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Original Research |
1 Clinical Department of Radiology II, Innsbruck Medical University,
Anichstrasse 35, A-6020 Innsbruck, Austria.
2 Clinical Department of Cardiology, Innsbruck Medical University, Innsbruck,
Austria.
3 Clinical Department of Cardiac Surgery, Innsbruck Medical University,
Innsbruck, Austria.
Received November 16, 2007;
accepted after revision January 8, 2008.
Address correspondence to G. M. Feuchtner
(gudrun.feuchtner{at}i-med.ac.at).
Abstract
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MATERIALS AND METHODS. Eighty-one consecutive patients were examined with ECG-gated CT coronary angiography using image reconstruction during end-diastole. The diagnostic criterion for aortic valve regurgitation by CT was an incomplete coadaptation of aortic valve leaflets, the central aortic regurgitation area (ARA), which was quantified. All patients underwent transthoracic echocardiography using semiquantitative grading of aortic valve regurgitation (i.e., mild, moderate, or severe).
RESULTS. Of the 81 patients, 45 had aortic valve regurgitation by transthoracic echocardiography. The diagnostic accuracy of CT in detecting aortic valve regurgitation was as follows: sensitivity of 73% (33/45), specificity of 97% (35/36), positive predictive value (PPV) of 97% (33/34), and negative predictive value (NPV) of 74% (35/47). All 12 false-negative findings by CT were graded as mild regurgitation by transthoracic echocardiography and were caused by severe valve calcification (mean, 3,053.1 ± 1,700 Agatston units; range, 937.7–5,632.5 Agatston units), bicuspid valves, or both. The sensitivity, specificity, PPV, and NPV of CT for the detection of moderate and severe aortic valve regurgitation were 95%, 100%, 100%, and 98%, respectively. Quantification of the ARA by CT (mean, 0.25 cm2 ± 0.34 cm2 [SD]) was significantly correlated with the severity of aortic valve regurgitation by trans thoracic echocardiography (p < 0.001).
CONCLUSION. Although 64-MDCT accurately detects moderate and severe aortic regurgitation in patients referred to coronary CT angiography, mild aortic regurgitation can be missed on 64-MDCT in the presence of severe valve calcification or bicuspid valves.
Keywords: aortic regurgitation • aortic valve disease • coronary artery disease • CT • CT coronary angiography • MDCT
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MDCT coronary angiography [2–7] is currently being increasingly used as a noninvasive imaging technique for exclusion of coronary artery disease [8] in patients with a low or intermediate likelihood of disease, such as asymptomatic patients with suspected coronary artery disease. Various studies have proven its high sensitivity and specificity for the detection of coronary artery stenosis greater than 50% [2–7]. MDCT is also highly accurate for the assessment of bypass graft patency [9–12].
The prevalence of aortic regurgitation in the Framingham Heart Study [13] population (mean age, 54 years) was found to be 13% and 8.5% for men and women, respectively, with prevalence increasing with increasing patient age. In patients older than 65 years, calcifying aortic valve disease is present in more than 25% of patients [14], and its association with a 50% increased risk of cardiovascular events reflects the high comorbidity of aortic valve disease and coronary artery disease [15–17].
During coronary CT angiography, the cardiac valves can be assessed in a comprehensive fashion. Using retrospective ECG gating during the entire cardiac cycle, functional assessment of valvular motion in a four-dimensional fashion has become feasible [18]. Several recently published studies have shown promising results for the evaluation of aortic stenosis by CT using planimetry of the area of the aortic valve orifice [19–24]. However, limited data are available regarding the value of MDCT for the diagnosis of aortic regurgitation [25, 26].
Recently introduced 64-MDCT scanners provide improved spatial and temporal
resolution [27] when compared
with 16-MDCT [28]—a
spatial resolution of 0.4 mm3 versus 0.5 x 0.5 x 0.6
mm3 and a temporal resolution of 
250 versus > 165
milliseconds, respectively, which might improve assessment of aortic
regurgitation. Therefore, the purpose of this study was to evaluate the
diagnostic accuracy of 64-MDCT for the diagnosis of concomitant aortic
regurgitation in patients referred to coronary CT angiography.
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CT Coronary Angiography Examination Technique
CT data were acquired using an MDCT scanner (Sensation 64, Siemens Medical
Solutions) with a 32-row detector collimation acquiring 64 x 0.6 mm
slices by applying the z-axis flying-focus technique
[27], a table translation
speed of 3.8 mm per rotation, and a gantry rotation time of 0.33 second. A
tube current of 120 kV and 600–900 mAs resulted in an estimated
radiation exposure of between 9.4 and 14.8 mSv (mean, 11 mSv)
[29]. The scanning direction
was craniocaudad during a single inspiratory breath-hold. A bolus of
90–120 mL of an iodinated contrast agent, either iodixanol with an
iodine concentration of 320 mg/dL (Visipaque 320, GE Healthcare) or iomeprol
with an iodine concen tration of 400 mg/dL (Iomeron 400, Bracco), was in
jected IV into an antecubital vein with a 20-gauge cannula at a flow rate of
4.5–6.0 mL/s using a power injector. Scanning was started auto mati
cally by applying a bolus-tracking tech nique (as cending aorta threshold =
100 H) as described for coronary CT angiography
[30]. A β-blocker
(5–10 mL of metoprolol [Beloc, Schering]) was given IV before CT if the
patient's heart rate was more than 65 beats per minute (bpm). ECG pulsing was
performed if the heart rate was regular and less than 65 bpm.
CT Image Reconstruction and Analysis
A data set containing transaxial slices (effective slice width, 0.75 mm;
increment, 0.4; medium-smooth convolution kernel B 25 F+) during mid to late
diastole (60–80% of R-R interval) was reconstructed using retrospective
ECG gating. This data set was transferred to an external workstation
(Leonardo, Siemens Medical Solutions) and reviewed by applying multiplanar
reformations. Several cross-sectional transverse images of the aortic valve
were reconstructed in a craniocaudal direction from the left coronal oblique
and left sagittal oblique views. A visible incomplete coadaptation of the
valve leaflets in the coronal oblique, sagittal oblique, and trans verse
cross-sectional images was regarded as the diagnostic criterion of aortic
regurgitation (Fig. 1A,
1B,
1C,
1D,
1E) by two independent
observers, one with 5 years' experience with cardiac CT and the other with 6
months' training in cardiac CT, who were blinded to the echo cardio graphy
results. The smallest measurable central aortic regurgitation area (ARA) was
quantified in square centimeters (cm2) on a transverse image
parallel to the valve annulus level by the two observers. The evaluation of
the more experienced observer, observer 1, was used for data analysis, but a
consensus read out session was appended after the less exper ienced observer,
observer 2, had evaluated the data.
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Transthoracic Echocardiography
All measurements were performed using a dedicated sonography unit (Sequoia
256, Acuson-Siemens Medical Solutions) equipped with a 3.5-1.75–MHz
transducer by experienced obser vers. The severity of aortic regurgitation was
classi fied as grade 1–3 (i.e., mild, moderate, or severe, respectively)
according to the guidelines of the American Heart Association (AHA) and
American College of Cardiology (ACC)
[1] quantitatively by
integrative combined use of the following specific and nonspecific parameters
[32].
First specific parameter (90% sensitivity) by color Doppler imaging: proximal width of proximal regur gitation jet—A proximal regurgitation jet width of < 25% of the left ventricular outflow tract (LVOT) was considered mild aortic valve regurgitation; 25–65% of LVOT, moderate aortic valve regurgi tation; and > 65% of LVOT, severe aortic valve regurgitation.
Second specific parameter (90% sensitivity) by color Doppler imaging: vena contracta length— A vena contracta length of < 0.3 cm was considered mild aortic valve regurgitation if the prerequisite, a Nyquist limit of 50–60 cm/s, was present; 0.3–0.6 cm, moderate aortic valve regur gitation; and > 0.6 cm, severe aortic valve regurgitation.
Supportive parameters (moderate sensitivity) by color Doppler imaging: pressure half-time method—Using the pressure half-time technique, a pressure half-time of > 500 milliseconds was considered mild aortic valve regurgitation; 200–500 milliseconds, moderate aortic valve regurgitation; and < 200 milliseconds, severe aortic valve regurgitation.
Mean and maximum transvalvular pressure gradients and velocities were measured to assess whether concomitant aortic valve stenosis was present.
Statistical Analysis
Statistical analysis was performed using SPSS software (version 8.0, SPSS).
The diagnostic accuracy (i.e., sensitivity, specificity, negative predictive
value [NPV], and positive predictive value [PPV] including 95% CIs) of CT for
the identification of patients with aortic regurgitation was calculated. The
independent unpaired Student's t test was used to test the
significance of differences in aortic valve calcification scores between
false-negative and true-positive findings. The correlation between the area
measurements of aortic valve regurgitation by CT and the severity of aortic
valve regurgitation by transthoracic echocardiography (grade 1–3) was
determined using Spearman's rank correlation coefficient. Interrater agreement
(aortic regurgitation: yes or no) was calculated using a weighted Cohen's
kappa value, and the results were interpreted according to Landis and Koch
[33] as follows: poor, a kappa
value of 0.20 or less; fair, 0.21–0.40; moderate, 0.41–0.60; good,
0.61–0.80; or excell ent, 0.81–1.00. The interobserver correlation
be tween ARA measurements of two independent observers was determined with
Pearson's correla tion coefficient after statistical testing of the
prerequisites.
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Table 1 lists the prevalence and severity of aortic regurgitation, the prevalence of aortic stenosis and aortic root dilatation, aortic valve morphology, and the severity of aortic valve calcification as quantified by the Agatston score in our study population.
The diagnostic accuracy of 64-MDCT for the detection of aortic regurgitation (Figs. 1A, 1B, 1C, 1D, 1E, 2A, 2B, 3A, 3B) was 84% (95% CI, 74.4–90.37), the sensitivity was 73% (33/45) (95% CI, 58.9–84), the specificity was 97% (35/36; 95% CI, 85.8–99.5), the PPV was 97% (33/34; 95% CI, 85.1–99.5), and the NPV was 74% (35/47; 95% CI, 60.5–84.7) using the consensus readout session (equivalent to the scoring results of the more experienced observer 1). Interrater agreement was excellent with a Cohen's kappa value of 0.98 ± 0.07.
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Quantification of the ARA by CT (mean, 0.25 ± 0.34 cm2; range, 0.02–1.31 cm2) was significantly correlated with the severity of aortic valve regurgitation by transthoracic echocardiography (r = 0.86, Spearman's correlation coefficient; p < 0.001). The box plot shown in Figure 6 illustrates the distribution of the ARA measurement values.
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Most false-negative findings were caused by severe valve calcification (Fig. 4A, 4B, 4C) with calcium scores of 937.7 Agatston units or greater. Moreover, visualizing aortic insufficiency in bicuspid valves was difficult (Fig. 5) because a triangular leakage area was not present, as is usually seen in tricuspid valves, because the leakage might be linear. However, in the absence of aortic valve calcification, even mild aortic regurgitation, which appeared as a tiny spotlike regurgitant area, could be detected (Fig. 3A, 3B). Our data are in accordance with the results of a recently published study [26] in which investigators also observed a low sensitivity and NPV of 70% and 79%, respectively, but a high specificity and PPV of 100% for MDCT.
The diagnostic accuracy of 64-MDCT is similar to the results reported in a previously published study using 16-MDCT [25]. However, the overall performance of 64-MDCT is improved compared with 16-MDCT because the central valvular leakage area could be "reliably" quantified in only 50% of patients by 16-MDCT [25] and not in patients with severe calcification. In contrast, in our study, we were able to measure the valve leakage area in all patients using 64-MDCT. This increased capability of 64-MDCT might be explained by its improved temporal and spatial resolution [27] that improved image quality because of a reduction in artifacts from calcification, such as beam-hardening artifacts, partial volume effect artifacts, or blurring from motion. Further, using dedicated scanner technology and the z-flying focus technique [27], artifacts from calcification—in particular, those related to the spiral acquisition—might have been minimized further.
The high reproducibility and the high correlation of ARA measurements by CT with the severity of aortic valve regurgitation by transthoracic echocardiography suggest that CT could also be used in the future to assess the severity of aortic valve regurgitation. However, further studies with more patients at different stages of disease and, in particular, with mixed causes (e.g., root dilatation; rheumatic, degenerative, or calcifying valve disease; infective endocarditis) are necessary for that purpose. Our data showed mean values of 0.04 cm2 for mild aortic valve regurgitation, 0.37 cm2 for moderate aortic valve regurgitation, and 0.81 cm2 for severe aortic valve regurgitation (Table 2) without significant overlap on the box plot (Fig. 6). These findings are, in fact, promising and are similar to those of two recently published studies [26, 34]. Alkadhi et al. [34] have suggested using cutoffs for the diagnosis of moderate and severe regurgitation of 25 and 75 mm2 ARA, respectively; however, they recruited mainly patients with root dilatation without marked valve calcification in whom quantification of the ARA may be more accurate and different than in patients with other causes of aortic regurgitation such as rheumatic, degenerative, or calcifying valve disease.
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Further technical developments of CT technology, such as dual-source imaging, may further improve the accuracy of CT to quantify aortic regurgitation.
Through the use of dedicated CT technology and retrospective ECG gating, images can be reconstructed throughout and at every arbitrary percentage throughout the entire cardiac cycle (see Fig. S7, dynamic imaging, which can be accessed from right upper corner of this article at www.ajronline.org). For the assessment of aortic valve regurgitation, image reconstruction is necessary during end-diastole, which is the time point of aortic valve closure in normal valves.
We used a planimetric approach to quantify the severity of aortic regurgitation that showed a high correlation (r = 0.86; p < 0.001) with grade of severity of aortic valve regurgitation by transthoracic echocardiography determined semiquantitatively. Planimetric mea surements of the anatomic regurgitation area by transesophageal echo cardio graphy also showed comparable good correlation (r = 0.9; p < 0.001) with the severity of aortic valve regurgitation by transthoracic echocardiography in a study conducted by Ozkan et al. [35].
In our experience, it is important to review all image series during late diastole (60%, 70%, and 80% of the R-R interval) because at the 60% series the valve may appear insufficient, although at 80% it is clearly closed.
Currently, 64-MDCT coronary angiography is being increasingly used in clinical practice for the exclusion of coronary artery disease [2–8]. However, those patients may not have undergone a recent echocardiography examination. Moreover, echocardiography has limitations because it is dependent on the level of experience of the observer, the position of the transducer, and the patient's morphology. Therefore, we recommend ev aluating the aortic valve simultaneously in all patients referred to coronary CT angiography to assess whether the valve is insufficient. Three patients in our study had previously unknown aortic regurgitation, and they were primarily referred to coronary angiography. Then, further reevaluation with transthoracic echocardiography confirmed aortic valve regurgitation. In particular, patients with aortic root dilatation must be evaluated carefully because aortic regurgitation frequently develops in those patients. In our study population, 28% of the patients had aortic root dilatation of greater than 4 cm.
MDCT has recently shown promising results, highlighting a high reproducibility and good correlation with the reference standard cardiac MRI for measurement of left ventricular function [36–38] compared with established imaging techniques. Left ventricular function is an important parameter to determine the optimal time point of surgical intervention in patients with aortic valve disease [1, 32].
Limitations
First, radiation exposure of cardiac 64-MDCT in our study ranged between
9.4 and 14.8 mSv (mean, 11 mSv)
[29], but values up to a
maximum of 21 mSv [3] have been
reported in patients scanned using full tube output and in females. However,
ECG pulsing (i.e., ECG tube current modulation), which reduces the radiation
exposure approximately 45–48%
[39], can be applied in this
setting and is important to reduce radiation dose. Second, the prevalence of
aortic regurgitation in our population was high, 56%, and does not reflect the
prevalence of aortic valve regurgitation in an outpatient coronary CT
angiography screening population with a low to intermediate pretest
probability of coronary artery disease according to ACC and AHA
appropriateness criteria [8]
because our patients were mainly referred to CT coronary angiography to rule
out coronary artery disease before valve surgery
[6], thus leading to a
preselection bias. Third, quantification of the ARA might be less accurate in
heavily calcified valves because this problem has been observed using 16-MDCT
[25]. However, our data
suggest that the improved temporal resolution of 64-MDCT has reduced this
problem. Moreover, in practice heavy valve calcification is rather rare and is
not typical for primary severe aortic regurgitation related to a
pathomechanism.
Conclusion
MDCT cannot be recommended as a first-line imaging technique for the
assessment of aortic regurgitation because transthoracic echocardiography is
safe, reliable, and radiation-free. However, given the emerging use of MDCT
coronary angiography in patients with suspected coronary heart disease in
clinical practice, the aortic valve can be evaluated in a comprehensive
fashion to determine whether coexistent moderate or severe regurgitation is
present. If valvular leakage is visible, the patient should be evaluated
further with echocardiography for accurate hemodynamic quantification of the
severity of regurgitation.
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