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Cardiac Imaging |
1 From the Institute of Diagnostic Radiology (H.A., L.D., L.H., S.L., H.S., B.M., T.F.), Clinic for Cardiovascular Surgery (A.P., R.V., M.G.), and Cardiovascular Center (T.S., O.G., R.J., P.A.K.), University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland; Siemens Medical Solutions, Computed Tomography, Forchheim, Germany (T.G.F.); and Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland (P.A.K.). Received September 4, 2006; revision requested November 3; revision received November 15; accepted December 20; final version accepted February 1, 2007. Supported by the National Center of Competence in Research, Computer Aided and Image Guided Medical Interventions of the Swiss National Science Foundation. Address correspondence to H.A. (e-mail: hatem.alkadhi{at}usz.ch).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE...References |
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Materials and Methods: The institutional review board approved this study; written informed consent was obtained. Thirty patients (23 men, seven women; mean age, 56.6 years) with AR underwent TTE and retrospective electrocardiographically gated 64-section CT. CT data sets were reconstructed in 5% steps from 40% to 90% of R-R interval for analysis. Maximum regurgitant orifice area (ROA) in diastole was planimetrically measured with CT, and measurements were compared with semiquantitative classification with TTE (Spearman rank order correlation coefficients). Receiver operating characteristic (ROC) curves were calculated for differentiation between degrees of AR with ROA measurements. Dimensions of the aortic root and left ventricular parameters were compared (Pearson correlation analysis).
Results: A significant correlation was observed between CT planimetric size of ROA (mean, 62 mm2 ± 63 [standard deviation]; range, 6–224 mm2) and TTE classification of mild, moderate, and severe AR (r = 0.84, P < .001). With ROC analysis, discrimination between degrees of AR with CT was highly accurate when cutoff ROAs (25 mm2 and 75 mm2) were used. A significant correlation was observed between methods in dimensions of aortic annulus (mean, 29.0 mm ± 4.6), sinus of Valsalva (mean, 38.3 mm ± 8.6), and ascending aorta (mean, 37.2 mm ± 8.0); mean values were 27.4 mm ± 4.9 (r = 0.76, P < .001), 37.7 mm ± 8.6 (r = 0.94, P < .001), and 38.2 mm ± 7.9 (r = 0.96, P < .001), respectively. Mean end-systolic volume (67 mL ± 38), end-diastolic volume (149 mL ± 48), and ejection fraction (57% ± 13) at CT correlated well with mean results at TTE (65 mL ± 36 [r = 0.96, P < .001], 140 mL ± 48 [r = 0.91, P < .001], 56% ± 13 [r = 0.98, P < .001], respectively).
Conclusion: Results of assessment of AR with 64-section CT are similar to those with TTE.
© RSNA, 2007
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE...References |
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Currently, a main application of 64-section computed tomography (CT) is for the evaluation of coronary artery disease (4–7). Also, CT allows quantification of LV function (8,9) and has been shown to provide accurate information about the dimensions of the ascending aorta (10). To further broaden the clinical applications of CT, it would be desirable to evaluate valvular morphology and function as well. Recent evidence has accumulated that the aortic (11,12) and mitral (13) valves can be accurately analyzed by using the same CT data set that has been acquired for the evaluation of coronary arteries. The results of the latter study (13) indicated the potential use of CT to help quantify the severity of mitral regurgitation by means of planimetric measurements of the regurgitant orifice area (ROA). The purpose of our study was to prospectively evaluate the diagnostic accuracy of 64-section CT for evaluation of AR, with transthoracic echocardiography (TTE) as the reference standard.
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MATERIALS AND METHODS |
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Patients
The study protocol was approved by the local ethics committee, and written informed consent was obtained from all patients.
Between June 2005 and February 2006, we prospectively enrolled 30 consecutive patients (23 men, seven women; mean age, 56.6 years ± 15 [standard deviation]; range, 22–83 years) with AR who were referred for 64-section coronary CT angiography. The CT scans were obtained for other reasons, as mentioned later, and not specifically for evaluation of AR. Exclusion criteria included renal insufficiency (creatinine level, >120 µmol/L) (n = 3), known adverse reaction to iodinated contrast medium (n = 2), non-sinus rhythm (n = 1), hemodynamic instability (n = 1), and previous cardiac surgery (n = 1). Fifteen patients (50%) were receiving oral ß-adrenergic blocking agents as part of their baseline medication at the time of CT; no additional ß-blockers were administered prior to CT. The patients had stable angina pectoris (n = 13), atypical chest pain (n = 9), or recurrent symptoms after previous balloon angioplasty (n = 8).
None of the patients underwent previous coronary stent grafting. Nineteen patients had coronary artery disease, and two of them had a history of myocardial infarction. Nineteen patients underwent aortocoronary bypass graft surgery, and two of them also underwent aortic valve replacement. Eight patients underwent aortic valve replacement only; three patients did not undergo valve replacement. The presence and degree of AR were determined by using TTE, the reference standard, in all patients. All CT examinations were performed within 7 days (mean, 3.8 days ± 1.3) after TTE.
Reference Standard
TTE was successfully performed in all patients without complications by two echocardiographers, one with 7 years and one with 15 years of experience (R.J.) with echocardiography. Both echocardiographers independently interpreted findings and were blinded to the results of CT.
Studies included M-mode and B-mode echocardiography, continuous-wave Doppler imaging, and color Doppler echocardiography. According to international guidelines, AR was assigned a grade on the basis of a combination of specific and supportive signs and complementary quantitative parameters (3). AR was classified as mild when the jet width was less than 25% of the LV outflow tract, the width of the vena contracta (ie, the narrowest and the highest-velocity region of the jet at or just downstream from the orifice) was smaller than 0.3 cm, the pressure halftime was longer than 500 msec, and no or brief early diastolic flow reversal was observed in the descending aorta. AR was classified as severe when the jet width was 65% or more of the LV outflow tract, the width of the vena contracta was larger than 0.6 cm, the pressure halftime was shorter than 200 msec, and holodiastolic flow reversal was observed in the descending aorta. AR was graded as moderate when the criteria exceeded the indexes for mild AR and no criteria for severe AR were fulfilled. As proposed by the guidelines (3), additional quantitative measurements were performed when evidence from the previously mentioned parameters was inconclusive or contradictory (as was the case in six patients from our study). These included calculation of the regurgitant volume and fraction and of the effective ROA.
Measurements of aortic root dimensions were made according to international standards during mid diastole by using the parasternal long-axis view (14). The diameters from the inner border to the opposite side were measured three times, and the mean diameter was included for further data analysis. The three segments included the hinge points of the aortic valve cusps that define the aortic annulus, the midpoint of the sinuses of Valsalva, and the proximal ascending aorta at the level of the right pulmonary artery.
LV volume and LV function, respectively, were assessed by using apical four-chamber and apical two-chamber views, with simultaneous electrocardiographic recording. LV end-diastolic and end-systolic volumes and ejection fraction were calculated by using the modified biplanar Simpson method, as discussed in Bashore and Grayburn (15).
CT Data Acquisition and Postprocessing
CT was successfully performed in all patients without complications. It was performed with a 64-section CT scanner (Somatom Sensation 64; Siemens Medical Solutions). The scanning range included the heart and ascending aorta. A bolus of 90 mL of iodixanol (Visipaque 320; GE Healthcare, Buckinghamshire, England), with a concentration of 320 mg/mL, followed by administration of 30 mL saline solution was injected into an antecubital vein via an 18-gauge catheter at an injection rate of 5 mL/sec. Contrast agent application was controlled by bolus tracking. One radiologist (L.D., with 7 years of experience in cardiac CT) placed a region of interest (mean diameter, 16.8 mm ± 6.3; range, 10.1–20.7 mm) on the aortic root, and image acquisition started 5 seconds after the attenuation reached the predefined threshold value of 100 HU.
Data acquisition was performed in a craniocaudal direction with a detector collimation of 32 x 0.6 mm, section collimation of 64 x 0.6 mm by means of a z-flying focal spot, gantry rotation time of 330 msec, pitch of 0.2, tube voltage of 120 kV, and tube current–time product of 700 mAs. The electrocardiogram was recorded during data acquisition, and electrocardiographic pulsing was applied to reduce radiation exposure (16). The adaptive cardio volume approach (17) was used for image reconstruction. Use of this approach resulted in a temporal resolution of 165 msec at heart rates of 65 beats per minute or fewer, and a temporal resolution of 83 msec was reached at higher heart rates by using dual-segment reconstruction. With synchronization to the elecrocardiogram, 11 data sets were retrospectively reconstructed from 40% to 90% of the cardiac cycle in 5% steps of the R-R interval.
Images were reconstructed with a section thickness of 2 mm and a reconstruction increment of 1.5 mm by using a medium-soft–tissue convolution kernel (B30f kernel). All reconstructed data were transferred to an external workstation (Leonardo; Siemens Medical Solutions). Data postprocessing was performed with dedicated postprocessing software (InSpace4D; Siemens Medical Solutions) that enables three-dimensional visualization of CT data in real time. After loading the 11 data sets into the software, imaging planes were adjusted to be parallel and perpendicular to the LV outflow tract and aortic valve, respectively. The four-dimensional option was then selected to obtain a cine-mode presentation of the moving aortic valve.
CT Image Interpretation
The velocity of presentation could be individually determined by the readers. For image quality and valve morphology readout, as well as for assignment of AR grade, the readers were allowed to individually adjust window center and window width settings. For quantification of aortic root dimensions, the readers used fixed window center and window level settings (window width, 600 HU; window center, 80 HU), as previously published (18).
Overall CT image quality.—Two blinded readers (L.D. and H.A., with 7 and 9 years of experience, respectively, in cardiovascular radiology) independently assessed image quality of the aortic valve and aortic root at CT as follows: grade 1, excellent image quality, with excellent visibility and differentiation of the anatomic details of the aortic valve and root; grade 2, good image quality, with good visibility of the anatomic details; grade 3, poor but still diagnostic, with poor visibility of the anatomic details; and grade 4, bad, with nondiagnostic image quality and delineation of anatomic structures of the valve and root not possible.
Aortic valve morphology.—All readers independently classified aortic valve morphology as bicuspid or tricuspid. When bicuspid valves were identified, a raphe was designated as being present or absent by all readers. The raphe represents the site of congenital fusion between the two components of the conjoined cusp (19).
Then, the degree of aortic valve calcification was semiquantitatively assessed by using a previously published scale (20) as follows: grade 1, mild with small isolated spots of calcification; grade 2, moderate with multiple larger spots of calcification; and grade 3, heavy with extensive calcification.
Quantification of aortic regurgitation.—With 64-section CT, the readers froze the cine-mode video presentation during the phase of the R-R interval in diastole at which the ROA was largest. As previously shown (13), the ROA was then planimetrically measured on the image on which the regurgitant orifice had the smallest diameter. This procedure (including phase selection and image plane selection for planimetric measurements) was repeated three times (two times by one reader and one time by the other reader), and the three values were averaged. Measurements were performed in consensus by the two readers, who were both blinded to the results of TTE. The phase of the R-R interval that showed the largest ROA was noted.
Quantification of aortic root dimensions.—With 64-section CT, the same three aortic root segments were measured by the two readers in consensus on the double-oblique reconstructed images at 60% of the R-R interval. In a manner similar to that with TTE, three measurements were performed for each segment with an electronic caliper, and the mean diameter was used for further analysis (Fig 1).
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Estimation of CT radiation dose.—The radiation dose of 64-section coronary CT angiography was estimated by using a scheme proposed in the European Guidelines on Quality Criteria for Computed Tomography (21). The effective dose was derived from the product of the dose-length product (mGy·cm) and a conversion coefficient (k = 0.017 mSv[mGy–1·cm–1]) for the chest as the investigated anatomic region. The individual dose-length product values were obtained from the CT patient protocol in which the radiation exposure parameters were summarized.
Statistical Analysis
All statistical analyses were performed by using commercially available software (SPSS, release 11.5; SPSS, Chicago, Ill). Continuous variables are expressed as the mean ± standard deviation, and categorical variables are expressed as frequencies or percentages. Differences between mean heart rates during CT and TTE were calculated by using the Wilcoxon signed-rank test. Interobserver agreement for image quality, aortic valve morphology, and valve calcification readout with CT were expressed as the Cohen 
statistic (22). Differences between grades of valve morphology with use of CT and of TTE were calculated by using the Fisher exact test. The relationship between the semiquantitative classifications assigned to AR with TTE and the quantitative ROA measurements performed with CT was examined by using Spearman rank order correlation coefficients. The receiver operating characteristic curve, along with the area under the curve, including 95% confidence intervals, was used to calculate the accuracy of cutoff ROA measurements with CT for differentiation between mild versus moderate and severe AR and between mild and moderate versus severe AR. Pearson correlation coefficients were computed for linear correlation analysis, and Bland-Altman analysis was performed for each pair of values in regard to aortic root dimensions, end-systolic volume, end-diastolic volume, and ejection fraction. Differences with P values less than .05 were considered significant.
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RESULTS |
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Overall CT Image Quality
Overall quality of CT images in all 30 patients was rated by both readers, with good interobserver agreement ( = 0.69), as grade 1 (excellent) in five (17%), as grade 2 (good) in 14 (47%), and as grade 3 (poor but still diagnostic) in 11 (37%) patients (median for both readers, grade 2). No reader rated CT image quality as grade 4 (bad and nondiagnostic).
Aortic Valve Morphology
Aortic valves were correctly classified with 64-section CT as tricuspid in 17 patients and as bicuspid in 13 patients. In 13 patients with bicuspid valves, a raphe was identified by using both TTE and CT in 10 (77%) patients.
The degree of aortic valve calcification as assessed with CT was classified by readers 1 and 2, with excellent interobserver agreement ( = 0.91), as mild in 11 (37%) and 10 (33%) patients and as heavy in three (10%) and four (13%) patients, respectively. Both readers classified aortic valve calcification as moderate in seven (23%) patients and as absent in nine (30%) patients. The degree of calcification, as assessed with TTE, was classified by both readers as mild in seven (23%) patients, as moderate in 11 (37%) patients, as heavy in three (10%) patients, and as absent in nine (30%) patients. Calcification assessment differed nonsignificantly between CT (mean of both readers) and TTE (P = .593).
Quantification of Aortic Regurgitation
TTE was used to identify 13 patients with mild AR, eight patients with moderate AR, and nine patients with severe AR (Fig 2). CT depicted incompetent valve closure during diastole in all 30 patients. The mean percentage of the R-R interval in which the maximum ROA was observed was 62% ± 10 (median, 60%; range, 40%–75%).
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Receiver operating characteristic analysis revealed a sensitivity of 85% and a specificity of 88% when we used a cutoff ROA of 25 mm2 for differentiating between mild versus moderate and severe AR with CT (area under the receiver operating characteristic curve, 0.93; 95% confidence interval: 0.85, 1.00). Use of a cutoff ROA of 75 mm2 allowed us to discriminate with CT between mild and moderate versus severe AR, with a sensitivity of 100% and a specificity of 95% (area under the receiver operating characteristic curve, 0.97; 95% confidence interval: 0.92, 1.00) (Fig 3b).
Examples of a patient with mild AR, another with moderate AR, and still another with severe AR are demonstrated in Figures 4–6.
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Estimation of CT Radiation Dose
Mean dose-length product of 64-section coronary CT angiography in all 30 patients was 624.5 mGy·cm ± 70.2 (range, 510–800 mGy·cm), and this value led to a calculated effective radiation dose in the overall study group of 10.6 mSv ± 1.2 (range, 8.8–13.6 mSv).
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DISCUSSION |
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In regard to the anatomic ROA, direct and exact planimetry with echocardiography is not yet clinically possible (24–26). Therefore, echocardiography employs a quantitative approach for calculating the effective ROA through an equation that includes the aortic area, the velocity time integral of diastolic flow in the ascending aorta, and the velocity time integral of the regurgitant jet. We observed an association between the degree of AR and the effective ROA as follows: Mild AR was associated with an effective ROA of smaller than 10 mm2; moderate AR, with an effective ROA of 10–29 mm2; and severe AR, with an effective ROA that exceeded 30 mm2 (1–3).
Another echocardiographic surrogate for the anatomic ROA is the vena contracta, defined as the narrowest and the highest-velocity region of the jet at or just downstream from the regurgitant orifice. Vena contracta widths that are 5 mm or more have a high sensitivity for the diagnosis of severe AR and widths that are 7 mm or more have a high specificity for the diagnosis (1–3). Compared with the anatomic ROA, the effective ROA and the vena contracta width have been suggested to be smaller (27). This finding agrees with results from our study, in which mild AR was associated with a mean anatomic ROA of 19 mm2, moderate AR was associated with a mean anatomic ROA of 48 mm2, and severe AR was associated with a mean anatomic ROA of 134 mm2.
The observed overlap between individual anatomic ROA values from CT measurements of different AR classifications (and particularly between mild and moderate AR) may have resulted from the fact that important information in regard to hemodynamic parameters cannot be assessed with CT. Another reason could be that the optimal phase during diastole in which the largest ROA was observed was missed at CT. Despite the overlap, CT allowed discrimination, with a high sensitivity and specificity, between the AR classifications, as determined by using TTE, when a cutoff ROA of 25 mm2 was used to distinguish between mild and moderate AR and a cutoff ROA of 75 mm2 was used to distinguish between moderate and severe AR.
We demonstrated excellent agreement for depiction of valve morphology and degenerative changes with CT in comparison with TTE. Findings in our study were similar to those in previous studies with CT (11,12) in that they indicated that aortic valve calcification did not affect evaluation by leading to nondiagnostic image quality. Diameter measurements of the aortic root showed a high correlation between CT and TTE, and this correlation was partly expected because both modalities can be used to measure similar anatomic structures. The low, though present, mean errors may be attributed to interobserver variability, real-time variation in vessel diameters caused by pulsatile blood flow, and inaccurate matching of anatomic landmarks and planes when moving from one modality to the other (28–30). Measurements that are based on CT data have been previously shown to show a high correlation with diameter measurements of vessel phantoms (10) and with intraoperative sizing (18).
Findings in reports (31,32) have suggested that two-dimensional echocardiography is a suboptimal modality to use in the assessment of LV volume and function when ventricular geometry is not uniform, and results in recent studies (9,33) have indicated that assessment of LV function was more accurate with CT than with echocardiography when a comparison was made with the current reference standard of MR imaging. Nevertheless, we found a high intermodality agreement, with small mean errors, between CT and echocardiography. This could be explained by relatively normal end-systolic and end-diastolic LV volumes, which indicate early compensated forms of AR, in the patients from our study (1). It is most likely that the intermodality agreement might have been worse if we had included more patients with nonuniform geometry or dilated ventricles. The main advantage of echocardiography in comparison with CT for LV functional analysis is the lack of radiation exposure. This advantage enables repeat measurements, which are recommended for patients with AR (34).
We acknowledge study limitations. First, CT is associated with considerable irradiation to the patient (in our study, approximately 10.6 mSv). However, the data set was primarily obtained for clinical assessment of the coronary arteries. In addition, electrocardographic pulsing for radiation dose reduction could be applied because AR occurs in diastole and planimetric ROA measurements were most often performed at 60% of the R-R interval. Second, no patients with other causes of AR, such as Marfan or Ehlers-Danlos syndrome, rheumatic disease, and infectious disease were included in our population. Data from a larger patient population with various causes of AR are needed in future studies. Third, ROA determination represents a mechanistic approach for classification of AR, particularly because a higher degree of AR may not necessarily be accompanied by an increased ROA. This holds particularly true for patients with eccentric regurgitation jets, commissural insufficiency, or valve protrusions where mismatch between ROA and degree of AR must be expected. Finally, results of TTE assessment were semiquantitative; quantitative parameters such as the effective ROA were available only in six patients, and this availability allowed only nonparametric statistical comparisons between CT and TTE data.
Our study demonstrates for the first time, to our knowledge, that planimetric measurements of the ROA during diastole with 64-section CT show a highly accurate correlation with classification of AR as determined with TTE. AR severity assessment can be performed from the same data set that has been acquired for the evaluation of coronary arteries. In addition, 64-section CT provides important morphologic information on the aortic valve and enables assessment of aortic root dimensions and LV function, all of which are required for a comprehensive work-up of patients with AR.
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ADVANCES IN KNOWLEDGE |
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IMPLICATION FOR PATIENT CARE |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE...References |
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FOOTNOTES |
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Abbreviations: AR = aortic regurgitation • LV = left ventricular • ROA = regurgitant orifice area • TTE = transthoracic echocardiography
See Materials and Methods for pertinent disclosures.
Author contributions: Guarantors of integrity of entire study, H.A., B.M., P.A.K., T.F.; 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, H.A., L.D., L.H., S.L., O.G., T.F.; clinical studies, H.A., L.D., A.P., S.L., R.V., R.J., P.A.K., T.F.; statistical analysis, H.A., L.D., L.H., S.L., H.S., T.S., P.A.K., T.F.; and manuscript editing, H.A., L.H., A.P., H.S., T.S., O.G., T.G.F., M.G., B.M., R.J., P.A.K., T.F.
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE...References |
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