Pulmonary Vein Sign on Computed Tomography Pulmonary Angiography in Proximal and Distal Chronic Thromboembolic Pulmonary Hypertension With Hemodynamic Correlation : Journal of Thoracic Imaging

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Pulmonary Vein Sign on Computed Tomography Pulmonary Angiography in Proximal and Distal Chronic Thromboembolic Pulmonary Hypertension With Hemodynamic Correlation

Gopalan, Deepa FRCP, FRCR*,†; Riley, Jan Y.J. MBBS; Leong, Kai’en MBBS§; Guo, Haiwei Henry MD, PhD; Zamanian, Roham T. MD, FCCP¶,#; Hsi, Andrew BS#; Auger, William MD, PhD**; Lindholm, Peter MD, PhD*,††

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Journal of Thoracic Imaging 38(3):p 159-164, May 2023. | DOI: 10.1097/RTI.0000000000000706
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Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive dual pulmonary vascular disorder characterized by organized thrombotic material causing obstruction in the larger pulmonary arteries of elastic type (>0.5 mm) and a secondary vasculopathy in the distal smaller muscular vessels (<0.5 mm).1 Computed tomography (CT) pulmonary angiography (CTPA) is a commonly performed investigation in the work-up of patients with suspected CTEPH. While the pulmonary arterial abnormalities that constitute large vessel disease are well delineated on CTPA, distal vessel disease is much more difficult to visualize on CT, although the presence of mosaic perfusion, a marker for regional perfusion differences, can provide a clue to identify this level of disease. Thus, unlike acute Pulmonary embolism (PE) where CTPA is considered the standard of care, a negative CT cannot conclusively exclude CTEPH as the distal segmental and subsegmental disease can be missed.

The appropriate identification of vascular abnormalities on CT underpins successful surgical outcomes2 and also has the potential to ensure that patients with inoperable disease can benefit from emerging treatments such as balloon pulmonary angioplasty (BPA) and medical therapy. The pulmonary arterial abnormalities of thromboembolic disease on CTPA have been extensively documented over the last 2 decades but only recently has there been interest in the concomitant flow abnormalities in the pulmonary veins. Heterogenous or nonopacification of a central pulmonary vein compared with the other major pulmonary veins during pulmonary arterial phase imaging on CT, named the pulmonary vein sign (PVS), was first described in small case series of acute PE and shown to be associated with poor prognosis.3–5 Uneven venous filling due to diminished flow secondary to varying degrees of upstream arterial obstruction manifests as PVS in the corresponding pulmonary vein on early enhanced imaging. Recently, the PVS was described in a cohort of proximal CTEPH cases where it was shown that the PVS was not only more prevalent in proximal CTPEH when compared with acute PE, but also had higher sensitivity and specificity for chronic thromboembolism.6 However, there is no published data on the association between PVS and distal vessel CTEPH. Also, while in acute PE, the PVS is associated with higher risk and poorer prognosis,3 it is not known if there is a corelation between PVS and CTEPH severity.

We performed this retrospective, multi-institutional observational study to (a) assess the presence of PVS in different categories of CTEPH and, in particular, identify if PVS is a feature of distal CTEPH, and (b) evaluate if PVS has any correlation with the right heart catheter (RHC) derived pulmonary hemodynamics


A retrospective analysis was performed with approval from the Institutional Review Board (IRAS project ID 280472 & IRB:12338) and the need for informed consent was waived. Pulmonary hypertension databases from 2 institutions (nonsurgical centers) were scrutinized between 2010 and 2020, and 93 consecutive cases of CTEPH cases with CTPA and RHC performed within a 3-month of each other were identified. Seventeen cases were excluded due to suboptimal CTPA (poor opacification of the left atrium with HU<160, beam hardening artifacts from dense contrast in the Superior Vena Cava obscuring the proximal pulmonary veins in the right upper lobe).

Clinical data of the patients were retrieved from the Radiology Information System database and age, sex, body mass index, and history of atrial fibrillation were recorded. The CT protocol parameters from both institutions are provided in Table 1.

TABLE 1 - CTPA Technical Specifications and Acquisition Parameters
Institution 1 Institution 2
Scanner Single-source 128-multislice configuration (Somatom Definition AS+; Siemens AG, Germany) Uses a variety of models from Siemens and GE but majority of the scans in this study were done on Siemens Somatom Force (Siemens AG, Germany)
ECG-gating No No
Breath-hold Single breath-hold (4, 5, 6 s) at end inspiration No breath-hold necessary as scan is <1 s. But patients are specifically instructed to avoid Valsalva
Coverage Craniocaudal from lung apices to diaphragm Craniocaudal from lung apices to diaphragm
Collimation (mm) 0.6 0.6
Table speed (mm per revolution) 61.4 89.2
Pitch 0.7-1.0 1.55
Rotation time (s) 0.5 0.28
Automatic tube current modulation (CARE Dose-4D) On On
Automatic tube potential control (CARE kv) On On (level 11)
Tube potential (ref) (KVp) 80–120 120
Tube current time product (ref) (mAs) 100–200 174
Length of Z-axis coverage per rotation 38.4 89.2
Reconstruction matrix 512 × 512 512 × 512
Reconstruction interval (mm) 1 1
Contrast medium protocol Care bolus software (Siemens Medical Solutions, Forchheim, Germany) with ROI in pulmonary artery. As soon as the trigger threshold of 130 HU was reached, the table moved to the cranial start position and scanning was started following a 4 s interval during which time the patient was instructed to take a breath in and hold before imaging (automated verbal breathing command) Care bolus software (Siemens Medical Solutions, Forchheim, Germany) with ROI in pulmonary artery. Delay is 2/3 of the contrast injection duration. (Default is 10 s interval delay if using 15 s injection duration)
Injection protocol 70-100 Omnipaque 350 (GE Healthcare) @ 5 mL/s followed by 20-mL saline chaser using power injector ISOVUE 370 (IOPAMIDOL)
Volume: 1.3 × (Pt weight in kg)
Flow rate: 4.0-8.0 mL/s
50 mL saline chaser using power injector.
Max injection rate up to 8 mL/s
Iterative reconstruction SAFIRE (Sinogram Affirmated Iterative Reconstruction, strength 3) ADMIRE (Advanced Modeled Iterative Reconstruction, Strength 3)

CTPAs were analyzed for PVS as per the previously described methodology.4–6 The CT data were anonymized and the proximal and distal cases were mixed randomly before being evaluated in consensus by 2 radiologists (R1 cardiovascular radiologist with >15 y’ experience, R2 thoracic radiologist with >10 y’ experience) using Vitrea Advanced Visualization multimodal platform (Vital Images Inc.). (Categorization definition: proximal CTEPH was categorized as the presence of organized thrombus in the main, lobar, and proximal segmental pulmonary arteries. Distal CTEPH was defined as a disease predominantly in the distal segmental and subsegmental pulmonary arteries.) While it was not possible to blind the readers to the pulmonary arterial abnormalities on the CTPA, they were asked only to mark the venous flow abnormalities. Flow in each of the 4 pulmonary veins was qualitatively graded: with 1 for normal flow, 2 for heterogenous opacification, and 3 for homogenous non-opacification. A “total pulmonary vein flow” score was calculated by summing the flow grades in all 4 veins such that a score of 4 would indicate normal flow in all 4 veins. The PV score was correlated with RHC-derived hemodynamic data.

Although all the proximal CTEPH cases had undergone pulmonary endarterectomy, only 38 had postop CTPA performed between 3 and 6 months after surgery. A subgroup analysis was done to evaluate the PVS in these 38 subjects before and after endarterectomy.

Statistical Analysis

Data were analyzed using SPSS Statistics (version 25, IBM Corp) and Microsoft Excel. Continuous normal data are presented as mean (±1 SD). Non-normal data are presented as median (interquartile range). Categorical variables are displayed as n (%). Continuous data were compared with the (paired) 2 tailed Student t test. Correlation analysis was performed using the Pearson correlation coefficient. A P-value of<0.05 was considered statistically significant.


The baseline characteristics and RHC data are outlined in Table 2. There were 52 cases of proximal CTEPH (29 male, 23 female) with a mean age of 55 years and 24 cases of distal CTEPH (11 male, 13 female) with a mean age of 62 years. All patients were in sinus rhythm. The mean body mass index was 29.1 and 27.3, respectively, for the 2 groups. There was no significant difference in the invasive hemodynamic measurements between the proximal and distal CTEPH cases. The mean pulmonary artery pressure (mPAP) was 46±11 and 41±12 mm Hg and pulmonary vascular resistance was 9.4±4.5 and 8.4±4.8 WU, respectively.

TABLE 2 - Baseline Characteristics of CTEPH Cases
Proximal CTEPH (n=52) Distal CTEPH (n=24)
Age (y) 55±15 62±14
Sex (%) 29 M (56%), 23 F (44%) 11 M (46%), 13 F (54%)
BMI (kg/m2) 29.1 (25.4-35.8) 27.3±4.7
mPAP (mm Hg) 46±11 41±12
PVR (WU) 9.4±4.5 8.4±4.8
CO (L/min) 3.9 (3.2-4.8) 4.1±1.2
CI (L/min/m2) 1.9 (1.7-2.4) 2.1±0.5
BMI indicates body mass index; mPAP, mean pulmonary artery pressure; PVR, pulmonary vascular resistance.

The pulmonary venous flow was abnormal in one or more of the central pulmonary veins in 41/52 (79%) of patients with proximal CTEPH and 7/24 (29%) of patients with distal CTEPH cases (Table 3). The majority (71%) of distal CTEPH cases exhibited normal pulmonary venous flow in all the 4 major veins, as compared with 29% of proximal CTEPH cases. Figures 1 and 2 are examples of pulmonary venous flow in proximal and distal CTEPH.

TABLE 3 - Pulmonary Vein Flow Grading in Proximal and Distal CTEPH
Proximal CTEPH (n=52) Distal CTEPH (n=24) P
LA opacification (HU) 250 (198-304) 289 (249-386) 0.034
Patients with normal flow in all 4 pulmonary veins, n (%) 11 (21) 17 (71) <0.001
Patients with abnormal flow in 1 or more pulmonary veins, n (%) 41 (79) 7 (29) <0.001
Total pulmonary vein flow score 5 (5-7) 4 (4-5) <0.001
LA indicates left atrium.

Pulmonary venous flow in proximal CTEPH before and after pulmonary endarterectomy with demonstration of the pulmonary vein sign. CTPA images from a 50-year-old male with proximal chronic thromboembolic disease (CTEPH). A–D are before and E–H are after pulmonary endarterectomy. The PVS (A, B) is defined as nonopacification of the pulmonary veins during pulmonary arterial phase imaging and is demonstrated in the right inferior and middle pulmonary vein and left inferior pulmonary veins (arrows). Following endarterectomy, the PVS has resolved as shown by homogenous opacification in the same pulmonary veins (E, F). This is mirrored by clearance of pulmonary arterial obstruction (A, E), decrease in the size of right atrium (RA) and right ventricle (RV) (C, G) and resolution of mosaic attenuation (D, H). LA indicates left atrium.
Pulmonary venous flow in distal CTEPH. CTPA images from a 42-year-old male with sickle cell disease and distal chronic thromboembolic disease (CTEPH). All 4 major pulmonary veins show uniform homogenous enhancement (A, C). The proximal pulmonary arteries show normal morphology but vessels in the peripheral one-third of the lungs are sparse (A). Central perfusion is preserved compared with peripheral perfusion (B, D). LA indicates left atrium; RA, right atrium; RV: right ventricle.

In the subgroup analysis of 38 patients with proximal CTEPH before and after endarterectomy, 29/38 (76%) of proximal CTEPH cases had PVS presurgery. Thus, the large majority of cases (33/38, 87%, P<0.001) demonstrated improvement of contrast enhancement in all 4 pulmonary veins following endarterectomy (Table 4). There was a concomitant reduction in mean mean pulmonary artery pressure from 46 to 25 mm Hg and pulmonary vascular resistance from 9.2 to 2.6 WU (P<0.001).

TABLE 4 - Pulmonary Vein Flow Grading in Proximal CTEPH Before and After Surgery
Preoperative proximal CTEPH (n=38) Postoperative proximal CTEPH (n=38) P
mPAP (mm Hg) 46±11 25 (20–34) <0.001
PVR (WU) 9.2±4.3 2.6 (1.7–3.7) <0.001
CO (L/min) 3.9 (3.4-5.3) 5.5 (4.3-6.7) 0.004
CI (L/min/m2) 2.0 (1.7-2.5) 2.6 (2.2-3.1) 0.004
Patients with normal flow in all 4 pulmonary veins, n (%) 9 (24) 33 (87) <0.001
Patients with abnormal flow in 1 or more pulmonary veins, n (%) 29 (76) 4 (11) <0.001
mPAP indicates mean pulmonary artery pressure; PVR, pulmonary vascular resistance.


The principal goals of this investigation were to examine flow disturbances in the central pulmonary veins in different CTEPH categories on CTPA and to correlate the impact of pulmonary hemodynamic parameters on PVS. Our results demonstrated for the first time that a significant majority (71%) of distal CTEPH patients have normal pulmonary venous flow. Only 7 patients in the distal CTEPH category showed PVS. Of these, 5 had a limited degree of proximal disease, mainly in the lower lobes: 4 cases in the right and 1 case in the left lower lobe with PVS in the corresponding inferior pulmonary vein. In the remaining 2 cases, 1 exhibited PVS in the right superior pulmonary vein but there was no proximal disease even on retrospective analysis while the other had an area of peripheral consolidation (possibly an infarct) in the lobe where there was PVS. This underscores the suggestion that compromise of lung perfusion due to proximal vessel chronic thromboembolic disease is the etiology for the presence of PVS as patients with true distal vessel disease did not exhibit this CT finding.

In addition, the histopathologic findings of microvascular disease accompanying distal vessel CTEPH are similar to those seen in idiopathic pulmonary arterial hypertension leading to the hypothesis that these disorders may represent extremes of a disease continuum.7 Interestingly, in a previous study that compared pulmonary venous flow in different groups of pulmonary hypertension, the PVS was not a feature of pulmonary arterial hypertension.6 Also, our observation that PVS is a dominant (76%) feature of proximal CTEPH is also comparable to this earlier study.6

While there are pathologic differences between proximal and distal CTEPH,7 previous publications have shown that both groups may share similar baseline hemodynamics.8,9 In line with this data, there was no significant difference in the invasive hemodynamic measurements between our proximal and distal CTEPH cases but there was a statistically significant proportion of distal CTEPH patients who had normal pulmonary venous flow. This finding might prove to be significant as a useful CTPA parameter in the pre-therapeutic evaluation of CTEPH patients. Objective determinants of surgical suitability have been difficult to establish, particularly in cases where the disease distribution is borderline for operability. The presence or absence of PVS can potentially lend a degree of CT-based objectivity to operability assessment.

Finally, our finding of PVS resolution in 87% of proximal CTEPH patients who underwent successful surgery is not surprising. Pulmonary endarterectomy provides clearance of the mechanical arterial obstruction and an improvement in regional lung perfusion with an acute reduction in right ventricle afterload and recovery of biventricular cardiac function.10–12 As a result, the removal of the upstream pulmonary arterial blockage leads to an improvement in the venous flow.

Further weight for the evaluation of the pulmonary vein flow is underscored by the evolving literature on BPA, a catheter-based alternative treatment for patients with inoperable CTEPH. Preprocedural target evaluation by CT includes morphologic classification of arterial lesions as well as identification of limited/delayed venous flow return.13 One of the metrics to evaluate the on-table procedural success is the rate of appearance and clearance of contrast material from the reperfused pulmonary venous bed after the opening of the stenotic or occluded pulmonary artery.14,15 For the first time, we have clearly demonstrated that, similar to BPA, the abnormal pulmonary venous flow apparent on CTPA improves following successful endarterectomy in a large majority of cases.

It should be emphasized that the identification of PVS on CTPA is dependent on ensuring a balance between good pulmonary vascular opacification and uniform enhancement of the left atrium. In both institutions involved in this study, the CTPAs were acquired with bolus tracking with the use of saline chaser as the latter helps to prolong the plateau-phase of the contrast medium bolus resulting in consistent and homogenous organ and vascular enhancement.

Limitations of this study include the following. This was a subjective analysis of a small cohort of CTEPH cases. The frequency of PVS in proximal CTEPH was similar to the published literature. Even with access to the PH database from 2 institutions, it was challenging to obtain predominantly distal CTEPH cases with matching CTPA and RHC hemodynamics. Nevertheless, the finding that PVS is infrequent in distal CTEPH was statistically significant. It was not possible to blind the readers to the presence of arterial abnormalities during the grading of the pulmonary veins. Inspite of optimization of injection parameters, 7 of the 17 cases that we excluded from analysis had heterogenous and low LA opacification. This may be a reflection of variation in the underlying cardiac function. We acknowledge that CT appearances of the pulmonary veins are dependent on the acquisition phase. A dual-energy–based study to assess lung perfusion in thromboembolic disease demonstrated significant differences in perfusion blood volume in the early and late phases in acute and chronic PE, reflecting the effect of systemic collaterals that could potentially modify the PVS presentation.16 This could potentially modify the PVS presentation but the effect of broncho-pulmonary collaterals on the visibility of PVS could not be evaluated in our study as delayed phase images were not available. Future prospective studies to evaluate PVS would need to ensure a standardized protocol to obtain high-quality CTPAs that can also assess the effects of collateral circulation.

In conclusion, we evaluated pulmonary venous flow abnormalities to seek insights into the pathophysiology of different CTEPH categories. PVS is an infrequent feature of distal CTEPH. There is no correlation between PVS and CTEPH disease severity as both proximal and distal patients exhibited similar baseline pulmonary hemodynamic measurements. The significant improvement in the venous flow after pulmonary endarterectomy as evidenced by the resolution of the PVS can be used as a simple measure of procedural success.


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pulmonary vein sign; abnormal pulmonary venous flow; chronic thromboembolic pulmonary hypertension

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