Published online before print November 7, 2006, 10.1148/radiol.2421052089
(Radiology 2007;242:78-84.)
© RSNA, 2006
Right Ventricular Function in Patients with Acute Pulmonary Embolism: Analysis with Electrocardiography-synchronized Multi–Detector Row CT1
Halil Do
an, MD,
Lucia J. M. Kroft, MD,
Menno V. Huisman, MD,
Rob J. van der Geest, MSc and
Albert de Roos, MD
1 From the Departments of Radiology (H.D., L.J.M.K., R.J.v.d.G., A.d.R.) and Vascular Medicine, Department of General Internal Medicine and Endocrinology (M.V.H.), Leiden University Medical Center, Albinusdreef 2, C2-S, 2333 ZA Leiden, the Netherlands. Received December 21, 2005; revision requested February 16, 2006; revision received March 17; accepted April 11; final version accepted July 10.
Address correspondence to A.d.R. (e-mail: A.de_Roos{at}lumc.nl).
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ABSTRACT
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Purpose: To prospectively assess electrocardiography (ECG)-synchronized multi–detector row computed tomography (CT) for the evaluation of right ventricular (RV) function in patients suspected of having pulmonary embolism (PE).
Materials and Methods: All patients gave informed consent after the study details, including radiation exposure, were explained; institutional ethical committee approval was obtained. Nonsynchronized multi–detector row CT of the chest was performed in 66 consecutive patients (29 men, 37 women; mean age, 58 years ± 15 [standard deviation]) who were suspected of having PE. ECG-synchronized cardiac multi–detector row CT was performed to assess cardiac function. Dimension ratios for the RV and left ventricle (LV) were measured on nonsynchronized transverse and angulated four-chamber views. Furthermore, the RV end-diastolic and end-systolic volumes were measured on ECG-synchronized multi–detector row CT scans. An independent samples t test was performed to compare the mean value of different groups. An analysis of variance post hoc test was performed to investigate whether the values of the variables varied between groups.
Results: PE was detected in 29 of 66 patients. The location of PE was categorized as central (n = 17) or peripheral (n = 12). The RV/LV dimension ratio was larger on the four-chamber view (P = .002), and RV end-systolic volume was larger (P = .01) and ejection fraction was lower (P = .01) in patients with PE. The RV end-systolic volumes and RV/LV volume ratios, as assessed by using ECG-synchronized multi–detector row CT, showed significant differences (P < .005) between patients with central PE and those with peripheral PE. However, the RV/LV dimensions on nonsynchronized images revealed no significant differences.
Conclusion: Retrospective ECG-synchronized multi–detector row CT facilitates detection of RV dysfunction, depending on pulmonary embolus location.
© RSNA, 2006
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INTRODUCTION
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In patients with acute pulmonary embolism (PE), rapid risk assessment is important because high-risk patients may benefit from thrombolytic therapy or more invasive therapies, including catheter-guided thrombosuction or thrombectomy (1). Right ventricular (RV) dysfunction, as assessed at echocardiography, has been shown to be independently predictive of 30-day mortality (2,3). In addition, it has been demonstrated that the ratio between the size of the RV and that of the left ventricle (LV), as measured at echocardiography, may indicate the location and burden of PE (4).
Currently, multi–detector row computed tomography (CT) is widely used as a first-line diagnostic test for the diagnosis of acute PE (5,6). Recently, the results of several studies have shown the clinical value of multi–detector row CT in measuring RV size in patients with PE (7–12). Initially, it was observed that simple measurements of the ratio between the RV and LV (RV/LV dimension ratio) on transverse multi–detector row CT scans have prognostic importance in patients with acute PE (7,10,12). In a recent article, researchers demonstrated that the reconstruction of an angulated four-chamber view can be used to estimate RV dysfunction more accurately in high-risk patients (9). However, these dimensions are obtained on routine breath-hold multi–detector row CT scans that are not electrocardiographically (ECG) synchronized. Reconstructed multi–detector row CT views obtained without ECG synchronization may either underestimate or overestimate the actual end-diastolic or end-systolic cardiac dimensions.
Multi–detector row CT with the aid of retrospective ECG synchronization is well suited for assessing ventricular function in a dynamic fashion (13–15). ECG-synchronized multi–detector row CT does not rely on geometric assumptions and allows volumetric assessment of the RV and LV at end-systolic and end-diastolic time points. We hypothesized that, compared with nonsynchronized approaches, the measurement of dynamic RV volumes at ECG-synchronized multi–detector row CT would better reflect the functional status of the RV in patients with PE relative to the location of emboli. Accordingly, the purpose of our study was to prospectively assess ECG-synchronized multi–detector row CT for the evaluation of RV function in patients suspected of having PE.
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MATERIALS AND METHODS
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Patients
Data from 66 consecutive patients (29 men, 37 women; mean age, 58 years ± 15 [standard deviation]) who were clinically suspected of having PE were evaluated. All patients gave informed consent after the study details, including radiation exposure, were explained. Our institutional ethical committee approved the study. The study protocol was successfully completed in all patients. Clinical characteristics in relation to PE and demographic findings were collected (H.D., M.V.H.).
Imaging Protocols
Standard contrast material–enhanced multi–detector row CT was performed by using a 16-section (Aquilion 16CFX; Toshiba Medical Systems, Otawara, Japan) or 64-section (Aquilion 64; Toshiba Medical Systems) CT scanner, and 0.5- or 1.0-mm sections of the entire chest were acquired for the diagnosis or exclusion of PE. The rotation time was 0.4 second, pitch factor was 1.4, tube current was 250–300 mA, and tube voltage was 100 kV. Acquisitions were performed during a single breath hold that lasted 10–12 seconds or less, depending on the scanner type. A total of 80–100 mL of contrast agent (Xenetix 300, Guerbet, Aulnay-sous-Bois, France; or Iomeron 400, Bracco, Milan, Italy) was injected into the antecubital vein with a double-barrel power injector (Medrad, Pittsburgh, Pa) at a rate of 4.0 mL/sec. Static pulmonary angiographic scanning was started after automated threshold enhancement detection in the main pulmonary artery. A threshold difference of 100 HU was selected for the start of acquisition. The effective dose varied between 2.8 and 3.9 mSv.
All patients underwent retrospective ECG-synchronized dynamic cardiac multi–detector row CT to assess ventricular function. Scans were acquired during a single breath hold that lasted 10–12 seconds or less. No ß-blocker preparation was used. For these scans, 35–50 mL of contrast agent was administered in the antecubital vein at a flow rate of 2.5–3.0 mL/sec. This injection was followed by a 30-mL saline bolus chaser, which was injected at a flow rate of 3.0 mL/sec. Cardiac scanning was started after a fixed delay of 15 seconds. The rotation time varied between 0.4 and 0.5 second, and the pitch factor varied between 0.25 and 0.50. The optimal combination of rotation time and pitch factor was chosen automatically by using SureCardio software (Toshiba Medical Systems) to obtain the best temporal resolution for a given heart rate. Temporal resolution, which varied between 50 and 250 msec, depends on pitch factor, heart rate, and the number of raw data segments that are used for image reconstruction. Data acquisition was performed with 16 detector rows and a 2-mm section thickness; tube current was 100 mA, and tube voltage was 120 kV. The effective dose varied between 3.0 and 4.2 mSv for cardiac scanning.
Adjacent sections that were 2 mm thick were retrospectively reconstructed in a 512 x 512 matrix by using a 200–240-mm field of view, with 20 cardiac phases in steps of 5% of the R-R interval (ranging from 0% to 95% for each investigation) by using a segmental reconstruction algorithm. The whole heart from the aortic root to the diaphragm was covered within the reconstructed 50–70 sections per cardiac phase point. Data were stored in Digital Imaging and Communications in Medicine format and were transferred to a personal computer workstation (Intel, Santa Clara, Calif) running on Linux software (SUSE; Linux, Nürnberg, Germany).
Data Analysis
Multi–detector row CT pulmonary angiography scans.—The diagnosis of PE was confirmed by the presence of at least one filling defect in the pulmonary artery tree. PE was classified according to two levels of thrombus occlusion: central (including central, interlobar, and lobar vessels) or peripheral (including segmental and subsegmental vessels). All scans were evaluated in consensus by two experienced observers (H.D. and L.J.M.K., with 2 and 7 years of experience, respectively, in chest CT).
The static multi–detector row CT scans were analyzed on a Vitrea workstation (version 3.5; Vital Images, Plymouth, Minn). This workstation allows two-dimensional reconstruction of standardized cardiac views, such as four-chamber views, automatically. RV and LV dimensions were measured with calipers on the four-chamber views and transverse sections by identifying the maximal distance between the ventricular endocardium and the interventricular septum, perpendicular to the long axis (Fig 1). RV/LV dimension ratios were also calculated from these images.
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Figure 1a: Multi–detector row CT scans show the measurement of maximum distance (arrows) between the interventricular septum and ventricular endocardium, perpendicular to the interventricular septum, in the RV and LV on (a) transverse section and (b) four-chamber view. The maximum diameter within the RV and LV was not always at the same level. LA = left atrium, RA = right atrium.
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Figure 1b: Multi–detector row CT scans show the measurement of maximum distance (arrows) between the interventricular septum and ventricular endocardium, perpendicular to the interventricular septum, in the RV and LV on (a) transverse section and (b) four-chamber view. The maximum diameter within the RV and LV was not always at the same level. LA = left atrium, RA = right atrium.
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ECG-synchronized cardiac images.—The dynamic cardiac multi–detector row CT scans were analyzed with dedicated cardiac function analysis software (CT-MASS; Medical Imaging Systems, Leiden, the Netherlands). After the smooth-running cine movies were inspected, the image in which the RV size was the largest was selected to represent the end-diastolic phase, and the image in which the RV size was the smallest was selected to represent the end-systolic phase. On every other transverse section, the end-diastolic and end-systolic endocardial border contours for the RV and LV were drawn (H.D., 2 years experience in cardiac multi–detector row CT). The entire ventricles were covered, including the outflow track to the level of the pulmonic valve (Fig 2). End-diastolic volume and end-systolic volume, stroke volume, and ejection fraction were calculated. Corresponding RV/LV volume ratios were also calculated. The image quality of the dynamic scans was technically adequate for quantitative analysis in all patients, as was shown by the good contrast enhancement of the ventricular cavities and the lack of motion artifacts.
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Figure 2a: Three-dimensional representations of the (a) end-diastolic and (b) end-systolic volumes of both ventricles are displayed. At contrast-enhanced multi–detector row CT of the RV and LV, endocardial border contours were drawn on end-diastolic and end-systolic images. Note the complex geometry of the RV. Lat = lateral, Sept = septal.
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Figure 2b: Three-dimensional representations of the (a) end-diastolic and (b) end-systolic volumes of both ventricles are displayed. At contrast-enhanced multi–detector row CT of the RV and LV, endocardial border contours were drawn on end-diastolic and end-systolic images. Note the complex geometry of the RV. Lat = lateral, Sept = septal.
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Statistical Analyses
The data were analyzed by using SPSS for Windows (version 12.0.1; SPSS, Chicago, Ill). Continuous data were expressed as the mean ± standard error. For all statistical testing, P values of less than .05 were considered to indicate a statistically significant difference.
To determine whether mean RV volumetrics, RV/LV volume ratios, and RV/LV dimension ratios in the transverse and four-chamber orientations were different between patients with PE and those without PE, an independent samples t test was performed. An analysis of variance post hoc test was used to investigate whether RV volumetrics, RV/LV volume ratios, and RV/LV dimension ratios in the transverse and four-chamber orientations were different between patients with and those without PE, as well as between central and peripheral PE locations.
A Bonferroni correction was applied to the a posteriori volumetric results to adjust for multiple testing. To implement this correction, we report P values calculated by using the statistical model but applied a more stringent threshold of .005 instead of the more usual .05 level.
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RESULTS
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Patients
Acute PE was detected at multi–detector row CT in 29 (44%) of 66 patients, whereas no emboli were found in 37 patients (56%). Seventeen (59%) of 29 patients had central PE, whereas 12 (41%) of 29 patients had peripheral PE. The demographic characteristics and clinical findings of the patients are displayed in Table 1.
RV Measurements in Patients with and Those without PE
ECG-synchronized multi–detector row CT measurements revealed significant differences between patients with and those without PE for the RV end-systolic volumes and RV ejection fraction (Table 2). Furthermore, the RV/LV volume ratios at end systole and end diastole were significantly different between the two patient groups. In addition, the nonsynchronized images showed a significant difference between patients with and those without PE on the angulated four-chamber views only.
RV Measurements in Patients with Central or Peripheral PE
All ECG-synchronized RV measurements (except RV end-diastolic volume) and RV/LV dimension ratios obtained on the nonsynchronized angulated four-chamber views showed significant differences between patients with central PE and those without PE. ECG-synchronized RV volumetrics for RV end-systolic volume and RV/LV volume ratios were significantly different between patients with central PE and those with peripheral PE. The RV/LV dimension ratio measured on nonsynchronized images, however, revealed no significant differences between central and peripheral PE (Table 3). When patients with peripheral PE were compared with those without PE, no significant differences were found in any of the RV functional parameters.
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DISCUSSION
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In this study, we evaluated ECG-synchronized cardiac multi–detector row CT and nonsynchronized CT for the assessment of RV dysfunction in patients suspected of having PE at initial presentation.
The results of echocardiographic studies have previously shown the prognostic importance of RV dysfunction in patients with PE (16). Among patients with PE, RV dysfunction has been associated with a doubling of the mortality rate at 14 days, and the rate of mortality at 3 months was 1.5 times the rate found in patients without RV dysfunction (16). In multiple studies, researchers have shown an increase in the mortality rate as RV dysfunction worsened (16).
The prognostic role of off-line CT measurements of RV and LV dimensions with the aid of transverse and two-dimensional reconstructed four-chamber views has been previously reported (11). The ventricular CT measurements obtained on four-chamber views helped to predict adverse clinical events and were superior to those obtained on transverse views for identifying high-risk patients (9). Furthermore, it has been demonstrated that the reconstructed four-chamber view is a predictor of early death in patients with acute PE (9). In our study, we observed that the RV/LV dimension ratios obtained with four-chamber views were significantly larger in patients with PE than in those without PE. No difference, however, was found between patients with central PE and those with peripheral PE.
Of note, the RV/LV dimension ratio obtained on the transverse CT scans was not significantly different between patients with and those without PE, thereby confirming the added value of using the four-chamber reconstruction for assessment of RV dysfunction with nonsynchronized multi–detector row CT. Furthermore, our results indicate that the RV end-systolic volumes are significantly larger and that the ejection fraction is significantly lower in patients with PE compared with those without PE when the ECG-synchronized data are used.
Traditionally, it has been argued that patients with central emboli face a more grave prognosis than do patients with more peripherally located clots (17). We observed that, in contrast to nonsynchronized RV measurements, the ECG-synchronized RV parameters demonstrated a significant difference between patients with central PE and those with PE in the more distal pulmonary arteries. It is conceivable that the CT assessment of RV dysfunction may become clinically useful in stratifying different treatment options for patients with central or peripheral emboli.
The RV dimension is commonly referenced to similar LV measurements and is expressed as an RV/LV ratio (9,11,12). In the current study, we assessed three-dimensional ventricular volumes of the RV and LV, thereby allowing for a more accurate estimation of the RV/LV volume ratio. The RV/LV volumes ratios demonstrated a significant difference between patients with and those without PE, as well as between patients with central emboli and those with peripheral emboli. Furthermore, our results show that direct measurements of RV end-systolic volume reveal significant differences between patients with central emboli and those with peripheral emboli.
In a recent study, researchers showed that the RV/LV end-diastolic area ratio at CT was correlated with PE obstruction and findings at echocardiography (8). In that study, transverse planimetry of a single CT scan was performed by passing through the mitral and tricuspid valves. At CT, an RV/LV area ratio of more than 1 was used as a marker of RV dysfunction to define the presence of central pulmonary emboli. Previously, it has already been demonstrated with the aid of echocardiography that the volumetric approach by using the two-dimensional RV/LV area ratio is more accurate for the detection of RV dysfunction than is the one-dimensional ratio of the diameters (4).
It is important to consider the relationship between direct measurements of heart function and the degree of obstruction caused by pulmonary emboli. In prognostic studies, it has been shown that RV dysfunction may correlate well with the obstruction index (12), whereas in other studies this relationship has been questioned (18). In the study by Ghuysen et al (18), the RV/LV ratio had the highest discriminant power for predicting survival and nonsurvival, whereas the pulmonary vascular obstruction index failed to demonstrate a significant difference. Therefore, assessment of RV dysfunction may provide more insight into the pathophysiologic consequences of PE than into the degree of pulmonary vascular obstruction (18).
ECG-synchronized multi–detector row CT for routine imaging of patients with PE is not generally recommended considering the increase in radiation exposure (19). In the current protocol, we acquired a cardiac CT scan separate from the breath-hold chest scan. This exposes the patient to an extra radiation burden and has to be weighed against the potential clinical benefit. In the current protocol, the total radiation exposure is well below the levels that are used in coronary CT imaging (20,21). Further modifications of the protocol should be explored to minimize the radiation burden to the patient. In addition, further optimization of the multi–detector row CT protocol may allow use of a single acquisition to assess the pulmonary vessels and heart.
This study has several limitations. In our observational study, consecutive patients were enrolled over a limited time period. Additional studies are required that include a formal power analysis to confirm our observations. Furthermore, it may be of additional value to assess regional myocardial contraction and dynamic changes in the shape of the interventricular septum as sign of RV dysfunction. Moreover, sizing of the pulmonary emboli may add to a more complete evaluation of the relationship between clot burden and RV dysfunction. Further studies are required to assess the value of the assessment of septal motion and the estimation of clot burden as predictors of RV dysfunction.
In conclusion, we have shown that ECG-synchronized RV measurements are useful in demonstrating RV dysfunction in patients with PE and that such measurements have potential value in patients with central or peripheral PE. This approach should be prospectively studied to determine its relationship to patient prognosis.
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ADVANCES IN KNOWLEDGE
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- Retrospective electrocardiography-synchronized multi–detector row CT reveals right ventricular dysfunction that is dependent on pulmonary embolus location.
- Dynamic multi–detector row CT reveals differences in right ventricular function in patients with central versus peripheral pulmonary embolism, whereas nonsynchronized multi–detector row CT is not discriminative.
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ACKNOWLEDGMENTS
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The authors thank Joost J. H. Roelofs, BSc, for technical assistance and protocol optimization and Annette van den Berg-Huysmans, MSc, for her statistical support.
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FOOTNOTES
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Abbreviations: ECG = electrocardiography • LV = left ventricle • PE = pulmonary embolism • RV = right ventricle
Authors stated no financial relationship to disclose.
Author contributions: Guarantors of integrity of entire study, all authors; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, all authors; clinical studies, all authors; statistical analysis, all authors; and manuscript editing, all authors
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ABSTRACT
INTRODUCTION
