Aortic Disease in Patients with Marfan Syndrome: Aortic Volume Assessment for Surveillance 1

Transcription

1 Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at Original Research n Cardiac Imaging Alexander W. den Hartog, MD Romy Franken, MD Piet de Witte, MD Teodora Radonic, MD, PhD Henk A. Marquering, PhD Wessel E. van der Steen, BSc Janneke Timmermans, MD Arthur J. Scholte, MD, PhD Maarten P. van den Berg, MD, PhD Aeilko H. Zwinderman, PhD Barbara J. M. Mulder, MD, PhD Maarten Groenink, MD, PhD Aortic Disease in Patients with Marfan Syndrome: Aortic Volume Assessment for Surveillance 1 Purpose: Materials and Methods: To assess the reproducibility of aortic volume estimates and to serially test their use in patients with Marfan syndrome. The study was approved by the medical ethics committee and all subjects gave written informed consent. In 81 patients with Marfan syndrome and seven healthy control subjects, aortic volumes and diameters at baseline were estimated by means of contrast material enhanced magnetic resonance (MR) imaging. At 3 years of follow-up, aortic expansion rate were calculated in a subgroup of 22 patients with Marfan syndrome. Total aortic volume was defined as volume measurement from the level of the aortic annulus to the aortic bifurcation. Intra- and interobserver agreement of aortic volume were calculated by using the intraclass correlation coefficient. Differences in variables were analyzed with the Student t test and logistic regression. Effect size was calculated. 1 From the Departments of Cardiology (A.W.d.H., R.F., P.d.W., W.E.v.d.S., B.J.M.M., M.G.), Clinical Epidemiology and Biostatistics (T.R., A.H.Z.), Biomedical Engineering and Physics (H.A.M.), and Radiology (H.A.M., M.G.), Academic Medical Center, Meibergdreef 9, B2-216, 1105 AZ Amsterdam, the Netherlands; Interuniversity Cardiology Institute of the Netherlands, Utrecht, the Netherlands (A.W.d.H., R.F., P.d.W., B.J.M.M., M.G.); Department of Cardiology, Radboud University Medical Center, Nijmegen, the Netherlands (J.T.); Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands (A.J.S.); and Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands (M.P.v.d.B.). Received October 23, 2012; revision requested December 11; revision received January 25, 2013; accepted February 13; final version accepted April 1. Supported by a grant from the Netherlands Heart Foundation (grant 2008B115) and the consortium Fighting Aneurysmal Disease (FAD) (EU FP 7). Address correspondence to M.G. ( m.groenink@ amc.uva.nl). q RSNA, 2013 Results: Conclusion: Intra- and interobserver agreement of aortic volume calculation was and 0.980, respectively. Mean aortic volume was significantly greater in patients with Marfan syndrome than in control subjects (104 ml/m 2 ; 95% confidence interval [CI]: 95, 114 ml/m 2 vs 74 ml/m 2 ; 95% CI: 62, 87 ml/m 2 ; P,.001). In 22 patients with Marfan syndrome, mean aortic volume was increased at 3 years of follow-up (17 ml; 95% CI: 8, 26 ml; P =.001; effect size, 0.29), while mean aortic diameter did not increase significantly (0.4 mm; 95% CI: 0.0, 0.9 mm; P =.171; effect size, 0.13). Assessment of aortic volume is highly reproducible and may be suited for use in the detection of aortic expansion in patients with Marfan syndrome. q RSNA, 2013 Supplemental material: /suppl/doi: /radiol /-/dc1 370 radiology.rsna.org n Radiology: Volume 269: Number 2 November 2013

2 Marfan syndrome (MFS) is an autosomal dominant systemic connective tissue disorder caused by mutations in the fibrillin-1 gene, with a prevalence of approximately two to three patients per individuals (1). In patients with MFS, the aorta gradually dilates, ultimately leading to aortic aneurysm formation and aortic dissection. Aortic complications are the leading cause of morbidity and mortality in patients with MFS (2,3). With the introduction of prophylactic aortic root surgery at an aortic root diameter of cm, type A aortic dissection can be prevented effectively, and life expectancy for patients with MFS has increased tremendously (4 6). This increased longevity has shown that aortic complications are not limited to the aortic root and can occur throughout the entire aorta (7). Therefore, visualization of the total aorta by means of magnetic resonance (MR) imaging or computed tomography (CT) at regular intervals is recommended (8). However, complications in the aortic trajectory beyond the aortic root are difficult to foresee by measuring aortic diameters (9). Therefore, in patients with MFS who do not have a localized aneurysm, diameter assessment may not be a good marker for the extent of aortic disease. Volume measurement of the aorta could potentially reflect the extent of aortic disease more sensitively. The purpose of our study was to assess the reproducibility of aortic volume estimates and to test their use serially in patients with MFS. Advances in Knowledge nn Aortic volume measurement based on three-dimensional contrast material enhanced MR imaging is highly reproducible, with an intra- and interobserver agreement of and 0.980, respectively. nn Total aortic dilation rate can be detected more accurately by using aortic volume assessment than by using mean aortic diameter assessment (effect size, 0.29 vs 0.13, respectively). Materials and Methods Analysis software for evaluation of functionality used in this study was 3Mensio Vascular (3Mensio Medical Imaging, Bilthoven, the Netherlands) and was provided without cost. Authors had full control of the data and information at all times. Study Subjects The study was approved by the Academic Medical Center medical ethics committee, and all participating subjects gave written informed consent. Between January 2008 and March 2010, total aortic volume and aortic diameters were measured in 81 patients with MFS by means of contrast material enhanced three-dimensional MR imaging. All patients were participants in a randomized, controlled trial to study the effect of losartan on the aortic expansion rate in patients with MFS (10). The inclusion criteria were diagnosis of MFS according to the Ghent criteria (11), aortic root diameter of less than 50 mm, a maximum of one vascular prosthesis, absence of aortic dissection, and age of 18 years or older. Twenty patients underwent prophylactic aortic root replacement before the study started, and eight patients underwent aortic root replacement during the study. All 28 patients underwent surgery because of progressive aortic root dilatation. Medical history and standardized measurements of height and weight were obtained from patients medical records. See Table 1 for patient characteristics. Total aortic volumes and aortic diameters of a subpopulation of 22 patients with MFS without a history of aortic surgery were compared with those of seven sex- and age-matched control subjects who were definitely shown to not have aortic disease. The 22 patients with MFS underwent a second contrast-enhanced Implication for Patient Care nn Aortic volume assessment may become a useful metric for monitoring global aortic expansion in patients with Marfan syndrome. three-dimensional MR imaging examination after 3 years of follow-up. In this follow-up cohort, aortic expansion rate, measured by means of aortic diameter and aortic volume, was calculated. MR Imaging All MR imaging was performed in a single center (Academic Medical Center, Amsterdam, the Netherlands), and images were acquired by using a standardized commercially available protocol with a 1.5-T MR system (Avanto; Siemens, Erlangen, Germany) and a phased-array cardiac receiver coil. Contrast-enhanced MR angiography of the total aorta was performed by using firstpass imaging with a bolus of gadobutrol (Gadovist; Bayer Schering, Berlin, Germany) with a molarity of 1 mmol/l at 0.2 ml per kilogram of body weight. Contrast material was injected intravenously in the brachial vein at an infusion rate of 2 ml/sec and was subsequently flushed with 20 ml of saline at 2 ml/ sec by using contrast-material power injectors (Mallinckrodt, St. Louis, Mo). Breath holding at end inspiration was performed. Contrast-enhanced MR angiograms were obtained by imaging the aorta continuously, and the MR angiographic imaging subsequently triggered Published online before print /radiol Content codes: Radiology 2013; 269: Abbreviations: BSA = body surface area CI = confidence interval ICC = intraclass correlation coefficient MFS = Marfan syndrome Author contributions: Guarantors of integrity of entire study, A.W.d.H., T.R., A.H.Z., M.G.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, A.W.d.H., P.d.W., W.E.v.d.S., J.T., M.G.; clinical studies, A.W.d.H., R.F., P.d.W., T.R., J.T., M.v.d.B., A.H.Z., B.J.M.M., M.G.; experimental studies, A.W.d.H., T.R., H.A.M., J.T., M.G.; statistical analysis, A.W.d.H., R.F., H.A.M., W.E.v.d.S., J.T., A.H.Z., M.G.; and manuscript editing, A.W.d.H., R.F., P.d.W., T.R., H.A.M., W.E.v.d.S., J.T., A.J.S., A.H.Z., B.J.M.M., M.G. Conflicts of interest are listed at the end of this article. Radiology: Volume 269: Number 2 November 2013 n radiology.rsna.org 371

3 Table 1 Patient Characteristics Characteristic No. of patients 81 Age (y) 34 (32 37)* Men 43 (53) Length (cm) 188 ( )* Weight (kg) 77 (73 80)* Body surface area (m 2 ) 2.0 ( )* Prior aortic root replacement 20 (25) Aortic volume Normalized for BSA (ml/m 2 ) 116 (109, 122) Normalized for BSA in men (ml/m 2 ) 119 (112, 127) Normalized for BSA in women (ml/m 2 ) 111 (100, 122) Aortic diameter normalized for BSA Aortic root (mm/m 2 ) 20.9 (19.9, 21.8) Ascending aorta (mm/m 2 ) 14.4 (13.9, 14.9) Aortic arch (mm/m 2 ) 12.0 (11.6, 12.4) Proximal descending aorta (mm/m 2 ) 11.9 (11.5, 12.4) Aorta at level of diaphragm (mm/m 2 ) 10.3 (9.8, 10.8) Abdominal aorta (mm/m 2 ) 8.4 (8.0, 8.8) Mean aortic diameter (mm/m 2 ) 12.9 (12.6, 13.3) Note. Unless otherwise indicated, data are the mean, with 95% confidence intervals (CIs) in parentheses. BSA = body surface area. * Data in parentheses are the range. Data are numbers, with percentages in parentheses. scout imaging of the contrast agent bolus in the ascending aorta, which was aimed to visualize the total aorta during first pass of the bolus in the aorta. The contrast-enhanced MR angiography of the full aorta was performed by means of a nonelectrocardiographically gated threedimensional T1-weighted spoiled gradient-echo fast low-angle shot (FLASH3D; Siemens) sequence (flip angle, 25 ; field of view, mm; matrix, ; sections per slab, 80; phase percentage, 60% 80%; section oversampling, 10%) with correction for gradient nonlinearity and without zero filling. This resulted in a near isotropic resolution of mm per voxel. To perform valid volume assessment of the total aorta (starting at the level of the aortic annulus and ending at the level of the aortic bifurcation), it was mandatory to visualize both the carotid vessels and iliac arteries on the contrast-enhanced MR angiographic images. Aortic root size was measured by using cine imaging sequences (steady-state free precession) Data perpendicular to the long axis of the aortic root, which was shown by using coronal and sagittal scout imaging (section thickness, 6 mm; flip angle, 80 ; field of view, 340 mm; matrix, ; frames per cardiac cycle, 25 50; resulting spatial resolution, mm per voxel) during end expiration. Image Processing The datasets were evaluated independently in a random order by two observers (A.W.d.H. and P.d.W., both with 2 years of experience in cardiovascular imaging). Evaluation of data was supervised by a cardiologist (M.G., with more than 15 years of experience in cardiovascular imaging and imaging of patients with MFS). Vessel analysis software (3Mensio Vascular; 3Mensio Medical Imaging) was used to calculate aortic volumes (12). Images were loaded in the software with window and level settings acquired from the Digital Imaging and Communications in Medicine data. Total aortic volume was determined by using the following technique: A central lumen line was created by manually placing a seeding point through the lumen of the aorta in the axial, sagittal, and coronal planes (Fig 1). A complete set of multiplanar reformations perpendicular to this central lumen line was constructed by the computer, resulting in a stretchedvessel view of the aorta from the aortic valve to the aortic bifurcation. The aortic lumen was manually separated from the surrounding tissue by placing in four cross-sections a cutoff line between the enhanced aortic lumen voxels and the surrounding voxels (Fig 1). The volume of the contrast-enhanced aortic lumen was reconstructed from the individually segmented axial sections. Aortic diameters were assessed at six landmark levels: the aortic root (greatest diameter of three cusp-to-cusp dimensions in diastole), the ascending and descending thoracic aorta at the level of the pulmonary bifurcation, the aortic arch at the level of the diaphragm, and the abdominal aorta. Aortic diameters beyond the aortic root were measured with electronic calipers perpendicular to the aortic lumen (inner wall to inner wall) in the long axis of a maximum intensity projection of a contrast-enhanced MR image (Fig 2). When the maximum intensity projection image was not conclusive, multiplanar reconstructions were used to assess the diameter. Mean aortic diameter was calculated as the average of these six measurements. Intra- and interobserver agreement of aortic volume and diameter were determined (W.E.v.d.S. analyzed 10 individual datasets twice and P.d.W. analyzed them once). Repeated measurements were obtained in a random order without observer knowledge of the previous values. Statistical Methods Statistical analysis was performed by using statistics software (SPSS 17.0 for Windows; SPSS, Chicago, Ill). Normally distributed quantitative data were expressed as means and 95% CIs. Intraand interobserver agreement for aortic diameter and total aortic volume were determined with intraclass correlation coefficients (ICCs) and were processed 372 radiology.rsna.org n Radiology: Volume 269: Number 2 November 2013

4 on a Bland-Altman plot. We evaluated correlations in characteristics of the patients by using the Pearson correlation coefficient. Differences in variables in the group were compared by using the Student t test and logistic regression. Effect sizes of aortic diameter and aortic volume to detect aortic growth were calculated as the ratio of the mean difference between baseline and follow-up measurements divided by the pooled standard deviation. Effect sizes were compared by using a t test, which is described in the Appendix (online). P values less than.05 were considered to indicate a significant difference. Figure 1 Results Results are shown in Table 1. Mean aortic volume and mean aortic diameter of the 81 patients with MFS were 231 ml (95% CI: 218, 245 ml) and 25.7 mm (95% CI: 25.1, 26.4 mm), respectively. No aortic aneurysms between the measured levels were detected. Intra- and interobserver variability of aortic volume determined in 10 patients with MFS were 4.63 ml (ICC = 0.996) and 0.06 ml (ICC = 0.980), respectively, and were as reproducible, as were mean aortic diameter measurements, 0.2 mm (ICC = 0.974) and 0.03 mm mm, (ICC = 0.901), respectively (Table 2, Fig 3). Aortic volume and mean aortic diameter were associated with body surface area, (R = 0.43, P,.001 for both) (Fig 4). The association of aortic volume and age was comparable with the association of mean aortic diameter and age (R = 0.55 and R = 0.56, respectively (P,.001 for both) (Fig E1 [online]). Aortic volume corrected for BSA in the 22 patients with MFS was significantly greater than that in the seven sex- and age-matched control subjects (104 ml/m 2 [95% CI: 95, 114 ml/m 2 ] vs 74 ml/m 2 [95% CI: 62, 87 ml/m 2 ]; P,.001), as was the mean aortic diameter corrected for BSA (12.5 mm/ m 2 [95% CI: 12.1, 12.9 mm/m 2 ] vs 11.4 mm/m 2 [95% CI: 10.3, 12.5 mm/m 2 ]; P =.042) (Table 3). Multiple logistic regression analysis showed a difference Figure 1: Image created by using postprocessing software shows seeding points placed manually in coronal, axial, and sagittal planes (left, top to bottom) of contrast-enhanced lumen of the aorta. Next to it is a multiplanar reconstructed stretched view (right) of the aorta with manually placed cutoff lines. in aortic volume corrected for BSA between patients with MFS and control subjects, with an odds ratio of (95% CI: 0.810, 0.959; P =.003), while there was not a difference in mean aortic diameter corrected for BSA, with an odds ratio of (95% CI: 0.257, 1.266; P =.167). Radiology: Volume 269: Number 2 November 2013 n radiology.rsna.org 373

5 Table 2 Intraobserver and Interobserver Variability of Aortic Volume and Aortic Diameter Variable Figure 2 Intraobserver Variability In 22 patients with MFS, mean aortic volume increased during the 3 years of the study (17 ml; 95% CI: 8, 26 ml; P =.001; effect size, 0.29), while mean Interobserver Variability M1 M2 ICC O1 O2 ICC Volume (ml) Mean diameter (mm) Note. Data are means 6 standard deviation. M = measurement, O = observer Figure 2: (a) Maximum intensity projection shows aorta of patient with MFS. Aortic diameter was calculated at indicated levels: A, ascending aorta; B, arch of the aorta; C, descending aorta; D, aorta at level of the diaphragm; E, abdominal aorta. (b) MR image shows aortic root in short axis of patient with MFS. Greatest aortic root diameter of three measured distances was used: 1, right coronary cusp to left coronary cusp; 2, noncoronary cusp to left coronary cusp; 3, noncoronary cusp to right coronary cusp. aortic diameter did not increase significantly (0.4 mm; 95% CI: 0.0, 0.9 mm; P =.171; effect size, 0.13) (Table 4). Mean aortic diameter corrected for BSA in patients with MFS who previously underwent aortic root replacement was comparable to that of patients with MFS who had not undergone aortic root replacement (12.5 mm/m 2 [95% CI: 11.6, 13.5 mm/m 2 ] vs 13.1 mm/m 2 [95% CI: 12.7, 13.5 mm/ m 2 ]; P =.238), while total aortic volume corrected for BSA was greater in patients with MFS who had undergone aortic root replacement than in patients who had not undergone aortic root replacement (127 ml/m 2 [95% CI: 109, 145 ml/m 2 ] vs 112 ml/m 2 [95% CI: 105, 118 ml/m 2 ]; P =.040) (Table 5). Discussion In this study we showed good reproducibility of total aortic volume assessment. A significant difference in aortic volume between patients with and those without global aortic disease was demonstrated. Furthermore, we showed a superior effect size of aortic volume assessment compared with that of diameter assessment in total aortic expansion rate by means of serial imaging at 3 years of follow-up. Reproducibility of aortic volume assessment in our study was comparable to that of volume measurements in abdominal aneurysms (13 15). However, these studies used CT images for aortic volume rendering. MR imaging offers the advantage of the lack of ionizing radiation exposure, which is important in relatively young patients with MFS who will receive frequent examinations throughout their lives. In daily clinical practice, patients with MFS undergo MR imaging of the entire aorta at regular intervals, as recommended in current guidelines (16,17). Generally, aortic diameter is measured at several aortic levels to quantify the extent of local aortic disease. Comparison of aortic diameter at several levels in patients with MFS with those of a limited number of control subjects only showed significant differences at the level of the aortic root, which is a major clinical feature of MFS. Still, mean aortic diameter remained significantly larger in patients with MFS, although the differences in aortic root size were averaged somewhat. In the 3 years of the study, the only significant increase in aortic diameter in patients with MFS was shown at the level of the ascending aorta. Although we do not advocate follow-up for known aortic aneurysms by using this method, we assessed the extent of total aortic disease in patients with MFS with estimates of mean aortic diameter and total aortic volume. This was performed in patients with 374 radiology.rsna.org n Radiology: Volume 269: Number 2 November 2013

6 Figure 3 Figure 3: Bland-Altman plots show (a) intraobserver variability and (b) interobserver variability of aortic volume measurements in 10 patients with MFS. SD = standard deviation. Figure 4 Figure 4: Scatterplots show correlation between (a) BSA and aortic volume in 81 patients with MFS and between (b) BSA and mean aortic diameter in 81 patients with MFS. MFS without localized aneurysms beyond the aortic root. Treatment of localized aortic aneurysms (as in the aortic root) is still based on the measurement of local aortic dimensions. However, a measure of total aortic size is relevant for estimation of the extent and progression of aortic disease, both in clinical studies and in clinical practice. Aortic volume measurement could limit follow-up time and sample size in clinical trials in which the effect of medicinal therapy on the rate of aortic dilation is assessed or the amount of aortic disease beyond the aortic root is estimated (10). The mean aortic diameter was a mere approximation of total aortic volume, due to a very limited sample size (six for mean aortic diameter and almost unlimited for volume assessment). Hence, no statistically significant differences were shown in mean aortic diameter between patients with MFS and control subjects. On the contrary, by means of aortic volume assessment, a statistically significant difference between patients with MFS and control subjects was shown. Repeated assessment of aortic diameter, especially that beyond the aortic root, does not often show an increase in aortic size. As a result, total aortic expansion rate, determined by measuring aortic diameter, was very small (0.1 mm per year) in our study and could easily be attributed to patient-, equipment- or techniciandependent factors. Total aortic expansion rate became more obvious when aortic volume was assessed (5.6 ml per year). Aortic volume in patients with MFS who had undergone surgery was significantly different from that in patients who had not undergone surgery. This difference could not be shown by using aortic diameter measurement. Patients with MFS who underwent prophylactic Radiology: Volume 269: Number 2 November 2013 n radiology.rsna.org 375

7 Table 3 Aortic Dimensions of 22 Patients with MFS and Seven Control Subjects Variable Patients with MFS Control Subjects P Value No. of patients 22 7 Age range (y) No. of men 12 (55)* 5 (71)*.430 Body surface area (m 2 ) 1.95 ( ) 1.96 (1.73, 2.21).856 Aortic diameter normalized for BSA Aortic root (mm/m 2 ) 22.9 (22.1, 23.7) 16.5 (14.5, 18.4),.001 Ascending aorta (mm/m 2 ) 13.2 (12.6, 13.9) 13.7 (11.6, 15.8).637 Aortic arch (mm/m 2 ) 11.0 (10.7, 11.4) 11.7 (10.7, 12.8).175 Proximal descending aorta (mm/m 2 ) 11.2 (10.6, 11.4) 10.3 (8.9, 11.7).201 Aorta at level of diaphragm (mm/m 2 ) 9.3 (8.9, 9.7) 9.3 (8.2, 10.3).912 Abdominal aorta (mm/m 2 ) 7.7 (6.9, 8.5) 6.9 (6.3, 7.5).078 Mean aortic diameter (mm/m 2 ) 12.5 (12.1, 12.9) 11.4 (10.3, 12.5).042 Aortic volume normalized for BSA (ml/m 2 ) 104 (95, 114) 74 (62, 87),.001 Note. Unless otherwise indicated, data are means, with 95% CIs in parentheses. * Data in parentheses are percentages. Table 4 Aortic Growth of 22 Patients with MFS at 3 Years Aortic Dimension Baseline Follow-up Growth Effect Size Aortic root (mm) 44.3 (42.5, 46.1) 44.9 (42.3, 47.5) 0.7 (21.0, 2.1) 0.10 Ascending aorta (mm) 25.6 (24.4, 26.9) 26.6 (25.1, 28.2) 0.9 (20.2, 2.1) 0.28 Aortic arch (mm) 21.4 (20.4, 22.4) 21.4 (20.5, 22.3) 0.0 (20.8, 0.8) 0.0 Proximal descending aorta (mm) 21.7 (20.4, 23.1) 22.0 (20.4, 23.7) 0.3 (20.4, 1.1) 0.08 Aorta at level of diaphragm (mm) 18.0 (17.2, 18.9) 18.4 (17.6, 19.3) 0.4 (20.2, 0.9) 0.16 Abdominal aorta (mm) 15.0 (13.4, 16.5) 15.4 (13.8, 17.6) 0.4 (20.6, 1.4) 0.11 Mean aortic diameter (mm) 24.3 (23.3, 25.2) 24.6 (23.6, 25.7) 0.4 (0.0, 0.9) 0.13 Aortic volume (ml) 203 (183, 224) 220 (194, 246) 17 (8, 26) 0.29 Note. Data are means, with 95% CIs in parentheses. are needed to assess the predictive value of aortic volume on complications such as dissection beyond the aortic root. To our knowledge, reference values for total aortic volume have not been established before in the literature. Therefore, the main limitation of our study was the absence of an independent reference standard for aortic volume. Furthermore, a control group of seven individuals for calculation of aortic volume is very small. In conclusion, total aortic volume measurement is a highly reproducible method that may be useful for surveillance of global aortic expansion in patients with MFS. Acknowledgment: The authors would like to thank 3Mensio Medical Imaging, suppliers of the semiautomated vessel analysis software. Disclosures of Conflicts of Interest: A.W.d.H. Financial activities related to the present article: grant from the Netherlands Heart Institute. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. R.F. No relevant conflicts of interest to disclose. P.d.W. No relevant conflicts of interest to disclose. T.R. No relevant conflicts of interest to disclose. H.A.M No relevant conflicts of interest to disclose. W.E.v.d.S. No relevant conflicts of interest to disclose. J.T. No relevant conflicts of interest to disclose. A.J.S. No relevant conflicts of interest to disclose. M.P.v.d.B. No relevant conflicts of interest to disclose. A.H.Z. No relevant conflicts of interest to disclose. B.J.M.M. No relevant conflicts of interest to disclose. M.G. No relevant conflicts of interest to disclose. Table 5 Aortic Volume in 81 Patients with and without Aortic Root Replacement Variable Aortic Root Replacement Yes (n = 20) No (n = 61) Age (y) No. of men 13 (65)* 30 (49)*.219 Aortic volume (ml) 257 (224, 289) 223 (208, 237).057 Aortic volume normalized for BSA (ml/m 2 ) 127 (109, 145) 112 (105, 118).040 Mean aortic diameter (mm) 25.2 (23.9, 26.6) 25.9 (25.2, 26.6).362 Mean aortic diameter normalized for BSA (mm/m 2 ) 12.5 (11.6, 13.5) 13.1 (12.7, 13.5).238 Note. Unless otherwise indicated data are means, with 95% CIs in parentheses. * Data in parentheses are percentages. P Value References 1. Judge DP, Dietz HC. Marfan s syndrome. Lancet 2005;366(9501): Chan YC, Ting CW, Ho P, Poon JT, Cheung GC, Cheng SW. Ten-year epidemiological review of in-hospital patients with Marfan syndrome. Ann Vasc Surg 2008;22(5): Murdoch JL, Walker BA, Halpern BL, Kuzma JW, McKusick VA. Life expectancy and causes of death in the Marfan syndrome. N Engl J Med 1972;286(15): Jondeau G, Detaint D, Tubach F, et al. Aortic event rate in the Marfan population: a cohort study. Circulation 2012;125(2): aortic root surgery have a more complicated clinical course (7). However, complications in the aortic trajectory beyond the aortic root have proved to be very difficult to predict by measuring aortic diameters (4,9). Future studies 5. Gott VL, Greene PS, Alejo DE, et al. Replacement of the aortic root in patients with Marfan s syndrome. N Engl J Med 1999;340(17): radiology.rsna.org n Radiology: Volume 269: Number 2 November 2013

8 6. Gott VL, Cameron DE, Alejo DE, et al. Aortic root replacement in 271 Marfan patients: a 24-year experience. Ann Thorac Surg 2002;73(2): Engelfriet PM, Boersma E, Tijssen JG, Bouma BJ, Mulder BJ. Beyond the root: dilatation of the distal aorta in Marfan s syndrome. Heart 2006;92(9): Kauffmann C, Tang A, Therasse E, et al. Measurements and detection of abdominal aortic aneurysm growth: Accuracy and reproducibility of a segmentation software. Eur J Radiol 2012;81(8): Trimarchi S, Jonker FH, Hutchison S, et al. Descending aortic diameter of 5.5 cm or greater is not an accurate predictor of acute type B aortic dissection. J Thorac Cardiovasc Surg 2011;142(3):e101 e Radonic T, de Witte P, Baars MJ, et al. Losartan therapy in adults with Marfan syndrome: study protocol of the multi-center randomized controlled COMPARE trial. Trials 2010;11: De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet 1996;62(4): van Prehn J, van der Wal MB, Vincken K, Bartels LW, Moll FL, van Herwaarden JA. Intra- and interobserver variability of aortic aneurysm volume measurement with fast CTA postprocessing software. J Endovasc Ther 2008;15(5): Kauffmann C, Tang A, Dugas A, Therasse E, Oliva V, Soulez G. Clinical validation of a software for quantitative follow-up of abdominal aortic aneurysm maximal diameter and growth by CT angiography. Eur J Radiol 2011;77(3): Wever JJ, Blankensteijn JD, Th M Mali WP, Eikelboom BC. Maximal aneurysm diameter follow-up is inadequate after endovascular abdominal aortic aneurysm repair. Eur J Vasc Endovasc Surg 2000;20(2): Parr A, Jayaratne C, Buttner P, Golledge J. Comparison of volume and diameter measurement in assessing small abdominal aortic aneurysm expansion examined using computed tomographic angiography. Eur J Radiol 2011;79(1): Baumgartner H, Bonhoeffer P, De Groot NM, et al. ESC Guidelines for the management of grown-up congenital heart disease (new version 2010). Eur Heart J 2010;31(23): Hiratzka LF, Bakris GL, Beckman JA, et al ACCF/AHA/AATS/ACR/ASA/SCA/ SCAI/SIR/STS/SVM Guidelines for the diagnosis and management of patients with thoracic aortic disease. A Report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology,American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons,and Society for Vascular Medicine. J Am Coll Cardiol 2010;55(14):e27 e129. Radiology: Volume 269: Number 2 November 2013 n radiology.rsna.org 377