Rationale and Objectives
This study aimed to calculate the multiple-level likelihood ratios (LRs) and posttest probabilities for a positive, indeterminate, or negative test result for multidetector computed tomography pulmonary angiography (MDCTPA) ± computed tomography venography (CTV) and magnetic resonance pulmonary angiography (MRPA) ± magnetic resonance venography (MRV) for each clinical probability level (two-, three-, and four-level) for the nine most commonly used clinical prediction rules (CPRs) (Wells, Geneva, Miniati, and Charlotte). The study design is a review of observational studies with critical review of multiple cohort studies. The settings are acute care, emergency room care, and ambulatory care (inpatients and outpatients).
Materials and Methods
Data were used to estimate pulmonary embolism (PE) pretest probability for each of the most commonly used CPRs at each probability level. Multiple-level LRs (positive, indeterminate, negative test) were generated and used to calculate posttest probabilities for MDCTPA, MDCTPA + CTV, MRPA, and MRPA + MRV from sensitivity and specificity results from Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) II and PIOPED III for each clinical probability level for each CPR. Nomograms were also created.
Results
The LRs for a positive test result were higher for MRPA compared to MDCTPA without venography (76 vs 20) and with venography (42 vs 18). LRs for a negative test result were lower for MDCTPA compared to MRPA without venography (0.18 vs 0.22) and with venography (0.12 vs 0.15). In the three-level Wells score, the pretest clinical probability of PE for a low, moderate, and high clinical probability score is 5.7, 23, and 49. The posttest probability for an initially low clinical probability PE for a positive, indeterminate, and negative test result, respectively, for MDCTPA is 54, 5 and 1; for MDCTPA + CTV is 52, 2, and 0.7; for MRPA is 82, 6, and 1; and for MRPA + MRV is 72, 3, and 1; for an initially moderate clinical probability PE for MDCTPA is 86, 22, and 5; for MDCTPA + CTV is 85, 10, and 4; for MRPA is 96, 25, and 6; and for MRPA + MRV is 93, 14, and 4; and for an initially high clinical probability of PE for MDCTPA is 95, 47, and 15; for MDCTPA + CTV is 95, 27, and 10; for MRPA is 99, 52, and 17; and for MRPA + MRV is 98, 34, and 13.
Conclusions
For a positive test result, LRs were considerably higher for MRPA compared to MDCTPA. However, both a positive MRPA and MDCTPA have LRs >10 and therefore can confirm the presence of PE. Performing venography reduced the LR for a positive and negative test for both MDCTPA and MRPA. The nomograms give posttest probabilities for a positive, indeterminate, or negative test result for MDCTPA and MRPA (with and without venography) for each clinical probability level for each of the CPR.
Introduction
Pulmonary embolism (PE) is a common and potentially fatal condition, and is the third most common cause of cardiovascular death, after myocardial ischemia and stroke . The signs and symptoms of PE may be nonspecific. Patient outcome has been shown to be greatly influenced by the prompt and accurate diagnosis of PE . Many tests and algorithms have been suggested for the evaluation of patients with suspected venous thromboembolism, from the history and physical examination to cross-sectional imaging with computed tomography pulmonary angiography (CTPA) and magnetic resonance pulmonary angiography (MRPA). Testing with imaging is recommended ( Fig 1 ). Clinical probability assessment is of utmost importance in the diagnostic approach of PE. The Wells and Geneva scores have received more attention because they are simple, easy to remember, and rely on readily available information. Three scoring systems (Wells score, Geneva score, and Pisa score) have been tested prospectively and validated in large clinical trials. All three scoring systems perform reasonably well in outpatients and emergency departments . The Pisa score is more optimized for use in inpatients . In the last decade, the most used rules were modified to increase their usefulness and acceptability for clinicians. Cutoff scores of the three-level rules that stratified patients into three levels of clinical probability (low, moderate, or high) were modified to obtain two-level rules classifying patients in only two categories (“PE likely/unlikely” for the Wells score or “safe/unsafe” for the Charlotte rule; Table 1 ).
TABLE 1
Clinical Scores From the Most Commonly Used Clinical Prediction Rules for Predicting the Pretest Probability of PE
Wells Points Wells Three-level Wells Two-level Wells Simplified (Two-level) Clinical signs of DVT 3.0 3.0 1.0 Recent surgery or immobilization 1.5 1.5 1.0 Heart rate >100 bpm 1.5 1.5 1.0 Previous history of PE or DVT 1.5 1.5 1.0 Hemoptysis 1.0 1.0 1.0 Malignancy 1.0 1.0 1.0 Alternative diagnosis less likely than PE 3.0 3.0 1.0Clinical probability Low <2 Intermediate 2–6 PE unlikely ≤4 PE unlikely ≤1 High >6 PE likely >4 PE likely >1
Geneva Points Miniati Coefficient Recent surgery 3.0 Male sex 0.81 Previous history of DVT or PE 2.0Age Heart rate >100 bpm 1.0 63–72 years old 0.59Age ≥73 years old 0.91 60–79 years old 1.0Preexisting disease 80 years old 2.0 Cardiovascular 0.56Chest radiograph Pulmonary −0.97 Atelectasis 1.0 History of thrombophlebitis 0.69 Elevated hemidiaphram 1.0 Dyspnea (sudden onset) 1.29PaO 2 Chest pain 0.64 <49 mm Hg (6.5 kPa) 4.0 Fever >38° −1.17 49–59 mm Hg (6.5–7.99 kPa) 3.0 ECG signs of acute right ventricular overload 1.53 60–71 mm Hg (8–9.49 kPa) 2.0Chest radiograph 72–82 mmHg (9.5–10.99 kPa) 1.0 Oligemia 3.86PaCO 2 Amputation of the hilar artery 3.92 <36 mmHg (4.8 kPa) 2.0 Consolidation (infarction) 3.55 36–38.9 mmHg (4.8–5.2 kPa) 1.0 Consolidation (no infarction) −1.23Clinical probability Pulmonary edema −2.83 Low 0–4 Constant −3.26 Intermediate 5–8Pretest probability (%) = 1/[1 + exp(−sum)] High ≥94 Levels Low ≤10% Intermediate 10–50% Moderately high 50–90% High >90%3 Levels Low ≤10% Intermediate 10–90% High >90%
Geneva Revised Points Revised Simplified Revised Age >65 years 1.0 1.0 Previous history of DVT or PE 3.0 1.0 Surgery (under general anesthesia) or fracture of the lower limbs within 1 mo 2.0 1.0 Active malignant condition (solid or hematological, currently active, or considered cured <1 year) 2.0 1.0 Pain on lower-limb deep venous palpation and unilateral edema 4.0 1.0 Unilateral lower-limb pain 3.0 1.0 Hemoptysis 2.0 1.0 Heart rate 75–94/min 3.0 1.0 Heart rate >94/min 5.0 1.0Clinical probability Low <3 <2 Intermediate 4–10 2–4 High >10 >4
bpm, beats per minute; DVT, deep vein thrombosis; ECG, electrocardiograph; PE, pulmonary embolism.
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Materials and Methods
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Clinical Prediction Rules
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TABLE 2
Pooled Prevalence (Pretest Probability in the Absence of Testing) of PE in Each Clinical Pretest Probability Level for the Different Retrieved CPR
Rules Level Wells three-level Low Moderate High 5.7 (3.7–8.2) 23.2 (18.3–28.4) 49.3 (42.6–56.0) Wells two-level Unlikely Likely 8.4 (6.4–10.6) 34.4 (29.4–39.7) Simplified Wells two-level Unlikely Likely 11.0 (10.0–12.0) 36.0 (33.0–38.0) Geneva Low Moderate High 12.8 (7.9–18.7) 34.7 (31.3–38.2) 71.1 (49.6–88.5) Revised Geneva Low Moderate High 9.0 (7.6–10.6) 26.2 (24.4–28.0) 75.7 (69.0–81.8) Revised Geneva simplified Low Moderate High 7.7 (5.2–10.8) 29.3 (25.7–33.0) 64.3 (48.0–78.4) Miniati three-level Low Moderate High 5.0 (1.0–12.0) 42.0 (31.0–53.0) 98.0 (91.0–100.0)
Miniati four-level Low Intermediate Moderately high High 4.0 (3.0–7.0) 22.0 (17.0–27.0) 74.0 (62.0–83.0) 98.0 (95.0–99.0) Charlotte Safe Unsafe 5.9 (3.3–9.3) 22.5 (11.4–36.2)
CPR, clinical prediction rule; PE, pulmonary embolism.
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Multiple-level LRs, Posttest Probability, and Nomogram Development
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TABLE 3
Sensitivity, Specificity, and Multiple-level (Positive, Indeterminate, and Negative Test Result) Likelihood Ratios for CTPA, CTPA + CTV, MRPA, and MRPA + MRV
Study Test Result Sensitivity Specificity Likelihood Ratio MDCTPA Positive test result (150/192) 0.78 (25/632) 0.04 19.75 Indeterminate (11/192) 0.06 (40/632) 0.06 0.91 Negative test result (31/192) 0.16 (567/632) 0.90 0.18 MDCTPA + CTV Positive test result (164/192) 0.85 (30/632) 0.05 17.99 Indeterminate (9/192) 0.05 (78/632) 0.12 0.38 Negative test result (19/192) 0.10 (524/632) 0.83 0.12 MRPA Positive test result (59/104) 0.57 (2/267) 0.01 75.74 Indeterminate (28/104) 0.27 (64/267) 0.24 1.12 Negative test result (17/104) 0.16 (201/267) 0.75 0.22 MRPA + MRV Positive test result (65/104) 0.63 (4/226) 0.02 41.56 Indeterminate (33/104) 0.32 (161/266) 0.61 0.52 Negative test result (6/104) 0.06 (101/266) 0.38 0.15
CTV, computed tomography venography; MDCTPA, multidetector computed tomography pulmonary angiography; MRPA, magnetic resonance pulmonary angiography; MRV, magnetic resonance venography.
TABLE 4
2 × 3 Table to Illustrate the Calculations of Sensitivity, Specificity, and Likelihood Ratio (LR) for a Multiple-level (Positive, Indeterminate, and Negative) Test Result
Pulmonary Embolism Total Present Absent Test result Positive a b Indeterminate c d Negative e f Total a + c + e b + d + f a + b + c + d + e + f
Prevalence/pretest probability, pretest odds, posttest odds, and posttest probability calculated as shown in the following:
Sensitivity for a positive test result = a/(a + c + e).
Sensitivity for an indeterminate test result = c/(a + c + e).
Sensitivity for a negative test result = e/(a + c + e).
Specificity for a positive test result = b/(b + d + f).
Specificity for an indeterminate test result = d/(b + d + f).
Specificity for a negative test result = f/(b + d + f).
LR for a positive test result = sensitivity for a positive test result/specificity for a positive test result ≡.
LR for a positive test result = (a/(a + c + e))/(b/(b + d + f)).
LR for an indeterminate test result = sensitivity for an indeterminate test result/specificity for an indeterminate test result ≡.
LR for a positive test result = (c/(a + c + e))/(d/(b + d + f)).
LR for a negative test result = sensitivity for a negative test result/specificity for a negative test result ≡.
LR for a negative test result = (e/(a + c + e))/(f/(b + d + f)).
Pretest probability (in the absence of testing) = prevalence.
Prevalence = (a + c + e)/(a + b + c + d + e + f).
Pretest odds = prevalence/(1 − prevalence).
Posttest odds = pretest odds × (multiple-level) LR.
Posttest probability = posttest odds/(posttest odds + 1).
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Results
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TABLE 5
Nomogram of Posttest Probability of PE for Three-level Clinical Prediction Rule: Wells Three-level, Geneva, Revised Geneva, Simplified Revised Geneva, and Miniati at Three Levels
Clinical Prediction Rule Wells Three-level Geneva Revised Geneva Simplified Revised Geneva Miniati Three-level Study Test Result Posttest Probability Posttest Probability Posttest Probability Posttest Probability Posttest Probability Low clinical probabilityNo test (pretest probability)0.0570.1280.0900.0770.050 MDCTPA Positive test result 0.544 0.744 0.661 0.622 0.510 Indeterminate 0.052 0.117 0.082 0.070 0.045 Negative test result 0.011 0.026 0.017 0.015 0.009 MDCTPA + CTV Positive test result 0.521 0.725 0.640 0.600 0.486 Indeterminate 0.022 0.053 0.036 0.031 0.020 Negative test result 0.007 0.017 0.012 0.010 0.006 MRPA Positive test result 0.821 0.917 0.882 0.863 0.799 Indeterminate 0.064 0.142 0.100 0.086 0.056 Negative test result 0.013 0.031 0.021 0.018 0.011 MRPA + MRV Positive test result 0.715 0.859 0.804 0.776 0.686 Indeterminate 0.031 0.071 0.049 0.042 0.027 Negative test result 0.009 0.022 0.015 0.013 0.008 Moderate clinical probabilityNo test (pretest probability)0.2320.3470.2620.2930.420 MDCTPA Positive test result 0.856 0.913 0.875 0.891 0.935 Indeterminate 0.215 0.325 0.243 0.273 0.396 Negative test result 0.052 0.087 0.060 0.069 0.115 MDCTPA + CTV Positive test result 0.845 0.905 0.865 0.882 0.929 Indeterminate 0.103 0.168 0.119 0.136 0.216 Negative test result 0.035 0.060 0.041 0.047 0.080 MRPA Positive test result 0.958 0.976 0.964 0.969 0.982 Indeterminate 0.253 0.374 0.285 0.318 0.449 Negative test result 0.062 0.103 0.072 0.083 0.136 MRPA + MRV Positive test result 0.926 0.957 0.937 0.945 0.968 Indeterminate 0.137 0.218 0.157 0.178 0.275 Negative test result 0.044 0.075 0.051 0.059 0.099 High clinical ProbabilityNo test (pretest probability)0.4930.7110.7570.6430.980 MDCTPA Positive test result 0.951 0.980 0.984 0.973 0.999 Indeterminate 0.468 0.690 0.738 0.620 0.978 Negative test result 0.149 0.307 0.359 0.245 0.898 MDCTPA + CTV Positive test result 0.946 0.978 0.982 0.970 0.999 Indeterminate 0.270 0.483 0.542 0.406 0.949 Negative test result 0.104 0.227 0.271 0.177 0.854 MRPA Positive test result 0.987 0.995 0.996 0.993 1.000 Indeterminate 0.522 0.734 0.778 0.669 0.982 Negative test result 0.174 0.348 0.403 0.281 0.914 MRPA + MRV Positive test result 0.976 0.990 0.992 0.987 1.000 Indeterminate 0.338 0.563 0.620 0.486 0.963 Negative test result 0.129 0.272 0.321 0.215 0.882
CTV, computed tomography venography; MDCTPA, multidetector computed tomography pulmonary angiography; MRPA, magnetic resonance pulmonary angiography; MRV, magnetic resonance venography; PE, pulmonary embolism.
TABLE 6
Nomogram of Posttest Probability of PE for Two-level Clinical Prediction Rules: Wells two-Level, Simplified Wells, and Charlotte
Clinical Prediction Rule Wells Two-level Simplified Wells Two-level Charlotte Study Test Result Posttest Probability Posttest Probability Posttest Probability PE unlikelyNo test (pretest probability)0.0840.110Safe0.059 MDCTPA Positive test result 0.644 0.709 0.553 Indeterminate 0.077 0.101 0.054 Negative test result 0.016 0.022 0.011 MDCTPA + CTV Positive test result 0.623 0.690 0.530 Indeterminate 0.034 0.045 0.023 Negative test result 0.011 0.015 0.007 MRPA Positive test result 0.874 0.903 0.826 Indeterminate 0.093 0.122 0.066 Negative test result 0.020 0.026 0.013 MRPA + MRV Positive test result 0.792 0.837 0.723 Indeterminate 0.046 0.061 0.032 Negative test result 0.014 0.018 0.009 PE likelyNo test (pretest probability)0.3440.360Unsafe0.225 MDCTPA Positive test result 0.912 0.917 0.851 Indeterminate 0.322 0.337 0.208 Negative test result 0.086 0.092 0.050 MDCTPA + CTV Positive test result 0.904 0.910 0.839 Indeterminate 0.166 0.176 0.099 Negative test result 0.059 0.063 0.033 MRPA Positive test result 0.975 0.977 0.956 Indeterminate 0.371 0.387 0.246 Negative test result 0.102 0.109 0.059 MRPA + MRV Positive test result 0.956 0.959 0.923 Indeterminate 0.216 0.228 0.132 Negative test result 0.074 0.079 0.042
CTV, computed tomography venography; MDCTPA, multidetector computed tomography pulmonary angiography; MRPA, magnetic resonance pulmonary angiography; MRV, magnetic resonance venography; PE, pulmonary embolism.
TABLE 7
Nomogram of Posttest Probability of PE for Miniati at Four-level Clinical Prediction Rule
Clinical Prediction Rule Miniati Four-level Study Test Result Posttest Probability Low clinical probabilityNo test (pretest probability)0.040 MDCTPA Positive test result 0.451 Indeterminate 0.036 Negative test result 0.007 MDCTPA + CTV Positive test result 0.428 Indeterminate 0.016 Negative test result 0.005 MRPA Positive test result 0.759 Indeterminate 0.045 Negative test result 0.009 MRPA + MRV Positive test result 0.634 Indeterminate 0.021 Negative test result 0.006 Intermediate clinical probabilityNo test (pretest probability)0.220 MDCTPA Positive test result 0.848 Indeterminate 0.203 Negative test result 0.048 MDCTPA + CTV Positive test result 0.835 Indeterminate 0.097 Negative test result 0.033 MRPA Positive test result 0.955 Indeterminate 0.241 Negative test result 0.058 MRPA + MRV Positive test result 0.921 Indeterminate 0.129 Negative test result 0.041 Moderately High Clinical ProbabilityNo test (pretest probability)0.740 MDCTPA Positive test result 0.983 Indeterminate 0.720 Negative test result 0.339 MDCTPA + CTV Positive test result 0.981 Indeterminate 0.519 Negative test result 0.254 MRPA Positive test result 0.995 Indeterminate 0.762 Negative test result 0.382 MRPA + MRV Positive test result 0.992 Indeterminate 0.599 Negative test result 0.302 High clinical probabilityNo test (pretest probability)0.980 MDCTPA Positive test result 0.999 Indeterminate 0.978 Negative test result 0.898 MDCTPA + CTV Positive test result 0.999 Indeterminate 0.949 Negative test result 0.854 MRPA Positive test result 1.000 Indeterminate 0.982 Negative test result 0.914 MRPA + MRV Positive test result 1.000 Indeterminate 0.963 Negative test result 0.882
CTV, computed tomography venography; MDCTPA, multidetector computed tomography pulmonary angiography; MRPA, magnetic resonance pulmonary angiography; MRV, magnetic resonance venography; PE, pulmonary embolism.
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Discussion
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Worked Example
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Limitations
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Conclusions
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