CT Diagnosis of Chronic Pulmonary Thromboembolism

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EDUCATION EXHIBIT
31
CT Diagnosis of
Chronic Pulmonary
Thromboembolism1
CME FEATURE
See accompanying
test at http://
www.rsna.org
/education
/rg_cme.html
LEARNING
OBJECTIVES
FOR TEST 1
After reading this
article and taking
the test, the reader
will be able to:
■■Describe
the risk
factors, clinical
manifestations, and
pathophysiology of
chronic pulmonary
thromboembolism.
■■Define
appropriate
CT techniques for
detecting and evaluating pulmonary
thromboembolic
disease.
■■Recognize
the CT
features of chronic
pulmonary thromboembolism, especially those that aid
selection of patients
for surgical treatment.
TEACHING
POINTS
See last page
Eva Castañer, MD • Xavier Gallardo, MD • Eva Ballesteros, MD • Marta
Andreu, MD • Yolanda Pallardó, MD • Josep Maria Mata, MD, PhD
Lluis Riera, MD
Chronic pulmonary thromboembolism is mainly a consequence of
incomplete resolution of pulmonary thromboembolism. Increased
vascular resistance due to obstruction of the vascular bed leads to
pulmonary hypertension. Chronic thromboembolic pulmonary hypertension is clearly more common than previously was thought, and
misdiagnosis is common because patients often present with nonspecific symptoms related to pulmonary hypertension. Computed
tomography (CT) is a useful alternative to conventional angiography
not only for diagnosing chronic pulmonary thromboembolism but also
for determining which cases are treatable with surgery and confirming
technical success postoperatively. The vascular CT signs include direct
pulmonary artery signs (complete obstruction, partial obstruction, eccentric thrombus, calcified thrombus, bands, webs, poststenotic dilatation), signs related to pulmonary hypertension (enlargement of main
pulmonary arteries, atherosclerotic calcification, tortuous vessels, right
ventricular enlargement, hypertrophy), and signs of systemic collateral
supply (enlargement of bronchial and nonbronchial systemic arteries).
The parenchymal signs include scars, a mosaic perfusion pattern, focal
ground-glass opacities, and bronchial anomalies. The presence of one
or more of these radiologic signs arouses suspicion and allows diagnosis of this entity. Early recognition of chronic pulmonary thromboembolism may help improve the outcome, since the condition is potentially curable with pulmonary thromboendarterectomy.
©
RSNA, 2009 • radiographics.rsnajnls.org
RadioGraphics 2009; 29:31–53 • Published online 10.1148/rg.291085061 • Content Codes:
1
From the Department of Radiology, UDIAT-Centre Diagnòstic, Institut Universitari Parc Taulí-UAB, Parc Taulí s/n, Sabadell 08208 (Barcelona),
Spain (E.C., X.G., E.B., M.A., J.M.M., L.R.); and Department of Radiology, Hospital de la Ribera, Alzira, Spain (Y.P.). Recipient of a Certificate of
Merit award for an education exhibit at the 2007 RSNA Annual Meeting. Received March 19, 2008; revision requested May 12 and received July 10;
accepted August 4. All authors have no financial relationships to disclose. Address correspondence to E.C. (e-mail: [email protected]).
See the commentary by Klein following this article.
©
RSNA, 2009
32 January-February 2009
Introduction
Teaching
Point
Most pulmonary thromboemboli resolve without
sequelae. For reasons that are still unclear, in a
small percentage of patients, the thromboemboli
do not resolve but rather form endothelialized
fibrotic obstructions of the pulmonary vascular
bed. The result is vascular stenosis, which may
lead to severe pulmonary hypertension and cor
pulmonale (1). The bronchial circulation responds to decreased pulmonary flow and ischemia with enlargement and hypertrophy (2); in
addition, transpleural systemic collateral vessels
(eg, intercostal arteries) may develop (3).
Clinical symptoms in patients with chronic
pulmonary thromboembolism are nonspecific
and are related to the development of pulmonary
hypertension. Symptoms worsen as the right
ventricular functional capacity deteriorates (4).
Chronic thromboembolic pulmonary hypertension often is identified during the diagnostic
work-up in patients with unexplained pulmonary
hypertension, and radiologists must be aware of
its radiologic manifestations because it is a treatable cause of pulmonary hypertension in some
patients.
The prevalence of chronic thromboembolic
pulmonary hypertension in the general population has yet to be accurately determined and may
have been significantly underestimated. Recent
prospective epidemiologic data indicate an incidence of approximately 4% after acute symptomatic pulmonary thromboembolism (5,6). Given
the growing number of patients undergoing chest
computed tomography (CT) who might have
experienced a previous episode of pulmonary
embolism (either known or unsuspected), incompletely resolved emboli are an increasingly common finding on chest CT images.
In this article, we review the risk factors, clinical characteristics, and pathogenesis of chronic
pulmonary embolism. We describe the optimal
technique for CT angiography and the CT diagnostic criteria for chronic pulmonary thromboembolism. Finally, we briefly discuss the differential diagnoses, diagnosis, and treatment of
this entity.
Risk Factors and
Clinical Manifestations
Women are affected slightly more frequently, and
patients with underlying malignant, cardiovascu-
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lar, or pulmonary disease are at increased risk of
developing this condition (6,7). Other reported
risk factors include splenectomy, ventriculoatrial
shunts, chronic inflammatory disorders, and
myeloproliferative syndromes (4,8). Ethnic differences in the clinical characteristics of chronic
thromboembolic pulmonary hypertension (eg, it
is more prevalent in Asian patients after an acute
episode of pulmonary thromboembolism) are
suggestive of the involvement of a genetic factor
in the etiology or pathogenesis of the condition
(9).
In a recent prospective study (5) in symptomatic patients with unexplained persistent dyspnea
after treatment for acute pulmonary thromboembolism, it was observed that multiple episodes
of pulmonary embolism, larger perfusion defect,
younger age, and idiopathic manifestation of pulmonary thromboembolism were associated with
an increased risk of chronic thromboembolic pulmonary hypertension.
Lupus anticoagulant, a prothrombotic factor, is detected in approximately 10% of patients
with chronic thromboembolic pulmonary hypertension (10), and 20% carry anticardiolipin
antibodies, lupus anticoagulant, or both (4).
Plasma levels of factor VIII and antiphospholipid
antibodies, two thrombophilic factors that are associated with recurrent thrombosis, are elevated
in patients with chronic thromboembolic pulmonary hypertension (11).
Symptoms are nonspecific and are related to the
development of pulmonary hypertension. The
extent of vascular obstruction is a major
determinant of the severity of pulmonary hypertension. In the majority of symptomatic patients,
more than 40% of the pulmonary vascular bed is
obstructed (10,12). Patients with chronic
thromboembolic pulmonary hypertension may
be asymptomatic for several years before their
presentation with symptoms such as recurrent
acute or progressive exertional dyspnea, chronic
nonproductive cough, atypical chest pain, tachycardia, syncope, and cor pulmonale (7,10,12,13).
The clinical deterioration parallels the loss of
right ventricular functional capacity. In these
patients, pulmonary arterial pressure is elevated,
right atrial pressures are high, cardiac output is
reduced, and pulmonary capillary wedge pressures are normal (12).
Pathogenesis
The natural history of pulmonary thromboemboli in more than 90% of patients includes total
Teaching
Point
RG ■ Volume 29 • Number 1
Figure 1. Diagram shows the various possible
results of disturbed resolution of a thrombus:
vascular stenosis, retraction with total obstruction, retraction with partial obstruction, recanalization, or residual fibrous cords (web or bands).
Teaching
Point
resolution or resolution with minimal residua and
restoration of normal pulmonary hemodynamics
within 30 days after treatment. Early resolution
of pulmonary vascular obstruction occurs by two
mechanisms: mechanical fragmentation and endogenous fibrinolysis (4).
The pathogenesis of chronic thromboembolism is
still unclear; extensive analyses of plasma
proteins in patients with chronic thromboembolic
pulmonary hypertension have shown no abnormalities in fibrinolysis. Nevertheless, the majority
opinion supports a thromboembolic pathogenesis, with a possible role for in situ thrombosis as
a factor in disease progression (contribution to
the persistence of thrombi) rather than initiation
(4,6,14,15). In this scenario, the pathologic process is linked mainly with disturbance of thrombus resolution (Fig 1). In a small percentage of
patients, particularly those with a large perfusion
defect or recurrent episodes of thromboembolism, the resolution of thrombi is incomplete (4,
16). The organization of a thromboembolus with
invasion by fibroblasts and capillary buds that
adhere to the vascular wall can be regarded as a
reparative response. Shrinkage of a thromboembolic mass allows restoration of a portion of
the original lumen. The remaining embolic
material is incorporated into the vessel wall and
covered over by a thin layer of endothelial cells.
The thromboembolic material may lead to obstruction, stenosis, and subsequent atrophy of the
vessel. Some blood flow may be restored by
recanalization through the obstructive mass. In
Castañer et al 33
some instances, all that remains of an organized
thromboembolus are fibrous cords, which may
occur singly, in bands, or may form a weblike
network (17).
The hemodynamic basis of continuing pulmonary hypertension in these patients is not only
the occlusion of pulmonary arteries but also the
development of distal arteriolar vasculopathy (in
nonobstructed areas as well as in partially or totally obstructed arteries) as a result of pulmonary
hypertension (15,18).
In the presence of chronic thromboembolic
disease, the bronchial and nonbronchial systemic
circulation is markedly increased as a result of the
development of systemic-to-pulmonary anastomoses, which help to maintain pulmonary blood
flow in the presence of vessel obstruction (19,20).
CT Technique
Chronic pulmonary thromboembolism is often
identified during the diagnostic work-up in patients with unexplained pulmonary hypertension.
At our institution, most cases of chronic pulmonary thromboembolism are discovered at CT
pulmonary angiography performed to rule out
acute pulmonary thromboembolism. We perform
CT pulmonary angiography with a multidetector
CT scanner (Sensation 16; Siemens, Erlangen,
Germany) (120 kV, 70–120 mAs, 0.5 second
scanning time, 0.75 mm detector width, pitch
of 1.5). Images are reconstructed with a 1-mm
section thickness at a 0.7-mm interval. Patients
receive 100 mL of contrast material (iopromide,
Ultravist 300; Schering, Berlin, Germany) at an
injection rate of 4 mL/sec. When chronic pulmonary embolism is suspected, we modify the CT
pulmonary angiography protocol: The intravenous administration of the contrast material bolus is timed so that both the pulmonary and the
systemic circulation are opacified. The bronchial
circulation, which usually originates from the descending aorta, is markedly increased in patients
with chronic pulmonary thromboembolism, and
the enhancement of bronchial vessels may aid
in the differential diagnosis (20). Bolus timing
also allows assessment of all cardiac chambers.
The desired opacification of the pulmonary and
systemic circulation can be achieved by using a
longer delay from contrast material injection to
image acquisition; we use a higher trigger threshold, 200 HU (21) (our threshold for evaluation
of acute pulmonary embolism is 120 HU) with a
34 January-February 2009
circular region of interest centered on the main
pulmonary artery.
We perform scanning in the caudal-cranial
direction because most pulmonary emboli
are found in the lower lung lobes (17) and, if
the patient is unable to sustain breath holding
throughout image acquisition, the lower lobes are
imaged in the initial seconds of the breath hold.
Because some signs of chronic thromboembolism
(eg, bands) may be overlooked with the highcontrast mediastinal window settings, we view the
images by using three different gray scales for interpretation: a lung window (window width, 1500
HU; window level, -600 HU), a mediastinal
window (window width, 350 HU; window level,
40 HU), and a pulmonary thromboembolism–
specific window (window width, 700 HU; window level, 100 HU) (22).
Multiplanar reformatted images and maximum intensity projection images that provide
longitudinal views of vessels may help clarify
confusing or questionable findings and may better depict obstructions, stenoses, and flattened
peripheral thrombotic material (Fig 2) that otherwise might be overlooked (23).
CT Features of Chronic
Pulmonary Thromboembolism
We classify the CT features of chronic pulmonary
thromboembolism as vascular signs or parenchymal signs. The vascular signs include direct
pulmonary artery signs (results of thrombus organization), signs due to pulmonary hypertension
(results of the sustained increase in pulmonary
vascular resistance), and signs due to systemic
collateral supply (results of decreased pulmonary artery flow). The parenchymal signs include
scars, a mosaic perfusion pattern, focal groundglass opacities, and bronchial dilatation. The
vascular and parenchymal signs are described in
greater detail in the next sections.
Vascular Signs
Pulmonary Arterial Signs
The signs seen in the pulmonary artery at CT are
similar to those seen at conventional angiography.
Complete Obstruction.—At angiography,
complete vessel cutoff results in a convex margin
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Figure 2. Chronic pulmonary thromboembolism in
a 47-year-old man. Coronal 10-mm-thick maximum
intensity projection image from CT shows a flattened
eccentric thrombus in the right pulmonary artery
(black arrows)—a feature not well depicted on axial
images—and abrupt stenosis and recanalization of the
right interlobar artery (arrowheads). Bronchial arteries
in the mediastinum and around the stenosed vessels
(white arrows) appear abnormally enlarged.
of the contrast material bolus, a feature that has
been described as a “pouch defect” (24). At CT,
this feature is difficult to see, and the additional
findings of an abrupt decrease in vessel diameter
and absence of contrast material in the vessel segment distal to the total obstruction are easier to
identify (Fig 3a) (25). The reduction in vessel diameter is persistent and is caused by contraction
of the thrombus (26). CT scans viewed at lung
window settings depict segmental and subsegmental vessels that are abnormally small in comparison with the accompanying bronchi (Fig 3b).
Partial Filling Defects.—An organized thrombus may cause vessel narrowing, intimal irregularities, bands, and webs. Abrupt vessel narrowing
is caused by recanalization within a large thrombus or by stenosis due to an organized thrombus
that lines the arterial wall (24). In the presence
of recanalization, contrast material is seen flowing through thickened and often smaller arteries
(Fig 2). The organized thrombus runs parallel to
the arterial lumen and appears as a thickening of
the artery wall (24,27), sometimes producing an
irregular contour of the intimal surface (Fig 4a).
A chronic thrombus in an artery with a course
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Castañer et al 35
Figure 3. Chronic pulmonary thromboembolism in a 65-year-old man with a history of multiple episodes of acute
pulmonary thromboembolism. (a) Axial contrast-enhanced CT scan shows complete occlusion and marked reduction in size of the right lower lobe pulmonary artery (arrows) in comparison with the left lower lobe pulmonary
artery, which contains a residual intraluminal band (arrowhead). (b) Axial CT scan (lung window) shows segmental
and subsegmental vessels in the right lower lobe that are abnormally small compared with their accompanying bronchi. Peripheral nodular opacities (arrowheads) in the right lower and right middle lobes are secondary to previous
infarction.
Figure 4. Chronic pulmonary thromboembolism in an 80-year-old woman with a history of
acute pulmonary thromboembolism. (a) Axial contrast-enhanced CT scan shows bilateral eccentric chronic thrombi producing irregular contours of the intimal surface of both main pulmonary
arteries (arrows) and poststenotic dilatation (arrowheads) in the posterior segmental artery of the
right upper lobe. (b) Axial contrast-enhanced CT scan shows an eccentrically located thrombus
with a broad base forming obtuse angles with the vessel wall in the left lower lobe pulmonary artery (arrows).
that is transverse to the scanning plane has the
appearance of a peripheral, crescent-shaped intraluminal defect that forms obtuse angles with
the vessel wall (25–27) (Fig 4b). Poststenotic
dilatation or aneurysm may be observed (24)
(Figs 4a, 5).
36 January-February 2009
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Figure 5. Chronic pulmonary thromboembolism in an 80-year-old woman with a history of acute pulmonary
thromboembolism (same patient as in Fig 4). (a) Oblique coronal 30-mm-thick maximum intensity projection CT
image shows aneurysms in the posterior segment of the right upper lobe pulmonary artery (*) and aneurysmal dilatation of the right lower lobe pulmonary artery (arrows) distal to a band (arrowhead). (b) Oblique coronal 10-mmthick maximum intensity projection CT image provides a closer view of the band (arrowhead) and the poststenotic
dilatation. The marked increase in diameter and the tortuosity of the pulmonary arteries (arrows in b) are indicative
of pulmonary hypertension.
Figure 6. Residual band from a pulmonary thrombus in an 83-year-old woman with dyspnea. (a) Axial
contrast-enhanced CT image shows a linear structure anchored to the vessel wall in the left lower lobe
pulmonary artery (arrow). (b) Coronal 10-mm-thick maximum intensity projection CT image shows
the attachment of the band to the vessel wall in more detail (arrows).
A band is defined as a linear structure that is
anchored at both ends to the vessel wall and has
a free, unattached midportion. A band generally
has a length of 0.3–2 cm and width of 0.1–0.3
cm. It is often oriented in the direction of blood
flow, along the long axis of the vessel (28). A web
consists of multiple bands that have branches
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Figure 7. Chronic pulmonary thromboembolism in
an 86-year-old woman. Axial contrast-enhanced CT
scan viewed with a wide window setting (width, 1100
HU; level, 100 HU) to facilitate calcium detection
shows a partially calcified thrombus in the right pulmonary artery.
forming a network. At CT angiography, bands
and webs are depicted as thin lines surrounded
by contrast material (Figs 3a, 5, 6). These features most frequently are found in lobar or segmental arteries and rarely are seen in the main
pulmonary artery (24,28).
Calcifications within chronic thrombi are
seen in a small number of patients. On contrastenhanced CT images with the usual mediastinal
window settings, calcified thrombi may be obscured by surrounding contrast material. Selection of a wider window setting or creation of
maximum intensity projections are helpful for
visualizing calcification (25) (Fig 7). Calcified
thrombi in subsegmental arteries are often indistinguishable from calcified lung nodules. However, their tubular shape and location at the site
of arterial branching may aid in their differentiation (25).
Signs of Pulmonary Hypertension
Increased vascular resistance due to the obstructed vascular bed leads to dilatation of the
central pulmonary arteries. Enlargement of the
main pulmonary artery to a diameter of more
than 29 mm (13,29) may occur in the presence of
Castañer et al 37
Figure 8. Chronic pulmonary thromboembolism
and pulmonary hypertension in a 42-year-old man.
Axial contrast-enhanced CT scan shows an enlarged
pulmonary trunk with a maximum diameter of 39 mm
(line) near its bifurcation and asymmetric enlargement
of the right pulmonary artery secondary to an extensive thrombus (*). Atherosclerotic calcification of the
left pulmonary artery also is visible (arrows).
pulmonary hypertension, regardless of the cause;
such enlargement is a common finding in patients
with chronic thromboembolic pulmonary hypertension (Figs 4a, 5, 7) (30). The CT diameter of
the main pulmonary artery is measured in the
scanning plane of its bifurcation, at a right angle
to its long axis and just lateral to the ascending
aorta (Fig 8). When the ratio of the diameter of
the main pulmonary artery to the diameter of
the aorta measured on CT scans is greater than
1:1, there is a strong correlation with elevated
pulmonary artery pressure, especially in patients
younger than 50 years (31) (Fig 8). In contrast to
the symmetric pulmonary enlargement typically
seen in nonthromboembolic pulmonary hypertension, central pulmonary arteries in patients
with chronic thromboembolic pulmonary hypertension often are asymmetric in size (32) (Figs
4a, 8). The walls of the pulmonary arteries may
show atherosclerotic calcification (13) (Fig 8).
Tortuous pulmonary vessels have been described
in patients with pulmonary hypertension and are
seen also in patients with chronic thromboembolic pulmonary hypertension (33) (Fig 5b).
38 January-February 2009
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Figure 9. Right heart abnormalities secondary to chronic thromboembolic pulmonary hypertension
in a 47-year-old man (same patient as in Fig 2). (a) Axial contrast-enhanced CT scan shows dilatation
of the right ventricle (RV), with a ratio of more than 1:1 between the right and left ventricle (LV) diameters (lines); leftward septal bowing (arrowheads); thickening of the free right ventricular wall (arrows);
and dilatation of the right atrium (RA). (b) Axial contrast-enhanced CT scan at a lower level shows
opacification of the inferior vena cava and suprahepatic veins because of retrograde flow of contrast material, which is often seen in patients with elevated right atrial and right ventricular pressures.
Right heart disease is a common and expected
finding secondary to pulmonary hypertension:
The increased workload borne by the right heart
results in right ventricular enlargement and
hypertrophy (right ventricular myocardial thickness greater than 4 mm) (25) (Fig 9a). Over
time, right ventricular function deteriorates, even
in the absence of recurrent embolism, presumably because of the development of hypertensive
vascular lesions in the nonobstructed pulmonary
artery bed and of vasculopathy in vessels distal to
obstructed arteries (18). Dilatation of the right
ventricle is considered present when the ratio of
the diameter of the right ventricle to that of the
left ventricle is greater than 1:1 and there is bowing of the interventricular septum toward the left
ventricle (34). At CT, these signs can be evaluated even without electrocardiographic gating.
The minor axes of the right and left ventricular
chambers can be measured in the axial plane at
their widest points, in diastole, between the inner surface of the free wall and the surface of the
interventricular septum (Fig 9a). The diastolic
maxima of the right and left ventricles may be
reached at slightly different levels. Right ventricular enlargement may be accompanied by dilatation of the tricuspid valve annulus and resultant
tricuspid valve regurgitation (Fig 9b).
Patients with severe pulmonary hypertension
may present with mild pericardial thickening or
a small pericardial effusion (35). The presence
of pericardial effusion implies a worse prognosis
(36). Patients with chronic thromboembolic pulmonary hypertension may have enlarged lymph
nodes (37). At histologic examination of these
enlarged nodes, a vascular transformation of the
lymph node sinus may be seen, often in association with sclerosis of varying degrees. Similar
histologic features may be observed also in lymph
nodes from patients with pulmonary hypertension due to other causes (25).
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Castañer et al 39
Figure 10. Chronic pulmonary thromboembolism in an 80-year-old woman with a history of acute pulmonary thromboembolism (same patient as in Fig 4). (a) Axial contrast-enhanced CT scan shows enlargement
of the proximal portion of the right bronchial artery (arrowhead) and aneurysmal dilatation of an upper lobe
artery (*). (b) Oblique coronal 20-mm-thick maximum intensity projection CT image better depicts the
course of the right bronchial artery (arrowheads) and shows a large eccentric thrombus in the main and left
lower lobe pulmonary arteries (*). The bronchial circulation appears as fine hyperattenuating lines inside the
thrombus.
Collateral Systemic Supply
Bronchial arterial flow increases in response to
chronic obstruction of the pulmonary arteries in
patients with chronic thromboembolic pulmonary hypertension. In addition, transpleural systemic collateral vessels (eg, intercostal arteries)
may develop (20,38). Normally, the bronchial arteries only supply nutrition to the bronchi and do
not take part in gas exchange. However, in pathologic conditions that diminish pulmonary artery
circulation, flow through the bronchial arteries
increases, and they participate in blood oxygenation (2). Systemic hypervascularization is a nonspecific response to stimuli such as reduced pulmonary artery flow, hypoxemia, fibrosis, chronic
inflammation, and chronic infection. The normal
bronchial arterial blood flow is of the order of
1%–2% of the cardiac output. In patients with
chronic thromboembolic pulmonary hypertension, bronchial flow may represent almost 30%
of the systemic blood flow (39,40). To fill pulmo-
nary arteries downstream, systemic-to-pulmonary
arterial anastomoses develop beyond the level of
obstruction (41). The bronchial arteries usually
arise from the descending aorta at the level of the
carina. Abnormal dilatation of the proximal portion of the bronchial arteries (diameter of more
than 2 mm) and arterial tortuosity (Figs 2, 10)
are CT findings indicative of bronchial artery
hypervascularization.
In a recent study (20), abnormally enlarged
bronchial and nonbronchial systemic arteries were
found more frequently in patients with chronic
thromboembolic pulmonary hypertension (73%)
than in patients with idiopathic pulmonary hypertension (14%); these findings could help distinguish between these two entities. In this study, the
most frequently depicted abnormal nonbronchial
systemic arteries were the inferior phrenic, intercostal (Fig 11), and internal mammary arteries.
40 January-February 2009
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Figure 11. Chronic pulmonary thromboembolism in a 47-year-old man with multiple episodes of acute pulmonary thromboembolism. (a) Coronal 30-mm-thick maximum intensity projection CT image shows marked
enlargement of branches of the right and left inferior phrenic arteries (straight arrows), right and left bronchial
arteries (arrowheads), and an intercostal artery (curved arrow). (b) Coronal 30-mm-thick maximum intensity
projection image shows enlargement of intercostal arteries on the right side compared with those on the left.
Acute pulmonary embolism does not appear
to cause dilatation of the bronchial arteries; in patients in whom the distinction between acute and
chronic or recurrent pulmonary embolism at CT
angiography is unclear, the presence of dilated
bronchial arteries should favor the diagnosis of
chronic or recurrent pulmonary embolism (38).
Another important finding is that dilated
bronchial arteries are positively correlated with
a lower mortality rate after pulmonary thromboendarterectomy (41). Development of systemic
hypervascularization may also be responsible for
hemoptysis in these patients (42).
Parenchymal Signs
Scars from prior pulmonary infarctions are
commonly depicted in areas of decreased lung
attenuation on CT scans obtained in patients
with chronic thromboembolic pulmonary hypertension (13). These scars may appear as parenchymal bands, wedge-shaped opacities (Fig 12),
peripheral nodules, cavities (Fig 3b), or irregular
peripheral linear opacities (Fig 13) (1,32,43).
The appearance most suggestive of scar tissue
from infarction is a wedge-shaped pleura-based
opacity; however, an infarct may constrict with
Figure 12. Chronic pulmonary thromboembolism.
CT scan (lung window) obtained in an 85-year-old
woman 2 years after an episode of massive acute
thromboembolism shows a subpleural wedge-shaped
area of consolidation (arrow) in a region of decreased
attenuation, a feature indicative of pulmonary infarction. The region did not enhance after contrast material was administered.
age and take on the more linear shape of a parenchymal band (Fig 14) (43). Parenchymal scars
often occur in multiples, generally are found in
the lower lobes, and often are accompanied by
pleural thickening (20).
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Figure 13. Chronic pulmonary thromboembolism.
CT scan (lung window) obtained in a 48-year-old man
shows multiple peripheral linear opacities in both lower
lung lobes, features that represent old infarcts.
Figure 14. Chronic pulmonary thromboembolism
in a 65-year-old man. CT scan (lung window) shows
a mosaic perfusion pattern with marked regional
variations in attenuation of the lung parenchyma and
disparity in the size of the segmental vessels, with
larger-diameter vessels in regions of increased attenuation (arrows). A peripheral parenchymal band or scar
(arrowhead) from infarction also is depicted.
A mosaic pattern of perfusion also is seen at
CT in the presence of chronic thromboembolic
pulmonary hypertension. This pattern appears
as sharply demarcated regions of decreased and
increased attenuation because of irregular perfusion (Figs 12, 14). Low attenuation is due either
to hypoperfusion in areas distal to occluded vessels or to distal vasculopathy in nonoccluded
Castañer et al 41
Figure 15. Chronic pulmonary thromboembolism in
an 80-year-old woman with a history of acute pulmonary thromboembolism (same patient as in Figs 4 and
10). Coronal 20-mm-thick maximum intensity projection CT image shows foci of ground-glass attenuation
in the right upper lobe (arrows) secondary to systemic
perfusion in peripheral areas, as well as bilateral enlargement of the bronchial arteries (arrowheads).
areas, and increased attenuation has been related
to the redistribution of blood flow to the patent
arterial bed (12,32). These assumptions can be
confirmed by several findings: larger vessels in regions of increased attenuation, stronger enhancement of the hyperattenuating areas after contrast
material administration (1,44), and correlation
between areas of low attenuation on CT images
and areas of hypoperfusion depicted at single
photon emission computed tomography (32).
Mosaic lung attenuation is nonspecific and
is seen more often in patients with pulmonary
hypertension due to vascular disease than in
those with pulmonary hypertension due to cardiac or lung disease. Mosaic perfusion is seen
much more commonly in patients with chronic
thromboembolic pulmonary hypertension than in
patients with idiopathic pulmonary hypertension
(45).
Systemic perfusion of the peripheral pulmonary arterial bed accounts for the presence of
isolated focal areas of ground-glass attenuation
(33,46) (Fig 15).
Arakawa et al (44) found direct evidence of
airway obstruction—air trapping on expiratory
CT images—in patients with chronic pulmonary
thromboembolism. Air trapping is commonly
42 January-February 2009
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Figure 16. Chronic pulmonary thromboembolism in an 82-year-old woman. (a) Axial inspiratory CT scan
(lung window) shows chronic thromboembolism of the left lower lobe pulmonary arteries. Note the mosaic
perfusion pattern and the diminished size of vessels in this lobe compared with the right lower lobe. (b) Axial
expiratory CT scan (lung window) at the same level as a shows evidence of air trapping in areas of lower attenuation. Air trapping is not specific to airway disease and may be a sign of chronic thromboembolism.
Figure 17. Chronic pulmonary thromboembolism in an 82-year-old woman. (a) Axial CT scan (lung window) shows increased bronchial diameters and an absence of normal distal tapering of the segmental and subsegmental bronchi of the left lower lobe (arrow). Note the small arterial segments (arrowhead) at the lateral
border of each dilated bronchus. (b) Axial contrast-enhanced CT scan at a level slightly higher than a shows a
marked reduction of arterial perfusion in the left lower lobe.
seen in areas of hypoperfusion due to chronic
embolism (Fig 16). Arakawa and colleagues
found significant associations between the appearance of air trapping and the presence of a
proximal arterial stenosis or clot and between the
extent of air trapping and the degree of impairment of pulmonary function of the small airways
in these patients (44).
Cylindrical bronchial airway dilatation is seen
in two thirds of patients with chronic thromboembolic pulmonary hypertension (47). It occurs at
the level of segmental and subsegmental bronchi, adjacent to severely stenosed or completely
obstructed and retracted pulmonary arteries
(Fig 17). Two different hypotheses might explain
this phenomenon. First, findings by Wetzel et al
(48) in an investigation of the airway response to
hypoxia in a pig model are suggestive of hypoxic
bronchodilatation. Another hypothesis involves
RG ■ Volume 29 • Number 1
Castañer et al 43
Figure 18. Evolution of chronic occlusive pulmonary thromboembolism from acute embolism in a
40-year-old man. (a) Axial contrast-enhanced CT scan shows acute embolism in the left lower lobe,
with increased arterial diameters (arrows) due to impacted thrombi. (b) Axial contrast-enhanced CT
scan obtained at the same level as a, 1 year later, when the patient presented with dyspnea, shows a permanent reduction in the diameters of the left lower lobe arteries (arrows) because of thrombus organization and retraction, findings indicative of chronic thromboembolism.
the bronchial circulation, which supplies nutrients to the bronchial walls: If the pulmonary
arteries are chronically obstructed, there is an
increased demand on the bronchial circulation
to provide pulmonary parenchymal perfusion,
possibly robbing the bronchial walls of nutrients
and weakening them, which leads to airway dilatation (47).
Although parenchymal findings (eg, mosaic attenuation with asymmetric artery size, pulmonary
infarcts) are nonspecific, in the appropriate clinical setting they may be regarded as supportive of
the diagnosis of chronic thromboembolic pulmonary hypertension.
Differential Diagnosis
Chronic thromboembolic pulmonary hypertension is often misdiagnosed, and the initial
thromboembolic event in most patients is asymptomatic or overlooked. Both congenital and
acquired conditions may cause pulmonary hypertension or obstruction of the pulmonary arteries
and mimic chronic thromboembolic pulmonary
hypertension.
Idiopathic Pulmonary Hypertension
Both chronic thromboembolic pulmonary hypertension and idiopathic pulmonary hypertension manifest clinically with exertional dyspnea,
pulmonary hypertension, and signs of right
heart failure. Although the diagnosis of chronic
thromboembolic disease relies on precise vascular features, its differentiation may be difficult
because in situ pulmonary artery thrombosis in
patients with idiopathic pulmonary hypertension
may mimic pulmonary artery occlusions caused
by thrombotic material of embolic origin (14).
Enlargement of bronchial and nonbronchial
systemic arteries is seen in 73% of patients with
chronic pulmonary thromboembolism but in only
14% of patients with idiopathic pulmonary hypertension (20).
The combination of mosaic lung attenuation and marked regional variation in the size of
segmental vessels is seen frequently in patients
with chronic thromboembolic pulmonary hypertension and is hardly ever seen in those with
idiopathic pulmonary hypertension (43,45). The
peripheral opacities typically produced by infarcts
are rarely seen in patients with idiopathic pulmonary hypertension (43).
Differentiation of Acute
and Chronic Thromboembolism
Chronic pulmonary thromboembolism often is
discovered during CT pulmonary angiography
performed to rule out acute pulmonary thromboembolism in a patient who presents with dyspnea. Acute and chronic thromboembolism commonly coexist.
In cases of acute complete obstruction, the diameter of the pulmonary artery may be increased
because of impaction of the thrombus by pulsatile flow (49) (Fig 18a). Conversely, in chronic
thromboembolic disease, the diameter of the vessel distal to a complete obstruction is markedly
decreased (Fig 18b).
44 January-February 2009
radiographics.rsnajnls.org
Figure 19. Acute pulmonary thromboembolism in a 58-year-old woman who presented
with dyspnea. (a) Axial contrast-enhanced CT scan depicts an eccentric partial filling defect
due to a thrombus that forms acute angles with the wall of the left lower lobe pulmonary
artery (arrows) (compare with Fig 4b). (b) Axial contrast-enhanced CT scan shows partial
filling defects surrounded by contrast material (“railway track” sign) (arrows), features produced by acute thrombi in the left upper lobe artery.
An acute nonobstructive filling defect may
be central or eccentric in location. In acute
thromboembolism, a nonobstructive eccentric
filling defect forms acute angles with the vessel
wall (Fig 19a). Conversely, partially obstructive
chronic thromboembolism appears as a peripheral crescent-shaped defect that forms obtuse
angles with the vessel wall (Fig 4b). An acute
nonobstructive central defect appears surrounded
by contrast-enhanced blood (Fig 19b) (50).
If the distinction between acute and chronic
or recurrent pulmonary thromboembolism is
unclear, the presence of dilated bronchial arteries
supports a diagnosis of recurrent or chronic pulmonary thromboembolism (38).
Wittram et al (51) defined the attenuation
values of acute and chronic pulmonary thromboembolism. The mean attenuation (± standard
deviation) in the presence of chronic thromboembolism (87 HU ± 30) is significantly higher than
that in acute thromboembolism (33 HU ± 15).
The higher mean attenuation in the presence of
chronic pulmonary thromboembolism is likely
related to enhancement of the organizing thrombus, retraction of the thrombus with its concentrations of hemoglobin and iron, and, possibly,
calcium deposition (Fig 7) (51).
Acute embolic obstruction of a significant
amount of the pulmonary circulation (usually esti-
Figure 20. Unilateral proximal interruption of the
right pulmonary artery in a 52-year-old woman with
progressive dyspnea. Axial contrast-enhanced CT scan
shows only the proximal portion of the right pulmonary artery (arrowhead), with enlargement of the main
and left pulmonary arteries secondary to pulmonary
hypertension. No endoluminal or periluminal changes
are depicted. (Reprinted, with permission, from reference 54.)
mated as more than 30%) increases pulmonary
vascular resistance and leads to acute pulmonary
hypertension and, in some cases, right ventricular
dysfunction and dilatation (52). However, since
pulmonary hypertension is not firmly established
in cases of acute obstruction, right ventricular hypertrophy has not yet developed.
RG ■ Volume 29 • Number 1
Castañer et al 45
Figure 21. Late-stage Takayasu arteritis with right pulmonary artery involvement in a 63-year-old woman. (a) Axial
contrast-enhanced CT scan shows right pulmonary artery occlusion (straight arrow), enlarged bronchial arteries
(curved arrow) in the right hilum, and an enlarged mammary artery (arrowhead). (b) Axial contrast-enhanced CT
scan at the level of the supra-aortic trunks shows soft tissue that surrounds the brachiocephalic trunk (curved arrows), occlusion of the left carotid artery (straight arrow), poor visibility of vessels in the right lung because of right
pulmonary artery involvement, and development of collateral vessels from intercostal arteries (arrowheads).
(Reprinted, with permission, from reference 54.)
Proximal Interruption
of the Pulmonary Artery
Interruption of the left pulmonary artery is usually associated with a congenital cardiovascular
anomaly, most commonly tetralogy of Fallot. Interruption of the right pulmonary artery is more
common and is an isolated finding in most instances (53). The pulmonary artery ends blindly at
the hilum, and blood is supplied through collateral
systemic vessels, mainly bronchial arteries. Unlike
chronic pulmonary embolism, proximal interruption of the pulmonary artery is characterized by
smooth, abrupt tapering of the pulmonary artery,
without endoluminal changes (Fig 20) (54).
A helpful diagnostic clue in most cases of
chronic pulmonary thromboembolism is the
presence of multiple bilateral arterial abnormalities. Occlusion of one main pulmonary artery,
mimicking proximal interruption, is rarely seen
and has been reported in only 3% of cases (55).
Takayasu Arteritis
Takayasu arteritis is an idiopathic arteritis that
mainly affects the elastic arteries. It frequently affects the aorta and its major branches; pulmonary
artery involvement occurs in 50%–80% of patients
and is a manifestation of late-stage disease (56).
The most characteristic findings are stenosis and occlusion, mainly of the segmental and
subsegmental arteries and less commonly of the
lobar or main pulmonary arteries (56). In the
presence of Takayasu arteritis, CT scans may
depict concentric inflammatory mural thickening in affected vessels. In addition, findings of
wall thickening in the aorta and aortic branches
and the absence of intraluminal thrombi in the
pulmonary arteries are diagnostic (57). Unilateral pulmonary artery occlusion may occur at
an advanced stage of the disease (Fig 21a), and
late-stage Takayasu arteritis should be considered
in cases of chronic pulmonary artery obstruction
of unknown origin (56). As in other conditions
involving decreased pulmonary flow, collateral
vessels may develop (Fig 21).
Primary Sarcoma
of the Pulmonary Artery
Primary sarcoma of the pulmonary artery is rare.
Undifferentiated sarcoma and leiomyosarcoma
are the types of sarcoma that most frequently
affect the pulmonary arteries. The main or proximal pulmonary arteries are most frequently involved. The clinical manifestations may mimic
those of acute or chronic pulmonary embolism
(58). Contrast-enhanced CT scans show the
46 January-February 2009
tumor as an intraluminal filling defect that resembles a thromboembolus. The filling defect
frequently spans the entire luminal diameter of
the main or proximal pulmonary artery (Fig 22),
a finding that is unusual in pulmonary thromboembolism. Other findings that may be helpful
for distinguishing a pulmonary artery sarcoma
from pulmonary thromboembolism include extension of the lesion into the lung parenchyma or
mediastinum and delayed enhancement at CT
angiography (58). Chong et al (59) reported a
case of pulmonary artery sarcoma that showed
positive uptake of fluorine 18 fluorodeoxyglucose
at positron emission tomography integrated with
CT; this feature may be helpful in differentiating a pulmonary artery sarcoma from pulmonary
thromboembolism.
Bronchial Abnormalities
Bronchial dilatation is a well-known hallmark of
chronic obstructive pulmonary disease (COPD).
In this setting, mucus-filled dilated bronchi, pulmonary infiltrates, or both are usually present.
From a clinical standpoint, bronchiectasis in
patients with COPD is related to sputum production. CT findings of bronchial dilatation in
patients without clinical and functional evidence
of COPD should arouse suspicion about the possibility of airway involvement in chronic thromboembolic disease (47) (Fig 17).
Diagnostic Evaluation
When chronic thromboembolic pulmonary hypertension is suspected, an extensive diagnostic
work-up is undertaken. Major goals are to determine whether thromboembolic disease is present,
quantify the degree of pulmonary hypertension,
and identify the cause or contributing factors.
Echocardiography
Transthoracic echocardiography allows diagnosis
of pulmonary hypertension by showing the pressures in the right atrium and the degree of tricuspid regurgitation. Echocardiography also may
help exclude other cardiac causes of pulmonary
hypertension (eg, cardiac shunts) (15).
Ventilation-Perfusion Scintigraphy
Recently, Tunariu et al (60) reported that ventilation-perfusion (V/Q) scintigraphy has a higher
sensitivity than CT pulmonary angiography for
detecting chronic thromboembolic pulmonary
hypertension. Normal findings at V/Q scintigraphy practically rule out the presence of chronic
thromboembolic pulmonary hypertension. By
radiographics.rsnajnls.org
Figure 22. Pulmonary artery sarcoma in a 70-yearold man with dyspnea. Axial contrast-enhanced CT
scan shows filling defects in the main, left, and right
pulmonary arteries and the right interlobar pulmonary
artery. The arterial lumina are expanded, and extravascular mediastinal invasion is seen. (Reprinted, with
permission, from reference 54.)
contrast, multiple segmental perfusion defects
that are unmatched by findings on ventilation
scintigrams make chronic thromboembolic pulmonary hypertension the most likely diagnosis,
although other conditions, including pulmonary
veno-occlusive disease, may result in similar findings (60). However, V/Q scintigraphy does not allow determination of the magnitude, location, or
proximal extent of disease and thus cannot predict its surgical operability. V/Q scintigraphy also
does not help identify other causes of pulmonary
hypertension (61).
Right Heart Catheterization
and Pulmonary Angiography
Combined right heart catheterization (to determine the severity of pulmonary hypertension) and selective pulmonary angiography (to
determine whether thromboembolic disease is
present) is considered the reference standard for
diagnosis of chronic thromboembolic pulmonary
hypertension.
At present, right ventricular catheterization is
the best method for determining the mean pulmonary artery pressure and pulmonary vascular
resistance, essential data for quantification of the
disease severity and determination of the postoperative prognosis (15).
Conventional pulmonary angiography is the
traditional cornerstone for evaluation of chronic
thromboembolic pulmonary hypertension. It
helps confirm the diagnosis and gives an indication of surgical operability (24,33). However, in
RG ■ Volume 29 • Number 1
the future, pulmonary angiography probably will
be performed only when an adequate surgical
roadmap has not been provided by CT and magnetic resonance (MR) imaging (62).
CT Angiography
Teaching
Point
CT angiography is a useful alternative to conventional angiography not only for diagnosing
chronic thromboembolic pulmonary hypertension but also for determining surgical operability
and confirming technical success postoperatively
(1,27,33). CT angiography is reported to be
more sensitive than conventional angiography in
depicting the presence of central thrombotic
disease (27) and equally sensitive to MR angiography in depicting the disease at the segmental
level. CT angiography is superior to MR angiography for the depiction of patent subsegmental
arteries and intraluminal webs and for the direct
demonstration of thrombotic wall thickening
(63). CT angiography also may provide evidence
pointing toward an alternative diagnosis or a different cause of pulmonary hypertension.
MR Imaging
Although CT is highly sensitive for the detection of proximal and subsegmental thrombi, it
does not yield sufficient quantitative information
about the severity of functional impairment. MR
imaging does enable sufficient characterization
of the impairment of function in the right side of
the heart (64). In addition, MR imaging permits
accurate estimation of flow in the bronchial arteries in patients with chronic thromboembolic
pulmonary hypertension (41). It also may play
an important role in postoperative follow-up.
However, MR imaging cannot take the place of
conventional angiography and right heart catheterization for the preoperative determination of
pulmonary vascular resistance and mean pulmonary artery pressure.
MR imaging certainly has the potential to
play a central role in the diagnosis, differential
diagnosis, treatment planning, and assessment of
postoperative outcome in patients with chronic
thromboembolic pulmonary hypertension (65).
Treatment
In chronic thromboembolic pulmonary hypertension, the thromboembolic material is endothelialized and incorporated into the vessel wall; therefore—unlike the situation in acute thromboembolism—anticoagulation therapy is not effective.
Nevertheless, lifelong anticoagulant therapy is
recommended to avoid recurrent thromboembolism or in situ growth of existing obstructions of
pulmonary arteries (14).
Castañer et al 47
The primary treatment for chronic thromboembolic pulmonary hypertension is surgical
pulmonary thromboendarterectomy, which leads
to a permanent improvement in pulmonary hemodynamics (66). In this surgical procedure, the
thrombus and the adjacent medial layer are carefully dissected. The reported mortality rate ranges
from 4% to 14% (67,68).
Pulmonary thromboendarterectomy is considered for symptomatic patients who have hemodynamic or ventilatory impairment at rest or with
exercise; it is also considered for patients who
have normal or nearly normal pulmonary hemodynamics at rest but in whom marked pulmonary
hypertension develops during exercise. The location and extent of the proximal thromboembolic
obstruction are the most critical determinants
of surgical operability: Occluding thrombi must
involve the main, lobar, or proximal segmental
arteries (10,67). If the hemodynamic impairment
derives mainly from more distal, surgically inaccessible disease or from the resistance conferred
by secondary small-vessel arteriopathy, then
pulmonary hypertension will persist postoperatively and may have adverse short-term and longterm consequences.
Some preoperative CT angiographic features
are considered predictive of a good response to
pulmonary thromboendarterectomy. For example, evidence of extensive central vessel disease
and limited small-vessel involvement is considered positive (69,70). Dilated bronchial arteries
are positively correlated with a lower mortality
rate after the surgical procedure (41). Heinrich
et al (71) suggested that patients without dilated
bronchial arteries have more severe distal vascular disease (either thromboembolism or secondary small-vessel disease) leading to higher postoperative pulmonary vascular resistance than that
in patients with dilated bronchial arteries.
Placement of a filter in the inferior vena cava
is recommended before surgery in all patients
except those with a clearly defined source of emboli other than deep veins in the legs. Lifelong
anticoagulant therapy is strongly recommended
to prevent recurrent thrombosis after pulmonary
thromboendarterectomy (14).
Conclusions
Chronic thromboembolic pulmonary hypertension is clearly more common than previously was
thought. It often has been misdiagnosed because
patients present with nonspecific symptoms.
Knowledge of the radiologic imaging signs is
required to detect and accurately diagnose the
Teaching
Point
48 January-February 2009
condition. Because chronic thromboembolism is
potentially curable with pulmonary thromboendarterectomy, early recognition may improve the
outcome in cases that are technically operable.
The main objective of cross-sectional imaging
in patients with chronic thromboembolic pulmonary hypertension (after confirming the diagnosis
and differentiating the disease from other causes
of pulmonary hypertension) is to correctly assess
the technical feasibility of surgery. In this regard,
CT and MR angiography represent the future
for diagnosis and management of chronic thromboembolic pulmonary hypertension.
Acknowledgments: The authors thank Ricard Valero,
MD, PhD, for his illustration of interrupted thrombus
resolution and John Giba for linguistic aid.
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This article meets the criteria for 1.0 credit hour in category 1 of the AMA Physician’s Recognition Award. To obtain
credit, see accompanying test at http://www.rsna.org/education/rg_cme.html.
RG
Volume 29 • Volume 1 • January-February 2009
Castañer et al
CT Diagnosis of Chronic Pulmonary Thromboembolism
Eva Castañer, MD, et al
RadioGraphics 2009; 29:31–53 • Published online 10.1148/rg.291085061 • Content Codes:
Page 32
The prevalence of chronic thromboembolic pulmonary hypertension in the general population has yet
to be accurately determined and may have been significantly underestimated. Recent prospective
epidemiologic data indicate an incidence of approximately 4% after acute symptomatic pulmonary
thromboembolism.
Page 32
Symptoms are nonspecific and are related to the development of pulmonary hypertension. The extent
of vascular obstruction is a major determinant of the severity of pulmonary hypertension. In the
majority of symptomatic patients, more than 40% of the pulmonary vascular bed is obstructed.
Page 33
The pathogenesis of chronic thromboembolism is still unclear [...]. The majority opinion supports a
thromboembolic pathogenesis, with a possible role for in situ thrombosis as a factor in disease
progression (contribution to the persistence of thrombi) rather than initiation. In this scenario, the
pathologic process is linked mainly with disturbance of thrombus resolution. In a small percentage of
patients, particularly those with a large perfusion defect or recurrent episodes of thromboembolism,
the resolution of thrombi is incomplete. The organization of a thromboembolus with invasion by
fibroblasts and capillary buds that adhere to the vascular wall can be regarded as a reparative
response.
Page 47
CT angiography is a useful alternative to conventional angiography not only for diagnosing chronic
thromboembolic pulmonary hypertension but also for determining surgical operability and confirming
technical success postoperatively.
Page 47
The location and extent of the proximal thromboembolic obstruction are the most critical
determinants of surgical operability: Occluding thrombi must involve the main, lobar, or proximal
segmental arteries.