Article

Clinical Validity of a Negative Computed Tomography Scan in Patients With Suspected Pulmonary Embolism

Harvard University, Cambridge, Massachusetts, United States
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 05/2005; 293(16):2012-7. DOI: 10.1001/jama.293.16.2012
Source: PubMed

ABSTRACT

The clinical validity of using computed tomography (CT) to diagnose peripheral pulmonary embolism is uncertain. Insufficient sensitivity for peripheral pulmonary embolism is considered the principal limitation of CT.
To review studies that used a CT-based approach to rule out a diagnosis of pulmonary embolism.
The medical literature databases of PubMed, MEDLINE, EMBASE, CRISP, metaRegister of Controlled Trials, and Cochrane were searched for articles published in the English language from January 1990 to May 2004.
We included studies that used contrast-enhanced chest CT to rule out the diagnosis of acute pulmonary embolism, had a minimum follow-up of 3 months, and had study populations of more than 30 patients.
Two reviewers independently abstracted patient demographics, frequency of venous thromboembolic events (VTEs), CT modality (single-slice CT, multidetector-row CT, or electron-beam CT), false-negative results, and deaths attributable to pulmonary embolism. To calculate the overall negative likelihood ratio (NLR) of a VTE after a negative or inconclusive chest CT scan for pulmonary embolism, we included VTEs that were objectively confirmed by an additional imaging test despite a negative or inconclusive CT scan and objectively confirmed VTEs that occurred during clinical follow-up of at least 3 months.
Fifteen studies met the inclusion criteria and contained a total of 3500 patients who were evaluated from October 1994 through April 2002. The overall NLR of a VTE after a negative chest CT scan for pulmonary embolism was 0.07 (95% confidence interval [CI], 0.05-0.11); and the negative predictive value (NPV) was 99.1% (95% CI, 98.7%-99.5%). The NLR of a VTE after a negative single-slice spiral CT scan for pulmonary embolism was 0.08 (95% CI, 0.05-0.13); and after a negative multidetector-row CT scan, 0.15 (95% CI, 0.05-0.43). There was no difference in risk of VTEs based on CT modality used (relative risk, 1.66; 95% CI, 0.47-5.94; P = .50). The overall NLR of mortality attributable to pulmonary embolism was 0.01 (95% CI, 0.01-0.02) and the overall NPV was 99.4% (95% CI, 98.7%-99.9%).
The clinical validity of using a CT scan to rule out pulmonary embolism is similar to that reported for conventional pulmonary angiography.

Full-text

Available from: Uwe Joseph Schoepf
REVIEW
Clinical V alidity of a Negative
Computed Tomography Scan in Patients
With Suspected Pulmonary Embolism
A Systematic Review
Rene Quiroz, MD, MPH
Nils Kucher, MD
Kelly H. Zou, PhD
Florian Kipfmueller, BS
Philip Costello, MD
Samuel Z. Goldhaber, MD
U. Joseph Schoepf, MD
T
HE OPTIMAL DIAGNOSTIC IMAG-
ing modality for acute pulmo-
nary embolism continues to be
debated. Computed tomogra-
phy (CT) is readily available at most in-
stitutions and is rapidly becoming the
first-line imaging test for the assess-
ment of patients with suspected acute
pulmonary embolism.
1,2
However, con-
ventional single-slice spiral CT has in-
sufficient sensitivity
3-5
for isolated pe-
ripheral pulmonary embolism. The
clinical importance of detecting and
treating peripheral pulmonary embo-
lism remains uncertain. However, many
patients with negative CT scans re-
ceive additional imaging tests to de-
finitively rule out a diagnosis of pul-
monary embolism. The additional tests
increase a patient’s exposure to radia-
tion and risk of complications,
6,7
and in-
crease societal health care costs.
The most reliable method to deter-
mine the accuracy of a diagnostic test
to rule out a disease is to perform a pro-
spective study in which a diagnostic cri-
terion with a high negative predictive
value (NPV) is used. Although pulmo-
Author Affiliations:Department of Radiology(Drs Quiroz,
Zou, Costello, and Schoepf andMr Kipfmueller) and Car-
diovascular Division,Department of Medicine(Drs Quiroz,
Kucher, and Goldhaber), Brigham and Women’s Hos-
pital, Boston, Mass; Department of Health Care Policy,
Harvard Medical School, Boston, Mass (Dr Zou); and
Department of Radiology, Medical University of South
Carolina, Charleston (Drs Costello and Schoepf ).
Corresponding Author: U. Joseph Schoepf, MD,
Department of Radiology, Medical University of
South Carolina, 169 Ashley Ave, Charleston, SC 29425
(schoepf@musc.edu).
Context The clinical validity of using computed tomography (CT) to diagnose pe-
ripheral pulmonary embolism is uncertain. Insufficient sensitivity for peripheral pul-
monary embolism is considered the principal limitation of CT.
Objective To review studies that used a CT-based approach to rule out a diagnosis
of pulmonary embolism.
Data Sources The medical literature databases of PubMed, MEDLINE, EMBASE, CRISP,
metaRegister of Controlled Trials, and Cochrane were searched for articles published
in the English language from January 1990 to May 2004.
Study Selection We included studies that used contrast-enhanced chest CT to rule
out the diagnosis of acute pulmonary embolism, had a minimum follow-up of 3 months,
and had study populations of more than 30 patients.
Data Extraction Two reviewers independently abstracted patient demographics,
frequency of venous thromboembolic events (VTEs), CT modality (single-slice CT, mul-
tidetector-row CT, or electron-beam CT), false-negative results, and deaths attribut-
able to pulmonary embolism. To calculate the overall negative likelihood ratio (NLR)
of a VTE after a negative or inconclusive chest CT scan for pulmonary embolism, we
included VTEs that were objectively confirmed by an additional imaging test despite a
negative or inconclusive CT scan and objectively confirmed VTEs that occurred during
clinical follow-up of at least 3 months.
Data Synthesis Fifteen studies met the inclusion criteria and contained a total of
3500 patients who were evaluated from October 1994 through April 2002. The
overall NLR of a VTE after a negative chest CT scan for pulmonary embolism was
0.07 (95% confidence interval [CI], 0.05-0.11); and the negative predictive value
(NPV) was 99.1% (95% CI, 98.7%-99.5%). The NLR of a VTE after a negative
single-slice spiral CT scan for pulmonary embolism was 0.08 (95% CI, 0.05-0.13);
and after a negative multidetector-row CT scan, 0.15 (95% CI, 0.05-0.43). There
was no difference in risk of VTEs based on CT modality used (relative risk, 1.66; 95%
CI, 0.47-5.94; P=.50). The overall NLR of mortality attributable to pulmonary embo-
lism was 0.01 (95% CI, 0.01-0.02) and the overall NPV was 99.4% (95% CI,
98.7%-99.9%).
Conclusion The clinical validity of using a CT scan to rule out pulmonary embolism
is similar to that reported for conventional pulmonary angiography.
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nary angiography is considered the
standard of reference to diagnose or ex-
clude pulmonary embolism, it has lim-
ited interobserver agreement for sub-
segmental pulmonary embolism
8
with
ranges of 45% to 66% reported.
8,9
Thus, a validation study of chest CT
compared with pulmonary angiogra-
phy will not necessarily determine the
true diagnostic accuracy. A practical ap-
proach to establish the validity of CT
for ruling out clinically significant pul-
monary embolism is to investigate the
rate of a subsequent venous thrombo-
embolic event (VTE) after anticoagu-
lant therapy was withheld after a nega-
tive chest CT scan. We performed a
systematic review of studies using a CT-
based approach to rule out suspected
pulmonary embolism.
METHODS
Literature Review
We searched the databases of PubMed,
MEDLINE, EMBASE, CRISP, meta-
Register of Controlled Trials, and Coch-
rane for articles published in the En-
glish language from January 1990 to
May 2004 using the Medical Subject
Heading terms negative predictive value,
pulmonary embolism, deep vein throm-
bosis, venous thromboembolism, com-
puted tomography, chest CT, and spiral
CT. We also hand-searched relevant
journals, corresponded with investiga-
tors and relevant experts in the field,
and used the Science Citation Index to
cross-reference any articles that met our
selection criteria. The inclusion crite-
ria were defined as (1) appropriate clini-
cal follow-up (ie, office visits, tele-
phone interviews, or questionnaires),
(2) minimum follow-up of 3 months,
(3) study population of more than 30
patients, and (4) chest CT performed
on all patients. Studies were graded and
given a quality score based on the fol-
lowing criteria: (1) published in peer-
reviewed journal, (2) prospective de-
sign, (3) imaging technique explicitly
described, (4) inclusion and exclu-
sion criteria accurately described, (5)
patient demographics collected, (6) fol-
low-up included, and (7) recurrences
and mortality reported.
Studies were excluded if (1)
D-dimer
testing was used as an initial triage tool
and included in the study design, (2)
follow-up or reporting of VTEs was in-
appropriate or absent, (3) the quality
score was less than 5, or (4) the article
was a review or editorial.
Data Abstraction
Two reviewers (R.Q., F.K.) indepen-
dently abstracted data and a third party
(U.J.S.) arbitrated discrepancies be-
tween investigators. Venous thrombo-
embolism was defined as either symp-
tomatic or asymptomatic pulmonary
embolism or deep vein thrombosis. We
also abstracted losses to follow-up, non-
diagnostic scans, CT modality (single-
slice CT, multidetector-row CT, or elec-
tron-beam CT), and death attributable
to a VTE.
Study Selection
Overall, the literature search revealed
22 studies potentially suitable for in-
clusion.
10-31
Seven studies
10-16
were ex-
cluded because they did not meet the
selection criteria or the minimum qual-
ity score, which left 15 studies
17-31
that
were available for analyses (T
ABLE 1).
Three studies had a quality score of 5,
five studies had a quality score of 6, and
7 studies had a quality score of 7. There
were 4 studies assessing recurrent VTEs
in which a negative CT scan was pre-
ceded by a negative ultrasound of the
lower extremities,
31
a ventilation per-
fusion scan,
23,27
or both
18
(Table 1).
Statistical Analysis
We identified the reported number of
cases of pulmonary embolism and deep
vein thrombosis for each study at
months 3, 6, and 12. To calculate the
overall negative likelihood ratio (NLR)
of a VTE after a negative or inconclu-
sive chest CT scan for pulmonary em-
bolism, we included VTEs that were ob-
jectively confirmed by an additional
imaging test despite a negative or in-
conclusive CT scan and objectively con-
firmed VTEs that occurred during clini-
cal follow-up. Patients who received
anticoagulant therapy for reasons other
than a VTE during follow-up were ex-
cluded from the analysis. We used
prevalence of pulmonary embolism
from each of the studies as an estimate
of prior probability. The posttest prob-
ability of a VTE was defined as the prod-
uct of prior odds and NLR. We used the
Q statistic to assess heterogeneity
among studies. Publication bias was ex-
amined by constructing funnel plots
based on the methods of Egger et al
32
and Begg and Berlin.
33
We con-
structed fixed- and random-effects
(DerSimonian-Laird) models
34
to ob-
tain a summary estimate and 95% con-
fidence interval (CI) for VTE and deaths
related to pulmonary embolism.
Because the Q statistic has limited
power and may fail to detect heteroge-
neity,
35,36
we also used meta-regres-
sion
37
to analyze the impact of addi-
tional imaging tests and CT modality
(single-slice CT or multidetector-row
CT) on VTEs. Therefore, we assessed
the difference in VTEs between stud-
ies that used additional imaging tests
prior to chest CT and studies that used
chest CT only by calculating the rela-
tive risk (RR) with 95% CIs. Meta-
regression was also used to investigate
differences in VTEs between studies
that used multidetector-row CT and
those that used single-slice CT. We also
used meta-regression to evaluate dif-
ferences in VTEs between studies that
performed 3 months of follow-up and
those that extended follow-up beyond
3 months. We performed influence
analysis
37,38
to evaluate the weight of in-
dividual studies on the summary effect
estimate by omitting 1 study at a time
and recalculating the summary statis-
tic for the NLR of the remaining stud-
ies. P.05 was considered statistically
significant. All analyses were per-
formed using STATA software version
8.0 (STATA Corp, College Station,
Tex).
RESULTS
Overall, 3500 patients were evaluated
from October 1994 through April 2002
in 15 studies originating from Austria,
Canada, France, Ireland, the Nether-
lands, Sweden, and the United States.
Three CT modalities were used in the
CT FOR SUSPECTED PULMONARY EMBOLISM
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included studies: 12 used single-slice
CT, 2 used multidetector-row CT, and
1 used electron-beam CT. Overall, there
were 153 nondiagnostic scans and 199
patients were lost to follow-up
(T
ABLE 2). Patient follow-up ranged
from 3 to 12 months (Table 1). One
study
30
failed to report VTEs in pa-
tients who underwent additional im-
aging tests after a negative or incon-
clusive chest CT scan (Table 2). For this
study, we included VTEs that oc-
curred during follow-up only.
A random-effects model was used for
the 15 relevant studies (
2
14
= 58.6;
P.001 for heterogeneity). The publi-
cation bias was P.20 for both evalu-
ation plots.
The overall NLR of a VTE after a
negative chest CT scan for pulmonary
embolism was 0.07 (95% CI, 0.05-
0.11) and the NPV was 99.1% (95% CI,
98.7%-99.5%; F
IGURE 1). The NLR of
a VTE after a negative single-slice CT
scan for pulmonary embolism was 0.08
(95% CI, 0.05-0.13); and after multide-
tector-row CT, 0.15 (95% CI, 0.05-
0.43). A total of 36 pulmonary embo-
lism events and 6 deep vein thrombosis
(without pulmonary embolism) events
were observed at months 3, 4, 6, or 12.
There were 15 deaths attributable to a
VTE, either by autopsy (10 studies) or
record review of death certificates (15
studies). The overall NPV for mortal-
ity attributable to pulmonary embo-
lism was 99.4% (95% CI, 98.7%-
99.9%) and the overall NLR was 0.01
(95% CI, 0.01-0.02).
Compared with studies that used chest
CT imaging only, the RR of VTEs in stud-
ies that used additional imaging tests
prior to chest CT was not significantly
reduced (RR, 0.51; 95% CI, 0.22-1.17;
P=.11). Compared with studies that used
multidetector-row CT, the RR of VTEs
in studies that used single-slice CT was
not significantly increased (RR, 1.66; 95%
Table 1. Study Characteristics and Reported Thromboembolic Events
Source
Total
Follow-up, mo
No. of Cases With
Thromboembolic Event
at End of Follow-up
Total No.
of Negative
CT Scans Diagnostic Process and Method
Pulmonary
Embolism
Deep Vein
Thrombosis
Donato et al,
17
2003 3 2 2 239 Sequential medical record review of CT scans;
pretest probability and alternate test results
recorded
Ferretti et al,
18
1997 3 3 3 112 Indeterminate ventilation perfusion scan, Doppler
ultrasonography of legs, CT within 72 h of
ventilation perfusion scan; angiography if CT scan
was negative
Garg et al,
19
1999 6 1 0 78 Medical record review of CT scans; data on alternate
test results unavailable
Goodman et al,
20
2000 3 2 0 198 Prospective, negative CT scan; risk factors recorded
at time of scan; Doppler ultrasonogram obtained
in 42% of patients
Gottsäter et al,
21
2001 3 3 0 215 Medical record review for negative results; alternate
imaging modalities recorded
Kavanagh et al,
22
2004 4 1 0 68 Prospective, CT scan only (1 patient with ventilation
perfusion scan, no ultrasound)
Krestan et al,
23
2004 6 1 0 220 Negative CT scan, recorded ventilation perfusion
scan, pulmonary angiogram, venogram, and
ultrasound
Lombard et al,
24
2003 3 2 0 51 Medical record review of radiology records; recorded
ventilation perfusion scan prior to CT
Lomis et al,
25
1999 6 0 0 100 Prospective CT scans; ultrasound, pulmonary
angiogram, and ventilation perfusion recorded
Nilsson et al,
26
2002 3 4 0 441 Medical record review of referrals to thoracic
radiology; auxiliary ventilation perfusion
information recorded
Ost et al,
27
2001 6 2 1 71 Prospective, clinical suspicion and nondiagnostic
ventilation perfusion scan; various laboratory
tests recorded; ultrasound results mentioned
Remy-Jardin et al,
28
2002 3 1 0 153 Referrals to specialty department; additional tests
could be ordered and were recorded (ventilation
perfusion, ultrasound, pulmonary angiography)
Swensen et al,
29
2002 3 8 0 993 Additional studies recorded, retrospective retrieval of
CT findings
Tillie-Leblond et al,
30
2002 12 3 0 185 Referrals to pulmonology department, recorded
additional tests
van Strijen et al,
31
2003 3 3 0 376 3-Center study, follow-up recorded use of other
imaging modalities
Abbreviation: CT, computed tomographic.
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CI, 0.47-5.94; P=.50). Compared with
studies that performed 3-month follow-
up, the RR of a VTE was not increased
in studies that performed follow-up be-
yond 3 months (RR, 1.05; 95% CI, 0.43-
2.52; P=.11). There was no evidence of
an individual study dominance on the
summary effect estimate by influence
analysis (F
IGURE 2).
COMMENT
Pooled results involving 15 studies and
3500 patients with suspected pulmo-
nary embolism suggest that clinical out-
come is not adversely affected if anti-
coagulant therapy is withheld based on
a negative CT scan. The overall NPV of
99.1% for VTEs in our analysis com-
pares favorably with previously re-
ported NPVs of 98.4%
39
and 100%
40
when pulmonary angiography was used
and is superior to a negative/low-
probability ventilation perfusion scan
(range, 75.9%-88%).
14,41
The im-
proved visualization of peripheral pul-
monary arteries that has been achieved
by the ongoing technical refinement of
CT techniques
42-44
should further in-
crease the clinical validity of chest CT.
Inaccurate detection of isolated pe-
ripheral pulmonary embolism is con-
sidered the principal limitation of CT,
although the clinical significance of
small isolated clots in the absence of
central embolism is not well under-
stood. The majority of studies that were
included in our analysis used conven-
tional single-slice CT for which rates of
Table 2. Patient Exclusion Criteria and False-Negative Findings
Source
Type of Scan
No. Lost to
Follow-up/
Total*
No. of Patients
With Exclusions/
Total*
False-Negative Results‡
Initial Negative
Nondiagnostic/
Total* Final
Pulmonary
Embolism
Deep Vein
Thrombosis
Donato et al,
17
2003 433 314 14/314 240 4/314 56/300 1 0
Ferretti et al,
18
1997 164 125 0 116 1/125 8/125 1 4
Garg et al,
19
1999 126 84 2/84 78 1/82 3/82 0 0
Goodman et al,
20
2000 393 285 NA 198 24/285 63/285 0 0
Gottsäter et al,
21
2001 305 244 17/244 220 3/244 21/244 0 5
Kavanagh et al,
22
2004 102 85 0 79 0 6/85 0 0
Krestan et al,
23
2004 485 325 26/485 230 56/325 41/325 2 8
Lombard et al,
24
2003 62 51 0 41 7/51 3/51 0 0
Lomis et al,
25
1999 143 121 8/121 91 13/121 9/121 0 3
Nilsson et al,
26
2002 751 593 12/593 449 45/593 87/593 1 0
Ost et al,
27
2001 103 81 8/81 73 0 0 1 1
Remy-Jardin et al,
28
2002 259 208 20/208 173 12/208 3/208 0 10
Swensen et al,
29
2002 1512 1010 NA 982 19/1010 9/1010 0 11
Tillie-Leblond et al,
30
2002 334 237 38/237 185 14/237 0 NR NR
van Strijen et al,
31
2003 510 386 8/386 378 0 0 0 5
Abbreviation: NR, data not reported by Tillie-Leblond et al.
30
*The total number of patients in a particular category is provided if the total is not the same as the total in the initial scan column.
†Anticoagulation.
‡Venous thromboembolism diagnosed by additional imaging test despite a negative or inconclusive chest computed tomographic scan.
Figure 1. Posttest Probability of a Venous Thromboembolism Event After a Negative Chest
Computed Tomographic Scan for Pulmonary Embolism
Overall
Source
Donato et al,
17
2003
Ferretti et al,
18
1997
Garg et al,
19
1999
Goodman et al,
20
2000
Gottsäter et al,
21
2001
Kavanagh et al,
22
2004
Krestan et al,
23
2004
Lombard et al,
24
2003
Lomis et al,
25
1999
Nilsson et al,
26
2002
Ost et al,
27
2001
Remy-Jardin et al,
28
2002
Swensen et al,
29
2002
Tillie-Leblond et al,
30
2002
van Strijen et al,
31
2003
Prior
Probability,
%
27.5
23.8
38.1
27.5
20.0
16.7
27.6
17.7
15.4
21.0
21.3
19.7
33.2
24.3
24.3
Posttest
Probability,
%
1.5
6.4
1.2
0.7
2.8
1.1
2.8
3.2
2.1
0.8
4.8
4.2
1.8
1.1
1.9
NLR (95% CI)
0.07 (0.05-0.11)
0.04 (0.02-0.10)
0.22 (0.13-0.37)
0.02 (0.01-0.14)
0.02 (0.01-0.07)
0.12 (0.06-0.22)
0.06 (0.01-0.37)
0.08 (0.04-0.13)
0.15 (0.04-0.55)
0.12 (0.04-0.35)
0.03 (0.01-0.07)
0.19 (0.08-0.41)
0.18 (0.10-0.30)
0.04 (0.02-0.06)
0.04 (0.01-0.11)
0.06 (0.03-0.12)
0.01 1.000.10
Negative Likelihood Ratio
The size of each square is proportional to the precision of the estimate (number of patients, number of events,
and variance). The dashed vertical line represents the overall negative likelihood ratio of 0.07.
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30% and higher were reported for miss-
ing a diagnosis of peripheral pulmo-
nary embolism.
3-5
Thus, it can be as-
sumed that a significant number of
patients in our pooled analysis had pe-
ripheral pulmonary embolism, which
was not diagnosed. However, the low
incidence of VTEs during follow-up
across all studies shows that even if pe-
ripheral emboli were missed and sub-
sequently not treated based on a nega-
tive CT scan, the patient outcome was
not adversely affected.
Chest CT to exclude pulmonary
embolism is often used in combina-
tion with other imaging tests, includ-
ing ventilation perfusion scan and
venous ultrasound of the lower
extremities, as it was done in the
majority of the studies included in our
meta-analysis. In addition, chest CT
can be combined with CT venography
of the lower extremity veins.
45,46
An
additional imaging test, however, may
affect the NLR and NPV for VTEs on a
subsequent chest CT scan. Therefore,
if CT is used as the sole imaging test
to rule out pulmonary embolism, the
actual NLR for a recurrent VTE may
be higher and the NPV may be lower
than in the present meta-analysis. The
posttest probability of having a VTE
following a negative chest CT scan is
directly related to the prevalence of
pulmonary embolism that varied
across the included studies. Thus, the
accuracy of chest CT to rule out pul-
monary embolism also depends on the
presence of risk factors in the popula-
tion. In contrast to a patient with a
low prior probability of a VTE, the
posttest probability of having a VTE
following a negative chest CT scan
may remain substantial in a high-risk
patient, and additional imaging tests
would be required.
In the absence of an independent
standard of reference, we systemati-
cally analyzed the clinical validity of a
negative CT scan using outcome-
based standards.
47
A 3-month fol-
low-up was deemed sufficient because
approximately half of all recurrences
occur in the first week after a diagno-
sis of pulmonary embolism has been
made.
48
By using follow-up as an out-
come measure, NPV may be underes-
timated if the study population has co-
morbidities that increase the risk of
developing subsequent pulmonary em-
bolism de novo.
22
Because of the substantial differ-
ences between the available diagnostic
chest CT modalities, a meta-analysis was
deemed necessary to investigate the
overall clinical validity of a negative chest
CT to rule out clinically significant pul-
monary embolism. Variation among
studies included direct or indirect fol-
low-up; use of electron-beam CT,
29
single-slice CT,
18-21,23-28,30,31
multidetector-
row CT,
22,28
or both single-slice and mul-
tidetector-row CT
17
; single
17,19-22,24-26,28-30
or multiple
18,23,27,31
screening methods;
overall prevalence of pulmonary embo-
lism (15%-38%); retrospective
19,21,23-26,29
or prospective
17,18,20,22,27,28,30,31
design;
academic or community-based set-
tings; and additional imaging tests dur-
ing enrollment.
18,23,27,31
Although meta-
regression and influence analysis did not
reveal a significant source of heteroge-
neity among studies, meta-regression
uses summarized data and may pro-
vide an inaccurate impression of pa-
tient characteristics.
Although guidelines exist for meta-
analyses in evaluating diagnostic
tests,
49,50
there is no agreed method to
assess publication bias for diagnostic
meta-analysis.
51
We recognize that we
undoubtedly overlooked foreign-
language studies and unpublished
data. Also, differential reference stan-
dard bias
52
may be present among
patients with negative findings, who
may represent a healthier population
than those with positive findings. The
patients from the included studies are
not necessarily representative of the
entire population of patients with sus-
pected pulmonary embolism because
contrast-enhanced chest CT was not
performed in patients with severe
renal dysfunction, or in patients with a
history of anaphylactic reaction to
iodine contrast, or in patients who
were pregnant.
Overall, our results suggest that with-
holding anticoagulant therapy after a
negative CT scan appears to be safe. Ad-
ditional imaging for ruling out pulmo-
nary embolism is not warranted. This
strategy may minimize radiation expo-
sure, invasive procedures, and health
care costs.
Author Contributions: Dr Schoepf had full access to
all of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data
analysis.
Study concept and design: Zou, Costello, Goldhaber,
Kucher, Schoepf.
Acquisition of data: Quiroz, Kipfmueller, Schoepf.
Analysis and interpretation of data: Quiroz, Zou,
Goldhaber, Kucher, Schoepf.
Drafting of the manuscript: Quiroz, Zou, Schoepf.
Critical revision of the manuscript for important in-
tellectual content: Zou, Kipfmueller, Costello,
Goldhaber, Kucher, Schoepf.
Statistical analysis: Quiroz, Zou, Kucher.
Administrative, technical, or material support:
Kipfmueller, Goldhaber.
Study supervision: Costello, Goldhaber, Kucher,
Schoepf.
Financial Disclosures: Dr Zou has received funding
from the National Institutes of Health. None of the
other authors reported financial disclosures.
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CT FOR SUSPECTED PULMONARY EMBOLISM
©2005 American Medical Association. All rights reserved. (Reprinted) JAMA, April 27, 2005—Vol 293, No. 16 2017
at Stroger Hospital, on February 22, 2006 www.jama.comDownloaded from
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  • Source
    • "A meta-analysis by Quiroz et al. with pooled results involving 15 studies and 3,500 patients with suspected PE suggested that clinical outcome is not adversely affected if anticoagulant therapy is withheld based on a negative CT scan with a negative predictive value of 99.1 % [45]. These studies were performed with older generation MDCT systems, and it is therefore possible that subsegmental pulmonary emboli remained undetected. "
    [Show abstract] [Hide abstract] ABSTRACT: Acute pulmonary embolism (PE) is diagnosed either by ventilation/perfusion (V/P) scintigraphy or pulmonary CT angiography (CTPA). In recent years both techniques have improved. Many nuclear medicine centres have adopted the single photon emission CT (SPECT) technique as opposed to the planar technique for diagnosing PE. SPECT has been shown to have fewer indeterminate results and a higher diagnostic value. The latest improvement is the combination of a low-dose CT scan with a V/P SPECT scan in a hybrid tomograph. In a study comparing CTPA, planar scintigraphy and SPECT alone, SPECT/CT had the best diagnostic accuracy for PE. In addition, recent developments in the CTPA technique have made it possible to image the pulmonary arteries of the lungs in one breath-hold. This development is based on the change from a single-detector to multidetector CT technology with an increase in volume coverage per rotation and faster rotation. Furthermore, the dual energy CT technique is a promising modality that can provide functional imaging in combination with anatomical information. Newer high-end CT scanners and SPECT systems are able to visualize smaller subsegmental emboli. However, consensus is lacking regarding the clinical impact and treatment. In the present review, SPECT and SPECT in combination with low-dose CT, CTPA and dual energy CT are discussed in the context of diagnosing PE.
    Full-text · Article · Nov 2013 · European Journal of Nuclear Medicine
  • Source
    • "The consequences of missing the diagnosis and the ease of recalling prior serious cases may lead to an overestimation of the probability of PE and lower the threshold for initiating a cascade of diagnostic testing, a phenomenon described as the availability heuristics in cognitive psychology [7] [8]. The widespread round-theclock availability, excellent accuracy [9] [10] of CT pulmonary angiography (CTPA), and ability to provide an alternative diagnosis [11] [12] may further lower the threshold for performing this imaging study and result in its overuse. On the other hand, outcome studies using clinical prediction rules to refine diagnostic certainty have shown that PE can be safely excluded in patients with low clinical probability and normal d-dimer levels without an imaging study [1] [2] [5]. "
    [Show abstract] [Hide abstract] ABSTRACT: Objectives. We conducted a study to answer 3 questions: (1) is CT pulmonary angiography (CTPA) overutilized in suspected pulmonary embolism (PE)? (2) What alternative diagnoses are provided by CTPA? (3) Can CTPA be used to evaluate right ventricular dilatation (RVD)? Methods. We retrospectively reviewed the clinical information of 231 consecutive emergency department patients who underwent CTPA for suspected PE over a one-year period. Results. The mean age of our patients was 53 years, and 58.4% were women. The prevalence of PE was 20.7%. Among the 136 patients with low clinical probability of PE, a d-dimer test was done in 54.4%, and it was normal in 24.3%; none of these patients had PE. The most common alternative findings on CTPA were emphysema (7.6%), pneumonia (7%), atelectasis (5.5%), bronchiectasis (3.8%), and congestive heart failure (3.3%). The sensitivity and negative predictive value of CTPA for (RVD) was 92% and 80%, respectively. Conclusions. PE could have been excluded without CTPA in ~1 out of 4 patients with low clinical probability of PE, if a formal assessment of probability and d-dimer test had been done. In patients without PE, CTPA did not provide an alternative diagnosis in 65%. In patients with PE, CTPA showed the potential to evaluate RVD.
    Full-text · Article · Aug 2013 · Pulmonary Medicine
  • Source
    • "There is actually a conclusive evidence that MDCT scan if positive provides reliable confirmation of the presence of PE and more importantly if negative rules out clinically significant PE with a high negative predictor value (99.4%).34,35 However, considering ultrasound of the lower extremities in patients with high clinical suspicion for acute PE and a negative CT would appear prudent.36,37 "
    [Show abstract] [Hide abstract] ABSTRACT: The contribution of lower extremity venous duplex scan to the diagnostic strategy for pulmonary embolism has been demonstrated by many authors. However, the positive diagnostic value of this noninvasive test in clinically suspected pulmonary embolism is not very high (10% - 18%). Since thromboembolic risks increase considerably in hospitalized patients with advanced age, this study aims to determine the importance of lower extremity venous color flow duplex scan in this particular subgroup of patients with clinically suspected pulmonary embolism. The effects of clinical presentation and risk factors on the results of duplex scan have been also studied. Between July 2007 and January 2010, 95 consecutive Lebanese geriatric (≥ 60 years of age) inpatients with clinically suspected pulmonary embolism assessed in an academic tertiary-care center for complete lower extremity venous color flow duplex scan were retrospectively reviewed. Age varied between 60 and 96 years (mean, 79.9 years). Forty patients were males and 55 females. Absence of compressibility was the most important criteria for detecting acute venous thrombosis. Out of 95 patients, 33 patients (34.7%) were diagnosed with recent deep venous thrombosis of lower extremities (14 proximal and 19 distal) using complete venous ultrasound. Nine of these 33 patients (27.2%) had a history of venous thromboembolism and eleven (33.3%) presented with edema of lower extremities. A total of 28 patients (84.8%) with positive duplex scan had associated risk factors for venous thromboembolism. Lower extremity venous color flow duplex scan appears to be a reasonable initial screening test in the diagnostic algorithm of pulmonary embolism in geriatric inpatients with clinically suspected pulmonary embolism. This is particularly true in patients with a history of venous thromboembolism, in patients with a clinical presentation suggesting venous thrombosis, in uremic patients and in patients with altered general and mental status who are not candidates for chest computed tomography.
    Full-text · Article · Sep 2011 · Vascular Health and Risk Management
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