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SUPPLEMENTAL APPENDIXADDITIONAL METHODSPatient PopulationPatients were prospectively recruited in 2 centers: Quebec Heart and Lung Institute the (PROGRESSA study: Metabolic Determinants of the Progression of Aortic Stenosis [NCT01679431]), and Edinburgh Heart Centre (NCT01755936) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DYXBvdWxhZGU8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFy
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ADDIN EN.CITE.DATA (1,2). The study inclusion criteria for the PROGRESSA study are age >21 years old and peak aortic jet velocity (Vpeak) >2.0 m/s. The exclusion criteria are symptomatic AS, significant (> mild) aortic regurgitation or mitral valve disease (mitral stenosis or regurgitation), LV ejection fraction (LVEF) <50% and if they are pregnant or lactating women ADDIN EN.CITE <EndNote><Cite><Author>Capoulade</Author><Year>2015</Year><RecNum>14097</RecNum><DisplayText>(1)</DisplayText><record><rec-number>14097</rec-number><foreign-keys><key app="EN" db-id="a00r2xsprrpt07e2dt35s2ztfadevpxdd5s5" timestamp="1457963366">14097</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Capoulade, R.</author><author>Mahmut, A.</author><author>Tastet, L.</author><author>Arsenault, M.</author><author>Bédard, E.</author><author>Dumesnil, J.G.</author><author>Després, J.P.</author><author>Larose, ?.</author><author>Arsenault, B.J.</author><author>Bossé, Y.</author><author>Mathieu, P.</author><author>Pibarot, P.</author><author>.</author></authors></contributors><titles><title>Impact of plasma Lp-PLA2 activity on the progression of aortic stenosis: the PROGRESSA study.</title><secondary-title>J Am Coll Cardiol Img</secondary-title></titles><periodical><full-title>J Am Coll Cardiol Img</full-title></periodical><pages>26-33</pages><volume>8</volume><number>1</number><reprint-edition>Not in File</reprint-edition><keywords><keyword>Aortic stenosis</keyword><keyword>Calcific aortic valve disease</keyword><keyword>Doppler Echocardiography</keyword><keyword>Lipoprotein-associated phospholipase A2</keyword></keywords><dates><year>2015</year><pub-dates><date>1/2015</date></pub-dates></dates><label>14415</label><urls><related-urls><url><style face="underline" font="default" size="100%">;(1). In Edinburgh, all stable patients with at least mild AS (Vpeak >2.0 m/s) were invited to participate in a prospective observational cohort study. The exclusion criteria were other forms of valvular heart disease (≥moderate severity), significant comorbidities with limited life expectancy, contraindications to gadolinium-enhanced cardiac magnetic resonance (CMR), acquired or inherited non-ischemic cardiomyopathies PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGluPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (2). The present study included all patients from both centers with comprehensive echocardiography and CMR exams (Online Figure S1).Clinical DataThe clinical data included age, sex, weight, height, body surface area (BSA), body-mass index (BMI), documented diagnoses of hypertension, dyslipidemia, diabetes mellitus, coronary artery disease, and renal function (plasma level of creatinine). Symptomatic status was assessed using the New York Heart Association (NYHA) functional classification.Doppler EchocardiographyThe aortic valve phenotype (i.e. bicuspid vs. tricuspid) was recorded. The Doppler-echocardiographic indices of AS severity included Vpeak, mean transvalvular pressure gradient (MG), and aortic valve area (AVA) calculated by the standard continuity equation and indexed to body surface area (AVAi). Stroke volume (SV) was calculated by multiplying the LV outflow tract area by the flow velocity-time integral and was indexed to BSA (SVi). Systemic arterial pressure was measured with the use of arm-cuff sphygmomanometer simultaneous to SV measurement. Brachial pulse pressure (PP) was calculated as the difference between systolic and diastolic arterial pressures. The ratio of SVi to PP was used as an indirect measure of systemic arterial compliance ADDIN EN.CITE <EndNote><Cite><Author>Briand</Author><Year>2005</Year><RecNum>6877</RecNum><DisplayText>(3)</DisplayText><record><rec-number>6877</rec-number><foreign-keys><key app="EN" db-id="a00r2xsprrpt07e2dt35s2ztfadevpxdd5s5" timestamp="1457963352">6877</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Briand, M.</author><author>Dumesnil, J.G.</author><author>Kadem, L.</author><author>Tongue, A.G.</author><author>Rieu, R.</author><author>Garcia, D.</author><author>Pibarot, P.</author></authors></contributors><titles><title>Reduced systemic arterial compliance impacts significantly on left ventricular afterload and function in aortic stenosis: Implications for diagnosis and treatment.</title><secondary-title>J Am Coll Cardiol</secondary-title></titles><periodical><full-title>J Am Coll Cardiol</full-title></periodical><pages>291-298</pages><volume>46</volume><number>2</number><reprint-edition>Not in File</reprint-edition><keywords><keyword>Aortic stenosis</keyword><keyword>Arterial</keyword><keyword>Compliance</keyword><keyword>Diagnosis</keyword><keyword>Function</keyword><keyword>Stenosis</keyword><keyword>Left</keyword><keyword>Left Ventricular</keyword><keyword>Ventricular</keyword></keywords><dates><year>2005</year><pub-dates><date>7/19/2005</date></pub-dates></dates><label>7030</label><urls><related-urls><url><style face="underline" font="default" size="100%">;(3). As a measure of global LV afterload, we calculated the valvulo-arterial impedance: Zva = (SBP + MG)/SVi, where SBP is the systolic blood pressure. LV mass was calculated with the corrected formula of the American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines and was indexed to body surface area ADDIN EN.CITE <EndNote><Cite><Author>Lang</Author><Year>2015</Year><RecNum>14216</RecNum><DisplayText>(4)</DisplayText><record><rec-number>14216</rec-number><foreign-keys><key app="EN" db-id="a00r2xsprrpt07e2dt35s2ztfadevpxdd5s5" timestamp="1457963366">14216</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lang, R.M.</author><author>Badano, L.P.</author><author>Mor-Avi, V.</author><author>Afilalo, J.</author><author>Armstrong, A.</author><author>Ernande, L.</author><author>Flachskampf, F.A.</author><author>Foster, E.</author><author>Goldstein, S.A.</author><author>Kuznetsova, T.</author><author>Lancellotti, P.</author><author>Muraru, D.</author><author>Picard, M.H.</author><author>Rietzschel, E.R.</author><author>Rudski, L.</author><author>Spencer, K.T.</author><author>Tsang, W.</author><author>Voigt, J.U.</author></authors></contributors><titles><title>Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the american society of echocardiography and the European association of cardiovascular imaging</title><secondary-title>J Am Soc. Echocardiogr</secondary-title></titles><periodical><full-title>J Am Soc. Echocardiogr</full-title></periodical><pages>1-39</pages><volume>28</volume><number>1</number><reprint-edition>Not in File</reprint-edition><keywords><keyword>Adult</keyword><keyword>ASSOCIATION</keyword><keyword>Cardiac</keyword><keyword>Cardiovascular</keyword><keyword>Echocardiography</keyword><keyword>Imaging</keyword><keyword>Societies</keyword></keywords><dates><year>2015</year><pub-dates><date>1/2015</date></pub-dates></dates><label>14536</label><urls><related-urls><url><style face="underline" font="default" size="100%">;(4). Left ventricular hypertrophy (LVH) was defined as LV mass index >95 g/m? in women and >115 g/m? in men. Relative wall thickness (RWT) was calculated (i.e. RWT = [PWT+IVST]/LVID) and, as previously recommended, RWT >0.42 was used to define concentric remodeling ADDIN EN.CITE <EndNote><Cite><Author>Lang</Author><Year>2015</Year><RecNum>14216</RecNum><DisplayText>(4)</DisplayText><record><rec-number>14216</rec-number><foreign-keys><key app="EN" db-id="a00r2xsprrpt07e2dt35s2ztfadevpxdd5s5" timestamp="1457963366">14216</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lang, R.M.</author><author>Badano, L.P.</author><author>Mor-Avi, V.</author><author>Afilalo, J.</author><author>Armstrong, A.</author><author>Ernande, L.</author><author>Flachskampf, F.A.</author><author>Foster, E.</author><author>Goldstein, S.A.</author><author>Kuznetsova, T.</author><author>Lancellotti, P.</author><author>Muraru, D.</author><author>Picard, M.H.</author><author>Rietzschel, E.R.</author><author>Rudski, L.</author><author>Spencer, K.T.</author><author>Tsang, W.</author><author>Voigt, J.U.</author></authors></contributors><titles><title>Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the american society of echocardiography and the European association of cardiovascular imaging</title><secondary-title>J Am Soc. Echocardiogr</secondary-title></titles><periodical><full-title>J Am Soc. Echocardiogr</full-title></periodical><pages>1-39</pages><volume>28</volume><number>1</number><reprint-edition>Not in File</reprint-edition><keywords><keyword>Adult</keyword><keyword>ASSOCIATION</keyword><keyword>Cardiac</keyword><keyword>Cardiovascular</keyword><keyword>Echocardiography</keyword><keyword>Imaging</keyword><keyword>Societies</keyword></keywords><dates><year>2015</year><pub-dates><date>1/2015</date></pub-dates></dates><label>14536</label><urls><related-urls><url><style face="underline" font="default" size="100%">;(4). By taking into account both values of LV mass index and RWT, patients were classified into four different patterns using the following criteria: i) normal pattern: absence of LVH and RWT ≤0.42; ii) concentric remodeling: absence of LVH and RWT >0.42; iii) concentric hypertrophy: presence of LVH and RWT >0.42; iv) eccentric hypertrophy: presence of LVH and RWT ratio ≤0.42 ADDIN EN.CITE <EndNote><Cite><Author>Lang</Author><Year>2015</Year><RecNum>14216</RecNum><DisplayText>(4)</DisplayText><record><rec-number>14216</rec-number><foreign-keys><key app="EN" db-id="a00r2xsprrpt07e2dt35s2ztfadevpxdd5s5" timestamp="1457963366">14216</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lang, R.M.</author><author>Badano, L.P.</author><author>Mor-Avi, V.</author><author>Afilalo, J.</author><author>Armstrong, A.</author><author>Ernande, L.</author><author>Flachskampf, F.A.</author><author>Foster, E.</author><author>Goldstein, S.A.</author><author>Kuznetsova, T.</author><author>Lancellotti, P.</author><author>Muraru, D.</author><author>Picard, M.H.</author><author>Rietzschel, E.R.</author><author>Rudski, L.</author><author>Spencer, K.T.</author><author>Tsang, W.</author><author>Voigt, J.U.</author></authors></contributors><titles><title>Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the american society of echocardiography and the European association of cardiovascular imaging</title><secondary-title>J Am Soc. Echocardiogr</secondary-title></titles><periodical><full-title>J Am Soc. Echocardiogr</full-title></periodical><pages>1-39</pages><volume>28</volume><number>1</number><reprint-edition>Not in File</reprint-edition><keywords><keyword>Adult</keyword><keyword>ASSOCIATION</keyword><keyword>Cardiac</keyword><keyword>Cardiovascular</keyword><keyword>Echocardiography</keyword><keyword>Imaging</keyword><keyword>Societies</keyword></keywords><dates><year>2015</year><pub-dates><date>1/2015</date></pub-dates></dates><label>14536</label><urls><related-urls><url><style face="underline" font="default" size="100%">;(4).Mitral annulus velocity was assessed using Doppler tissue imaging and diastolic function was classified according to guidelines ADDIN EN.CITE <EndNote><Cite><Author>Lang</Author><Year>2015</Year><RecNum>14216</RecNum><DisplayText>(4)</DisplayText><record><rec-number>14216</rec-number><foreign-keys><key app="EN" db-id="a00r2xsprrpt07e2dt35s2ztfadevpxdd5s5" timestamp="1457963366">14216</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Lang, R.M.</author><author>Badano, L.P.</author><author>Mor-Avi, V.</author><author>Afilalo, J.</author><author>Armstrong, A.</author><author>Ernande, L.</author><author>Flachskampf, F.A.</author><author>Foster, E.</author><author>Goldstein, S.A.</author><author>Kuznetsova, T.</author><author>Lancellotti, P.</author><author>Muraru, D.</author><author>Picard, M.H.</author><author>Rietzschel, E.R.</author><author>Rudski, L.</author><author>Spencer, K.T.</author><author>Tsang, W.</author><author>Voigt, J.U.</author></authors></contributors><titles><title>Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the american society of echocardiography and the European association of cardiovascular imaging</title><secondary-title>J Am Soc. Echocardiogr</secondary-title></titles><periodical><full-title>J Am Soc. Echocardiogr</full-title></periodical><pages>1-39</pages><volume>28</volume><number>1</number><reprint-edition>Not in File</reprint-edition><keywords><keyword>Adult</keyword><keyword>ASSOCIATION</keyword><keyword>Cardiac</keyword><keyword>Cardiovascular</keyword><keyword>Echocardiography</keyword><keyword>Imaging</keyword><keyword>Societies</keyword></keywords><dates><year>2015</year><pub-dates><date>1/2015</date></pub-dates></dates><label>14536</label><urls><related-urls><url><style face="underline" font="default" size="100%">;(4). Cardiac Magnetic ResonanceAcquisitionMagnetic resonance imaging was performed with 1.5 and 3 Tesla scanners (Quebec: Philips Achieva or Philips Ingenia, Philips Healthcare, Best, The Netherlands; Edinburgh: Magnetom Verio, Siemens AG, Erlangen, Germany). 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ADDIN EN.CITE.DATA (2,5). The inversion time was optimized to achieve satisfactory nulling of the myocardium.Diffuse myocardial fibrosis was assessed using Modified Look-Locker Inversion-recovery (MOLLI) with built-in motion correction. The heart beat acquisition scheme was 5(3)-3 in Quebec (with a post-contrast acquisition scheme of 4(1)3(1)2 used in patients scanned at 3T) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LZWxsbWFuPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LZWxsbWFuPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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NDwvZGF0ZT48L3B1Yi1kYXRlcz48L2RhdGVzPjxpc2JuPjEwOTctNjY0NzwvaXNibj48YWNjZXNz
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ZT48L3JlY29yZD48L0NpdGU+PC9FbmROb3RlPn==
ADDIN EN.CITE.DATA (6), whilst the acquisition scheme was 3(3)-3(3)-5 in Edinburgh (flip angle 35; minimum TI 100 ms; TI increment of 80 ms; time delay of 150 ms) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZXNzcm9naGxpPC9BdXRob3I+PFllYXI+MjAwNDwvWWVh
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ADDIN EN.CITE.DATA (7-9). A gradient echo field map and associated shim were performed to minimize off-frequency artefact.AnalysisImage analysis was performed offline in a core laboratory using a standardized approach (cmr42 version 3.4.1, Circle Vascular Imaging, Canada). In Quebec, images were quantified by trained operators supervised by an experienced cardiologist (Quebec: E.L.; Edinburgh: M.D.) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DZXJxdWVpcmE8L0F1dGhvcj48WWVhcj4yMDAyPC9ZZWFy
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Tm90ZT5=
ADDIN EN.CITE.DATA (10-12). Left ventricular volume, mass and function measurements were performed using the contiguous short-axis multi-slice acquisition with delineation of atria/ventricles confirmed in matched long-axis planes. Papillary muscles and trabeculations were included when measuring mass (equivalent to weighting the LV) and excluded when measuring volumes (equivalent to blood pool techniques) in line with recommendations PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5QZW5uZWxsPC9BdXRob3I+PFllYXI+MjAwMjwvWWVhcj48
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ADDIN EN.CITE.DATA (12,13).LV hypertrophy was defined as LV mass indexed to BSA >95th centile using age- and sex-specific reference ranges ADDIN EN.CITE <EndNote><Cite><Author>Maceira</Author><Year>2006</Year><RecNum>9758</RecNum><DisplayText>(14)</DisplayText><record><rec-number>9758</rec-number><foreign-keys><key app="EN" db-id="a00r2xsprrpt07e2dt35s2ztfadevpxdd5s5" timestamp="1457963357">9758</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Maceira, A.M.</author><author>Prasad, S.K.</author><author>Khan, M.</author><author>Pennell, D.J.</author></authors></contributors><titles><title>Normalized left ventricular systolic and diastolic function by steady state free precession cardiovascular magnetic resonance</title><secondary-title>J Cardiovasc Magn Reson</secondary-title></titles><periodical><full-title>J Cardiovasc Magn Reson</full-title></periodical><pages>417-426</pages><volume>8</volume><number>3</number><reprint-edition>Not in File</reprint-edition><keywords><keyword>Cardiovascular</keyword><keyword>Function</keyword><keyword>Left</keyword><keyword>Left Ventricular</keyword><keyword>Ventricular</keyword></keywords><dates><year>2006</year><pub-dates><date>2006</date></pub-dates></dates><label>9968</label><urls></urls></record></Cite></EndNote>(14). LV remodeling was determined as the ratio of LV mass index to LV end-diastolic volume index. By taking into account the presence of LV hypertrophy (LVH) and increased LV mass-volume ratio (i.e., ratio ≥1.15) PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYWNlaXJhPC9BdXRob3I+PFllYXI+MjAwNjwvWWVhcj48
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ADDIN EN.CITE.DATA (14,15), four patterns of LV remodeling were defined: i) normal pattern: no LVH and LV mass-volume ratio <1.15; ii) concentric remodeling: no LVH and LV mass-volume ratio ≥1.15; iii) concentric hypertrophy: LVH and LV mass-volume ratio ≥1.15; iv) eccentric hypertrophy: LVH and LV mass-volume ratio <1.15.Focal replacement fibrosis and extracellular volume (ECV) fraction were assessed using late gadolinium enhancement (LGE). LGE was performed 15 min following administration of gadobutrol (Gadovist, Bayer Pharma AG, Germany; 0.2 mmol/kg [Quebec], 0.1 mmol/kg [Edinburgh]). In Quebec, quantitative assessment of LGE was performed on short-axis inversion recovery images by semi-automated signal intensity analysis, using the full width at half-maximum technique on the 17-segment model PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DZXJxdWVpcmE8L0F1dGhvcj48WWVhcj4yMDAyPC9ZZWFy
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ADDIN EN.CITE.DATA (2). LGE was quantified in a semi-automated manner using a signal intensity threshold of >3 standard deviations above the mean value in a region of normal myocardium. Areas of inversion artefact, infarct pattern LGE or signal contamination by epicardial fat or blood pool were manually excluded. Sub-endocardial LGE was also identified and quantified using the same analysis technique.T1 mapping was performed using the Modified Look-Locker Inversion Recovery PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGluPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48UmVj
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGluPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (2). The regions of the endocardium and epicardium on the native motion-corrected T1 maps were manually contoured to avoid partial-volume or cardiac-motion-related blurring of the myocardium-blood boundary, where blood signal may contaminate myocardial data PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5FdmVyZXR0PC9BdXRob3I+PFllYXI+MjAxODwvWWVhcj48
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ADDIN EN.CITE.DATA (16). These contours were then copied onto the corresponding post-contrast maps (Quebec: 15-min post-contrast maps; Edinburgh: 20-min post-contrast maps) with minor adjustments made to avoid partial volume effects. Regions of interest (ROIs) were then drawn in the blood, avoiding myocardium and papillary muscles. The extracellular volume (ECV) fraction was calculated according to: ECV fraction = partition coefficient x [1-hematocrit], where partition coefficient = [?R1myocardium/?R1blood-pool] and ?R1 = (1/post-contrast T1-1/native T1). Hematocrit was measured as per protocol before cardiovascular magnetic resonance PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5DaGluPC9BdXRob3I+PFllYXI+MjAxNzwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (2,6).Statistical AnalysisA frequency-matched analysis where the matched pairs were selected according to the nearest neighbour method was performed to further compare the distribution of ECV and LGE between women and men. The confounding factors used in the analysis included age, sex, SBP, hypertension, dyslipidemia, diabetes mellitus, coronary artery disease, LVH, AS severity (i.e. Vpeak).TABLE S1: Frequency-Matched Characteristics of the Study Population according to SexAll Patients(n = 112)Men(n = 56, 50%)Women(n = 56, 50%)p ValueClinical Age, years68 ± 12 68 ± 1268 ± 120.98Body surface area, m21.83 ± 0.191.94 ± 0.171.73 ± 0.16<0.0001Body mass index, kg/m228 ± 528 ± 428 ± 60.89Systolic blood pressure, mmHg145 ± 23145 ± 22145 ± 240.89Diastolic blood pressure, mmHg82 ± 1283 ± 1281 ± 130.58Hypertension, %6261630.85Dyslipidemia, %4545451.00Diabetes, %9991.00Coronary artery disease, %2020201.00Creatinine, ?mol/l76 ± 1583 ± 1569 ± 12<0.0001Hematocrit0.40 ± 0.040.42 ± 0.040.38 ± 0.03<0.0001NYHA functional class, %I5764500.19II302932III11516IV222MedicationACEIs/ARBs, %3229360.42Beta-blockers, %2929291.00Diuretics, %2836200.06Statins, %4645480.71Doppler-echocardiographic dataBicuspid aortic valve, %2527230.63Peak aortic jet velocity, m/s3.4 ± 0.93.3 ± 0.83.4 ± 1.00.77Mean transvalvular gradient, mmHg27 ± 1527 ± 1327 ± 160.82Aortic valve area, cm21.01 ± 0.311.07 ± 0.310.96 ± 0.310.07Indexed aortic valve area, cm?/m20.55 ± 0.170.55 ± 0.150.55 ± 0.180.98AS severity, %0.78Mild454346Moderate212318Severe353436Stroke volume index, mL/m?42 ± 941 ± 843 ± 90.28Systemic arterial compliance, mL/m?/mmHg0.70 ± 0.230.69 ± 0.220.71 ± 0.230.76Valvulo-arterial impedance, mmHg/mL/m24.3 ± 1.24.4 ± 1.24.2 ± 1.20.53Mean e’, cm/s6.7 ± 2.17.1 ± 2.06.3 ± 2.10.06Mean E/e’ ratio14.4 ± 8.412.6 ± 7.116.2 ± 9.30.02LV mass index, g/m2108 (91 - 125)115 (98 - 127)101 (85 - 122)0.06Relative wall thickness ratio0.57 (0.48 - 0.67)0.55 (0.48 - 0.65)0.57 (0.48 - 0.67)0.98LV hypertrophy, %5451570.56LV remodeling patterns, %0.43Normal pattern11811Concentric remodeling364232Concentric hypertrophy525153Eccentric hypertrophy204Cardiac magnetic resonance dataEnd-diastolic volume index, ml/m269 (62 - 79)73 (64 - 82)68 (60 - 76)0.05End-systolic volume index, ml/m222 (18 - 27)23 (20 - 27)22 (18 - 26)0.09Stroke volume index, ml/m247 (41 - 54)48 (42 - 56)45 (40 - 52)0.09LV ejection fraction, %67 (63 - 71)67 (64 - 70)68 (62 - 72)0.84LV mass index, g/m270 (59 - 86)74 (62 - 92)63 (56 - 80)0.004LV mass/volume ratio0.99 (0.80 - 1.31)0.98 (0.80 - 1.41)1.01 (0.81 - 1.25)0.34LV hypertrophy, %2929291.00LV remodeling patterns, %0.80Normal pattern605763Concentric remodeling12149Concentric hypertrophy242523Eccentric hypertrophy445Presence of LGE, %3438300.43LGE, %4.0 (1.9 - 7.6)3.2 (1.7 - 7.5)4.5 (2.5 - 7.6)0.46Presence of non-infarct LGE, %3136270.31Non-infarct LGE, %3.4 (1.7 - 7.5)3.0 (1.7 - 6.7)4.5 (2.3 - 7.6)0.52Extracellular volume fractionMean, %28.1 ± 2.927.2 ± 2.929.0 ± 2.90.002Median, %28.4 (25.6 - 29.8)27.2 (25.0 - 29.2)28.9 (27.3 - 30.3)0.002Value are mean±SD, % or median [25th – 75th percentiles].ACEIs = angiotensin-converting-enzyme inhibitors; ARBs = angiotensin receptor blockers; LGE = late gadolinium enhancement; LV = left ventricular; NYHA = New York Heart Association.TABLE S2: Correlates of Extracellular Volume Fraction.Univariable AnalysisMultivariable Analysisβeta Coeff. ± SEp valueβeta Coeff. ± SEp valueAge, years0.14±0.020.030.14±0.020.07Female sex0.29±0.43<0.00010.29±0.50<0.0001Hypertension-0.03±0.430.65-0.11±0.450.11Diabetes0.04±570.480.07±0.520.25Coronary artery disease-0.03±0.430.640.04±0.420.57Creatinine clairance-0.12±0.010.06-0.06±0.010.37Hematocrit-0.39±4.67<0.0001-0.30±5.07<0.0001NYHA functional class0.13±0.270.040.08±0.280.25Peak aortic jet velocity, m/s0.05±0.210.48-0.09±0.270.27SAC, mL/m?/mmHg-0.05±0.840.430.05±0.880.47E/e’ ratio0.18 ±0.030.004-0.04 ±0.030.58LV mass index, g/m?0.11 ±0.0090.080.45 ±0.01<0.0001βeta coeff. are standardized regression coefficient. SAC = systemic arterial compliance; other abbreviations as in Online Table 1.FIGURE S1: Study Flow ChartCaption: Description of the inclusion of the study population. CMR = cardiac magnetic resonance; LGE = late gadolinium enhancement.FIGURE S2: Comparison of Late Gadolinium Enhancement between Women and Men According to Centre.Caption: Comparison of late gadolinium enhancement (LGE) between women and men (A) and non-infarct LGE (B) in the Quebec Centre, and non-infarct LGE in the Edinburgh Centre (C).-176531626110003128644302259001442720395033400FIGURE S3: Comparison of Extracellular Volume Fraction between Women and Men According to Centre.Caption: Comparison of extracellular volume fraction between women and men in the Quebec Centre (A) and in the Edinburgh Centre (B).FIGURE S4: Comparison of Left Ventricular Mass Index between Women and Men According to Aortic Valve Stenosis Severity.Caption: Comparison of extracellular volume fraction between women and men in each class of severity of aortic valve stenosis.REFERENCES ADDIN EN.REFLIST 1.Capoulade R, Mahmut A, Tastet L et al. Impact of plasma Lp-PLA2 activity on the progression of aortic stenosis: the PROGRESSA study. J Am Coll Cardiol Img 2015;8:26-33.2.Chin CW, Everett RJ, Kwiecinski J et al. Myocardial fibrosis and cardiac decompensation in aortic stenosis. JACC Cardiovasc Imaging 2017;10:1320-33.3.Briand M, Dumesnil JG, Kadem L et al. Reduced systemic arterial compliance impacts significantly on left ventricular afterload and function in aortic stenosis: Implications for diagnosis and treatment. J Am Coll Cardiol 2005;46:291-298.4.Lang RM, Badano LP, Mor-Avi V 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. J Am Soc Echocardiogr 2015;28:1-39.5.Larose ?, Rodés-Cabau J, Pibarot P et al. Predicting late myocardial recovery and outcomes in the early hours of ST-segment elevation myocardial infarction: Traditional measures compared with microvascular obstruction, salvaged myocardium, and necrosis characteristics by cardiovalcular magnetic resonance. J Am Coll Cardiol 2010;55:2459-2469.6.Kellman P, Xue H, Chow K, Spottiswoode BS, Arai AE, Thompson RB. Optimized saturation recovery protocols for T1-mapping in the heart: influence of sampling strategies on precision. J Cardiovasc Magn Reson 2014;16:55.7.Messroghli DR, Radjenovic A, Kozerke S, Higgins DM, Sivananthan MU, Ridgway JP. Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart. Magn Reson Med 2004;52:141-146.8.Messroghli DR, Greiser A, Frohlich M, Dietz R, Schulz-Menger J. Optimization and validation of a fully-integrated pulse sequence for modified look-locker inversion-recovery (MOLLI) T1 mapping of the heart. J Magn Reson Imaging 2007;26:1081-1086.9.Moon JC, Messroghli DR, Kellman P et al. Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement. J Cardiovasc Magn Reson 2013;15:92.10.Cerqueira MD, Weissman NJ, Dilsizian V et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation 2002;105:539-42.11.Friedrich MG, Larose E, Patton D, Dick A, Merchant N, Paterson I. Canadian Society for Cardiovascular Magnetic Resonance (CanSCMR) recommendations for cardiovascular magnetic resonance image analysis and reporting. Can J Cardiol 2013;29:260-5.12.Schulz-Menger J, Bluemke DA, Bremerich J et al. Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) board of trustees task force on standardized post processing. J Cardiovasc Magn Reson 2013;15:35.13.Pennell DJ. Ventricular volume and mass by CMR. J Cardiovasc Magn Reson 2002;4:507-13.14.Maceira AM, Prasad SK, Khan M, Pennell DJ. Normalized left ventricular systolic and diastolic function by steady state free precession cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2006;8:417-426.15.Treibel TA, Kozor R, Fontana M et al. Sex dimorphism in the myocardial response to aortic stenosis. JACC Cardiovasc Imaging 2018;11:962-973.16.Everett RJ, Tastet L, Clavel MA et al. Progression of hypertrophy and myocardial fibrosis in aortic stenosis: A multicenter cardiac magnetic resonance study. Circ Cardiovasc Imaging 2018;11:e007451. ................
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