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CTA
CT is a frontline technique for the assessment of sus-
pected acute thromboembolic disease. Excellent spatial and
contrast resolution, rapid scan times, and detailed evalua-
tion of the lung parenchyma are some of the advantages
that CTA oers. For routine clinical purposes, a standard
nonelectrocardiogram (ECG)-gated CTA is usually su-
cient, although some studies have shown the added value of
ECG gating and of newer protocols such as high pitch
imaging.38
CT ndings in patients with CTEPH may vary
according to the severity of the disease, the amount of
vascular obstruction, and the degree of PH.39 These imag-
ing ndings can be divided into those related to CTED and
those related to PH, each of which can be subdivided into
vascular signs and lung parenchymal signs.
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J Thorac Imaging Volume 32, Number 2, March 2017 Imaging in CTEPH
FIGURE 4. Planar V/Q scans in a patient with CTEPH. Images on the left panel are ventilation images, whereas perfusion images are
shown on the right. Multiple mismatched perfusion defects are noted (arrow), a typical finding in CTEPH.
thrombosis.44 Dierentiation of in situ thrombosis from In the setting of CTEPH, the regions of lower lung paren-
CTEPH has clinical implications as anticoagulation would chyma attenuation usually represent hypoperfused lung
increase the risk of bleeding in patients with in situ tissue and are associated with attenuated vascular mark-
thrombosis. ings51 (Fig. 9). In some situations, air trapping may also
Enlargement of the bronchial arteries is a nonspecic contribute to lower lung parenchymal attenuation in
response to chronically occluded PAs.45,46 The degree of patients with CTEPH, most likely because of secondary
systemic collaterization including the pleural and inter- impairment of the small airways.52 Regions of higher lung
costal arteries is related to the degree of obstruction and is parenchymal attenuation in CTEPH usually represent
more common with centrally located thromboembolic dis- hyperperfused lung tissue resulting from redistribution of
ease. In severe cases of CTEPH, enlarged bronchial arteries pulmonary blood ow. Augmented perfusion from collat-
may contribute to up to 30% of the pulmonary blood eral vessels may also contribute to focal areas of hyper-
ow.47 Interestingly, 1 study found a higher incidence of attenuation. Dierentiation from small airway disorders
bronchial artery hypervascularization in patients with can be aided by assessing the size of vessels within the low
CTEPH (73%) compared with that in patients with IPAH attenuation zones (attenuated with small vessel and normal
(14%).46 Identication of the collaterals, particularly the with small airway disorders) and by expiratory imaging,
bronchial arteries, is important, as these patients have an which can highlight air trapping in areas of low attenuation
increased incidence of hemoptysis.48 Presence of dilated with small airway disorders. Minimum-intensity projection
bronchial arteries has prognostic signicance and is asso- CT technique improves the detection of the mosaic
ciated with lower mortality after PEA, possibly related to attenuation pattern, whereas maximum-intensity projection
distal pulmonary microvasculature sparing.49 Thin-section images highlight variations in vessel caliber.
maximum-intensity projection coronal images are fairly Cylindrical bronchiectasis is occasionally observed
eective in depicting bronchial arteries. However, bronchial within segmental and subsegmental bronchi in the setting of
hypervascularization is not specic to CTEPH; these can be CTED, adjacent to severely stenosed or thrombosed PAs.53
encountered in other conditions leading to chronic hypoxia, Although the exact cause is unknown, hypoxic bronchodi-
such as interstitial brotic lung disease, bronchiectasis, and lation has been suggested as a possible mechanism.54
chronic infection. Patients with CTE typically show changes related to
old infarcts, although acute infarcts secondary to super-
CT Findings Related to CTEDLung Parenchymal imposed acute thromboembolic disease are not uncommon.
Signs On CT, in its most acute form, the infarct appears as an
Mosaic attenuation is a term used to describe a mul- area of consolidation and/or ground-glass opacity, in
tilobular patchwork of varying lung parenchymal attenu- keeping with an area of pulmonary hemorrhage. As the
ation50 that is often observed in patients with CTEPH. The infarction evolves, it acquires the typical appearance of an
imaging pattern of mosaic attenuation is by and large infarct, seen as a peripheral wedge-shaped, pleura-based
nonspecic and can be seen in several pathologies, such as density. Other characteristic ndings include internal air
small airway disease, small vessel disease, and primary lung lucencies, truncated apex (cuto tip), and a thickened vessel
parenchymal disease such as hypersensitivity pneumonitis. leading to the apex of the infarct, the vascular sign.55 Over
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Renapurkar et al J Thorac Imaging Volume 32, Number 2, March 2017
FIGURE 5. A 54-year-old-man with false-positive V/Q scans. A, Planar V/Q scans show severely decreased perfusion to the right lung. B,
Axial CTA image shows expansile filling defect in the right pulmonary artery (arrow), which is totally occluded. C, Coronal positron
emission tomography/CT fused image shows 18F-Fluorodeoxyglucose uptake in the mass-like filling defect (arrow), which was proven to
be a pulmonary artery sarcoma.
time, the infarct contracts and resolves, leaving residual CT Findings Related to PHVascular Signs
scars or bands. There may be an associated pleural reac- Increasing PVR can act in concert with other factors
tion, manifested as pleural thickening or uid.56 Nodules and lead to the development of PH, which is reected on CT
and cavitary opacities are not uncommon. as enlargement of central PAs. PA diameters over 29 mm are
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J Thorac Imaging Volume 32, Number 2, March 2017 Imaging in CTEPH
FIGURE 6. Abnormal representative SPECT and fused SPECT-CT images of a patient with CTEPH. Top panel images show fused
perfusion images, whereas bottom panel images show ventilation. Areas of hypoperfusion and decreased ventilation are seen as dark
defects. Mismatched perfusion defects are noted, predominantly in the upper lobes bilaterally (arrows). Note that ventilation images
show tracer retention in the central airways, which is a limitation of aerosol imaging.
often used as a threshold for PH. The measurement is per- of mortality in patients with bronchiectasis.59 A ratio of distal
formed at the plane of the pulmonary bifurcation orthogonal main PA to aortic diameter of over 1 is also suggestive of PH,
to the vessel course57,58 (Fig. 10). In a recent study, right and particularly in younger patients.58 ECG-gated examinations
left PAs over 18 mm in size were found to be best predictors have been shown to improve the evaluation of functional
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Renapurkar et al J Thorac Imaging Volume 32, Number 2, March 2017
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J Thorac Imaging Volume 32, Number 2, March 2017 Imaging in CTEPH
FIGURE 8. CTA appearances of chronic thrombi in different patients with CTEPH: web (arrow in A), vessel atrophy with poor contrast
opacification (arrow in B), eccentric thrombus (arrow) and calcified mural thickening (yellow arrowhead) (C), and stenosis with
poststenotic dilation (arrow in D).
Dual-Energy CT (DECT)
DECT uses attenuation dierences at various energy
levels to dierentiate between tissue materials. X-ray
attenuation is dependent on Compton scatter and photo-
electric absorption, which vary with photon energies and
material compositions. The probability of photoelectric
eect increases with increasing atomic number and
decreases with increasing photon energy.77 For materials
with higher atomic numbers, such as iodine, the photo-
FIGURE 9. Coronal CT image in lung window settings shows electric eect markedly decreases with increasing photon
mosaic attenuation of the lung parenchyma in a patient with energy, resulting in a rapid decrease in Hounseld unit
CTEPH. value. Thus, by using low and high voltages, relative
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Renapurkar et al J Thorac Imaging Volume 32, Number 2, March 2017
FIGURE 10. CT evaluation of pulmonary hypertension and RV parameters: A, Axial CTA image shows measurement of the main
pulmonary artery (MPA) just proximal to the bifurcation. The MPA measures 39 mm, consistent with pulmonary hypertension. B, ECG-
gated axial CTA image shows dilated RV (5.7 cm) with RV hypertrophy (arrowhead) in a patient with CTEPH. C, Axial CTA image shows
calculation of the septal angle from a line drawn between the midpoint of the sternum to the spinous process of a vertebral body and a
line drawn through the interventricular septum. Septal angle >67 degrees is a specific indicator of increased PVR.
dierences in the absorption characteristics of materials this factor. As on V/Q and magnetic resonance imaging
such as iodine and xenon can be exploited to characterize (MRI) scans, acute perfusion defects on DECT are seen as
their content within the tissue. The iodine within a voxel is wedge-shaped areas of decreased attenuation and corre-
quantied, and iodine perfusion maps are generated. It sponding decreased iodine content (Fig. 12). Some studies
should be noted that these are not true perfusion images, as have shown excellent correlation between the perfusion maps
they measure iodine content at a single time point. How- obtained using DECT and those obtained using V/Q scans
ever, these images do serve as an eective surrogate for the and SPECT-CT examinations.79,80 Limited but encouraging
assessment of perfusion.78 Automated quantication of data correlating regional perfusion maps with hemodynamic
perfused blood volume (PBV) images can be done, which parameters and lung parenchymal ndings have been
allows objective comparison of perfusion abnormalities in reported. In 1 study, DECT allowed the identication of
dierent lung segments. areas of mismatching, using a partition value of 20 Houns-
Hemodynamic impairment is a critical factor in deter- eld unit to dierentiate areas of residual perfusion distal to
mining whether a patient is eligible for surgical intervention, proximally occluded segments.81 These areas were postulated
and DECT oers the potential for one-stop assessment of to be perfused by collaterals (such as bronchial arteries); the
presence of such segments could be predictive of greater
postoperative success than matched defects. In the same
study, no signicant correlation was found between PBV
maps and RHC-derived mPAP and PVR.81 However, in
another study in 25 patients with CTEPH, automated PBV
values inversely correlated with PASP and mPAP.82 There
was also a trend of PBV values to correlate inversely with
PVR.82 Similarly, a recent study showed that automated
lung PBV scoring can serve as a noninvasive estimator of
clinical CTEPH severity, especially in comparison with the
mPAP and PVR.83 Another study on 391 patients demon-
strated that PH patients demonstrate increased main PA
enhancement with a reciprocal reduction and greater varia-
tion in parenchymal enhancement; a DECT ratio of central
to parenchymal enhancement correlated with PVR.84
Another novel application of DECT is the ability to
dierentiate between acute and CTED and assess the
amount of bronchial artery collaterization (Fig. 13). As
FIGURE 11. Axial lung window CT image shows multifocal noted earlier, some studies have shown that the presence of
ground-glass and centrilobular nodules (arrows) in a patient with bronchial artery collaterization is associated with better
IPAH. postoperative success.42,66 Using a 2-phase scanning
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J Thorac Imaging Volume 32, Number 2, March 2017 Imaging in CTEPH
protocol, in a study on 114 patients, it was shown that Although DECT oers considerable promise in
chronic PE segments showed more enhancement on delayed CTEPH, PBV maps require careful interpretation. Pseu-
phases than did acute PE segments, suggesting more col- dodefects can be seen because of artifacts such as beam-
lateral supply to these regions.85 hardening artifacts or motion artifacts near the heart or the
DECT can also help in the assessment of the various diaphragm. These artifacts need to be avoided or recog-
causes of mosaic attenuation and provide results that point nized before a diagnosis is reached.87 Typical beam-
to a specic vascular pathology.86 For example, in areas of hardening defects aect the medial right lung (predom-
ground-glass opacities, by demonstrating increased or no inantly in the right upper lobe) due to contrast in SVC.
perfusion, it can aid in dierentiating a vascular process As noted above, PBV maps always require interpretation
from primary lung inltration. DECT also aids in the dif- in relation to morphologic pulmonary reconstructions in
ferential diagnosis of various groups of PH.87 Typically, order to exclude underlying lung process such as
group 1 diseases such as IPAH demonstrate mottled per- emphysema.
fusion as compared with the segmental defects with
CTEPH. Perfusion abnormalities may also be caused by
parenchymal destruction as in ILD, diuse small airway
disease, or pulmonary emphysema. Correlating the PBV MRI and MR Angiography (MRA)
maps with lung reconstructions can show that these defects MRI and MRA play a growing role in the evaluation
match the areas of parenchymal destruction and thus help of pulmonary thrombotic disease. Some tools, such as cine
dierentiate group 3 PH disorders. Finally, DECT can be imaging and phase-contrast velocity-encoded MRI (PC-
used to assess V/Q. Use of inert agents such as xenon has MRI), provide valuable functional information and have a
been applied to map distribution in the lung parenchyma denite role in the follow-up of patients.90 However, tech-
and thereby generate information on ventilation.88 Initial nical demands and suboptimal evaluation of lung paren-
study results have been encouraging, suggesting that a true chyma currently limit the use of MRI as a single imaging
DECT V/Q study may be possible.89 test in CTEPH.
FIGURE 12. DECT images of a 51-year-old man with CTEPH with angiographic correlation. A, Coronal perfusion iodine map shows
wedge-shaped defects in the right upper and both lower lobes (arrowheads) corresponding to stenotic right upper lobe segmental
branch (arrow). B, Corresponding blood vessel map shows patchy distribution of contrast-enhanced arteries, consistent with chronic
thrombotic disease (greenish blue arteries: iodine containing arteries; red arteries: non-iodine-containing arteries). C, Parenchymal
phase image from a conventional right pulmonary angiogram shows excellent correlation with DECT images, showing the stenotic right
upper lobe segmental branch (arrow) and oligemia in the right upper and lower lobes (arrowheads).
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Renapurkar et al J Thorac Imaging Volume 32, Number 2, March 2017
FIGURE 13. Two-phase DECT in a patient with CTEPH. A, Axial CT image shows severely attenuated left lower lobe pulmonary artery
(arrow). B, Coronal PBV image shows large perfusion defect in the left lower lobe; on the delayed phase done 70 seconds later (C), the
perfusion to the left lower lobe has improved, which may suggest significant collateral supply to this region.
MR Findings Related to Pulmonary Thromboembolic interobserver and intraobserver variability.96 PC-MRI and
DiseaseAnatomy cine steady state free precession imaging can also be com-
Imaging features of pulmonary thromboembolic dis- bined to quantify shunt fraction (Qp/Qs), which indirectly
ease on contrast-enhanced MRA are similar to those seen reects the degree of bronchopulmonary shunting in these
on CTA, including irregular eccentric lling defects within patients.42
the PAs, intraluminal webs and bands, and areas of sten- Recent research has shown good correlation between
oses and occlusion91 (Fig. 14, Cine clip 2, Supplemental MRI-derived mPAP and PVR measurements and angio-
Digital Content 2, http://links.lww.com/JTI/A76). A lack graphic measurements.97,98 MRI can highlight indirect signs
of signal intensity in the normal lung limits evaluation of of elevated PAP, including delayed enhancement at the
the peripheral vasculature, as the low signal intensity of the septal insertion points of the myocardium and systolic
occluded vessel is indistinguishable from that of the sur- bowing of the interventricular septum toward the LV, which
rounding lung.92 Typically, branches down to the segmental is explained by the mechanical dyssynchrony resulting from
levels can be reliably assessed with MRI.93 Because of its RV overload and elongation and LV underlling.99,100
higher spatial resolution, better contrast-noise ratio, and Functional indices such as PVR, mPAP, and RV function
faster imaging times (enabling better breath-holding), CT is have important prognostic implications and can be used to
better suited for subsegmental vasculature assessment than assess functional improvement after pulmonary thromo-
MRI and remains the diagnostic test of choice for the bendarterectomy.91,101,102 Emerging techniques such as 4D
evaluation of morphologic abnormalities.94 However, as velocity ow mapping may provide additional insights into
most surgically accessible thrombi are limited to the central ow patterns in pulmonary circulation.103
and segmental branches, the ultimate signicance of sub- In theory, MRI seems to be a good option for perfusion
segmental disease characterization is unknown. imaging, which could make this modality a true one-stop
test for assessing PH and CTEPH. Limited data evaluating
MR Findings Related to Pulmonary Thromboembolic the assessment of lung perfusion with MRI have shown good
DiseaseFunction correlation with perfusion scintigraphy.93,104 One of the
Cine steady state free precession imaging is an constraints involved in assessing lung perfusion is the
accepted reference standard for the evaluation of LV and dynamic nature of pulmonary microcirculation. Quantitative
RV function, with excellent accuracy and reproducibility.95 perfusion parameters, including mean transit time, time to
PC-MRI allows for estimation of cardiac output with low peak, and blood volume, can be estimated on the basis of the
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Renapurkar et al J Thorac Imaging Volume 32, Number 2, March 2017
CLINICAL DECISION MAKING IN CTEPH PASP.117 Several noninvasive tools can be used in con-
PTE is a complex surgical procedure and a true junction with clinical tools such as 6-minute walk test to
endarterectomy in which surgically accessible thrombotic assess functional recovery. Echocardiography is the easiest
material is removed. Typically, thromboembolic burden in and readily available test and can be used to assess post-
main, lobar, and segmental branches is deemed operable, therapy LV and RV remodeling. Newer techniques such as
whereas distal (subsegmental/microvascular) disease is 2D speckle tracking may allow better assessment of cardiac
usually considered inoperable. However, assessment of function after therapy.118 One of the disadvantages of echo-
surgical candidacy can often be inuenced by several other cardiography, however, is that direct visualization of the
factors such as age, conditioning, degree of hemodynamic disease burden is not possible. CTA and MRI are well suited
impairment, and preoperative PVR.116 Often, a multi- for depiction of improvement of thrombus burden, although
disciplinary discussion among surgeons, pulmonologists, they are not routinely used. MRI, although slightly inferior to
and radiologists is necessary in clinical decision making. CTA in the assessment of pulmonary vascular thrombotic
For radiologists, one of the key points to note is that if the disease, can be extremely helpful in the evaluation of func-
extent of anatomic disease correlates with the degree of tional recovery. Several MRI-based noninvasive biomarkers
increased PVR, the disease is usually deemed operable. such as PA maximum ow velocity, acceleration time/ejec-
However, if the disease burden appears mild or relatively tion time, and distensibility can be evaluated using MRI.119
normal in the context of disporoportionately elevated PVR, RV remodeling and adaptation is also better evaluated with
the possibility of small vessel arteriopathy is likely.116 MRI than with any other imaging technique.120
The roles of various imaging modalities in the evalu- A major role of imaging is in the assessment of com-
ation of common causes of PH are summarized in Table 3. plications. After PTE, some of the early complications
The roles of various imaging techniques in assessing the include reperfusion pulmonary edema and PA steal syn-
morphologic and functional changes of CTEPH are sum- drome. PA steal syndrome, seen in approximately 70% of
marized in Table 4. patients after PTE, is characterized by new areas of V/Q
mismatching and reects the redistribution of blood ow
from normally perfused lung to the newly endarterectom-
ROLE OF IMAGING IN FOLLOW-UP ized segments.121 One of the intermediate to long-term
Imaging is often used to monitor patients on medical complications of PTE is residual PH, seen in approximately
therapy and for assessment of response to therapy following one-third of patients.122 Causes include distal inoperable
PEA and BPA. Successful PTE is associated with immediate subsegmental disease and/or coexisting small vessel arte-
improvement in hemodynamics, with reduction in PVR and riopathy.122 Recurrent PH is less common and is due to a
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J Thorac Imaging Volume 32, Number 2, March 2017 Imaging in CTEPH
new thromboembolic event after successful PTE.116 CTA 5. Berghaus TM, Barac M, von Scheidt W, et al. Echocardio-
and MRI are promising tools for assessing residual/recur- graphic evaluation for pulmonary hypertension after
rent PH, with both having their respective strengths. DECT recurrent pulmonary embolism. Thromb Res. 2011;128:
with its ability to provide perfusion information along with e144e147.
6. Kapitan KS, Buchbinder M, Wagner PD, et al. Mechanisms
excellent depiction of thrombotic disease might evolve as a of hypoxemia in chronic thromboembolic pulmonary hyper-
frontline test for evaluation of complications. tension. Am Rev Respir Dis. 1989;139:11491154.
7. Held M, Kolb P, Grun M, et al. Functional characterization
of patients with chronic thromboembolic disease. Respiration.
FUTURE DIRECTIONS 2016;91:503509.
The role of imaging in the diagnosis and management 8. Berger G, Azzam ZS, Hardak E, et al. Idiopathic pulmonary
of CTEPH continues to expand rapidly. With the success of arterial hypertension or chronic thromboembolic pulmonary
newer minimally invasive therapies such as BPA, a variety hypertension: can we be certain? Isr Med Assoc J. 2011;13:
of therapy options are available. One of the holy grails in 106110.
the imaging of CTEPH remains the identication of 9. Riedel M, Stanek V, Widimsky J, et al. Long-term follow-up
microvascular disease. So far, there is no gold standard for of patients with pulmonary thromboembolism: late prognosis
and evolution of hemodynamic and respiratory data. Chest.
direct identication of microvascular disease. Angiography-
1982;81:151158.
based partitioning of PVR by a PA occlusion technique 10. Fedullo P, Kerr KM, Kim NH, et al. Chronic thromboem-
may allow the identication of patients with small vessel bolic pulmonary hypertension. Am J Respir Crit Care Med.
disease but is invasive and technically demanding.111 A 2011;183:16051613.
handful of studies have shown the potential role of echo- 11. Corsico AG, DArmini AM, Cerveri I, et al. Long-term
cardiography and MRI in identifying these patients. Using outcome after pulmonary endarterectomy. Am J Respir Crit
Pulsed Doppler and PC-MRI, the PA systolic prole is Care Med. 2008;178:419424.
mapped and assessed for the presence of systolic notching. 12. Kim NH, Delcroix M, Jenkins DP, et al. Chronic throm-
The timing of the systolic notch is used as a predictor of the boembolic pulmonary hypertension. J Am Coll Cardiol. 2013;
site of obstruction, with a late systolic notch indicating the 62(suppl):D92D99.
13. Taboada D, Pepke-Zaba J, Jenkins DP, et al. Outcome of
presence of microvascular disease.123 Although such pulmonary endarterectomy in symptomatic chronic throm-
advances are promising, larger studies are needed to fully boembolic disease. Eur Respir J. 2014;44:16351645.
assess the benet of these noninvasive markers of micro- 14. Ogawa A, Matsubara H. Balloon pulmonary angioplasty: a
vascular disease. treatment option for inoperable patients with chronic
thromboembolic pulmonary hypertension. Front Cardiovasc
Med. 2015;2:4.
CONCLUSIONS 15. Simonneau G, Gatzoulis MA, Adatia I, et al. Updated clinical
Imaging plays an important role in the diagnosis of classification of pulmonary hypertension. J Am Coll Cardiol.
CTEPH, its preoperative evaluation, and in the assessment 2013;62(suppl):D34D41.
of a patients response to therapy. Although V/Q scanning 16. Auger WR, Fedullo PF. Chronic thromboembolic pulmonary
continues to be favored as the initial screening test of hypertension. Semin Respir Crit Care Med. 2009;30:471483.
choice, CT has emerged as the denitive imaging test of 17. Kyrle PA, Minar E, Hirschl M, et al. High plasma levels of
factor VIII and the risk of recurrent venous thromboembo-
choice in depicting the structural and vascular abnormal- lism. N Engl J Med. 2000;343:457462.
ities in CTEPH. MRI plays a complementary role, pro- 18. Wolf M, Boyer-Neumann C, Parent F, et al. Thrombotic risk
viding crucial functional and physiological information that factors in pulmonary hypertension. Eur Respir J. 2000;15:
carries prognostic value. The emergence of new methods 395399.
such as DECT, SPECT V/Q, SPECT-CT V/Q, and newer 19. Lang IM, Pesavento R, Bonderman D, et al. Risk factors and
MRI techniques heralds an exciting and promising shift in basic mechanisms of chronic thromboembolic pulmonary
imaging paradigms that may improve clinical decision hypertension: a current understanding. Eur Respir J. 2013;41:
making and ultimately lead to more favorable patient 462468.
outcomes. 20. Hansell DM. Small-vessel diseases of the lung: CT-pathologic
correlates. Radiology. 2002;225:639653.
21. Raisinghani A, Ben-Yehuda O. Echocardiography in chronic
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