateral flexion and rotation segment C4 to C7 and Th1 to Th8. (2) Prone motion joint-play restriction segment Th1 to Th8. (3) Prone evaluation paraspinal tenderness segment Th1 to Th8. (4) Supine manual palpation muscular tenderness of 14 points anterior chest wall. 5) Supine evaluation of tenderness of the costosternal junctions of costa 2 to 6 and xiphoid process Diagnosis using a standardized examination protocol: 37 1.52 0.03
(1) A semistructured interview: pain characteristics, lung and gastrointestinal symptoms, past medical history, height, weight, cardiovascular risk factors
(2) A general health examination: blood pressure, pulse, heart and lung stethoscopy, abdominal palpation, neck auscultation, signs of left ventricular failure, neurological examination
(3) Manual examination of the muscles and joints (neck, thoracic spine and thorax): active range of motion, manual palpation 14 points muscular tenderness of the anterior chest wall and segmental paraspinal muscles, motion palpation for joint-play restriction of the thoracic spine (Th1 to 8), and end play restriction of the cervical and thoracic spine
Bosner et al. [45] Chest wall symptom (CWS) score: localized muscle tension, stinging pain, pain reproducible by palpation, absence of cough Interdisciplinary consensus: cardiologist, GP, research associate (based on reviewed baseline, follow-up data at 6 weeks and 6 months) 47 1.82 0.20
Cut-off test negative 0 to 1 points
Bosner et al. [45] CWS score: localized muscle tension, stinging pain, pain reproducible by palpation, absence of cough Interdisciplinary consensus 47 3.02 0.47
Cut-off test negative 0 to 2 points
Stochkendahl et al. [44] Biomechanical dysfunction (part of the standardized examination protocol)a Standardized examination protocol 37 1.58 0.00
Stochkendahl et al. [44] Anterior chest wall tenderness Standardized examination protocol 37 1.39 0.06
Stochkendahl et al. [44] Angina pectoris (uncertain or negative) Standardized examination protocol 37 1.26 0.12
Stochkendahl et al. [44] Pain worse on movement of torso Standardized examination protocol 37 3.39 0.78
Bosner et al. [45] Pain worse with movement Interdisciplinary consensus 47 2.13 0.75
Stochkendahl et al. [44] Positive/possible belief in pain origin from muscle/joints Standardized examination protocol 37 1.17 0.20
Stochkendahl et al. [44] Pain relief on pain medication Standardized examination protocol 37 3.26 0.83
Bosner et al. [45] Pain reproducible by palpation Interdisciplinary consensus 47 2.08 0.54
Stochkendahl et al. [44] Paraspinal tenderness Standardized examination protocol 37 1.36 0.48
Bosner et al. [45] Localized muscle tension Interdisciplinary consensus 47 2.41 0.52
Stochkendahl et al. [44] Chest pain present now Standardized examination protocol 37 1.35 0.46
Bosner et al. [45] Pain now Interdisciplinary consensus 47 1.15 0.85
Stochkendahl et al. [44] Pain debut not during a meal Standardized examination protocol 37 1.10 0.23
Stochkendahl et al. [44] Sharp pain Standardized examination protocol 37 1.89 0.80
Bosner et al. [45] Stinging pain Interdisciplinary consensus 47 1.87 0.66
Stochkendahl et al. [44] Hard physical exercise at least once a week Standardized examination protocol 37 1.19 0.91
Stochkendahl et al. [44] Pain not provoked during a meal Standardized examination protocol 37 1.09 0.25
Stochkendahl et al. [44] Not sudden debut Standardized examination protocol 37 2.90 0.63
Bosner et al. [45] Pain >24 h Interdisciplinary consensus 47 1.30 0.92
Stochkendahl et al. [44] Age ≤49 years old Standardized examination protocol 37 2.10 0.56
Bosner et al. [45] Pain mostly at noon time Interdisciplinary consensus 47 0.50 1.02
Bosner et al. [45] Cough Interdisciplinary consensus 47 0.28 1.18
Bosner et al. [45] Known IHD Interdisciplinary consensus 47 0.52 1.11
Bosner et al. [45] Pain worse with breathing Interdisciplinary consensus 47 1.28 0.93
Psychiatric diseases
Kuijpers et al. [47] Anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A score, cut-off ≥8) Diagnosis anxiety disorders (Mini International Neuropsychiatric Interview (gold standard)) 58 2.03 0.03
Demiryoguran et al. [48] Chills or hot flushes Anxiety disorder: HADS-A score (cut-off ≥10) 31 4.85 0.81
Demiryoguran et al. [48] Fear of dying Anxiety disorder: HADS-A score (cut-off ≥10) 31 4.04 0.82
Demiryoguran et al. [48] Diaphoresis Anxiety disorder: HADS-A score (cut-off ≥10) 31 3.49 0.69
Demiryoguran et al. [48] Light-headedness, dizziness, faintness Anxiety disorder: HADS-A score (cut-off ≥10) 31 3.03 0.84
Demiryoguran et al. [48] Palpitation Anxiety disorder: HADS-A score (cut-off ≥10) 31 1.54 0.83
Demiryoguran et al. [48] Shortness of breath Anxiety disorder: HADS-A score (cut-off ≥10) 31 1.30 0.92
Demiryoguran et al. [48] Nausea or gastric discomfort Anxiety disorder: HADS-A score (cut-off ≥10) 31 1.98 0.90
Foldes-Busque et al. [49] The Panic Screening Score (derivation population); does the patient have a history of anxiety disorders? Please indicate how often this thought occurs when you are nervous: ‘I will choke to death’. Did the patient arrive in the ED by ambulance? Please answer the statement by circling the number that best applies to you: ‘When I notice my heart beating rapidly, I worry that I might be having a heart attack’. Sum score 22, A total score ≥6 indicates probable panic. Panic disorder Diagnosis (structured Anxiety Disorders Interview Schedule for Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) (ADIS-IV)) 42 3.89 0.44
Foldes-Busque et al. [49] The Panic Screening Score (validation population). Panic disorder diagnosis (structured ADIS-IV) 43 3.44 0.55
Fleet et al. [50] Panic disorder diagnosis: formula including Agoraphobia Cognitions QA, Mobility Inventory for Agoraphobia, Zone 12 Dermatome Pain Map, Sensory McGill Pain QA, Gender, Zone 25 (validation population) Panic disorder (ADIS-R structured interview by psychologist) 23 2.60 0.46
Katerndahl et al. [51] GP diagnosis of panic disorder Panic disorder (structured clinical interview of Diagnostic and Statistical Manual of Mental Disorders, based on DSM-III-R) 55 0.82 1.02

LR+: >10; LR-: <0.1; good: LR + 5 to 10, LR- 0.1 to 0.2; fair: LR + 2 to 5, LR- 0.2 to 0.5; poor: LR + 1 to 2, LR- 0.5 to 1.

aBiomechanical dysfunction defined as chest pain presumably caused by mechanical joint and muscle dysfunction related to C4 to Th8 somatic structures of the spine and chest wall established by means of joint-play and/or end-play palpation.

Reference tests are as follows. Endoscopic classification: LA classification: grade A, ≥1 mucosal break ≤5 mm, that does not extend between the tops of two mucosal folds; grade B, ≥1 mucosal break >5 mm long that does not extend between the tops of two mucosal folds; grade C, ≥1 mucosal break that is continuous between the tops of two or more mucosal folds but which involves <75% of the circumference; grade D, ≥1 mucosal break which involves at least 75% of the esophageal circumference [52]. Savary-Miller system: grade I, single or isolated erosive lesion(s) affecting only one longitudinal fold; grade II multiple erosive lesions, non-circumferential, affecting more than one longitudinal fold, with or without confluence; grade III, circumferential erosive lesions; grade IV, chronic lesions: ulcer(s), stricture(s) and/or short esophagus. Alone or associated with lesions of grades 1 to 3; grade V, columnar epithelium in continuity with the Z line, non-circular, star-shaped, or circumferential. Alone or associated with lesions of grades 1 to 4 [53]. Hentzel-Dent grades: grade 0, no mucosal abnormalities; grade 1, no macroscopic lesions but erythema, hyperemia, or mucosal friability; grade 2, superficial erosions involving <10% of mucosal surface of the last 5 cm of esophageal squamous mucosa; grade 3, superficial erosions or ulceration involving 10% to 50% of the mucosal surface of the last 5 cm of esophageal squamous mucosa; grade 4, deep peptide ulceration anywhere in the esophagus or confluent erosion of >50% of the mucosal surface of the last 5 cm of esophageal squamous mucosa [54]. pH-metry: De Meester criteria: (1) total number of reflux episodes; (2) number of reflux episodes with pH <4 for more than 5 minutes; (3) duration of the longest episode; (4) percentage total time pH <4; (5) percentage upright time pH <4; and (6) percentage recumbent time pH <4. [55]. Manometry: Spechler criteria is diagnosis of ineffective esophageal motility, nutcracker esophagus, spasm, achalasia based on basal lower esophageal sphincter pressure, relaxation, wave progression, distal wave amplitude [56].

24-h pH-metry 24-h pH monitoring, GERD gastroesophageal reflux disease, GP general practitioner, IHD ischemic heart disease, QA questionnaire, Sensory McGill McGill Pain Questionnaire sensory subscale, SIS symptom index score calculated by adding the reported daily severity (mild = 1; moderate = 2; severe = 3; and disabling = 4) multiplied by the reported daily frequency values during each week).

Wertli et al.

Wertli et al. BMC Medicine 2013 11:239   doi:10.1186/1741-7015-11-239

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