Ascending aorta dilatation rates in patients with tricuspid and bicuspid aortic stenosis: the COFRASA/GENERAC study

Ascending aorta dilatation rates in patients with tricuspid and bicuspid aortic stenosis: the... Abstract Background Ascending aorta (AA) dilatation is common in aortic valve stenosis (AS) but data regarding AA progression, its determinants and impact of valve anatomy [bicuspid (BAV), or tricuspid (TAV)] are scarce. Methods and Results Asymptomatic AS patients enrolled in a prospective cohort (COFRASA/GENERAC) with at least 2 years of follow-up were considered in the present analysis. A transthoracic echocardiography (TTE) and a computed tomography (CT) scan were performed at inclusion and yearly thereafter. We enrolled 195 patients [mean gradient 22 ± 11 mmHg, 42 BAV patients (22%)]. Mean aorta diameters assessed using TTE were 35 ± 4 and 36 ± 5 mm at the sinuses of Valsalva and tubular level, respectively. Ascending aorta diameter was >40 mm in 29% of patients (24% in TAV vs. 52% in BAV, P < 0.01). Determinants of AA diameters were age, sex, BSA, and BAV, but not AS severity. After a mean follow-up of 3.8 ± 1.5years, AA enlargement rate assessed using TTE was +0.18 ± 0.34 mm/year and +0.36 ± 0.54 mm/year at the Valsalva and tubular level, respectively. Determinants of the progression of AA size were smaller AA diameter (P < 0.01) but not baseline AS severity or valve anatomy (all P > 0.05). Only four patients presented an AA progression ≥2 mm/year. Correlations between TTE and CT scan were excellent (all r >0.74) and similar results were obtained using CT. During follow-up, two BAV patients underwent a combined AA surgery; no surgery was primarily performed for AA aneurysm and no dissection was observed. Conclusion In this prospective cohort of AS patients determinants of AA diameters were age, sex, BSA, and valve anatomy but not AS severity. AA progression rates were low and not influenced by AS severity or valve anatomy. aortic stenosis , ascending aorta , echocardiography , computed tomography Introduction Aortic valve stenosis (AS) is the most common valvular heart disease in Western countries.1 Aortic valve stenosis affects 2–7% of the population aged over 70 years, and its prevalence is going to dramatically increase with the ageing of the population.2 Ascending aorta (AA) enlargement is a common feature in AS patients, especially in those with bicuspid aortic valve (BAV). According to the current guidelines, a combined AA surgery at the same time than the valve surgery is recommended at significantly lower threshold (45 mm) than for isolated ascending aorta aneurysm (55 mm).3 The rational for this strategy is that AA will progress over years and that a preventive combined surgery will prevent the need for a second intervention. However a combined AA replacement is associated with an increase surgical morbidity and mortality4 and the natural history of the AA progression in patients with AS, by far the most common indication for valve replacement is poorly known. These gaps are even further crucial to address as transcatheter aortic valve replacement (TAVR) has profoundly change the clinical management of AS patients and indications will extend in the near future to intermediate- risk and possibly low-risk patients.5 Thus, the aims of this study were to evaluate the determinants of AA size and of its enlargement in patients with AS and more specifically to assess the impact of AS severity and valve anatomy. Methods Study design Patients with degenerative AS enrolled between November 2006 and February 2015 in the COFRASA/GENERAC cohort (clinicalTrial.gov number NCT00338676 and NCT00647088) which aimed to evaluate the determinants of AS occurrence and progression and with at least 2 years of follow-up constituted our study population. Inclusion criteria were pure, at least mild (defined by a mean pressure gradient (MPG) ≥10 mm Hg and aortic valve structural changes (thickening/calcification)] asymptomatic AS (patients had to be free of dyspnoea, angina and chest pain). Exclusion criteria were AS due to rheumatic disease or radiotherapy, previous infective endocarditis, more than mild coexisting aortic regurgitation (defined by a vena contracta width ≥3 mm or a regurgitant volume ≥30 mL), associated valvular disease or severe renal insufficiency (creatinine clearance ≤30 mL/min). All patients underwent, the same day, a clinical evaluation, a transthoracic echocardiography (TTE) and a multi-slice computed tomography (MSCT) at inclusion and yearly thereafter blinded of each other. Our regional ethic committee approved the study and all patients gave a written informed consent. Echocardiography All echocardiographies were performed at baseline and on yearly basis by one single trained echographer (D.M.-Z). The AA was measured at the sinuses of Valsalva and at the tubular portion, according to the American Society of Echocardiography and the European Association of Cardiovascular Imaging recommendations,6,7 i.e. in end-diastole (onset of the QRS) from the leading edge of the anterior aortic wall to the leading edge of the posterior aortic wall, on the parasternal long-axis view, perpendicular to the long axis of the aorta (Figure 1). We subsequently indexed the AA size to the body surface area (BSA). AS severity was assessed by MPG, aortic peak velocity (PV), and aortic valve area (AVA) calculated by continuity equation, secondarily indexed to the BSA (AVAi).8 Mild AS was defined as a MPG <20 mmHg, moderate AS as a MPG between 20 and 40 mmHg, and severe AS as a MPG ≥40 mmHg. Aortic valvular anatomy (bicuspid or trileaflet) was determined using TTE at inclusion in a parasternal short axis view. Figure 1 View largeDownload slide Parasternal long-axis view illustrating measurement of the ascending aorta at the sinuses of Valsalva and tubular level at end-diastole (leading edge–to–leading-edge method) using transthoracic echocardiography. Figure 1 View largeDownload slide Parasternal long-axis view illustrating measurement of the ascending aorta at the sinuses of Valsalva and tubular level at end-diastole (leading edge–to–leading-edge method) using transthoracic echocardiography. MSCT measurements Multi-slice computed tomography was performed at baseline and yearly thereafter the same day than TTE using a Philips scanner (MX 8000 IDT 16, Phillips Medical Systems, Andover, MA, USA) or a General Electric scanner (Light speed VCTTM, General Electric Company, Fairfield, Connecticut, USA). All MSCT were electrocardiogram-gated without contrast enhancement or any B-blockers use. Ascending aorta size was measured by one single experienced radiologist (N.P.) blinded from TTE measurements. According to the European Association of Cardiovascular Imaging recommendations,6 AA was measured from inner edge to inner edge. At the level of the sinuses of Valsalva, four diameters were measured, three from a short axis view: diameter from the left coronary cusp (LCC) to the right coronary cusp (RCC) (Valsalva 1), diameter from the left coronary cusp (LCC) to the non-coronary cusp (NCC) (Valsalva 2), and diameter from the right coronary cusp (RCC) to the non-coronary cusp (NCC) (Valsalva 3). The fourth diameter of the sinuses was measured in a 3-chambers view (Valsalva 4). The tubular ascending aorta was measured on a plane strictly perpendicular to the main axis of the aorta, at the larger AA level. MSCT measurements are illustrated in Figure 2. Figure 2 View largeDownload slide Ascending aorta measured by MSCT according to the American Society of Echocardiography and the European Association of Cardiovascular Imaging 2015. (A and C): diameters at the level of the sinuses of Valsalva. (B) Diameter at the level of tubular aorta. (D) Example of a bicuspid aortic valve. Figure 2 View largeDownload slide Ascending aorta measured by MSCT according to the American Society of Echocardiography and the European Association of Cardiovascular Imaging 2015. (A and C): diameters at the level of the sinuses of Valsalva. (B) Diameter at the level of tubular aorta. (D) Example of a bicuspid aortic valve. Statistical analysis Categorical variables were expressed as number of patients (per cent) and analysed with the χ2 test or Fisher exact test. Continuous variables were expressed as mean ± standard deviation or median and 25–75th percentile for non-normally distributed variables and analysed using the Student’s t-test or the Mann–Whitney–Wilcoxon test as appropriate. Correlation between TTE and MSCT measurements was calculated using Pearson correlation coefficient. Aortic aneurysm was defined as an aorta diameter ≥40 mm (at the sinuses or at the tubular level). Yearly AA enlargement rate (in mm/year) was calculated as: final AA diameter—baseline AA diameter/follow-up duration. Enlargement rate was calculated at the level of the sinuses of Valsalva and at the level of the tubular aorta for both TTE and MSCT. Based on previous studies9,10 and on the upper tertile of tubular progression rate in our study population, rapid progression was defined as AA enlargement rate  ≥ +0.50 mm/year. Linear regressions in univariate analysis and in multivariate analysis after adjustment for age, gender, valve anatomy (bicuspid or trileaflet aortic valve) and baseline AS severity were performed to assess the determinants of AA size and enlargement. A P-value <0.05 was considered statistically significant. All the statistical analyses used JMP 9 software. Results Baseline characteristics Among the 374 asymptomatic AS patients enrolled between November 2006 and February 2015, 58 patients did not yet reach the 2 years visit, 62 were operated on within 2 years and 59 refused to remain in the study or were lost of follow-up. Thus, 195 patients with at least 2 years of follow-up constituted our study population. Most patients were men (n = 147, 75%) and mean age was 72 ± 9 years. Mean MPG was 22 ± 11 mmHg; 99 patients (51%) had mild AS, 82 (42%) moderate, and 14 patients (7%) severe AS. Aortic valve was tricuspid in 153 patients (78%) and bicuspid in 42 (22%). Most patients had normal systolic function and mean LVEF was 64 ± 4%. Characteristics of the population are presented in Table 1 (left part). Table 1 Baseline characteristics of the population and progression overall, according to the size of the ascending aorta above or below 40 mm (at the Valsalva and/or tubular level) and according to the progression rate of the ascending aorta   Overall (N = 195)  AA size <40 mm (N = 138)  AA size ≥40 mm (N = 57)  P-value  AA progression rate <0.5 mm/ year (n = 130)  AA progression rate ≥0.5 mm/ year (n = 65)  P-value  Age (years)  72 ± 9  72 ± 9  72 ± 9  0.82  72 ± 10  74 ± 8  0.16  Sex (male)  147 (75%)  98 (71%)  49 (86%)  0.03  98 (75%)  49 (75%)  0.99  Body mass index (kg/m2)  28 ± 5  28 ± 5  28 ± 5  0.97  28 ± 5  28 ± 6  0.89  Body surface area (m2)  1.9 ± 0.2  1.9 ± 0.2  2.0 ± 0.2  0.04  1.9 ± 0.2  1.9 ± 0.2  0.81  Treated hypertension  128 (66%)  87 (63%)  41 (72%)  0.23  85 (65%)  43 (66%)  0.92  Smoking  93 (48%)  64 (46%)  29 (51%)  0.57  63 (48%)  30 (46%)  0.76  Aortic severity                 Mean pressure gradient (mmHg)  22 ± 11  22 ± 12  23 ± 11  0.19  22 ± 11  24 ± 13  0.06   Peak velocity (cm/s)  297 ± 65  294 ± 66  305 ± 64  0.21  293 ± 61  305 ± 73  0.14   Aortic valve area (cm2)  1.43 ± 0.39  1.39 ± 0.35  1.55 ± 0.46  0.03  1.45 ± 0.39  1.39 ± 0.40  0.22   Indexed aortic valve area (cm2/m2)  0.75 ± 0.20  0.74 ± 0.17  0.80 ± 0.23  0.22  0.77 ± 0.19  0.73 ± 0.20  0.20  Mild aortic stenosis  99 (51%)  72 (52%)  27 (47%)  0.77  72 (55%)  27 (42%)  0.18  Moderate aortic stenosis  82 (42%)  57 (41%)  25 (44%)  0.77  50 (38%)  32 (49%)  0.18  Severe aortic stenosis  14 (7%)  9 (7%)  5 (9%)  0.77  8 (6%)  6 (9%)  0.18  Bicuspid aortic valve  42 (22%)  20 (15%)  22 (39%)  <0.01  30 (23%)  12 (19%)  0.49  Left ventricle ejection fraction (%)  64 ± 4  64 ± 5  64 ± 3  0.45  64 ± 5  64 ± 4  0.49  Ascending aorta—echocardiography (mm)                 Valsalva  35.3 ± 3.9  33.8 ± 3.1  38.9 ± 3.4  <0.01  35.7 ± 4.0  34.5 ± 3.7  0.02   Tubular aorta  36.2 ± 4.5  34.1 ± 3.0  41.1 ± 3.7  <0.01  36.6 ± 4.5  35.4 ± 4.5  0.07  Ascending aorta—computed tomography (mm)                 Valsalva 1  36.0 ± 4.2  34.7 ± 3.5  39.1 ± 4.1  <0.01  36.0 ± 4.2  35.8 ± 4.2  0.81   Valsalva 2  35.8 ± 4.0  34.3 ± 3.3  39.3 ± 3.4  <0.01  35.9 ± 4.1  35.4 ± 3.8  0.50   Valsalva 3  34.9 ± 4.1  33.5 ± 3.3  38.5 ± 3.7  <0.01  35.0 ± 4.2  34.6 ± 3.8  0.49   Valsalva 4  34.1 ± 3.8  32.8 ± 3.1  37.3 ± 3.4  <0.01  34.2 ± 3.8  33.8 ± 3.6  0.60   Tubular aorta  37.7 ± 4.3  35.8 ± 2.9  42.2 ± 4.0  <0.01  37.5 ± 4.1  37.8 ± 4.7  0.84  Aortic stenosis progression                 Mean pressure gradient progression (mmHg/year)  +3.1 ± 3.0  +3.1 ± 2.9  +3.0 ± 3.2  0.70  +2.6 ± 2.8  +4.0 ± 3.3  <0.01   Peak velocity progression (cm/s/year)  +15.6 ± 13.8  +16.2 ± 14.4  +14.2 ± 12.3  0.53  +13 ± 13  +20 ± 14  <0.01   AVA progression (cm2/year)  −0.08 ± 0.07  −0.08 ± 0.06  −0.09 ± 0.08  0.31  −0.08 ± 0.07  −0.09 ± 0.07  0.11  Ascending aorta progression— echocardiography (mm/year)                 Valsalva  +0.18 ± 0.34  +0.18 ± 0.32  +0.20 ± 0.40  0.86  +0.07 ± 0.13  +0.42 ± 0.48  <0.01   Tubular aorta  +0.36 ± 0.54  +0.39 ± 0.56  +0.27 ± 0.46  0.14  +0.10 ± 0.15  +0.88 ± 0.65  <0.01  Ascending aorta progression—computed tomography (mm/year)                 Valsalva 1  +0.30 ± 0.50  +0.26 ± 0.44  +0.40 ± 0.61  0.18  +0.32 ± 0.52  +0.26 ± 0.46  0.39   Valsalva 2  +0.26 ± 0.48  +0.27 ± 0.47  +0.23 ± 0.51  0.18  +0.24 ± 0.45  +0.31 ± 0.54  0.40   Valsalva 3  +0.20 ± 0.38  +0.23 ± 0.42  +0.14 ± 0.22  0.26  +0.17 ± 0.32  +0.27 ± 0.47  0.55   Valsalva 4  +0.17 ± 0.28  +0.16 ± 0.27  +0.19 ± 0.30  0.84  +0.18 ± 0.28  +0.14 ± 0.27  0.18   Tubular aorta  +0.16 ± 0.21  +0.17 ± 0.22  +0.13 ± 0.19  0.19  +0.14 ± 0.19  +0.21 ± 0.25  0.07    Overall (N = 195)  AA size <40 mm (N = 138)  AA size ≥40 mm (N = 57)  P-value  AA progression rate <0.5 mm/ year (n = 130)  AA progression rate ≥0.5 mm/ year (n = 65)  P-value  Age (years)  72 ± 9  72 ± 9  72 ± 9  0.82  72 ± 10  74 ± 8  0.16  Sex (male)  147 (75%)  98 (71%)  49 (86%)  0.03  98 (75%)  49 (75%)  0.99  Body mass index (kg/m2)  28 ± 5  28 ± 5  28 ± 5  0.97  28 ± 5  28 ± 6  0.89  Body surface area (m2)  1.9 ± 0.2  1.9 ± 0.2  2.0 ± 0.2  0.04  1.9 ± 0.2  1.9 ± 0.2  0.81  Treated hypertension  128 (66%)  87 (63%)  41 (72%)  0.23  85 (65%)  43 (66%)  0.92  Smoking  93 (48%)  64 (46%)  29 (51%)  0.57  63 (48%)  30 (46%)  0.76  Aortic severity                 Mean pressure gradient (mmHg)  22 ± 11  22 ± 12  23 ± 11  0.19  22 ± 11  24 ± 13  0.06   Peak velocity (cm/s)  297 ± 65  294 ± 66  305 ± 64  0.21  293 ± 61  305 ± 73  0.14   Aortic valve area (cm2)  1.43 ± 0.39  1.39 ± 0.35  1.55 ± 0.46  0.03  1.45 ± 0.39  1.39 ± 0.40  0.22   Indexed aortic valve area (cm2/m2)  0.75 ± 0.20  0.74 ± 0.17  0.80 ± 0.23  0.22  0.77 ± 0.19  0.73 ± 0.20  0.20  Mild aortic stenosis  99 (51%)  72 (52%)  27 (47%)  0.77  72 (55%)  27 (42%)  0.18  Moderate aortic stenosis  82 (42%)  57 (41%)  25 (44%)  0.77  50 (38%)  32 (49%)  0.18  Severe aortic stenosis  14 (7%)  9 (7%)  5 (9%)  0.77  8 (6%)  6 (9%)  0.18  Bicuspid aortic valve  42 (22%)  20 (15%)  22 (39%)  <0.01  30 (23%)  12 (19%)  0.49  Left ventricle ejection fraction (%)  64 ± 4  64 ± 5  64 ± 3  0.45  64 ± 5  64 ± 4  0.49  Ascending aorta—echocardiography (mm)                 Valsalva  35.3 ± 3.9  33.8 ± 3.1  38.9 ± 3.4  <0.01  35.7 ± 4.0  34.5 ± 3.7  0.02   Tubular aorta  36.2 ± 4.5  34.1 ± 3.0  41.1 ± 3.7  <0.01  36.6 ± 4.5  35.4 ± 4.5  0.07  Ascending aorta—computed tomography (mm)                 Valsalva 1  36.0 ± 4.2  34.7 ± 3.5  39.1 ± 4.1  <0.01  36.0 ± 4.2  35.8 ± 4.2  0.81   Valsalva 2  35.8 ± 4.0  34.3 ± 3.3  39.3 ± 3.4  <0.01  35.9 ± 4.1  35.4 ± 3.8  0.50   Valsalva 3  34.9 ± 4.1  33.5 ± 3.3  38.5 ± 3.7  <0.01  35.0 ± 4.2  34.6 ± 3.8  0.49   Valsalva 4  34.1 ± 3.8  32.8 ± 3.1  37.3 ± 3.4  <0.01  34.2 ± 3.8  33.8 ± 3.6  0.60   Tubular aorta  37.7 ± 4.3  35.8 ± 2.9  42.2 ± 4.0  <0.01  37.5 ± 4.1  37.8 ± 4.7  0.84  Aortic stenosis progression                 Mean pressure gradient progression (mmHg/year)  +3.1 ± 3.0  +3.1 ± 2.9  +3.0 ± 3.2  0.70  +2.6 ± 2.8  +4.0 ± 3.3  <0.01   Peak velocity progression (cm/s/year)  +15.6 ± 13.8  +16.2 ± 14.4  +14.2 ± 12.3  0.53  +13 ± 13  +20 ± 14  <0.01   AVA progression (cm2/year)  −0.08 ± 0.07  −0.08 ± 0.06  −0.09 ± 0.08  0.31  −0.08 ± 0.07  −0.09 ± 0.07  0.11  Ascending aorta progression— echocardiography (mm/year)                 Valsalva  +0.18 ± 0.34  +0.18 ± 0.32  +0.20 ± 0.40  0.86  +0.07 ± 0.13  +0.42 ± 0.48  <0.01   Tubular aorta  +0.36 ± 0.54  +0.39 ± 0.56  +0.27 ± 0.46  0.14  +0.10 ± 0.15  +0.88 ± 0.65  <0.01  Ascending aorta progression—computed tomography (mm/year)                 Valsalva 1  +0.30 ± 0.50  +0.26 ± 0.44  +0.40 ± 0.61  0.18  +0.32 ± 0.52  +0.26 ± 0.46  0.39   Valsalva 2  +0.26 ± 0.48  +0.27 ± 0.47  +0.23 ± 0.51  0.18  +0.24 ± 0.45  +0.31 ± 0.54  0.40   Valsalva 3  +0.20 ± 0.38  +0.23 ± 0.42  +0.14 ± 0.22  0.26  +0.17 ± 0.32  +0.27 ± 0.47  0.55   Valsalva 4  +0.17 ± 0.28  +0.16 ± 0.27  +0.19 ± 0.30  0.84  +0.18 ± 0.28  +0.14 ± 0.27  0.18   Tubular aorta  +0.16 ± 0.21  +0.17 ± 0.22  +0.13 ± 0.19  0.19  +0.14 ± 0.19  +0.21 ± 0.25  0.07  AA, ascending aorta; AVA, aortic valve area. Table 1 Baseline characteristics of the population and progression overall, according to the size of the ascending aorta above or below 40 mm (at the Valsalva and/or tubular level) and according to the progression rate of the ascending aorta   Overall (N = 195)  AA size <40 mm (N = 138)  AA size ≥40 mm (N = 57)  P-value  AA progression rate <0.5 mm/ year (n = 130)  AA progression rate ≥0.5 mm/ year (n = 65)  P-value  Age (years)  72 ± 9  72 ± 9  72 ± 9  0.82  72 ± 10  74 ± 8  0.16  Sex (male)  147 (75%)  98 (71%)  49 (86%)  0.03  98 (75%)  49 (75%)  0.99  Body mass index (kg/m2)  28 ± 5  28 ± 5  28 ± 5  0.97  28 ± 5  28 ± 6  0.89  Body surface area (m2)  1.9 ± 0.2  1.9 ± 0.2  2.0 ± 0.2  0.04  1.9 ± 0.2  1.9 ± 0.2  0.81  Treated hypertension  128 (66%)  87 (63%)  41 (72%)  0.23  85 (65%)  43 (66%)  0.92  Smoking  93 (48%)  64 (46%)  29 (51%)  0.57  63 (48%)  30 (46%)  0.76  Aortic severity                 Mean pressure gradient (mmHg)  22 ± 11  22 ± 12  23 ± 11  0.19  22 ± 11  24 ± 13  0.06   Peak velocity (cm/s)  297 ± 65  294 ± 66  305 ± 64  0.21  293 ± 61  305 ± 73  0.14   Aortic valve area (cm2)  1.43 ± 0.39  1.39 ± 0.35  1.55 ± 0.46  0.03  1.45 ± 0.39  1.39 ± 0.40  0.22   Indexed aortic valve area (cm2/m2)  0.75 ± 0.20  0.74 ± 0.17  0.80 ± 0.23  0.22  0.77 ± 0.19  0.73 ± 0.20  0.20  Mild aortic stenosis  99 (51%)  72 (52%)  27 (47%)  0.77  72 (55%)  27 (42%)  0.18  Moderate aortic stenosis  82 (42%)  57 (41%)  25 (44%)  0.77  50 (38%)  32 (49%)  0.18  Severe aortic stenosis  14 (7%)  9 (7%)  5 (9%)  0.77  8 (6%)  6 (9%)  0.18  Bicuspid aortic valve  42 (22%)  20 (15%)  22 (39%)  <0.01  30 (23%)  12 (19%)  0.49  Left ventricle ejection fraction (%)  64 ± 4  64 ± 5  64 ± 3  0.45  64 ± 5  64 ± 4  0.49  Ascending aorta—echocardiography (mm)                 Valsalva  35.3 ± 3.9  33.8 ± 3.1  38.9 ± 3.4  <0.01  35.7 ± 4.0  34.5 ± 3.7  0.02   Tubular aorta  36.2 ± 4.5  34.1 ± 3.0  41.1 ± 3.7  <0.01  36.6 ± 4.5  35.4 ± 4.5  0.07  Ascending aorta—computed tomography (mm)                 Valsalva 1  36.0 ± 4.2  34.7 ± 3.5  39.1 ± 4.1  <0.01  36.0 ± 4.2  35.8 ± 4.2  0.81   Valsalva 2  35.8 ± 4.0  34.3 ± 3.3  39.3 ± 3.4  <0.01  35.9 ± 4.1  35.4 ± 3.8  0.50   Valsalva 3  34.9 ± 4.1  33.5 ± 3.3  38.5 ± 3.7  <0.01  35.0 ± 4.2  34.6 ± 3.8  0.49   Valsalva 4  34.1 ± 3.8  32.8 ± 3.1  37.3 ± 3.4  <0.01  34.2 ± 3.8  33.8 ± 3.6  0.60   Tubular aorta  37.7 ± 4.3  35.8 ± 2.9  42.2 ± 4.0  <0.01  37.5 ± 4.1  37.8 ± 4.7  0.84  Aortic stenosis progression                 Mean pressure gradient progression (mmHg/year)  +3.1 ± 3.0  +3.1 ± 2.9  +3.0 ± 3.2  0.70  +2.6 ± 2.8  +4.0 ± 3.3  <0.01   Peak velocity progression (cm/s/year)  +15.6 ± 13.8  +16.2 ± 14.4  +14.2 ± 12.3  0.53  +13 ± 13  +20 ± 14  <0.01   AVA progression (cm2/year)  −0.08 ± 0.07  −0.08 ± 0.06  −0.09 ± 0.08  0.31  −0.08 ± 0.07  −0.09 ± 0.07  0.11  Ascending aorta progression— echocardiography (mm/year)                 Valsalva  +0.18 ± 0.34  +0.18 ± 0.32  +0.20 ± 0.40  0.86  +0.07 ± 0.13  +0.42 ± 0.48  <0.01   Tubular aorta  +0.36 ± 0.54  +0.39 ± 0.56  +0.27 ± 0.46  0.14  +0.10 ± 0.15  +0.88 ± 0.65  <0.01  Ascending aorta progression—computed tomography (mm/year)                 Valsalva 1  +0.30 ± 0.50  +0.26 ± 0.44  +0.40 ± 0.61  0.18  +0.32 ± 0.52  +0.26 ± 0.46  0.39   Valsalva 2  +0.26 ± 0.48  +0.27 ± 0.47  +0.23 ± 0.51  0.18  +0.24 ± 0.45  +0.31 ± 0.54  0.40   Valsalva 3  +0.20 ± 0.38  +0.23 ± 0.42  +0.14 ± 0.22  0.26  +0.17 ± 0.32  +0.27 ± 0.47  0.55   Valsalva 4  +0.17 ± 0.28  +0.16 ± 0.27  +0.19 ± 0.30  0.84  +0.18 ± 0.28  +0.14 ± 0.27  0.18   Tubular aorta  +0.16 ± 0.21  +0.17 ± 0.22  +0.13 ± 0.19  0.19  +0.14 ± 0.19  +0.21 ± 0.25  0.07    Overall (N = 195)  AA size <40 mm (N = 138)  AA size ≥40 mm (N = 57)  P-value  AA progression rate <0.5 mm/ year (n = 130)  AA progression rate ≥0.5 mm/ year (n = 65)  P-value  Age (years)  72 ± 9  72 ± 9  72 ± 9  0.82  72 ± 10  74 ± 8  0.16  Sex (male)  147 (75%)  98 (71%)  49 (86%)  0.03  98 (75%)  49 (75%)  0.99  Body mass index (kg/m2)  28 ± 5  28 ± 5  28 ± 5  0.97  28 ± 5  28 ± 6  0.89  Body surface area (m2)  1.9 ± 0.2  1.9 ± 0.2  2.0 ± 0.2  0.04  1.9 ± 0.2  1.9 ± 0.2  0.81  Treated hypertension  128 (66%)  87 (63%)  41 (72%)  0.23  85 (65%)  43 (66%)  0.92  Smoking  93 (48%)  64 (46%)  29 (51%)  0.57  63 (48%)  30 (46%)  0.76  Aortic severity                 Mean pressure gradient (mmHg)  22 ± 11  22 ± 12  23 ± 11  0.19  22 ± 11  24 ± 13  0.06   Peak velocity (cm/s)  297 ± 65  294 ± 66  305 ± 64  0.21  293 ± 61  305 ± 73  0.14   Aortic valve area (cm2)  1.43 ± 0.39  1.39 ± 0.35  1.55 ± 0.46  0.03  1.45 ± 0.39  1.39 ± 0.40  0.22   Indexed aortic valve area (cm2/m2)  0.75 ± 0.20  0.74 ± 0.17  0.80 ± 0.23  0.22  0.77 ± 0.19  0.73 ± 0.20  0.20  Mild aortic stenosis  99 (51%)  72 (52%)  27 (47%)  0.77  72 (55%)  27 (42%)  0.18  Moderate aortic stenosis  82 (42%)  57 (41%)  25 (44%)  0.77  50 (38%)  32 (49%)  0.18  Severe aortic stenosis  14 (7%)  9 (7%)  5 (9%)  0.77  8 (6%)  6 (9%)  0.18  Bicuspid aortic valve  42 (22%)  20 (15%)  22 (39%)  <0.01  30 (23%)  12 (19%)  0.49  Left ventricle ejection fraction (%)  64 ± 4  64 ± 5  64 ± 3  0.45  64 ± 5  64 ± 4  0.49  Ascending aorta—echocardiography (mm)                 Valsalva  35.3 ± 3.9  33.8 ± 3.1  38.9 ± 3.4  <0.01  35.7 ± 4.0  34.5 ± 3.7  0.02   Tubular aorta  36.2 ± 4.5  34.1 ± 3.0  41.1 ± 3.7  <0.01  36.6 ± 4.5  35.4 ± 4.5  0.07  Ascending aorta—computed tomography (mm)                 Valsalva 1  36.0 ± 4.2  34.7 ± 3.5  39.1 ± 4.1  <0.01  36.0 ± 4.2  35.8 ± 4.2  0.81   Valsalva 2  35.8 ± 4.0  34.3 ± 3.3  39.3 ± 3.4  <0.01  35.9 ± 4.1  35.4 ± 3.8  0.50   Valsalva 3  34.9 ± 4.1  33.5 ± 3.3  38.5 ± 3.7  <0.01  35.0 ± 4.2  34.6 ± 3.8  0.49   Valsalva 4  34.1 ± 3.8  32.8 ± 3.1  37.3 ± 3.4  <0.01  34.2 ± 3.8  33.8 ± 3.6  0.60   Tubular aorta  37.7 ± 4.3  35.8 ± 2.9  42.2 ± 4.0  <0.01  37.5 ± 4.1  37.8 ± 4.7  0.84  Aortic stenosis progression                 Mean pressure gradient progression (mmHg/year)  +3.1 ± 3.0  +3.1 ± 2.9  +3.0 ± 3.2  0.70  +2.6 ± 2.8  +4.0 ± 3.3  <0.01   Peak velocity progression (cm/s/year)  +15.6 ± 13.8  +16.2 ± 14.4  +14.2 ± 12.3  0.53  +13 ± 13  +20 ± 14  <0.01   AVA progression (cm2/year)  −0.08 ± 0.07  −0.08 ± 0.06  −0.09 ± 0.08  0.31  −0.08 ± 0.07  −0.09 ± 0.07  0.11  Ascending aorta progression— echocardiography (mm/year)                 Valsalva  +0.18 ± 0.34  +0.18 ± 0.32  +0.20 ± 0.40  0.86  +0.07 ± 0.13  +0.42 ± 0.48  <0.01   Tubular aorta  +0.36 ± 0.54  +0.39 ± 0.56  +0.27 ± 0.46  0.14  +0.10 ± 0.15  +0.88 ± 0.65  <0.01  Ascending aorta progression—computed tomography (mm/year)                 Valsalva 1  +0.30 ± 0.50  +0.26 ± 0.44  +0.40 ± 0.61  0.18  +0.32 ± 0.52  +0.26 ± 0.46  0.39   Valsalva 2  +0.26 ± 0.48  +0.27 ± 0.47  +0.23 ± 0.51  0.18  +0.24 ± 0.45  +0.31 ± 0.54  0.40   Valsalva 3  +0.20 ± 0.38  +0.23 ± 0.42  +0.14 ± 0.22  0.26  +0.17 ± 0.32  +0.27 ± 0.47  0.55   Valsalva 4  +0.17 ± 0.28  +0.16 ± 0.27  +0.19 ± 0.30  0.84  +0.18 ± 0.28  +0.14 ± 0.27  0.18   Tubular aorta  +0.16 ± 0.21  +0.17 ± 0.22  +0.13 ± 0.19  0.19  +0.14 ± 0.19  +0.21 ± 0.25  0.07  AA, ascending aorta; AVA, aortic valve area. Table 2 Ascending aorta measurements using MSCT and correlation coefficient with TTE   Correlation coefficient TTE/MSCT  P-value  Difference MSCT-TTE (mm)  Valsalva 1  0.74  <0.01  +0.6 ± 0.2  Valsalva 2  0.77  0.03  +0.4 ± 0.2  Valsalva 3  0.81  0.02  −0.4 ± 0.2  Valsalva 4  0.83  <0.01  −1.2 ± 0.2  Tubular aorta  0.89  <0.01  +1.5 ± 0.2    Correlation coefficient TTE/MSCT  P-value  Difference MSCT-TTE (mm)  Valsalva 1  0.74  <0.01  +0.6 ± 0.2  Valsalva 2  0.77  0.03  +0.4 ± 0.2  Valsalva 3  0.81  0.02  −0.4 ± 0.2  Valsalva 4  0.83  <0.01  −1.2 ± 0.2  Tubular aorta  0.89  <0.01  +1.5 ± 0.2  TTE, transthoracic echocardiography; MSCT, multi-slice computed tomography. Table 2 Ascending aorta measurements using MSCT and correlation coefficient with TTE   Correlation coefficient TTE/MSCT  P-value  Difference MSCT-TTE (mm)  Valsalva 1  0.74  <0.01  +0.6 ± 0.2  Valsalva 2  0.77  0.03  +0.4 ± 0.2  Valsalva 3  0.81  0.02  −0.4 ± 0.2  Valsalva 4  0.83  <0.01  −1.2 ± 0.2  Tubular aorta  0.89  <0.01  +1.5 ± 0.2    Correlation coefficient TTE/MSCT  P-value  Difference MSCT-TTE (mm)  Valsalva 1  0.74  <0.01  +0.6 ± 0.2  Valsalva 2  0.77  0.03  +0.4 ± 0.2  Valsalva 3  0.81  0.02  −0.4 ± 0.2  Valsalva 4  0.83  <0.01  −1.2 ± 0.2  Tubular aorta  0.89  <0.01  +1.5 ± 0.2  TTE, transthoracic echocardiography; MSCT, multi-slice computed tomography. Determinants of ascending aorta size Mean AA size measured by TTE was 35.3 ± 3.9 mm (18.6 ± 2.2 mm/m2) at the sinuses of Valsalva and 36.2 ± 4.5 mm (19.1 ± 3.1 mm/m2) at the tubular level (Table 1 and Figure 3). Fifty-seven patients (29%) presented an AA diameter ≥40 mm at the Valsalva or at the tubular level (definition for aneurysm). As shown in Table 1, patients with AA aneurysms tend to be more frequently male, with larger BSA but there was no other difference in term of clinical characteristics or AS severity. Importantly, the rate of patients with BAV was significantly higher in patients with AA ≥40 mm (39% vs. 15% P < 0.01). In multivariate analysis, independent determinants of indexed AA size were age and BAV at the sinuses of Valsalva level (all P < 0.01) and age, female sex, and BAV at the tubular level (all P < 0.01). Ascending aorta size was not related to AS severity either assessed in categorical variables (P = 0.45 and P = 0.22 for Valsalva and tubular level, respectively) (Figure 4), or as a continuous variable (r <0.01, P = 0.99 between MPG and indexed Valsalva diameters; r = 0.02 and P = 0.75 between AVA and indexed Valsalva diameters; r = 0.05, P = 0.52 between MPG and indexed tubular diameters, and r = 0.09, P = 0.23 between AVA and indexed tubular diameters). Figure 3 View largeDownload slide Distribution of ascending aorta size at inclusion (at the sinuses of Valsalva in red and the tubular level in blue). Figure 3 View largeDownload slide Distribution of ascending aorta size at inclusion (at the sinuses of Valsalva in red and the tubular level in blue). Figure 4 View largeDownload slide Ascending aorta size measured by transthoracic echocardiography according to AS severity. (A) at the Valsalva level. (B) at the tubular level. Figure 4 View largeDownload slide Ascending aorta size measured by transthoracic echocardiography according to AS severity. (A) at the Valsalva level. (B) at the tubular level. Mean AA diameters measured using MSCT at the level of the Valsalva and at the tubular level, presented in Table 1, were highly correlated to TTE measurements (r between 0.74 and 0.89, all P < 0.05) and mean differences between MSCT and TTE measurements were small (–1.2 ± 0.2 to +1.5 ± 0.2 mm) (Table 2). After multivariate analysis determinants of indexed AA diameters measured using MSCT were similar: age and valve anatomy for Valsalva diameters (all P < 0.01) and age, valve anatomy and female sex for tubular diameters (all P < 0.01). Intra-observer and inter-observer variability was 1.9 ± 2.6% and 4.0 ± 5.8% (1.15 ± 0.44 mm and 1.69 ± 0.68 mm) for TTE and 3.3 ± 1.4%, and 4.8 ± 1.8% (0.64 ± 0.69 mm and 1.06 ± 1.34 mm) for MSCT measurements, respectively. Determinants of the progression of ascending aorta size After a mean follow-up of 3.8 ± 1.5 years [median 3.4 years (2.5–5.0)], the AA enlargement rate assessed using TTE was +0.18 ± 0.34 mm/year at the level of sinuses of Valsalvas and approximately twice, +0.36 ± 0.54 mm/year, at the tubular level (Figure 5). Sixty-six patients (34%) had no progression at both the sinuses of Valsalva and the tubular level, and sixty-five patients (37%) were considered as rapid progressors (progression rate ≥0.5 mm/year at either the Valsalva or tubular level). Rapid progressors were characterized by smaller aorta at baseline and a higher AS progression rate according to their PV and MPG progression rates (Table 1, right part). Among patients with initially non-dilated aorta at baseline, only 24 patients (13%) developed AA aneurysm >40 mm during follow-up. The threshold of 2 mm/year for rapid AA enlargement rate proposed in ESC guidelines was never reached at the sinuses of Valsalva and was reached in only 4 patients (2%) at the tubular level. These four patients had tricuspid aortic valve (TAV) and all but one had a small aorta at baseline (mean diameter was 34 mm at sinuses level and 31 mm at the tubular level); the other patient had 42 mm and 39 mm at the sinuses of Valsalva and at the tubular level, respectively. Figure 5 View largeDownload slide Ascending aorta progression rate measured at the Valsalva (red) and tubular levels (blue). Figure 5 View largeDownload slide Ascending aorta progression rate measured at the Valsalva (red) and tubular levels (blue). Age, gender, BSA, valve anatomy (Figure 6), and AS severity were not associated with AA enlargement rate in univariate analysis. In multivariate analysis, AA enlargement rate at the Valsalva level was associated with baseline diameters (smaller Valsalva diameters presented higher AA enlargement rate, P < 0.01) and with PV yearly progression rate (Valsalva’s enlargement rate increased with PV progression rate, P = 0.01), whereas AA enlargement rate at the tubular level was only associated with tubular diameter at baseline (smaller tubular diameter had higher AA enlargement rate, P < 0.01). Using MSCT, the only determinant of AA enlargement rate was also the AA diameters measured at baseline. Figure 6 View largeDownload slide Ascending aorta progression rate measured by transthoracic echocardiography according to the valve anatomy. (A) at the Valsalva level. (B) at the tubular level. Figure 6 View largeDownload slide Ascending aorta progression rate measured by transthoracic echocardiography according to the valve anatomy. (A) at the Valsalva level. (B) at the tubular level. Clinical outcome Forty-three patients underwent an aortic valve replacement (AVR) for severe AS. Four of them presented AA diameters ≥45 mm. Two patients underwent a TAVI due to fragile condition, and the two others—with BAV—underwent a combined aortic valve replacement and AA surgery for AA aneurysm with supra-coronary tube implantation. No aortic dissection was reported, and no surgery for AA aneurysm as primary indication was performed. Discussion In this large prospective cohort of patients with AS, AA size was independently determined by age, gender, BSA, and BAV, but not by AS severity. The mean AA enlargement rate was overall low, twice at the tubular level than at the sinuses of Valsalva, and was determined neither by AS severity nor by valve anatomy. Ascending aorta size and determinants in aortic stenosis Ascending aorta diameters measured in the present study were similar to those previously described in AS patients,11,12 and AA aneurysm was observed in one-quarter of AS patients, which is higher than its prevalence in normal subjects.13,14 Most importantly, even if AA dilatation was common in AS, AA size was not related to AS severity, which is consistent with the results described by Crawford and Roldan.11 Ascending aorta size was determined by aortic valve anatomy, with larger diameters among BAV patients. A large number of studies have previously analysed BAV-associated aortopathy, characterized by fibrilline reduction, elastin fragmentation, and increased collagen within aortic wall.15,16 Clinically, BAV patients present more frequently with AA dilatation, leading to a higher risk of life-threatening complications such as AA dissection or rupture, that hopefully remained rare thanks to early detection and treatment of these patients.17,18 For Hahn etal.19 aortic wall disease associated to BAV was more related to genetic anomalies than to hemodynamic valve dysfunction, as AA size was similar in BAV patients regardless of the aortic valve function (normal, regurgitation, or stenosis). Some studies suggested that AA size is related to the type of BAV,20,21 but this is still debated,9 and our limited population of BAV did not allowed us to draw any conclusion relative to this particular point. Finally, AA diameters were also independently associated with age, gender, and BSA, which are well-known determinants of AA size in normal subjects.22,23 One explanation for the larger diameters among older patients is that, with ageing, increased collagen production within aortic wall results in increasing AA stiffness. It is also important to mention that even if male patients presented larger absolute AA diameters, when indexed to the BSA, female sex that was associated with larger AA size. Rate of ascending aorta enlargement and determinants We found that the AA enlargement rate was overall low, using both TTE or MSCT, and similar to the AA enlargement rate (0.16 mm/year after 6 years of follow-up) observed in normal subjects.24 This AA enlargement observed in normal population seems to be an adaptive response to the aortic stiffness augmentation aiming at limiting the pulsed pressure increase.25 Moreover, we observed that AA enlargement rate in AS was twice higher at the tubular level than at the sinuses of Valsalva level. This phenotype of predominant tubular progression was primarily described in BAV population in opposition to patients with Marfan syndrome.9 In the present study, AA enlargement rate was not determined by AS severity at baseline. Detaint et al.9 also found no impact of AS severity on AA enlargement rate, although they studied only a small number of AS patients, all with BAV. However, Yasuda etal.26 observed that the AA enlargement rate was slower after AVR for AS, suggesting a possible hemodynamic impact of AS on AA enlargement rate. Moreover in our population, we found that AA enlargement rate was associated with AS yearly progression rate: patients with faster PV or MPG increase had higher AA enlargement rate, according to TTE measurements. Yet, we were not able to confirm these results when we used AVA progression rate, or MSCT diameters. Thus, these results need to be confirmed in further studies. We found that the AA enlargement rate was not determined by aortic valve anatomy. These results could be seen alongside those of La Canna etal.27 who studied consecutive transoesophageal echocardiographies in BAV and TAV patients presenting AA aneurysm and normally functioning aortic valve during a mean follow-up of 3 years. The rate of AA aneurysms progression was similar regardless of the valve anatomy. Moreover, studying 325 patients with AA aneurysm and AS followed up to 15 years after isolated AVR, Girdauskas et al.28 found that the proportion of proximal aortic redo surgery was similar in BAV and TAV patients (only 3% and 5%, respectively). Finally, the main determinant of AA enlargement rate was the AA size at baseline. Patients with smaller AA diameters had higher AA enlargement rate. This finding was previously reported.9 We are not sure whether this reflects a true phenomenon. One hypothesis is that minimal error measurements may have a greater impact in this population. Clinical implications The aim of this study was not to validate the actual proposed threshold of 45 mm for combined surgery at the time of AVR. However, given the relatively low AA progression rates observed in our AS patients, combined surgery indications should be discussed in heart team, in order to individualize this decision. It seems even more crucial given the frailty of some AS elderly patients, and the increasing number of percutaneous aortic valve replacements. Moreover, the upper limit of 2 mm/year of AA enlargement rate suggested in the European guidelines for BAV and Marfan patients3 was almost never reached in our population, suggesting that this threshold may be not appropriate in AS patients, regardless of valve anatomy. Study limitations This study has several limitations. First, this is a single-centre study, with mostly old-male patients. However, very few studies aimed at evaluating prospectively AA size and enlargement rate in AS with both BAV and TAV patients. Moreover, we prospectively included a relatively large population of 195 patients, with a wide range of AS severity. Second, a limited number of patients with severe AS (n = 14) were enrolled. The low number of patients with severe AS is explained by the fact that only patients with at least 2 years of follow-up were considered for the present study. Therefore, conclusions related to this subgroup of patients should be confirmed in larger sample. Finally, MSCT measurements were not performed with contrast enhancement. However, a major strength of this study is the use of two independent imaging modalities. Both TTE and MSCT were performed by one single trained specialist and showed similar results with excellent correlation and small variability. In addition, each measurement was performed blindly one of each other. Conclusion In this prospective study, AA size was associated with age, gender, BSA and BAV, but not with AS severity. Overall AA enlargement rates remained low, larger at the tubular than at the Valsalva level, and were not determined by AS severity or valve anatomy. Given the overall low progression of AA diameters, even for BAV patients, our results suggest individualizing the decision to perform a combined AA surgery above 45 mm at the time of AS surgery especially in elderly patients. Funding C.K. was supported by a grant from the Federation Française de Cardiologie; The COFRASA (clinicalTrial.gov number NCT 00338676) and GENERAC (clinicalTrial.gov number NCT00647088) studies are supported by grants from the Assistance Publique—Hôpitaux de Paris (PHRC National 2005 and 2010, and PHRC regional 2007). Conflict of interest: None declared. References 1 Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet  2006; 368: 1005– 11. Google Scholar CrossRef Search ADS PubMed  2 Iung B, Baron G, Butchart EG, Delahaye F, Gohlke-Barwolf C, Levang OW et al.   A prospective survey of patients with valvular heart disease in Europe: the Euro Heart Survey on Valvular Heart Disease. Eur Heart J  2003; 24: 1231– 43. Google Scholar CrossRef Search ADS PubMed  3 Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H et al.   Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J  2012; 33: 2451– 96. Google Scholar CrossRef Search ADS PubMed  4 Rankin JS, Hammill BG, Ferguson TBJr, Glower DD, O'brien SM, DeLong ER et al.   Determinants of operative mortality in valvular heart surgery. J Thorac Cardiovasc Surg  2006; 131: 547– 57. Google Scholar CrossRef Search ADS PubMed  5 Leon MB, Smith CR, Mack MJ, Makkar RR, Svensson LG, Kodali SK et al.   Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med  2016; 374: 1609– 20. Google Scholar CrossRef Search ADS PubMed  6 Goldstein SA, Evangelista A, Abbara S, Arai A, Asch FM, Badano LP et al.   Multimodality imaging of diseases of the thoracic aorta in adults: from the American Society of Echocardiography and the European Association of Cardiovascular Imaging: endorsed by the Society of Cardiovascular Computed Tomography and Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr  2015; 28: 119– 82. Google Scholar CrossRef Search ADS PubMed  7 Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L et al.   Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging  2015; 16: 233– 70. Google Scholar CrossRef Search ADS PubMed  8 Baumgartner H, Hung J, Bermejo J, Chambers JB, Evangelista A, Griffin BP et al.   Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Eur J Echocardiogr  2009; 10: 1– 25. Google Scholar CrossRef Search ADS PubMed  9 Detaint D, Michelena HI, Nkomo VT, Vahanian A, Jondeau G, Sarano ME. Aortic dilatation patterns and rates in adults with bicuspid aortic valves: a comparative study with Marfan syndrome and degenerative aortopathy. Heart  2014; 100: 126– 34. Google Scholar CrossRef Search ADS PubMed  10 Vriz O, Driussi C, Bettio M, Ferrara F, D'andrea A, Bossone E. Aortic root dimensions and stiffness in healthy subjects. Am J Cardiol  2013; 112: 1224– 9. Google Scholar CrossRef Search ADS PubMed  11 Crawford MH, Roldan CA. Prevalence of aortic root dilatation and small aortic roots in valvular aortic stenosis. Am J Cardiol  2001; 87: 1311– 3. Google Scholar CrossRef Search ADS PubMed  12 Morgan-Hughes GJ, Roobottom CA, Owens PE, Marshall AJ. Dilatation of the aorta in pure, severe, bicuspid aortic valve stenosis. Am Heart J  2004; 147: 736– 40. Google Scholar CrossRef Search ADS PubMed  13 Coady MA, Rizzo JA, Goldstein LJ, Elefteriades JA. Natural history, pathogenesis, and etiology of thoracic aortic aneurysms and dissections. Cardiol Clin  1999; 17: 615– 35; vii. Google Scholar CrossRef Search ADS PubMed  14 Roman MJ, Devereux RB, Kramer-Fox R, O'loughlin J. Two-dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol  1989; 64: 507– 12. Google Scholar CrossRef Search ADS PubMed  15 Fedak PW, Verma S, David TE, Leask RL, Weisel RD, Butany J. Clinical and pathophysiological implications of a bicuspid aortic valve. Circulation  2002; 106: 900– 4. Google Scholar CrossRef Search ADS PubMed  16 Tzemos N, Lyseggen E, Silversides C, Jamorski M, Tong JH, Harvey P et al.   Endothelial function, carotid-femoral stiffness, and plasma matrix metalloproteinase-2 in men with bicuspid aortic valve and dilated aorta. J Am Coll Cardiol  2010; 55: 660– 8. Google Scholar CrossRef Search ADS PubMed  17 Michelena HI, Khanna AD, Mahoney D, Margaryan E, Topilsky Y, Suri RM et al.   Incidence of aortic complications in patients with bicuspid aortic valves. JAMA  2011; 306: 1104– 12. Google Scholar CrossRef Search ADS PubMed  18 Tzemos N, Therrien J, Yip J, Thanassoulis G, Tremblay S, Jamorski MT et al.   Outcomes in adults with bicuspid aortic valves. JAMA  2008; 300: 1317– 25. Google Scholar CrossRef Search ADS PubMed  19 Hahn RT, Roman MJ, Mogtader AH, Devereux RB. Association of aortic dilation with regurgitant, stenotic and functionally normal bicuspid aortic valves. J Am Coll Cardiol  1992; 19: 283– 8. Google Scholar CrossRef Search ADS PubMed  20 Schaefer BM, Lewin MB, Stout KK, Gill E, Prueitt A, Byers PH et al.   The bicuspid aortic valve: an integrated phenotypic classification of leaflet morphology and aortic root shape. Heart  2008; 94: 1634– 8. Google Scholar CrossRef Search ADS PubMed  21 Thanassoulis G, Yip JW, Filion K, Jamorski M, Webb G, Siu SC et al.   Retrospective study to identify predictors of the presence and rapid progression of aortic dilatation in patients with bicuspid aortic valves. Nat Clin Pract Cardiovasc Med  2008; 5: 821– 8. Google Scholar CrossRef Search ADS PubMed  22 Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM et al.   Heart disease and stroke statistics–2011 update: a report from the American Heart Association. Circulation  2011; 123: e18– e209. Google Scholar CrossRef Search ADS PubMed  23 Vasan RS, Larson MG, Levy D. Determinants of echocardiographic aortic root size. The Framingham Heart Study. Circulation  1995; 91: 734– 40. Google Scholar CrossRef Search ADS PubMed  24 Hannuksela M, Lundqvist S, Carlberg B. Thoracic aorta–dilated or not? Scand Cardiovasc J  2006; 40: 175– 8. Google Scholar CrossRef Search ADS PubMed  25 Lam CS, Gona P, Larson MG, Aragam J, Lee DS, Mitchell GF et al.   Aortic root remodeling and risk of heart failure in the Framingham Heart study. JACC Heart Fail  2013; 1: 79– 83. Google Scholar CrossRef Search ADS PubMed  26 Yasuda H, Nakatani S, Stugaard M, Tsujita-Kuroda Y, Bando K, Kobayashi J et al.   Failure to prevent progressive dilation of ascending aorta by aortic valve replacement in patients with bicuspid aortic valve: comparison with tricuspid aortic valve. Circulation  2003; 108 (Suppl. 1): II291– 4. Google Scholar CrossRef Search ADS PubMed  27 La Canna G, Ficarra E, Tsagalau E, Nardi M, Morandini A, Chieffo A et al.   Progression rate of ascending aortic dilation in patients with normally functioning bicuspid and tricuspid aortic valves. Am J Cardiol  2006; 98: 249– 53. Google Scholar CrossRef Search ADS PubMed  28 Girdauskas E, Disha K, Borger MA, Kuntze T. Long-term prognosis of ascending aortic aneurysm after aortic valve replacement for bicuspid versus tricuspid aortic valve stenosis. J Thorac Cardiovasc Surg  2014; 147: 276– 82. Google Scholar CrossRef Search ADS PubMed  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Heart Journal – Cardiovascular Imaging Oxford University Press

Loading next page...
 
/lp/ou_press/ascending-aorta-dilatation-rates-in-patients-with-tricuspid-and-eU6qjCilOu
Publisher
Oxford University Press
Copyright
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.
ISSN
2047-2404
D.O.I.
10.1093/ehjci/jex176
Publisher site
See Article on Publisher Site

Abstract

Abstract Background Ascending aorta (AA) dilatation is common in aortic valve stenosis (AS) but data regarding AA progression, its determinants and impact of valve anatomy [bicuspid (BAV), or tricuspid (TAV)] are scarce. Methods and Results Asymptomatic AS patients enrolled in a prospective cohort (COFRASA/GENERAC) with at least 2 years of follow-up were considered in the present analysis. A transthoracic echocardiography (TTE) and a computed tomography (CT) scan were performed at inclusion and yearly thereafter. We enrolled 195 patients [mean gradient 22 ± 11 mmHg, 42 BAV patients (22%)]. Mean aorta diameters assessed using TTE were 35 ± 4 and 36 ± 5 mm at the sinuses of Valsalva and tubular level, respectively. Ascending aorta diameter was >40 mm in 29% of patients (24% in TAV vs. 52% in BAV, P < 0.01). Determinants of AA diameters were age, sex, BSA, and BAV, but not AS severity. After a mean follow-up of 3.8 ± 1.5years, AA enlargement rate assessed using TTE was +0.18 ± 0.34 mm/year and +0.36 ± 0.54 mm/year at the Valsalva and tubular level, respectively. Determinants of the progression of AA size were smaller AA diameter (P < 0.01) but not baseline AS severity or valve anatomy (all P > 0.05). Only four patients presented an AA progression ≥2 mm/year. Correlations between TTE and CT scan were excellent (all r >0.74) and similar results were obtained using CT. During follow-up, two BAV patients underwent a combined AA surgery; no surgery was primarily performed for AA aneurysm and no dissection was observed. Conclusion In this prospective cohort of AS patients determinants of AA diameters were age, sex, BSA, and valve anatomy but not AS severity. AA progression rates were low and not influenced by AS severity or valve anatomy. aortic stenosis , ascending aorta , echocardiography , computed tomography Introduction Aortic valve stenosis (AS) is the most common valvular heart disease in Western countries.1 Aortic valve stenosis affects 2–7% of the population aged over 70 years, and its prevalence is going to dramatically increase with the ageing of the population.2 Ascending aorta (AA) enlargement is a common feature in AS patients, especially in those with bicuspid aortic valve (BAV). According to the current guidelines, a combined AA surgery at the same time than the valve surgery is recommended at significantly lower threshold (45 mm) than for isolated ascending aorta aneurysm (55 mm).3 The rational for this strategy is that AA will progress over years and that a preventive combined surgery will prevent the need for a second intervention. However a combined AA replacement is associated with an increase surgical morbidity and mortality4 and the natural history of the AA progression in patients with AS, by far the most common indication for valve replacement is poorly known. These gaps are even further crucial to address as transcatheter aortic valve replacement (TAVR) has profoundly change the clinical management of AS patients and indications will extend in the near future to intermediate- risk and possibly low-risk patients.5 Thus, the aims of this study were to evaluate the determinants of AA size and of its enlargement in patients with AS and more specifically to assess the impact of AS severity and valve anatomy. Methods Study design Patients with degenerative AS enrolled between November 2006 and February 2015 in the COFRASA/GENERAC cohort (clinicalTrial.gov number NCT00338676 and NCT00647088) which aimed to evaluate the determinants of AS occurrence and progression and with at least 2 years of follow-up constituted our study population. Inclusion criteria were pure, at least mild (defined by a mean pressure gradient (MPG) ≥10 mm Hg and aortic valve structural changes (thickening/calcification)] asymptomatic AS (patients had to be free of dyspnoea, angina and chest pain). Exclusion criteria were AS due to rheumatic disease or radiotherapy, previous infective endocarditis, more than mild coexisting aortic regurgitation (defined by a vena contracta width ≥3 mm or a regurgitant volume ≥30 mL), associated valvular disease or severe renal insufficiency (creatinine clearance ≤30 mL/min). All patients underwent, the same day, a clinical evaluation, a transthoracic echocardiography (TTE) and a multi-slice computed tomography (MSCT) at inclusion and yearly thereafter blinded of each other. Our regional ethic committee approved the study and all patients gave a written informed consent. Echocardiography All echocardiographies were performed at baseline and on yearly basis by one single trained echographer (D.M.-Z). The AA was measured at the sinuses of Valsalva and at the tubular portion, according to the American Society of Echocardiography and the European Association of Cardiovascular Imaging recommendations,6,7 i.e. in end-diastole (onset of the QRS) from the leading edge of the anterior aortic wall to the leading edge of the posterior aortic wall, on the parasternal long-axis view, perpendicular to the long axis of the aorta (Figure 1). We subsequently indexed the AA size to the body surface area (BSA). AS severity was assessed by MPG, aortic peak velocity (PV), and aortic valve area (AVA) calculated by continuity equation, secondarily indexed to the BSA (AVAi).8 Mild AS was defined as a MPG <20 mmHg, moderate AS as a MPG between 20 and 40 mmHg, and severe AS as a MPG ≥40 mmHg. Aortic valvular anatomy (bicuspid or trileaflet) was determined using TTE at inclusion in a parasternal short axis view. Figure 1 View largeDownload slide Parasternal long-axis view illustrating measurement of the ascending aorta at the sinuses of Valsalva and tubular level at end-diastole (leading edge–to–leading-edge method) using transthoracic echocardiography. Figure 1 View largeDownload slide Parasternal long-axis view illustrating measurement of the ascending aorta at the sinuses of Valsalva and tubular level at end-diastole (leading edge–to–leading-edge method) using transthoracic echocardiography. MSCT measurements Multi-slice computed tomography was performed at baseline and yearly thereafter the same day than TTE using a Philips scanner (MX 8000 IDT 16, Phillips Medical Systems, Andover, MA, USA) or a General Electric scanner (Light speed VCTTM, General Electric Company, Fairfield, Connecticut, USA). All MSCT were electrocardiogram-gated without contrast enhancement or any B-blockers use. Ascending aorta size was measured by one single experienced radiologist (N.P.) blinded from TTE measurements. According to the European Association of Cardiovascular Imaging recommendations,6 AA was measured from inner edge to inner edge. At the level of the sinuses of Valsalva, four diameters were measured, three from a short axis view: diameter from the left coronary cusp (LCC) to the right coronary cusp (RCC) (Valsalva 1), diameter from the left coronary cusp (LCC) to the non-coronary cusp (NCC) (Valsalva 2), and diameter from the right coronary cusp (RCC) to the non-coronary cusp (NCC) (Valsalva 3). The fourth diameter of the sinuses was measured in a 3-chambers view (Valsalva 4). The tubular ascending aorta was measured on a plane strictly perpendicular to the main axis of the aorta, at the larger AA level. MSCT measurements are illustrated in Figure 2. Figure 2 View largeDownload slide Ascending aorta measured by MSCT according to the American Society of Echocardiography and the European Association of Cardiovascular Imaging 2015. (A and C): diameters at the level of the sinuses of Valsalva. (B) Diameter at the level of tubular aorta. (D) Example of a bicuspid aortic valve. Figure 2 View largeDownload slide Ascending aorta measured by MSCT according to the American Society of Echocardiography and the European Association of Cardiovascular Imaging 2015. (A and C): diameters at the level of the sinuses of Valsalva. (B) Diameter at the level of tubular aorta. (D) Example of a bicuspid aortic valve. Statistical analysis Categorical variables were expressed as number of patients (per cent) and analysed with the χ2 test or Fisher exact test. Continuous variables were expressed as mean ± standard deviation or median and 25–75th percentile for non-normally distributed variables and analysed using the Student’s t-test or the Mann–Whitney–Wilcoxon test as appropriate. Correlation between TTE and MSCT measurements was calculated using Pearson correlation coefficient. Aortic aneurysm was defined as an aorta diameter ≥40 mm (at the sinuses or at the tubular level). Yearly AA enlargement rate (in mm/year) was calculated as: final AA diameter—baseline AA diameter/follow-up duration. Enlargement rate was calculated at the level of the sinuses of Valsalva and at the level of the tubular aorta for both TTE and MSCT. Based on previous studies9,10 and on the upper tertile of tubular progression rate in our study population, rapid progression was defined as AA enlargement rate  ≥ +0.50 mm/year. Linear regressions in univariate analysis and in multivariate analysis after adjustment for age, gender, valve anatomy (bicuspid or trileaflet aortic valve) and baseline AS severity were performed to assess the determinants of AA size and enlargement. A P-value <0.05 was considered statistically significant. All the statistical analyses used JMP 9 software. Results Baseline characteristics Among the 374 asymptomatic AS patients enrolled between November 2006 and February 2015, 58 patients did not yet reach the 2 years visit, 62 were operated on within 2 years and 59 refused to remain in the study or were lost of follow-up. Thus, 195 patients with at least 2 years of follow-up constituted our study population. Most patients were men (n = 147, 75%) and mean age was 72 ± 9 years. Mean MPG was 22 ± 11 mmHg; 99 patients (51%) had mild AS, 82 (42%) moderate, and 14 patients (7%) severe AS. Aortic valve was tricuspid in 153 patients (78%) and bicuspid in 42 (22%). Most patients had normal systolic function and mean LVEF was 64 ± 4%. Characteristics of the population are presented in Table 1 (left part). Table 1 Baseline characteristics of the population and progression overall, according to the size of the ascending aorta above or below 40 mm (at the Valsalva and/or tubular level) and according to the progression rate of the ascending aorta   Overall (N = 195)  AA size <40 mm (N = 138)  AA size ≥40 mm (N = 57)  P-value  AA progression rate <0.5 mm/ year (n = 130)  AA progression rate ≥0.5 mm/ year (n = 65)  P-value  Age (years)  72 ± 9  72 ± 9  72 ± 9  0.82  72 ± 10  74 ± 8  0.16  Sex (male)  147 (75%)  98 (71%)  49 (86%)  0.03  98 (75%)  49 (75%)  0.99  Body mass index (kg/m2)  28 ± 5  28 ± 5  28 ± 5  0.97  28 ± 5  28 ± 6  0.89  Body surface area (m2)  1.9 ± 0.2  1.9 ± 0.2  2.0 ± 0.2  0.04  1.9 ± 0.2  1.9 ± 0.2  0.81  Treated hypertension  128 (66%)  87 (63%)  41 (72%)  0.23  85 (65%)  43 (66%)  0.92  Smoking  93 (48%)  64 (46%)  29 (51%)  0.57  63 (48%)  30 (46%)  0.76  Aortic severity                 Mean pressure gradient (mmHg)  22 ± 11  22 ± 12  23 ± 11  0.19  22 ± 11  24 ± 13  0.06   Peak velocity (cm/s)  297 ± 65  294 ± 66  305 ± 64  0.21  293 ± 61  305 ± 73  0.14   Aortic valve area (cm2)  1.43 ± 0.39  1.39 ± 0.35  1.55 ± 0.46  0.03  1.45 ± 0.39  1.39 ± 0.40  0.22   Indexed aortic valve area (cm2/m2)  0.75 ± 0.20  0.74 ± 0.17  0.80 ± 0.23  0.22  0.77 ± 0.19  0.73 ± 0.20  0.20  Mild aortic stenosis  99 (51%)  72 (52%)  27 (47%)  0.77  72 (55%)  27 (42%)  0.18  Moderate aortic stenosis  82 (42%)  57 (41%)  25 (44%)  0.77  50 (38%)  32 (49%)  0.18  Severe aortic stenosis  14 (7%)  9 (7%)  5 (9%)  0.77  8 (6%)  6 (9%)  0.18  Bicuspid aortic valve  42 (22%)  20 (15%)  22 (39%)  <0.01  30 (23%)  12 (19%)  0.49  Left ventricle ejection fraction (%)  64 ± 4  64 ± 5  64 ± 3  0.45  64 ± 5  64 ± 4  0.49  Ascending aorta—echocardiography (mm)                 Valsalva  35.3 ± 3.9  33.8 ± 3.1  38.9 ± 3.4  <0.01  35.7 ± 4.0  34.5 ± 3.7  0.02   Tubular aorta  36.2 ± 4.5  34.1 ± 3.0  41.1 ± 3.7  <0.01  36.6 ± 4.5  35.4 ± 4.5  0.07  Ascending aorta—computed tomography (mm)                 Valsalva 1  36.0 ± 4.2  34.7 ± 3.5  39.1 ± 4.1  <0.01  36.0 ± 4.2  35.8 ± 4.2  0.81   Valsalva 2  35.8 ± 4.0  34.3 ± 3.3  39.3 ± 3.4  <0.01  35.9 ± 4.1  35.4 ± 3.8  0.50   Valsalva 3  34.9 ± 4.1  33.5 ± 3.3  38.5 ± 3.7  <0.01  35.0 ± 4.2  34.6 ± 3.8  0.49   Valsalva 4  34.1 ± 3.8  32.8 ± 3.1  37.3 ± 3.4  <0.01  34.2 ± 3.8  33.8 ± 3.6  0.60   Tubular aorta  37.7 ± 4.3  35.8 ± 2.9  42.2 ± 4.0  <0.01  37.5 ± 4.1  37.8 ± 4.7  0.84  Aortic stenosis progression                 Mean pressure gradient progression (mmHg/year)  +3.1 ± 3.0  +3.1 ± 2.9  +3.0 ± 3.2  0.70  +2.6 ± 2.8  +4.0 ± 3.3  <0.01   Peak velocity progression (cm/s/year)  +15.6 ± 13.8  +16.2 ± 14.4  +14.2 ± 12.3  0.53  +13 ± 13  +20 ± 14  <0.01   AVA progression (cm2/year)  −0.08 ± 0.07  −0.08 ± 0.06  −0.09 ± 0.08  0.31  −0.08 ± 0.07  −0.09 ± 0.07  0.11  Ascending aorta progression— echocardiography (mm/year)                 Valsalva  +0.18 ± 0.34  +0.18 ± 0.32  +0.20 ± 0.40  0.86  +0.07 ± 0.13  +0.42 ± 0.48  <0.01   Tubular aorta  +0.36 ± 0.54  +0.39 ± 0.56  +0.27 ± 0.46  0.14  +0.10 ± 0.15  +0.88 ± 0.65  <0.01  Ascending aorta progression—computed tomography (mm/year)                 Valsalva 1  +0.30 ± 0.50  +0.26 ± 0.44  +0.40 ± 0.61  0.18  +0.32 ± 0.52  +0.26 ± 0.46  0.39   Valsalva 2  +0.26 ± 0.48  +0.27 ± 0.47  +0.23 ± 0.51  0.18  +0.24 ± 0.45  +0.31 ± 0.54  0.40   Valsalva 3  +0.20 ± 0.38  +0.23 ± 0.42  +0.14 ± 0.22  0.26  +0.17 ± 0.32  +0.27 ± 0.47  0.55   Valsalva 4  +0.17 ± 0.28  +0.16 ± 0.27  +0.19 ± 0.30  0.84  +0.18 ± 0.28  +0.14 ± 0.27  0.18   Tubular aorta  +0.16 ± 0.21  +0.17 ± 0.22  +0.13 ± 0.19  0.19  +0.14 ± 0.19  +0.21 ± 0.25  0.07    Overall (N = 195)  AA size <40 mm (N = 138)  AA size ≥40 mm (N = 57)  P-value  AA progression rate <0.5 mm/ year (n = 130)  AA progression rate ≥0.5 mm/ year (n = 65)  P-value  Age (years)  72 ± 9  72 ± 9  72 ± 9  0.82  72 ± 10  74 ± 8  0.16  Sex (male)  147 (75%)  98 (71%)  49 (86%)  0.03  98 (75%)  49 (75%)  0.99  Body mass index (kg/m2)  28 ± 5  28 ± 5  28 ± 5  0.97  28 ± 5  28 ± 6  0.89  Body surface area (m2)  1.9 ± 0.2  1.9 ± 0.2  2.0 ± 0.2  0.04  1.9 ± 0.2  1.9 ± 0.2  0.81  Treated hypertension  128 (66%)  87 (63%)  41 (72%)  0.23  85 (65%)  43 (66%)  0.92  Smoking  93 (48%)  64 (46%)  29 (51%)  0.57  63 (48%)  30 (46%)  0.76  Aortic severity                 Mean pressure gradient (mmHg)  22 ± 11  22 ± 12  23 ± 11  0.19  22 ± 11  24 ± 13  0.06   Peak velocity (cm/s)  297 ± 65  294 ± 66  305 ± 64  0.21  293 ± 61  305 ± 73  0.14   Aortic valve area (cm2)  1.43 ± 0.39  1.39 ± 0.35  1.55 ± 0.46  0.03  1.45 ± 0.39  1.39 ± 0.40  0.22   Indexed aortic valve area (cm2/m2)  0.75 ± 0.20  0.74 ± 0.17  0.80 ± 0.23  0.22  0.77 ± 0.19  0.73 ± 0.20  0.20  Mild aortic stenosis  99 (51%)  72 (52%)  27 (47%)  0.77  72 (55%)  27 (42%)  0.18  Moderate aortic stenosis  82 (42%)  57 (41%)  25 (44%)  0.77  50 (38%)  32 (49%)  0.18  Severe aortic stenosis  14 (7%)  9 (7%)  5 (9%)  0.77  8 (6%)  6 (9%)  0.18  Bicuspid aortic valve  42 (22%)  20 (15%)  22 (39%)  <0.01  30 (23%)  12 (19%)  0.49  Left ventricle ejection fraction (%)  64 ± 4  64 ± 5  64 ± 3  0.45  64 ± 5  64 ± 4  0.49  Ascending aorta—echocardiography (mm)                 Valsalva  35.3 ± 3.9  33.8 ± 3.1  38.9 ± 3.4  <0.01  35.7 ± 4.0  34.5 ± 3.7  0.02   Tubular aorta  36.2 ± 4.5  34.1 ± 3.0  41.1 ± 3.7  <0.01  36.6 ± 4.5  35.4 ± 4.5  0.07  Ascending aorta—computed tomography (mm)                 Valsalva 1  36.0 ± 4.2  34.7 ± 3.5  39.1 ± 4.1  <0.01  36.0 ± 4.2  35.8 ± 4.2  0.81   Valsalva 2  35.8 ± 4.0  34.3 ± 3.3  39.3 ± 3.4  <0.01  35.9 ± 4.1  35.4 ± 3.8  0.50   Valsalva 3  34.9 ± 4.1  33.5 ± 3.3  38.5 ± 3.7  <0.01  35.0 ± 4.2  34.6 ± 3.8  0.49   Valsalva 4  34.1 ± 3.8  32.8 ± 3.1  37.3 ± 3.4  <0.01  34.2 ± 3.8  33.8 ± 3.6  0.60   Tubular aorta  37.7 ± 4.3  35.8 ± 2.9  42.2 ± 4.0  <0.01  37.5 ± 4.1  37.8 ± 4.7  0.84  Aortic stenosis progression                 Mean pressure gradient progression (mmHg/year)  +3.1 ± 3.0  +3.1 ± 2.9  +3.0 ± 3.2  0.70  +2.6 ± 2.8  +4.0 ± 3.3  <0.01   Peak velocity progression (cm/s/year)  +15.6 ± 13.8  +16.2 ± 14.4  +14.2 ± 12.3  0.53  +13 ± 13  +20 ± 14  <0.01   AVA progression (cm2/year)  −0.08 ± 0.07  −0.08 ± 0.06  −0.09 ± 0.08  0.31  −0.08 ± 0.07  −0.09 ± 0.07  0.11  Ascending aorta progression— echocardiography (mm/year)                 Valsalva  +0.18 ± 0.34  +0.18 ± 0.32  +0.20 ± 0.40  0.86  +0.07 ± 0.13  +0.42 ± 0.48  <0.01   Tubular aorta  +0.36 ± 0.54  +0.39 ± 0.56  +0.27 ± 0.46  0.14  +0.10 ± 0.15  +0.88 ± 0.65  <0.01  Ascending aorta progression—computed tomography (mm/year)                 Valsalva 1  +0.30 ± 0.50  +0.26 ± 0.44  +0.40 ± 0.61  0.18  +0.32 ± 0.52  +0.26 ± 0.46  0.39   Valsalva 2  +0.26 ± 0.48  +0.27 ± 0.47  +0.23 ± 0.51  0.18  +0.24 ± 0.45  +0.31 ± 0.54  0.40   Valsalva 3  +0.20 ± 0.38  +0.23 ± 0.42  +0.14 ± 0.22  0.26  +0.17 ± 0.32  +0.27 ± 0.47  0.55   Valsalva 4  +0.17 ± 0.28  +0.16 ± 0.27  +0.19 ± 0.30  0.84  +0.18 ± 0.28  +0.14 ± 0.27  0.18   Tubular aorta  +0.16 ± 0.21  +0.17 ± 0.22  +0.13 ± 0.19  0.19  +0.14 ± 0.19  +0.21 ± 0.25  0.07  AA, ascending aorta; AVA, aortic valve area. Table 1 Baseline characteristics of the population and progression overall, according to the size of the ascending aorta above or below 40 mm (at the Valsalva and/or tubular level) and according to the progression rate of the ascending aorta   Overall (N = 195)  AA size <40 mm (N = 138)  AA size ≥40 mm (N = 57)  P-value  AA progression rate <0.5 mm/ year (n = 130)  AA progression rate ≥0.5 mm/ year (n = 65)  P-value  Age (years)  72 ± 9  72 ± 9  72 ± 9  0.82  72 ± 10  74 ± 8  0.16  Sex (male)  147 (75%)  98 (71%)  49 (86%)  0.03  98 (75%)  49 (75%)  0.99  Body mass index (kg/m2)  28 ± 5  28 ± 5  28 ± 5  0.97  28 ± 5  28 ± 6  0.89  Body surface area (m2)  1.9 ± 0.2  1.9 ± 0.2  2.0 ± 0.2  0.04  1.9 ± 0.2  1.9 ± 0.2  0.81  Treated hypertension  128 (66%)  87 (63%)  41 (72%)  0.23  85 (65%)  43 (66%)  0.92  Smoking  93 (48%)  64 (46%)  29 (51%)  0.57  63 (48%)  30 (46%)  0.76  Aortic severity                 Mean pressure gradient (mmHg)  22 ± 11  22 ± 12  23 ± 11  0.19  22 ± 11  24 ± 13  0.06   Peak velocity (cm/s)  297 ± 65  294 ± 66  305 ± 64  0.21  293 ± 61  305 ± 73  0.14   Aortic valve area (cm2)  1.43 ± 0.39  1.39 ± 0.35  1.55 ± 0.46  0.03  1.45 ± 0.39  1.39 ± 0.40  0.22   Indexed aortic valve area (cm2/m2)  0.75 ± 0.20  0.74 ± 0.17  0.80 ± 0.23  0.22  0.77 ± 0.19  0.73 ± 0.20  0.20  Mild aortic stenosis  99 (51%)  72 (52%)  27 (47%)  0.77  72 (55%)  27 (42%)  0.18  Moderate aortic stenosis  82 (42%)  57 (41%)  25 (44%)  0.77  50 (38%)  32 (49%)  0.18  Severe aortic stenosis  14 (7%)  9 (7%)  5 (9%)  0.77  8 (6%)  6 (9%)  0.18  Bicuspid aortic valve  42 (22%)  20 (15%)  22 (39%)  <0.01  30 (23%)  12 (19%)  0.49  Left ventricle ejection fraction (%)  64 ± 4  64 ± 5  64 ± 3  0.45  64 ± 5  64 ± 4  0.49  Ascending aorta—echocardiography (mm)                 Valsalva  35.3 ± 3.9  33.8 ± 3.1  38.9 ± 3.4  <0.01  35.7 ± 4.0  34.5 ± 3.7  0.02   Tubular aorta  36.2 ± 4.5  34.1 ± 3.0  41.1 ± 3.7  <0.01  36.6 ± 4.5  35.4 ± 4.5  0.07  Ascending aorta—computed tomography (mm)                 Valsalva 1  36.0 ± 4.2  34.7 ± 3.5  39.1 ± 4.1  <0.01  36.0 ± 4.2  35.8 ± 4.2  0.81   Valsalva 2  35.8 ± 4.0  34.3 ± 3.3  39.3 ± 3.4  <0.01  35.9 ± 4.1  35.4 ± 3.8  0.50   Valsalva 3  34.9 ± 4.1  33.5 ± 3.3  38.5 ± 3.7  <0.01  35.0 ± 4.2  34.6 ± 3.8  0.49   Valsalva 4  34.1 ± 3.8  32.8 ± 3.1  37.3 ± 3.4  <0.01  34.2 ± 3.8  33.8 ± 3.6  0.60   Tubular aorta  37.7 ± 4.3  35.8 ± 2.9  42.2 ± 4.0  <0.01  37.5 ± 4.1  37.8 ± 4.7  0.84  Aortic stenosis progression                 Mean pressure gradient progression (mmHg/year)  +3.1 ± 3.0  +3.1 ± 2.9  +3.0 ± 3.2  0.70  +2.6 ± 2.8  +4.0 ± 3.3  <0.01   Peak velocity progression (cm/s/year)  +15.6 ± 13.8  +16.2 ± 14.4  +14.2 ± 12.3  0.53  +13 ± 13  +20 ± 14  <0.01   AVA progression (cm2/year)  −0.08 ± 0.07  −0.08 ± 0.06  −0.09 ± 0.08  0.31  −0.08 ± 0.07  −0.09 ± 0.07  0.11  Ascending aorta progression— echocardiography (mm/year)                 Valsalva  +0.18 ± 0.34  +0.18 ± 0.32  +0.20 ± 0.40  0.86  +0.07 ± 0.13  +0.42 ± 0.48  <0.01   Tubular aorta  +0.36 ± 0.54  +0.39 ± 0.56  +0.27 ± 0.46  0.14  +0.10 ± 0.15  +0.88 ± 0.65  <0.01  Ascending aorta progression—computed tomography (mm/year)                 Valsalva 1  +0.30 ± 0.50  +0.26 ± 0.44  +0.40 ± 0.61  0.18  +0.32 ± 0.52  +0.26 ± 0.46  0.39   Valsalva 2  +0.26 ± 0.48  +0.27 ± 0.47  +0.23 ± 0.51  0.18  +0.24 ± 0.45  +0.31 ± 0.54  0.40   Valsalva 3  +0.20 ± 0.38  +0.23 ± 0.42  +0.14 ± 0.22  0.26  +0.17 ± 0.32  +0.27 ± 0.47  0.55   Valsalva 4  +0.17 ± 0.28  +0.16 ± 0.27  +0.19 ± 0.30  0.84  +0.18 ± 0.28  +0.14 ± 0.27  0.18   Tubular aorta  +0.16 ± 0.21  +0.17 ± 0.22  +0.13 ± 0.19  0.19  +0.14 ± 0.19  +0.21 ± 0.25  0.07    Overall (N = 195)  AA size <40 mm (N = 138)  AA size ≥40 mm (N = 57)  P-value  AA progression rate <0.5 mm/ year (n = 130)  AA progression rate ≥0.5 mm/ year (n = 65)  P-value  Age (years)  72 ± 9  72 ± 9  72 ± 9  0.82  72 ± 10  74 ± 8  0.16  Sex (male)  147 (75%)  98 (71%)  49 (86%)  0.03  98 (75%)  49 (75%)  0.99  Body mass index (kg/m2)  28 ± 5  28 ± 5  28 ± 5  0.97  28 ± 5  28 ± 6  0.89  Body surface area (m2)  1.9 ± 0.2  1.9 ± 0.2  2.0 ± 0.2  0.04  1.9 ± 0.2  1.9 ± 0.2  0.81  Treated hypertension  128 (66%)  87 (63%)  41 (72%)  0.23  85 (65%)  43 (66%)  0.92  Smoking  93 (48%)  64 (46%)  29 (51%)  0.57  63 (48%)  30 (46%)  0.76  Aortic severity                 Mean pressure gradient (mmHg)  22 ± 11  22 ± 12  23 ± 11  0.19  22 ± 11  24 ± 13  0.06   Peak velocity (cm/s)  297 ± 65  294 ± 66  305 ± 64  0.21  293 ± 61  305 ± 73  0.14   Aortic valve area (cm2)  1.43 ± 0.39  1.39 ± 0.35  1.55 ± 0.46  0.03  1.45 ± 0.39  1.39 ± 0.40  0.22   Indexed aortic valve area (cm2/m2)  0.75 ± 0.20  0.74 ± 0.17  0.80 ± 0.23  0.22  0.77 ± 0.19  0.73 ± 0.20  0.20  Mild aortic stenosis  99 (51%)  72 (52%)  27 (47%)  0.77  72 (55%)  27 (42%)  0.18  Moderate aortic stenosis  82 (42%)  57 (41%)  25 (44%)  0.77  50 (38%)  32 (49%)  0.18  Severe aortic stenosis  14 (7%)  9 (7%)  5 (9%)  0.77  8 (6%)  6 (9%)  0.18  Bicuspid aortic valve  42 (22%)  20 (15%)  22 (39%)  <0.01  30 (23%)  12 (19%)  0.49  Left ventricle ejection fraction (%)  64 ± 4  64 ± 5  64 ± 3  0.45  64 ± 5  64 ± 4  0.49  Ascending aorta—echocardiography (mm)                 Valsalva  35.3 ± 3.9  33.8 ± 3.1  38.9 ± 3.4  <0.01  35.7 ± 4.0  34.5 ± 3.7  0.02   Tubular aorta  36.2 ± 4.5  34.1 ± 3.0  41.1 ± 3.7  <0.01  36.6 ± 4.5  35.4 ± 4.5  0.07  Ascending aorta—computed tomography (mm)                 Valsalva 1  36.0 ± 4.2  34.7 ± 3.5  39.1 ± 4.1  <0.01  36.0 ± 4.2  35.8 ± 4.2  0.81   Valsalva 2  35.8 ± 4.0  34.3 ± 3.3  39.3 ± 3.4  <0.01  35.9 ± 4.1  35.4 ± 3.8  0.50   Valsalva 3  34.9 ± 4.1  33.5 ± 3.3  38.5 ± 3.7  <0.01  35.0 ± 4.2  34.6 ± 3.8  0.49   Valsalva 4  34.1 ± 3.8  32.8 ± 3.1  37.3 ± 3.4  <0.01  34.2 ± 3.8  33.8 ± 3.6  0.60   Tubular aorta  37.7 ± 4.3  35.8 ± 2.9  42.2 ± 4.0  <0.01  37.5 ± 4.1  37.8 ± 4.7  0.84  Aortic stenosis progression                 Mean pressure gradient progression (mmHg/year)  +3.1 ± 3.0  +3.1 ± 2.9  +3.0 ± 3.2  0.70  +2.6 ± 2.8  +4.0 ± 3.3  <0.01   Peak velocity progression (cm/s/year)  +15.6 ± 13.8  +16.2 ± 14.4  +14.2 ± 12.3  0.53  +13 ± 13  +20 ± 14  <0.01   AVA progression (cm2/year)  −0.08 ± 0.07  −0.08 ± 0.06  −0.09 ± 0.08  0.31  −0.08 ± 0.07  −0.09 ± 0.07  0.11  Ascending aorta progression— echocardiography (mm/year)                 Valsalva  +0.18 ± 0.34  +0.18 ± 0.32  +0.20 ± 0.40  0.86  +0.07 ± 0.13  +0.42 ± 0.48  <0.01   Tubular aorta  +0.36 ± 0.54  +0.39 ± 0.56  +0.27 ± 0.46  0.14  +0.10 ± 0.15  +0.88 ± 0.65  <0.01  Ascending aorta progression—computed tomography (mm/year)                 Valsalva 1  +0.30 ± 0.50  +0.26 ± 0.44  +0.40 ± 0.61  0.18  +0.32 ± 0.52  +0.26 ± 0.46  0.39   Valsalva 2  +0.26 ± 0.48  +0.27 ± 0.47  +0.23 ± 0.51  0.18  +0.24 ± 0.45  +0.31 ± 0.54  0.40   Valsalva 3  +0.20 ± 0.38  +0.23 ± 0.42  +0.14 ± 0.22  0.26  +0.17 ± 0.32  +0.27 ± 0.47  0.55   Valsalva 4  +0.17 ± 0.28  +0.16 ± 0.27  +0.19 ± 0.30  0.84  +0.18 ± 0.28  +0.14 ± 0.27  0.18   Tubular aorta  +0.16 ± 0.21  +0.17 ± 0.22  +0.13 ± 0.19  0.19  +0.14 ± 0.19  +0.21 ± 0.25  0.07  AA, ascending aorta; AVA, aortic valve area. Table 2 Ascending aorta measurements using MSCT and correlation coefficient with TTE   Correlation coefficient TTE/MSCT  P-value  Difference MSCT-TTE (mm)  Valsalva 1  0.74  <0.01  +0.6 ± 0.2  Valsalva 2  0.77  0.03  +0.4 ± 0.2  Valsalva 3  0.81  0.02  −0.4 ± 0.2  Valsalva 4  0.83  <0.01  −1.2 ± 0.2  Tubular aorta  0.89  <0.01  +1.5 ± 0.2    Correlation coefficient TTE/MSCT  P-value  Difference MSCT-TTE (mm)  Valsalva 1  0.74  <0.01  +0.6 ± 0.2  Valsalva 2  0.77  0.03  +0.4 ± 0.2  Valsalva 3  0.81  0.02  −0.4 ± 0.2  Valsalva 4  0.83  <0.01  −1.2 ± 0.2  Tubular aorta  0.89  <0.01  +1.5 ± 0.2  TTE, transthoracic echocardiography; MSCT, multi-slice computed tomography. Table 2 Ascending aorta measurements using MSCT and correlation coefficient with TTE   Correlation coefficient TTE/MSCT  P-value  Difference MSCT-TTE (mm)  Valsalva 1  0.74  <0.01  +0.6 ± 0.2  Valsalva 2  0.77  0.03  +0.4 ± 0.2  Valsalva 3  0.81  0.02  −0.4 ± 0.2  Valsalva 4  0.83  <0.01  −1.2 ± 0.2  Tubular aorta  0.89  <0.01  +1.5 ± 0.2    Correlation coefficient TTE/MSCT  P-value  Difference MSCT-TTE (mm)  Valsalva 1  0.74  <0.01  +0.6 ± 0.2  Valsalva 2  0.77  0.03  +0.4 ± 0.2  Valsalva 3  0.81  0.02  −0.4 ± 0.2  Valsalva 4  0.83  <0.01  −1.2 ± 0.2  Tubular aorta  0.89  <0.01  +1.5 ± 0.2  TTE, transthoracic echocardiography; MSCT, multi-slice computed tomography. Determinants of ascending aorta size Mean AA size measured by TTE was 35.3 ± 3.9 mm (18.6 ± 2.2 mm/m2) at the sinuses of Valsalva and 36.2 ± 4.5 mm (19.1 ± 3.1 mm/m2) at the tubular level (Table 1 and Figure 3). Fifty-seven patients (29%) presented an AA diameter ≥40 mm at the Valsalva or at the tubular level (definition for aneurysm). As shown in Table 1, patients with AA aneurysms tend to be more frequently male, with larger BSA but there was no other difference in term of clinical characteristics or AS severity. Importantly, the rate of patients with BAV was significantly higher in patients with AA ≥40 mm (39% vs. 15% P < 0.01). In multivariate analysis, independent determinants of indexed AA size were age and BAV at the sinuses of Valsalva level (all P < 0.01) and age, female sex, and BAV at the tubular level (all P < 0.01). Ascending aorta size was not related to AS severity either assessed in categorical variables (P = 0.45 and P = 0.22 for Valsalva and tubular level, respectively) (Figure 4), or as a continuous variable (r <0.01, P = 0.99 between MPG and indexed Valsalva diameters; r = 0.02 and P = 0.75 between AVA and indexed Valsalva diameters; r = 0.05, P = 0.52 between MPG and indexed tubular diameters, and r = 0.09, P = 0.23 between AVA and indexed tubular diameters). Figure 3 View largeDownload slide Distribution of ascending aorta size at inclusion (at the sinuses of Valsalva in red and the tubular level in blue). Figure 3 View largeDownload slide Distribution of ascending aorta size at inclusion (at the sinuses of Valsalva in red and the tubular level in blue). Figure 4 View largeDownload slide Ascending aorta size measured by transthoracic echocardiography according to AS severity. (A) at the Valsalva level. (B) at the tubular level. Figure 4 View largeDownload slide Ascending aorta size measured by transthoracic echocardiography according to AS severity. (A) at the Valsalva level. (B) at the tubular level. Mean AA diameters measured using MSCT at the level of the Valsalva and at the tubular level, presented in Table 1, were highly correlated to TTE measurements (r between 0.74 and 0.89, all P < 0.05) and mean differences between MSCT and TTE measurements were small (–1.2 ± 0.2 to +1.5 ± 0.2 mm) (Table 2). After multivariate analysis determinants of indexed AA diameters measured using MSCT were similar: age and valve anatomy for Valsalva diameters (all P < 0.01) and age, valve anatomy and female sex for tubular diameters (all P < 0.01). Intra-observer and inter-observer variability was 1.9 ± 2.6% and 4.0 ± 5.8% (1.15 ± 0.44 mm and 1.69 ± 0.68 mm) for TTE and 3.3 ± 1.4%, and 4.8 ± 1.8% (0.64 ± 0.69 mm and 1.06 ± 1.34 mm) for MSCT measurements, respectively. Determinants of the progression of ascending aorta size After a mean follow-up of 3.8 ± 1.5 years [median 3.4 years (2.5–5.0)], the AA enlargement rate assessed using TTE was +0.18 ± 0.34 mm/year at the level of sinuses of Valsalvas and approximately twice, +0.36 ± 0.54 mm/year, at the tubular level (Figure 5). Sixty-six patients (34%) had no progression at both the sinuses of Valsalva and the tubular level, and sixty-five patients (37%) were considered as rapid progressors (progression rate ≥0.5 mm/year at either the Valsalva or tubular level). Rapid progressors were characterized by smaller aorta at baseline and a higher AS progression rate according to their PV and MPG progression rates (Table 1, right part). Among patients with initially non-dilated aorta at baseline, only 24 patients (13%) developed AA aneurysm >40 mm during follow-up. The threshold of 2 mm/year for rapid AA enlargement rate proposed in ESC guidelines was never reached at the sinuses of Valsalva and was reached in only 4 patients (2%) at the tubular level. These four patients had tricuspid aortic valve (TAV) and all but one had a small aorta at baseline (mean diameter was 34 mm at sinuses level and 31 mm at the tubular level); the other patient had 42 mm and 39 mm at the sinuses of Valsalva and at the tubular level, respectively. Figure 5 View largeDownload slide Ascending aorta progression rate measured at the Valsalva (red) and tubular levels (blue). Figure 5 View largeDownload slide Ascending aorta progression rate measured at the Valsalva (red) and tubular levels (blue). Age, gender, BSA, valve anatomy (Figure 6), and AS severity were not associated with AA enlargement rate in univariate analysis. In multivariate analysis, AA enlargement rate at the Valsalva level was associated with baseline diameters (smaller Valsalva diameters presented higher AA enlargement rate, P < 0.01) and with PV yearly progression rate (Valsalva’s enlargement rate increased with PV progression rate, P = 0.01), whereas AA enlargement rate at the tubular level was only associated with tubular diameter at baseline (smaller tubular diameter had higher AA enlargement rate, P < 0.01). Using MSCT, the only determinant of AA enlargement rate was also the AA diameters measured at baseline. Figure 6 View largeDownload slide Ascending aorta progression rate measured by transthoracic echocardiography according to the valve anatomy. (A) at the Valsalva level. (B) at the tubular level. Figure 6 View largeDownload slide Ascending aorta progression rate measured by transthoracic echocardiography according to the valve anatomy. (A) at the Valsalva level. (B) at the tubular level. Clinical outcome Forty-three patients underwent an aortic valve replacement (AVR) for severe AS. Four of them presented AA diameters ≥45 mm. Two patients underwent a TAVI due to fragile condition, and the two others—with BAV—underwent a combined aortic valve replacement and AA surgery for AA aneurysm with supra-coronary tube implantation. No aortic dissection was reported, and no surgery for AA aneurysm as primary indication was performed. Discussion In this large prospective cohort of patients with AS, AA size was independently determined by age, gender, BSA, and BAV, but not by AS severity. The mean AA enlargement rate was overall low, twice at the tubular level than at the sinuses of Valsalva, and was determined neither by AS severity nor by valve anatomy. Ascending aorta size and determinants in aortic stenosis Ascending aorta diameters measured in the present study were similar to those previously described in AS patients,11,12 and AA aneurysm was observed in one-quarter of AS patients, which is higher than its prevalence in normal subjects.13,14 Most importantly, even if AA dilatation was common in AS, AA size was not related to AS severity, which is consistent with the results described by Crawford and Roldan.11 Ascending aorta size was determined by aortic valve anatomy, with larger diameters among BAV patients. A large number of studies have previously analysed BAV-associated aortopathy, characterized by fibrilline reduction, elastin fragmentation, and increased collagen within aortic wall.15,16 Clinically, BAV patients present more frequently with AA dilatation, leading to a higher risk of life-threatening complications such as AA dissection or rupture, that hopefully remained rare thanks to early detection and treatment of these patients.17,18 For Hahn etal.19 aortic wall disease associated to BAV was more related to genetic anomalies than to hemodynamic valve dysfunction, as AA size was similar in BAV patients regardless of the aortic valve function (normal, regurgitation, or stenosis). Some studies suggested that AA size is related to the type of BAV,20,21 but this is still debated,9 and our limited population of BAV did not allowed us to draw any conclusion relative to this particular point. Finally, AA diameters were also independently associated with age, gender, and BSA, which are well-known determinants of AA size in normal subjects.22,23 One explanation for the larger diameters among older patients is that, with ageing, increased collagen production within aortic wall results in increasing AA stiffness. It is also important to mention that even if male patients presented larger absolute AA diameters, when indexed to the BSA, female sex that was associated with larger AA size. Rate of ascending aorta enlargement and determinants We found that the AA enlargement rate was overall low, using both TTE or MSCT, and similar to the AA enlargement rate (0.16 mm/year after 6 years of follow-up) observed in normal subjects.24 This AA enlargement observed in normal population seems to be an adaptive response to the aortic stiffness augmentation aiming at limiting the pulsed pressure increase.25 Moreover, we observed that AA enlargement rate in AS was twice higher at the tubular level than at the sinuses of Valsalva level. This phenotype of predominant tubular progression was primarily described in BAV population in opposition to patients with Marfan syndrome.9 In the present study, AA enlargement rate was not determined by AS severity at baseline. Detaint et al.9 also found no impact of AS severity on AA enlargement rate, although they studied only a small number of AS patients, all with BAV. However, Yasuda etal.26 observed that the AA enlargement rate was slower after AVR for AS, suggesting a possible hemodynamic impact of AS on AA enlargement rate. Moreover in our population, we found that AA enlargement rate was associated with AS yearly progression rate: patients with faster PV or MPG increase had higher AA enlargement rate, according to TTE measurements. Yet, we were not able to confirm these results when we used AVA progression rate, or MSCT diameters. Thus, these results need to be confirmed in further studies. We found that the AA enlargement rate was not determined by aortic valve anatomy. These results could be seen alongside those of La Canna etal.27 who studied consecutive transoesophageal echocardiographies in BAV and TAV patients presenting AA aneurysm and normally functioning aortic valve during a mean follow-up of 3 years. The rate of AA aneurysms progression was similar regardless of the valve anatomy. Moreover, studying 325 patients with AA aneurysm and AS followed up to 15 years after isolated AVR, Girdauskas et al.28 found that the proportion of proximal aortic redo surgery was similar in BAV and TAV patients (only 3% and 5%, respectively). Finally, the main determinant of AA enlargement rate was the AA size at baseline. Patients with smaller AA diameters had higher AA enlargement rate. This finding was previously reported.9 We are not sure whether this reflects a true phenomenon. One hypothesis is that minimal error measurements may have a greater impact in this population. Clinical implications The aim of this study was not to validate the actual proposed threshold of 45 mm for combined surgery at the time of AVR. However, given the relatively low AA progression rates observed in our AS patients, combined surgery indications should be discussed in heart team, in order to individualize this decision. It seems even more crucial given the frailty of some AS elderly patients, and the increasing number of percutaneous aortic valve replacements. Moreover, the upper limit of 2 mm/year of AA enlargement rate suggested in the European guidelines for BAV and Marfan patients3 was almost never reached in our population, suggesting that this threshold may be not appropriate in AS patients, regardless of valve anatomy. Study limitations This study has several limitations. First, this is a single-centre study, with mostly old-male patients. However, very few studies aimed at evaluating prospectively AA size and enlargement rate in AS with both BAV and TAV patients. Moreover, we prospectively included a relatively large population of 195 patients, with a wide range of AS severity. Second, a limited number of patients with severe AS (n = 14) were enrolled. The low number of patients with severe AS is explained by the fact that only patients with at least 2 years of follow-up were considered for the present study. Therefore, conclusions related to this subgroup of patients should be confirmed in larger sample. Finally, MSCT measurements were not performed with contrast enhancement. However, a major strength of this study is the use of two independent imaging modalities. Both TTE and MSCT were performed by one single trained specialist and showed similar results with excellent correlation and small variability. In addition, each measurement was performed blindly one of each other. Conclusion In this prospective study, AA size was associated with age, gender, BSA and BAV, but not with AS severity. Overall AA enlargement rates remained low, larger at the tubular than at the Valsalva level, and were not determined by AS severity or valve anatomy. Given the overall low progression of AA diameters, even for BAV patients, our results suggest individualizing the decision to perform a combined AA surgery above 45 mm at the time of AS surgery especially in elderly patients. Funding C.K. was supported by a grant from the Federation Française de Cardiologie; The COFRASA (clinicalTrial.gov number NCT 00338676) and GENERAC (clinicalTrial.gov number NCT00647088) studies are supported by grants from the Assistance Publique—Hôpitaux de Paris (PHRC National 2005 and 2010, and PHRC regional 2007). Conflict of interest: None declared. References 1 Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet  2006; 368: 1005– 11. Google Scholar CrossRef Search ADS PubMed  2 Iung B, Baron G, Butchart EG, Delahaye F, Gohlke-Barwolf C, Levang OW et al.   A prospective survey of patients with valvular heart disease in Europe: the Euro Heart Survey on Valvular Heart Disease. Eur Heart J  2003; 24: 1231– 43. Google Scholar CrossRef Search ADS PubMed  3 Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Baron-Esquivias G, Baumgartner H et al.   Guidelines on the management of valvular heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J  2012; 33: 2451– 96. Google Scholar CrossRef Search ADS PubMed  4 Rankin JS, Hammill BG, Ferguson TBJr, Glower DD, O'brien SM, DeLong ER et al.   Determinants of operative mortality in valvular heart surgery. J Thorac Cardiovasc Surg  2006; 131: 547– 57. Google Scholar CrossRef Search ADS PubMed  5 Leon MB, Smith CR, Mack MJ, Makkar RR, Svensson LG, Kodali SK et al.   Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med  2016; 374: 1609– 20. Google Scholar CrossRef Search ADS PubMed  6 Goldstein SA, Evangelista A, Abbara S, Arai A, Asch FM, Badano LP et al.   Multimodality imaging of diseases of the thoracic aorta in adults: from the American Society of Echocardiography and the European Association of Cardiovascular Imaging: endorsed by the Society of Cardiovascular Computed Tomography and Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr  2015; 28: 119– 82. Google Scholar CrossRef Search ADS PubMed  7 Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L et al.   Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging  2015; 16: 233– 70. Google Scholar CrossRef Search ADS PubMed  8 Baumgartner H, Hung J, Bermejo J, Chambers JB, Evangelista A, Griffin BP et al.   Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Eur J Echocardiogr  2009; 10: 1– 25. Google Scholar CrossRef Search ADS PubMed  9 Detaint D, Michelena HI, Nkomo VT, Vahanian A, Jondeau G, Sarano ME. Aortic dilatation patterns and rates in adults with bicuspid aortic valves: a comparative study with Marfan syndrome and degenerative aortopathy. Heart  2014; 100: 126– 34. Google Scholar CrossRef Search ADS PubMed  10 Vriz O, Driussi C, Bettio M, Ferrara F, D'andrea A, Bossone E. Aortic root dimensions and stiffness in healthy subjects. Am J Cardiol  2013; 112: 1224– 9. Google Scholar CrossRef Search ADS PubMed  11 Crawford MH, Roldan CA. Prevalence of aortic root dilatation and small aortic roots in valvular aortic stenosis. Am J Cardiol  2001; 87: 1311– 3. Google Scholar CrossRef Search ADS PubMed  12 Morgan-Hughes GJ, Roobottom CA, Owens PE, Marshall AJ. Dilatation of the aorta in pure, severe, bicuspid aortic valve stenosis. Am Heart J  2004; 147: 736– 40. Google Scholar CrossRef Search ADS PubMed  13 Coady MA, Rizzo JA, Goldstein LJ, Elefteriades JA. Natural history, pathogenesis, and etiology of thoracic aortic aneurysms and dissections. Cardiol Clin  1999; 17: 615– 35; vii. Google Scholar CrossRef Search ADS PubMed  14 Roman MJ, Devereux RB, Kramer-Fox R, O'loughlin J. Two-dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol  1989; 64: 507– 12. Google Scholar CrossRef Search ADS PubMed  15 Fedak PW, Verma S, David TE, Leask RL, Weisel RD, Butany J. Clinical and pathophysiological implications of a bicuspid aortic valve. Circulation  2002; 106: 900– 4. Google Scholar CrossRef Search ADS PubMed  16 Tzemos N, Lyseggen E, Silversides C, Jamorski M, Tong JH, Harvey P et al.   Endothelial function, carotid-femoral stiffness, and plasma matrix metalloproteinase-2 in men with bicuspid aortic valve and dilated aorta. J Am Coll Cardiol  2010; 55: 660– 8. Google Scholar CrossRef Search ADS PubMed  17 Michelena HI, Khanna AD, Mahoney D, Margaryan E, Topilsky Y, Suri RM et al.   Incidence of aortic complications in patients with bicuspid aortic valves. JAMA  2011; 306: 1104– 12. Google Scholar CrossRef Search ADS PubMed  18 Tzemos N, Therrien J, Yip J, Thanassoulis G, Tremblay S, Jamorski MT et al.   Outcomes in adults with bicuspid aortic valves. JAMA  2008; 300: 1317– 25. Google Scholar CrossRef Search ADS PubMed  19 Hahn RT, Roman MJ, Mogtader AH, Devereux RB. Association of aortic dilation with regurgitant, stenotic and functionally normal bicuspid aortic valves. J Am Coll Cardiol  1992; 19: 283– 8. Google Scholar CrossRef Search ADS PubMed  20 Schaefer BM, Lewin MB, Stout KK, Gill E, Prueitt A, Byers PH et al.   The bicuspid aortic valve: an integrated phenotypic classification of leaflet morphology and aortic root shape. Heart  2008; 94: 1634– 8. Google Scholar CrossRef Search ADS PubMed  21 Thanassoulis G, Yip JW, Filion K, Jamorski M, Webb G, Siu SC et al.   Retrospective study to identify predictors of the presence and rapid progression of aortic dilatation in patients with bicuspid aortic valves. Nat Clin Pract Cardiovasc Med  2008; 5: 821– 8. Google Scholar CrossRef Search ADS PubMed  22 Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM et al.   Heart disease and stroke statistics–2011 update: a report from the American Heart Association. Circulation  2011; 123: e18– e209. Google Scholar CrossRef Search ADS PubMed  23 Vasan RS, Larson MG, Levy D. Determinants of echocardiographic aortic root size. The Framingham Heart Study. Circulation  1995; 91: 734– 40. Google Scholar CrossRef Search ADS PubMed  24 Hannuksela M, Lundqvist S, Carlberg B. Thoracic aorta–dilated or not? Scand Cardiovasc J  2006; 40: 175– 8. Google Scholar CrossRef Search ADS PubMed  25 Lam CS, Gona P, Larson MG, Aragam J, Lee DS, Mitchell GF et al.   Aortic root remodeling and risk of heart failure in the Framingham Heart study. JACC Heart Fail  2013; 1: 79– 83. Google Scholar CrossRef Search ADS PubMed  26 Yasuda H, Nakatani S, Stugaard M, Tsujita-Kuroda Y, Bando K, Kobayashi J et al.   Failure to prevent progressive dilation of ascending aorta by aortic valve replacement in patients with bicuspid aortic valve: comparison with tricuspid aortic valve. Circulation  2003; 108 (Suppl. 1): II291– 4. Google Scholar CrossRef Search ADS PubMed  27 La Canna G, Ficarra E, Tsagalau E, Nardi M, Morandini A, Chieffo A et al.   Progression rate of ascending aortic dilation in patients with normally functioning bicuspid and tricuspid aortic valves. Am J Cardiol  2006; 98: 249– 53. Google Scholar CrossRef Search ADS PubMed  28 Girdauskas E, Disha K, Borger MA, Kuntze T. Long-term prognosis of ascending aortic aneurysm after aortic valve replacement for bicuspid versus tricuspid aortic valve stenosis. J Thorac Cardiovasc Surg  2014; 147: 276– 82. Google Scholar CrossRef Search ADS PubMed  Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Journal

European Heart Journal – Cardiovascular ImagingOxford University Press

Published: Jul 25, 2017

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off