Keywords
cancer - incidental findings - pulmonary embolism - thrombosis - venous thromboembolism
Introduction
Cancer and its treatment increase the risk of developing venous thromboembolism (VTE)
including deep vein thrombosis (DVT) and pulmonary embolism (PE). There has been a
progressive rise in the incidence of cancer-associated VTE compared with a steady
incidence of VTE in the general population[1] within the context of (1) global longer life expectancy in the general population
leading to more cancer diagnosis, (2) recent advances in tumor treatment significantly
prolonging the survival of patients with cancer,[2] and (3) technological advances improving computerized tomography (CT) equipment
and the broader use of CT scans resulting in the diagnosis of incidental or unsuspected
VTE during routine examinations.[3]
In this regard, incidental VTE and, especially, unsuspected PE (UPE) currently represent
up to half of the VTE events in patients with cancer.[4]
[5]
[6]
[7]
[8]
[9] UPE is defined as an unsuspected filling defect in the pulmonary arteries identified
on CT imaging performed for another indication, such as a routine staging scan to
assess cancer disease status. The diagnosis and treatment of UPE is challenging for
radiologists and clinicians.
In a recent systematic review, the median prevalence of UPE was reported to be 3.36%,
ranging widely according to the underlying primary tumor.[10] Several cumulative observational studies have suggested similar outcomes regarding
mortality when comparing incidental versus symptomatic VTE events.[11]
[12]
[13] Thus, in the absence of further knowledge, the current clinical guidelines of international
societies recommend treating UPE similar to acute symptomatic PE.[8]
[14]
[15]
[16]
The clinical severity of patients with PE ranges widely from completely asymptomatic
to potentially life-threatening events. Risk-stratification models for acute PE include
variables related to hemodynamic instability, right ventricle (RV) overload, and cardiac
biomarkers.[16]
[17]
[18]
[19] The thrombotic burden of PE is not included in these models, since data regarding
their prognostic impact is controversial.[20]
In this regard, saddle PE represents a prime example of large thrombotic burden. The
term “saddle PE” is a radiological concept commonly used in daily practice by clinicians
and radiologists which is classically defined as a visible thrombus that straddles
the bifurcation of the main pulmonary artery trunk,[21]
[22] as shown in [Fig. 1].
Fig. 1 Chest CT angiography depicting a saddle PE. Image shows thrombus straddling the bifurcation
of the pulmonary artery trunk (arrow) with extension into both main pulmonary arteries
(arrowheads). CT, computed tomography; PE, pulmonary embolism.
There is scarce information regarding the prevalence, clinical characteristics, and
outcomes of patients with cancer and saddle PE apart from a few case reports in patients
with suspected PE[23]
[24] and, more recently, in patients with UPE.[25]
[26]
The aim of the present study was to assess the prevalence, clinical findings, and
short-term outcomes of patients with cancer and saddle PE including acute symptomatic
and unsuspected events.
Methods
Study Design and Setting
We performed a retrospective analysis of data prospectively collected from consecutive
patients with cancer-associated PE from a local registry at the Medical Oncology Department
in the Hospital Clinic Barcelona (Spain), an urban teaching hospital covering an area
of 500,000 inhabitants as reported elsewhere.[5]
[27]
[28]
[29] Patients with radiologically confirmed PE with either acute symptomatic or unsuspected
events between March 1, 2006, and October 31, 2014, were evaluated.
Eligible patients had been previously diagnosed with cancer, were >18 years of age
and were diagnosed with cancer-associated PE by either CT angiography, specifically
ordered to depict PE (acute suspected events), or a scheduled conventional CT scan
(UPE). Patients diagnosed with lung perfusion scintigraphy were excluded from the
present analysis. Patient management and follow-up was made according to the standard
local clinical practice protocol as part of previous research and reported elsewhere.[27]
The primary objective was to assess the prevalence, clinical characteristics, management,
and short-term outcomes within 30 days of PE diagnosis in patients with saddle versus
nonsaddle PE including patients with acute symptomatic and UPE events.
Secondary objectives included: (1) In-hospital outcomes, (2) radiological findings
related to RV overload and additional radiological findings according to the presence
of saddle versus nonsaddle PE, and (3) overall comparison of baseline characteristics
and outcomes among patients with saddle PE according to the presence of acute symptomatic
versus unsuspected events.
The study was approved by the local clinical research ethics board. Informed written
consent was obtained from all the prospectively enrolled participants. Patient data
were anonymized and deidentified prior to analysis.
Demographic and Clinical Variables
Demographic and Clinical Variables
The variables analyzed were collected from the hospital medical records and included
demographic variables at PE diagnosis, as well as cancer-related variables, such as
the location of primary tumor, the presence of metastases, anticancer treatment at
PE diagnosis, and performance status according to the Eastern Cooperative Oncology
Group scale.
Patients were considered to have an outpatient diagnosis of PE if the thrombotic event
was detected during or before attendance to the emergency department (ED). Patients
presenting an episode of VTE more than 7 days before PE diagnosis were classified
having previous VTE, whereas those with a diagnosis of DVT within 7 days of PE diagnosis
were considered to have concomitant DVT. Symptoms (dyspnea, chest pain, or hemoptysis)
and vital signs (heart rate, systolic blood pressure, and oxygen saturation) were
assessed on hospital arrival in patients diagnosed in the outpatient setting. In the
case of hospital-acquired PE events, we collected the last vital signs registered
before the diagnosis of PE. Causes of death were recorded according to a multiple-choice
classification by the clinician in charge including pulmonary embolism, cancer progression,
and/or other causes.
Systematic Radiological Examination
Systematic Radiological Examination
CT scans were thoroughly reviewed by either one of two senior chest radiologists (M.B.
and M.S.) as part of previously reported research.[5]
[27]
[28]
[29] Radiologist were blinded to clinical data and outcomes.
Conventional CT scans were performed with a dual CT scanner (Somatom scanner; Siemens
Medical Solutions, Somatom Healthcare, Erlangen, Germany) using a 100-mL intravenous
injection of nonionic contrast medium (300 mg/mL) infused at a rate of 3 mL/s. Conventional
CT of the thorax was performed with an automatic detection (care bolus) of contrast
in the ascending aorta, with 1.2-mm collimation and 5-mm reconstruction. Conventional
CT of the abdomen and pelvis was performed from the diaphragm to the pubic symphysis
70 to 90 seconds after the infusion of the contrast medium for the chest CT.
The CT scan specific for the depiction of PE was performed with the 64 multidetector
CT scan, with 0.6-mm collimation and 1-mm reconstruction including a CT pulmonary
angiogram (CTPA) of the pulmonary arteries and lower limb venography. A thrombus in
either scan was defined as a definite intraluminal filling defect identified on at
least two consecutive transverse images.[30]
[31]
Saddle PE is radiologically defined as “a thrombus that straddles the bifurcation
of the pulmonary artery trunk, often with extension into both the right and left main
pulmonary arteries.”[21]
[22]
A thrombus was considered peripheral if its most proximal occluded artery was either
a segmental or subsegmental artery. The presence of either a RV to left ventricle
(LV) diameter ratio greater than or equal to 1, septum displacement, or contrast reflux
to suprahepatic veins were considered signs of RV overload.
Analysis included other additional findings not directly related to PE such as the
presence of lung nodules, cancer progression, carcinomatous lymphangitis, pleural
effusion, pericardial effusion, and “other findings” (atelectasia, pneumonia, additional
thrombus diagnosis, emphysema, pulmonary edema, pulmonary fibrosis, pneumothorax,
ground-glass opacities, or chronic pulmonary embolism).
Outcome Measures
The following 30-day outcome measures were included the following: (1) overall mortality,
(2) PE-related mortality, (3) VTE recurrence defined as an objectively confirmed (with
the Doppler ultrasound, CTPA, or lung perfusion scintigraphy) new episode of PE or
DVT, and (4) major bleeding according to the International Society on Thrombosis and
Haemostasis criteria (fatal bleed and/or symptomatic plus critical organ or reduction
in hemoglobin >2 g/dL or transfusion of >2U of red blood cells).[32]
All clinical data were reviewed and evaluated by the authors and collected in a specific
database designed for the purpose of this study.
Data Analysis
Descriptive statistics, including means, standard deviation, and percentages were
used to summarize patient characteristics. Comparisons between saddle and nonsaddle
PEs were made. The two-sided t-test was used to assess statistical significance for continuous variables and the
Chi-square test or Fisher's exact test was used for categorical variables. A p < 0.05 was deemed to be statistically significant. The analyses were performed using
SPSS v24 software.
Results
A total of 315 patients with cancer and PE were collected during the study period.
Of these, 289 cases (39% female; mean age: 64 years) were diagnosed by CT scan with
available imaging tests for radiological reviewing and were included in the study.
No patient was lost to follow-up. Saddle PE was diagnosed in 36 of the 289 cases (12.5%
of the overall cohort) including 21 (58%) acute symptomatic events and 15 (42%) cases
of UPE as shown in the flowchart ([Fig. 2]). Of note, saddle PE was found in 15 (8.8%) out of 170 patients with UPE.
Fig. 2 Flow chart of patient selection for the study. CT, computed tomography; PE, pulmonary
embolism.
Saddle Pulmonary Embolism versus Nonsaddle Pulmonary Embolism
The main baseline characteristics and clinical features at presentation according
to the presence of saddle versus nonsaddle PE are shown in [Table 1]. No differences regarding gender, age, chronic lung or heart conditions, proportion
of inpatients at PE diagnosis, and cancer type and anticancer therapies were observed
on comparing patients with saddle versus nonsaddle PE. Of note, patients with saddle
PE more frequently had a history of VTE than those with nonsaddle PE (31 and 13%,
respectively; p = 0.008).
Table 1
Baseline characteristics according to the presence of saddle versus nonsaddle pulmonary
embolism
|
Overall (n = 289)
Mean ± SD/n (%)
|
Saddle PE (n = 36)
Mean ± SD/n (%)
|
Nonsaddle PE (n = 253)
Mean ± SD/n (%)
|
p-Value
|
|
Age (y)
|
64 ± 11.5
|
65 ± 10.8
|
64 ± 11.8
|
>0.5
|
|
Gender (F)
|
112 (39)
|
14 (39)
|
98 (39)
|
>0.5
|
|
Chronic lung condition
|
62 (21)
|
7 (19)
|
55 (22)
|
>0.5
|
|
Chronic heart disease
|
18 (6)
|
1 (3)
|
17 (7)
|
>0.5
|
|
Inpatient at PE diagnosis
|
39 (13)
|
3 (8)
|
36 (14)
|
0.44
|
|
Previous VTE
|
45 (16)
|
11 (31)
|
34 (13)
|
0.008
|
|
Concomitant DVT
|
63 (22)
|
9 (25)
|
54 (21)
|
>0.5
|
|
Cancer type
|
0.45
|
|
Lung
|
99 (34)
|
10 (28)
|
89(35)
|
|
|
Colorectal
|
40 (14)
|
7 (19)
|
33 (13)
|
|
Genitourinary
|
39 (13)
|
4 (11)
|
35 (14)
|
|
Gynecologic
|
33 (11)
|
5 (14)
|
28 (11)
|
|
Upper GI
|
33 (11)
|
4 (11)
|
29 (11)
|
|
Breast
|
15 (5)
|
2 (6)
|
13 (5)
|
|
Other
|
30 (10)
|
4 (11)
|
26 (10)
|
|
Metastatic cancer
|
236 (82)
|
27 (75)
|
209 (83)
|
0.27
|
|
Surgery
|
23 (8)
|
4 (11)
|
19 (8)
|
0.455
|
|
Chemotherapy
|
149 (52)
|
21 (58)
|
128 (51)
|
0.385
|
|
Radiological test
|
0.025
|
|
CT scan angiography (acute suspected PE)
|
119 (41)
|
21 (58)
|
98 (39)
|
|
Conventional CT scan (UPE)
|
170 (59)
|
15 (42)
|
155 (61)
|
|
PE symptoms
|
|
|
None
|
134 (46)
|
11 (31)
|
123 (49)
|
0.042
|
|
Dyspnea
|
136 (47)
|
24 (67)
|
112 (45)
|
0.005
|
|
Chest pain
|
40 (14)
|
6 (17)
|
34 (13)
|
>0.5
|
|
Syncope
|
20 (7)
|
4 (11)
|
16 (6)
|
0.29
|
|
Hemoptysis
|
4 (1)
|
0 (0)
|
4 (2)
|
>0.5
|
|
Vital signs
|
|
Arterial hypotension BP < 100 mm Hg
|
21 (7)
|
1 (3)
|
20 (8)
|
0.49
|
|
Tachycardia HR > 100 beats per minute
|
77 (27)
|
16 (44)
|
61 (24)
|
0.01
|
|
Oxygen saturation <90%
|
35 (12)
|
7 (19)
|
28 (11)
|
0.17
|
|
Oxygen saturation <95%
|
99 (34)
|
20 (56)
|
79 (31)
|
0.004
|
Abbreviations: BP, blood pressure; CT, computerized tomography; DVT, deep vein thrombosis;
F, female; GI, gastrointestinal; HR, heart rate; PE, pulmonary embolism; SD, standard
deviation; UPE, unsuspected pulmonary embolism; VTE, venous thromboembolism.
Note: Bold p-values are statistically significant.
The rate of saddle PE was greater among patients with acute symptomatic PEs (21 out
of 119; 18%) than in patients with UPE (15 out of 170; 9%), being this difference
statistically significant (p = 0.025).
Of note, a greater proportion of patients with saddle PE were diagnosed as having
acute symptomatic PE (58 vs. 39%; p = 0.025) compared with those with nonsaddle PE.
Patients with saddle PE were more likely to have PE-related symptoms (69 vs. 51%;
p = 0.042), tachycardia (44 vs. 24%; p = 0.01), and oxygen saturation <95% (56 vs. 31%; p = 0.004) compared with patients with nonsaddle PE.
[Table 2] summarizes the main information regarding PE management and PE treatment with no
differences according to saddle versus nonsaddle PE. Regarding the outcomes, notably
the overall and PE-related mortality within 30 days were 15 and 2%, respectively,
with no significant differences according to saddle versus nonsaddle PE. The overall
rate of 30-day VTE recurrence (5%) and major bleeding (2%) were also found to be similar
in both groups.
Table 2
Management of patients and 30-day outcomes according to the presence of saddle versus
nonsaddle pulmonary embolism
|
Overall (n = 289)
n (%)
|
Saddle PE (n = 36)
n (%)
|
Nonsaddle PE (n = 253)
n (%)
|
p-Value
|
|
Management setting
|
0.21
|
|
Inpatient at PE diagnosis
|
39 (14)
|
3 (8)
|
36 (14)
|
|
Outpatient (<24 hours after diagnosis)
|
128 (44)
|
13 (36)
|
115 (46)
|
|
Hospital admission in general ward
|
122 (42)
|
20 (56)
|
102 (40)
|
|
Management
|
|
Anticoagulation
|
289 (100)
|
36 (100)
|
253 (100)
|
>0.5
|
|
Fibrinolysis
|
5 (2)
|
1 (3)
|
4 (2)
|
0.49
|
|
Cava filter
|
12 (3)
|
3 (8)
|
9 (4)
|
0.18
|
|
Outcomes within 30 days
|
|
Overall mortality
|
42 (15)
|
5 (14)
|
37 (15)
|
>0.5
|
|
PE-related mortality
|
5 (2)
|
2 (6)
|
3 (1)
|
0.12
|
|
Cancer-related mortality
|
34 (12)
|
3 (8)
|
31 (12)
|
>0.5
|
|
VTE recurrence
|
6 (2)
|
1 (3)
|
5 (2)
|
>0.5
|
|
Major bleeding
|
14 (5)
|
1 (3)
|
13 (5)
|
>0.5
|
|
In-hospital outcomes
|
|
In-hospital overall mortality
|
23 (8)
|
4 (11)
|
19 (8)
|
>0.5
|
|
In-hospital PE related mortality
|
4 (1)
|
2 (6)
|
2 (1)
|
0.07
|
|
In-hospital cancer related mortality
|
19 (7)
|
2 (6)
|
17 (7)
|
>0.5
|
|
In-hospital VTE recurrence
|
5 (2)
|
1 (3)
|
4 (2)
|
>0.5
|
|
In-hospital major bleeding
|
6 (2)
|
0 (0)
|
6 (2)
|
>0.5
|
Abbreviations: PE, pulmonary embolism; VTE, venous thromboembolism.
Radiological Findings of Saddle versus Nonsaddle Pulmonary Embolism
The radiological findings are shown in [Table 3]. Of note, signs of RV overload including a RV/LV ratio ≥1 (22 vs. 4%; p < 0.001) and interventricular septum displacement (53 vs. 20%; p < 0.001) were more common in patients with saddle compared with nonsaddle PE.
Table 3
Radiological findings according to the presence of saddle versus non-saddle pulmonary
embolism
|
Overall (n = 289)
n (%)
|
Saddle PE (n = 36)
n (%)
|
Non-saddle PE (n = 253)
n (%)
|
p-Value
|
|
Radiological findings related to RV overload
|
|
|
|
|
|
RV/LV ratio ≥1
|
18 (6)
|
8 (22)
|
10 (4)
|
<0.001
|
|
Septum displacement
|
69 (24)
|
19 (53)
|
50 (20)
|
<0.001
|
|
Suprahepatic vein reflux
|
38 (13)
|
8 (22)
|
30 (12)
|
0.11
|
|
At least one of the above
|
88 (30)
|
21 (58)
|
67 (27)
|
<0.001
|
|
Pulmonary arteries involved
|
|
|
|
<0.001
|
|
Central (main/lobar)
|
42 (15)
|
8 (22)
|
34 (13)
|
|
Peripheral (segmentary/subsegmentary)
|
91 (31)
|
0 (0)
|
91 (36)
|
|
Both central and peripheral
|
156 (54)
|
28 (78)
|
128 (51)
|
|
Additional findings
|
|
|
|
|
|
Lung nodules
|
113 (39)
|
11 (31)
|
102 (40)
|
0.26
|
|
Cancer progression[a]
|
74 (26)
|
9 (25)
|
65 (26)
|
>0.5
|
|
Carcinomatous lymphangitis
|
13 (4)
|
0 (0)
|
13 (5)
|
0.38
|
|
Pleural effusion
|
90 (31)
|
10 (28)
|
80 (32)
|
>0.5
|
|
Pericardial effusion
|
27 (9)
|
5 (11)
|
22 (9)
|
>0.5
|
|
Other radiological findings
|
148 (51)
|
18 (50)
|
130 (51)
|
>0.5
|
Abbreviations: LV, left ventricle; PE, pulmonary embolism; RV, right ventricle.
Note: Bold p-values are statistically significant.
a According to RECIST criteria. RECIST criteria are a set of radiological criteria
that standardizes and simplifies treatment response criteria for neoplastic diseases
and classifies them into 4 clearly defined categories: Complete response, Partial
response, Progressive disease and Stable disease.
Saddle Pulmonary Embolism According to an Acute Symptomatic versus Unsuspected Event
The main differences between patients with acute symptomatic saddle PE and patients
diagnosed with unsuspected saddle PE are shown in [Table 4]. Among the 36 patients with saddle PE, 15 (42%) were incidentally diagnosed. Patients
with unsuspected saddle PE were more often receiving chemotherapy than those with
acute symptomatic saddle PE (80 vs. 43%, respectively). Among patients with unsuspected
saddle PE, 73% presented no symptoms on evaluation. Compared with unsuspected saddle
PE, acute symptomatic saddle PE was associated with abnormal vital signs at diagnosis
(5 vs. 0% with blood pressure <100 mm Hg, 71 vs. 7% with heart rate >100 bpm, and
33 vs. 0% with oxygen saturation below 90%, p > 0.5, <0.001. and 0.027, respectively), as well as septum displacement in the CT
scan (71 vs. 27%, p = 0.008).
Table 4
Comparison of the main clinical features and outcomes of patients with cancer and
saddle pulmonary embolism according to acute symptomatic versus unsuspected events
|
Acute symptomatic saddle PE (n = 21)
Mean ± SD/n (%)
|
Unsuspected saddle PE (n = 15)
Mean ± SD/n (%)
|
p-Value
|
|
Age (y)
|
63.86 ± 10.9
|
67.33 ± 10.6
|
0.35
|
|
Gender (F)
|
8 (38)
|
6 (40)
|
>0.5
|
|
Previous VTE
|
8 (38)
|
3 (20)
|
0.3
|
|
Chronic heart condition
|
0 (0)
|
1 (7)
|
0.42
|
|
Chronic lung condition
|
6 (29)
|
1 (7)
|
0.2
|
|
Metastatic disease on presentation
|
17 (81)
|
10 (67)
|
0.44
|
|
Active chemotherapy treatment
|
9 (43)
|
12 (80)
|
0.026
|
|
Outpatient diagnosis
|
19 (91)
|
14 (93)
|
>0.5
|
|
Management setting
|
<0.001
|
|
Inpatient at PE diagnosis
|
2 (10)
|
1 (7)
|
|
Outpatient (<24 hours after diagnosis)
|
0 (0)
|
13 (86)
|
|
Hospital admission in general ward
|
19 (90)
|
1 (7)
|
|
Symptoms
|
|
None
|
0 (0)
|
11 (73)
|
<0.001
|
|
Dyspnea
|
20 (95)
|
4 (27)
|
<0.001
|
|
Chest pain
|
5 (24)
|
1 (7)
|
0.37
|
|
Syncope
|
4 (19)
|
0 (0)
|
0.13
|
|
Vital signs
|
|
|
Arterial hypotension BP < 100 mm Hg
|
1 (5)
|
0 (0)
|
>0.5
|
|
Tachycardia HR > 100 bpm
|
15 (71)
|
1 (7)
|
<0.001
|
|
Oxygen saturation <90%
|
7 (33)
|
0 (0)
|
0.027
|
|
Oxygen saturation <95%
|
20 (95)
|
0 (0)
|
<0.001
|
|
Radiological findings related to RV overload
|
|
RV/LV ratio ≥1
|
6 (29)
|
2 (13)
|
0.42
|
|
Septum displacement
|
15 (71)
|
4 (27)
|
0.008
|
|
Suprahepatic vein reflux
|
6 (29)
|
2 (13)
|
0.42
|
|
At least one of the above
|
16 (76)
|
5 (33)
|
0.01
|
|
Additional radiological findings
|
|
Lung nodules
|
6 (29)
|
5 (33)
|
>0.5
|
|
Cancer progression[a]
|
6 (29)
|
3 (20)
|
>0.5
|
|
Carcinomatous lymphangitis
|
0 (0)
|
0 (0)
|
>0.5
|
|
Pleural effusion
|
7 (33)
|
3 (20)
|
0.47
|
|
Pericardial effusion
|
4 (19)
|
0 (0)
|
0.125
|
|
Other radiological findings
|
11 (52)
|
7 (47)
|
>0.5
|
|
Outcomes within 30 days
|
|
Overall mortality
|
5 (24)
|
0 (0)
|
= 0.06
|
|
PE-related mortality
|
2 (10)
|
0 (0)
|
>0.5
|
|
Cancer-related mortality
|
3 (14)
|
0 (0)
|
0.25
|
|
VTE recurrence
|
1 (5)
|
0 (0)
|
>0.5
|
|
Major bleeding
|
1 (5)
|
0 (0)
|
>0.5
|
Abbreviations: BP, blood pressure; HR, heart rate; LV, left ventricle; PE, pulmonary
embolism; RV, right ventricle; VTE, venous thromboembolism.
Note: Bold p-values are statistically significant.
a According to RECIST criteria. RECIST criteria are a set of radiological criteria
that standardizes and simplifies treatment response criteria for neoplastic diseases
and classifies them into 4 clearly defined categories: Complete response, Partial
response, Progressive disease and Stable disease.
Only one patient (7%) with saddle UPE diagnosed in the outpatient setting required
hospitalization while all the patients (100%) with acute symptomatic saddle PE were
admitted to hospital (p < 0.001). There was a trend toward a lower overall 30-day mortality in patients with
unsuspected saddle PE compared with acute symptomatic PE (0 vs. 24%, p = 0.06).
Discussion
We report a large cohort of consecutive patients with cancer-associated PE showing
a notable prevalence of saddle PE of 12.5% in the overall cohort and 9% in those with
UPE, taking into account that the imaging tests were specifically reviewed by a senior
chest radiologist. Our results show a slightly higher prevalence of saddle PE than
previously reported in two recent retrospective studies by Prentice et al[33] (10,660 hospital admissions, 49% metastatic cancer, and saddle PE prevalence of
4.5%) and by Banala et al[34] (193 episodes of UPE, 75% metastatic cancer, and saddle PE prevalence of 3.6%).
We hypothesize that these differences might be explained by the fact that a large
proportion (82%) of our patients had metastatic cancer, representing a larger proportion
of patients with advanced disease compared with the aforementioned studies.[31]
[32] However, our data do not support this theory, as the association of metastatic cancer
and saddle PE was not significant and the proportion of patients with metastatic cancer
was actually lower in saddle PE than nonsaddle PE (75 vs. 83%). Additionally, differences
in the prevalence of saddle PE among studies might be related to the fact that the
two previous real-world studies[33]
[34] did not include a thorough radiological review of CT scans, and thus saddle PE could
have been underreported. In this regard, another retrospective study by Kwak et al,[35] in the general population, reported a prevalence of 9.1% of saddle PE after specific
radiological review similar to what was done in our study.
In our dataset, patients with saddle PE were more likely to be symptomatic and present
with altered vital signs at PE diagnosis compared with patients with nonsaddle PE.
Interestingly, 31% of patients with saddle PE were asymptomatic. However, in view
of the lack of studies in this regard, comparison with other studies could not be
made, since Prentice et al[33] provided no data on either symptoms or vital signs and Banala et al[34] did not specifically analyzed saddle PE. Nonetheless, we believe that this is an
original finding in patients with cancer that emphasizes the clinical-radiological
dissociation previously described in isolated case reports.[36]
[37]
Notably, patients with saddle PE in our study more frequently had signs of RV overload
compared with nonsaddle PE, in line with the study by Kwak et al.[35] In contrast, in a retrospective study of 52 patients with cancer and central acute
symptomatic PE with thorough revision of CT scans, Yusuf et al[38] did not find differences in signs of RV overload according to saddle versus nonsaddle
central PE.
Despite having found significant differences in PE presentation and signs of RV overload
in our study, we could not demonstrate a worse overall or PE-related 30-day mortality
according to saddle versus nonsaddle PE. Up to now, only Prentice et al[33] and Yusuf et al[38] have published data regarding the prognostic value of saddle PE in patients with
cancer, albeit with conflicting results.
Similarly to our results, many of the studies regarding saddle PE in the general population
found no difference in overall mortality between saddle and nonsaddle PE at 30 days,[35]
[39]
[40]
[41]
[42] although data from other heterogenous uncontrolled observational studies[43]
[44] suggest a greater risk of in-hospital mortality in patients with saddle PE. Taking
all of this into account, the prognostic impact of saddle PE remains inconclusive.
Unsuspected PE has shifted the paradigm of PE in patients with cancer, but very little
information is available regarding unsuspected saddle PE and short-term outcomes.
To the best of our knowledge, no other study has compared unsuspected saddle PE with
acute symptomatic saddle PE. In our series, saddle PE was diagnosed as an incidental
finding in a high proportion of patients (42%). This proportion exceeded our initial
expectations and, we believe, has not been previously reported, suggesting that unsuspected
saddle PE is a common presentation of VTE in patients with cancer.
From an epidemiological point of view (baseline characteristics), it is noteworthy
patients with unsuspected saddle PE were more frequently receiving active chemotherapy
treatment compared with patients with acute saddle PE. This difference might be influenced
by this group of patients more frequently undergoing scheduled CT studies with the
subsequent identification of unsuspected VTE events.
Related to clinical presentation and outcomes, it is remarkable that patients with
unsuspected saddle PE were often asymptomatic (73%) and rarely required hospital admission
(7%). Septum displacement was consistently less frequent in patients with unsuspected
saddle PE compared with those with acute symptomatic saddle PE, although no differences
in other variables related to RV overload were found. Taking into account, the absence
of significant differences in 30-day outcomes in patients with unsuspected saddle
PE compared with acute saddle PE, it is further underscored that patients with saddle
PE presented a high degree of clinical-radiological dissociation, and that clinical
signs may be better predictors of short-term major adverse outcomes.
Strengths and Limitations
Strengths and Limitations
While from a clinical point of view, the present study has several strengths that
have been indicated above, there are also several limitations. Our study was conducted
in a single center, retrospective, and not randomized/interventional in nature. Even
though patients were consecutively included, the retrospective nature of the study
and patient recruitment from the Medical Oncology Department (and not every PE diagnosed
in the Radiology Department) are potential sources of selection bias. It is of note
that the differences found in signs of RV overload on CT may be affected by the fact
that conventional CT scans used in 59% of the patients, without pulmonary angiography,
cannot usually identify these signs. Moreover, the assessment of clinical outcomes
among patients with and without saddle PE lacks precision due to low numbers of the
outcomes of interest. In addition, RV overload with transthoracic echocardiogram and
cardiac biomarkers were seldom studied in our cohort because they were not routinely
measured during the study period. This precluded the adjustment of 30-day outcomes
with the current guideline-recommended risk-stratification tools.[16]
[45] In this regard, it would be interesting to design specific prospective multicentric
studies addressed to overcome this particular drawback to determine the prognostic
impact of saddle PE more precisely.
Sample size was a limitation to find more conclusive results regarding short-term
prognostic impact of saddle PE in patients with cancer. Further prospective studies
are needed to assess the safety of outpatient management of cancer-related PE.
Conclusion
In conclusion, the present study sheds light on the prevalence, clinical characteristics,
and outcomes of patients with cancer and saddle PE versus nonsaddle PE. Saddle PE
was found in a relevant proportion of patients, including those with UPE.
