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J Thromb Thrombolysis

DOI 10.1007/s11239-016-1438-0

Estimation of right ventricular dysfunction by computed


tomography pulmonary angiography: a valuable adjunct for
evaluating the severity of acute pulmonary embolism
DongJia1,3 Xiao-mingZhou2 GangHou3

Springer Science+Business Media New York 2016

Abstract To evaluate the feasibility and the efficacy of the ROC curve to confirm the optimal cut-off value of the
computed tomography pulmonary angiography (CTPA) in statistically significant parameter in the logistic regression
differentiating acute pulmonary embolism (PE) patients with model. After an initial screening, 113 acute PE patients were
or without right ventricular dysfunction and to evaluate the enrolled in our study. Among them, 42 patients showed
severity of right ventricular dysfunction in acute PE patients right ventricular dysfunction (37.2 %), and 71 patients
with CPTA. We retrospectively collected and measured the showed no right ventricular dysfunction (62.8%). The dif-
following parameters: right ventricular diameter by short ference between the patients with right ventricular dysfunc-
axis in the axial plane (RVDaxial), left ventricular diameter tion and patients without right ventricular dysfunction was
by short axis in the axial plane (LVDaxial), right ventricular statistical significant in RVD4CH/LVD4CH ratio. Logistic
diameter by level on the reconstructed four-chamber views regression model analysis revealed that RVDaxial/LVDaxial
(RVD4CH), left ventricular diameter by level on the recon- ratio and interventricular septum deviation were correlated
structed four-chamber views (LVD4CH), main pulmonary to right ventricular dysfunction with statistical significance
artery diameter (MPAD), ascending aorta diameter (AOD), (p=0.001 and 0.03 respectively). RVDaxial/LVDaxial>1.02
coronary sinus diameter (CSD), superior vena cava diam- (95% CI: 0.8180.958, p<0.0001, sensitivity: 90.2%,
eter (SVCD), inferior vena cava (IVC) reflux and interven- specificity: 88.7%) and RVD4CH/LVD4CH ratio>0.999
tricular septum deviation by CTPA, and we calculated the (95% CI 0.7220.898, p<0.0001) were determined as the
RVDaxial/LVDaxial, RVD4CH/LVD4CH and MPAD/AOD optimal cut-off values following ROC analysis. There was
ratios in acute PE patients. We assessed right ventricular a positive correlation between the MPAD/AOD ratio and
function and pulmonary artery systolic pressure (PASP) by PASP (r=0.408, p=0.01). Based on the analysis of the
echocardiography (ECHO) and then divided the patients parameters obtained by CTPA, the RVDaxial/LVDaxial ratio
into two groups: group A had right ventricular dysfunction, and interventricular septum deviation could be utilized for
and group B did not have right ventricular dysfunction. We predicting right ventricular dysfunction. The MPAD/AOD
utilized a logistic regression model to analyse the relation- ratio is a potential adjunct to judge the severity of right
ship between right ventricular dysfunction and the measure- ventricular dysfunction in acute PE.
ment parameters obtained from CTPA, and we constructed
Keywords Pulmonary embolism Computed
tomography pulmonary angiography Right ventricular
Gang Hou dysfunction Echocardiography
hougangcmu@163.com
1
Department of Emergency, Shengjing Hospital of China
Medical University, Shenyang 110004, China Introduction
2
Department of Respiratory Medicine, Shengjing Hospital of
China Medical University, Shenyang 110004, China Acute pulmonary embolism (PE) is a common cardiopul-
3
Institute of Respiratory Disease, The First Hospital of China monary emergency and severe disease and is the third lead-
Medical University, Shenyang 110001, China ing cause of death by cardiopulmonary system diseases

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2 D. Jia et al.

[1, 2]. In principle, risk stratification of acute PE is gen- Inclusion criteria


erally divided into a high-risk group, an intermediate-risk
group, and a low-risk group. Haemodynamically unstable 1. Acute PE confirmed by CTPA examination
acute PE patients would be classified as a high-risk group 2. Age18 years
with a high mortality. Once an acute PE patient with hae-
modynamic instability is diagnosed, close monitoring and Exclusion criteria
an urgent reperfusion treatment must be initially taken into
account, due to its high mortality [3]. However, a majority 1. Definitive diagnosis of cor pulmonale
of acute PE patients are normotensive. It is reported that 2. Malignant tumour
approximately 80% of acute PE patients are normotensive 3. Chronic pulmonary embolism
[4, 5]. Normotensive acute PE patients are not absolutely 4. Chronic heart failure
stable. Haemodynamically stable acute PE patients with a 5. Pregnancy
right ventricular dysfunction have a worse prognosis than 6. Acute coronary syndrome
patients without right ventricular dysfunction [6, 7], and 7. Reperfusion treatment between CTPA and
they also need close monitoring and reperfusion treatment. echocardiography
Patient deaths from acute PE generally occur within the 8. Either CTPA or echocardiograph was absent
first 4h after admission to the hospital [8]. Thus, the time
involved in evaluating acute PE patients with or without CTPA acquisition
right ventricular dysfunction is precious. Although echo-
cardiography (ECHO) is the standard for the evaluation CTPA was performed using a 64-detector-row scanner
of right ventricular dysfunction, conducting an echocar- (AquilionKV-120; Toshiba Medical Systems Corporation,
diography requires an ultrasound specialist, who may not Tokyo, Japan) with the following scanning parameters:
be available all the time in many hospitals [8]. Finding a 380mAs, 120kV, 5mm reconstruction interval, and 5mm
simple and effective method for identifying right ventricu- reconstruction section thickness. The scanning range of
lar dysfunction and evaluating its severity is essential for CTPA was set from the thoracic inlet to the upper abdomen.
emergency department physician. Computed tomography A bolus of 100ml of iodinated nonionic contrast medium
pulmonary angiography (CTPA) is more convenient and was injected by catheter into the antecubital vein at a rate
has been widely used for diagnosing and excluding acute of 4ml/s using an automatic dual-tube high pressure injec-
PE [9, 10]. But CTPA should be used appropriately. One is tor (Ulrich REF XD 2051; Ulrich Medical GmbH, Ulm,
mastering the indication of CTPA according to the analysis Germany).
of risk and possibility of PE [11], the other is careful analysis We measured parameters including right ventricular
of CTPA with reconstructive techniques which can provide diameter (RVD), left ventricular diameter (LVD), main pul-
more useful information for the making of clinical strategy. monary artery diameter (MPAD), ascending aorta diameter
Evaluating right ventricular (RV) function by CTPA may be (AOD), coronary sinus diameter (CSD), and superior vena
time saving and reasonable. However, there have been few cava diameter (SVCD) using a CT-Sensation64 (v5.5.51116,
studies focused on this topic. Aiming to evaluate the value Neusoft, Shenyang, China).
of CTPA image analysis in the diagnosis of right ventricu-
lar dysfunction in acute PE, we retrospectively collected RVDaxial,LVDaxial and RVDaxial/LVDaxial ratio
the relevant cardiovascular parameters, measured by CTPA
and ECHO in acute PE patients to explore the relationship RVDaxial was measured by short axis in the axial plane
between these observed parameters and right ventricular which was measured from the endocardial margin of the
dysfunction, particularly in correlation with the pulmonary RV free wall to the interventricular septum (Fig. 2a). The
artery systolic pressure (PASP) value. same measurement method as RVDaxial was used to measure
LVDaxial at the same level (Fig.2b). The RVDaxial/LVDaxial
ratio was calculated. The measurement method was accord-
Patients and methods ing to Aribas et al. [12].

Patient selection RVDfourchamber (RVD4CH), LVDfourchamber (LVD4CH) and


RVD4CH/LVD4CH ratio
This was a retrospective study of 210 patients diagnosed
with acute PE confirmed by CTPA examination from June RVD4CH was measured by level on the reconsgructed four-
2013 to December 2015. After the screening, 113 patients chamber views at the maximal distance between the ven-
were finally enrolled in our study (Fig.1). tricular endocardium and interventricular septum for right

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Estimation of right ventricular dysfunction by computed tomography pulmonary angiography: a valuable 3

Fig. 1 The flow chart of case enrollment of our study according to the inclusive and exclusive criteria

ventricular and left ventricular according to the previous to the long axis. The measurement method was according to
study (Fig.2c, d) [13]. The ratio of RVD4CH/LVD4CH ratio Cok et al. [8].
was calculated.
CSD
MPAD, AOD and MPAD/AOD ratio
CSD was measured in its axial plane, proximal to its open-
The MPAD was measured perpendicular to the long axis, ing at the level of the right margin of the interventricular
from the inner wall to the other inner wall at the widest septum. The measurement of CSD was according to Gursel
diameter at the level of the pulmonary artery bifurcation. et al. [14].
The AOD was measured at the same slice using the same
method. The ratio of MPAD and AOD was then calculated. Deviation of the interventricular septum

SVCD Deviation of the interventricular septum was evaluated as


follow: If the interventricular septum was convex toward the
SVCD was transversely measured at the level of its conflu- RV, we identified the deviation of the interventricular sep-
ence from the inner wall to the other inner wall with respect tum (); If the interventricular septum was convex toward

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4 D. Jia et al.

Fig. 2 Computed Tomogra-


phy Signs of RV Dysfunc-
tion in a 55-Year-old man. a
Right ventricular diameter by
short axis in the axial plane
(RVDaxial=52.86 mm). b Left
ventricular diameter by short
axis in the axial plane
(LVFaxial=33.98 mm)
(RVDaxial/LVDaxial ratio=1.56).
c Right ventricular
diameter in 4-charmber
(RVD4CH=50.87 mm).
d Left ventricular diameter in
4-charmber; (LVD4CH=
32.66mm) (RVD4CH/LVD4CH
radio=1.56). e A 4-chamber
(4-CH) view reconstruction by
CTPA shows interventricular
septum deviation (arrows).
f An interior vena cava reflux
(arrows)

the LV or flattened septum we identified the deviation of performed using an IE Elite ultrasound machine (Philips)
the interventricular septum (+) (Fig.2e). The measurement equipped with an S 51 transducer (frequency conversion
method was referred to the Kang et al. [13]. 15MHz) and by an experienced ultrasound specialist.
Right ventricular dysfunction defined by ECHO met the fol-
Inferior vena cava reflux lowing conditions: RV dilation, an increased RV-LV diam-
eter ratio (>0.9), hypokinesia of the free RV wall, increased
If there was no reflux into inferior vena cava (IVC) we velocity of the jet of tricuspid regurgitation, decreased
identified the IVC reflux (); otherwise, we identified IVC tricuspid annulus plane systolic excursion, or combina-
reflux (+) (Fig.2f). The measurement method was referred tions [16, 17]. We used the standard above when evaluat-
to the Aviram et al [15]. ing enrolled PE patients for right ventricular dysfunction.
If right ventricular dysfunction was present, we defined the
Echocardiography and grouping patients as right ventricular dysfunction (+), allocated them
into group A, and recorded the PASP value; otherwise, they
We obtained the echocardiographic (ECHO) parameters were defined as right ventricular dysfunction () and allo-
of the enrolled patients. All the echocardiography was cated into group B.

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Estimation of right ventricular dysfunction by computed tomography pulmonary angiography: a valuable 5

Statistical analysis Table 1 Comparison of parameters between group A and group B


Group A Group B (n=71) p value
Statistical analysis was performed using a personal com- (n=42)
puter with SPSS version 22 (Chicago, IL, USA). Continuous
Age (year) 59.0711.88 54.98.2416.46 0.007
data are expressed as the meanstandard deviation (SD).
The t-test was used to evaluate the difference of continuous Gander (male/female) 20/22 39/32 0.578
data. The 2 test was used to evaluate differences in quali- RVDaxial (mm) 46.045.85 35.527.49 0.062
tative data. To analyse the relationship between right ven- LVDaxial (mm) 35.405.84 41.216.29 0.364
tricular dysfunction and the observed parameters measured RVDaxial/LVDaxial ratio 1.330.26 0.880.25 0.302
by CTPA, a logistic regression analysis model was used to RVD4CH (mm) 44.987.48 36.697.65 0.975
select the parameter in which a forward conditional method LVD4CH (mm) 38.317.69 42.766.53 0.102
was used for determining the goodness of fit. The area under RVD4CH/LVD4CH ratio 1.230.39 0.870.23 0.001
the ROC curve was used to confirm the optimal cut-off value, AOD (mm) 32.794.32 31.044.76 0.225
and the best sensitivity to specificity ratios were calculated. MPAD (mm) 32.194.77 27.485.25 0.735
Spearmans rank correlative analysis was used to analyse the MPAD/AOD ratio 0.990.18 0.890.15 0.820
correlation between PASP and the observed parameters in CSD (mm) 8.542.18 7.332.18 0.827
group A. A p value <0.05 was considered to indicate a sig- SCVD (mm) 18.413.11 17.414.03 0.072
nificant difference in all statistical analyses.

ROC curve of the RVDaxial/LVDaxial ratio and


Results RVD4CH/LVD4CH ratio from CTPA in the prediction
of right ventricular dysfunction
Demographics and baseline characteristics of the
patients ROC curve analysis revealed that the area under the curve
for the RVDaxial/LVDaxial ratio was 0.888 (95% CI: 0.818
After an initial screening, 113 acute PE patients were 0.958, p<0.0001) (Fig.3) and 0.801 for RVD4CH/LVD4CH
enrolled in our study (Fig.1). All the demographic and ratio (95% CI 0.7220.898, p<0.0001) (Fig. 4). The opti-
measurement parameters characterized were summarized as mum cut-off value for the prediction of the RVDaxial/LVDaxial
meanstandard deviation and male/female ratio (Table1). ratio was 1.02 (sensitivity 90.2%, specificity 88.7%) and
Forty-two patients showed right ventricular dysfunction was 0.999 for RVD4CH/LVD4CH ratio (sensitivity 71.4%,
(37.2%), and 71 patients did not show right ventricular specificity 88.7%).
dysfunction (62.8%). The average age of group A was
59.0711.88years and was 55.2416.14years for group Correlation of characteristics of CTPA with PASP of
B. There were 20 males and 22 females in group A and 39 ECHO
males and 32 females in group B (Table1).
Spearmans correlative analysis revealed that there was a
Comparison of characteristics of CTPA between group positive correlation between PASP and the MPAD/AOD
A and group B ratio (r=0.408, p=0.01), and there was no significant dif-
ference between PASP and the other observed parameters
The averge age and RVD4CH/LVD4CH ratio of group A (Table3).
was significantly higher than that of group B. The other dif-
ferences of demographic and measurement parameters were
not significant between group A and group B (Table1).
Table 2 Results of logistic regression analysis model
Correlation between observed parameters and right
ventricular dysfunction Beta OR p value 95.0% CI
Lower Upper
Logistic regression analysis showed that interventricular
septum deviation and RVDaxial/LVDaxial ratio ratio were cor- MPAD 0.139 1.149 0.057 0.996 1.326
related to right ventricular dysfunction with statistical sig- RVDaxial/LVDaxial ratio 3.393 29.764 0.003 3.173 279.210
nificance (p=0.001 and 0.03 respectively), and there were CSD 0.259 1.296 0.058 0.991 1.695
no statistically significant differences in the other param- Interventricular septum 2.046 7.739 0.001 2.232 26.834
deviation
eters (Table2).

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6 D. Jia et al.

Discussion

Rapid diagnosis and severity stratification is crucial for the


treatment of acute PE. If an examination could not only
diagnose the acute PE but also be used for severity strati-
fication or prediction, it would be beneficial for evaluation
of acute PE. CTPA may be such a useful examination that
satisfies the requirements of diagnosis and stratification for
acute PE [18]. In our study, interventricular septum devia-
tion and RVDaxial/LVDaxial ratio were correlated strongly to
right ventricular dysfunction evaluated by EHCO in acute
PE patients. Emergency department physicians could utilize
the interventricular septum deviation and RVDaxial/LVDaxial
ratio to predict right ventricular dysfunction once the diag-
nosis of PE was confirmed. ROC curve analysis revealed
that the optimal cut-off value of RVDaxial/LVDaxial ratio was
1.02 and was 0.999 for RVD4CH/LVD4CH ratio. Spear-
mans rank correlative analysis between the observed
parameter and PASP in group A showed that only the
MPAD/AOD ratio was positively correlated with PASP and
that the greater the MPAD/AOD ratio, the greater the PASP. Fig. 4ROC curve with calculated area under the curve and optimal
cut-off point for RVD4CH/LVD4CH ratio predicting right ventricu-
So the MPAD/AOD ratio can be used in preliminary predic-
lar dysfunction: Optimal cut-off point is 0.999 (sensitivity 71.4%,
tion of the severity of right ventricular dysfunction. specificity 88.7%). AUC is calculated at 0.888 (95% CI 0.7140.887,
The RVDaxial/LVDaxial ratio was the most common indi- p<0.0001)
cator measured by CTPA that predicted right ventricular
dysfunction. Some retrospective studies [19, 20], reported patients with acute pulmonary embolism [21]. Once the clot
that an RVD/LVD ratio >1.0 was an independent risk fac- flowed to the pulmonary artery, the resistance immediately
tor for right ventricular dysfunction. The RVDaxial/LVDaxial increases, and the RV afterload correspondingly increases. If
ratio could be utilized for predicting 30-day mortality in its compensatory capacity limit is exceeded, the RV muscle
must enlarge its dimensions to adapt to the increasing after-
load because of its thinner wall, compared to the left ven-
tricle. This RV dilation for compensatory pressure change
occurs in just a few minutes [22]. If the RV fails to adapt
to the afterload due to too much pressure, the back-flow
of blood to the left ventricle would be obviously reduced.
The circulation would congest, and the blood-flow of the
coronary arteries would also reduce. All factors mentioned
above can lead to circulation collapse, shock, and death in
acute PE patients [22].
RVD4CH/LVD4CH ratio was another common indica-
tor currently measured by CTPA with different measure-
ment method comparing with RVDaxial/LVDaxial ratio.
Kang et al. [13] utilized both RVD4CH/LVD4CH ratio and
RVDaxial/LVDaxial ratio for predicting the right ventricular
dysfunction and concluded that the correlation coefficient
for RVD4CH/LVD4CH ratio was slightly lower compared
with RVDaxial/LVDaxial ratio which were similar with our
study.
The interventricular septum bows toward the RV nor-
Fig. 3ROC curve with calculated area under the curve and optimal mally, but it may shift toward to LV due to the increased pres-
cut-off point for RVDaxial/LVDaxial ratio predicting right ventricular
sure caused by sever pulmonary artery embolism [13, 23].
dysfunction: Optimal cut-off point is 1.02 (sensitivity 90.2%, speci-
ficity 88.7%). AUC is calculated at 0.888 (95% CI 0.8180.958, The interventricular septum deviation is a direct response to
p<0.0001) the increased pressure in RV. In our study interventricular

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Estimation of right ventricular dysfunction by computed tomography pulmonary angiography: a valuable 7

Table 3 Spearman correlative analysis between observed parameters of right ventricular dysfunction, but is positively correlated
and PASP value in group A with PASP.
Parameter r p value Our study has several limitations. The strength of the
conclusions is limited due to the retrospective research
Age (year) 0.038 0.812
design. The small sample size further limits the results of
MPAD (mm) 0.413 0.07 our study. Whether the enrolled patients received other
AOD (mm) 0.09 0.568 treatments, except anticoagulants and thrombolytics, may
SVCD (mm) 0.108 0.495 also have influenced our results. Finally, the cross-sectional
CSD (mm) 0.164 0.307 study design and being unable to follow-up on the short-
RVDaxial (mm) 0.273 0.08 term and long-term mortality of the patients also limited our
LVDaxial (mm) 0.212 0.178 study.
RVDaxial/LVDaxial ratio 0.287 0.065
RVD4CH 0.240 0.126
LVD4CH 0.218 0.165 Conclusions
RVD4CH/LVD4CH ratio 0.263 0.093
MPAD/AOD ratio 0.408 0.010 Once PE is confirmed by CTPA, the measurement of the
interventricular septum deviation, RVDaxial/LVDaxial ratio,
and the MPAD/AOD ratio by using quantitative analysis
septum deviation was another indicator correlated with of CTPA are valuable adjuncts for the prediction of right
right ventricular dysfunction with statistical significance. It ventricular dysfunction and the evaluation of the severity
can be utilized for predicting right ventricular dysfunction of acute PE.
in acute PE. IVC reflux is another indicator for increased
Compliance with ethical standards
RV pressure for various diseases. Kang et al. also reported
the efficacy for predicting the right ventricular dysfunction Conflict of interest The authors declare that no conflict of interest
[13], The different evaluation and statistical method of IVC exists.
reflux may cause the different opposite results. The purpose
of our study was that finding out a timesaving effective and
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