Sex differences in aortic stenosis: from pathophysiology to treatment

References

• Regitz-Zagrosek V, Oertelt-Prigione S, Prescott E, et al.; EUGenMed, cardiovascular clinical study group. Gender in cardiovascular diseases: impact on clinical manifestations, management, and outcomes. Eur Heart J. 2016;37:24–34.
   PubMed Web of Science ®Google Scholar
• Carroll JD, Carroll EP, Feldman T, et al. Sex-associated differences in left ventricular function in aortic stenosis of the elderly. Circulation. 1992;86:1099–1107.
   PubMed Web of Science ®Google Scholar
• Thaden JJ, Nkomo VT, Suri RM, et al. Sex‐related differences in calcific aortic stenosis: correlating clinical and echocardiographic characteristics and computed tomography aortic valve calcium score to excised aortic valve weight. Eur Heart J. 2016;37:693–699.
   PubMed Web of Science ®Google Scholar
• Aggarwal SR, Clavel MA, Messika-Zeitoun D, et al. Sex differences in aortic valve calcification measured by multidetector computed tomography in aortic stenosis. Circ Cardiovasc Imaging. 2013;6:40–47.
   PubMed Web of Science ®Google Scholar
• Clavel MA, Messika-Zeitoun D, Pibarot P, et al. The complex nature of discordant severe calcified aortic valve disease grading: new insights from combined Doppler echocardiographic and computed tomographic study. J Am Coll Cardiol. 2013;62:2329–2338.
   PubMed Web of Science ®Google Scholar
• Simard L, Côté N, Dagenais F, et al. Sex-related discordance between aortic valve calcification and hemodynamic severity of aortic stenosis: is valvular fibrosis the explanation? Circ Res. 2017;120:681–691.
   PubMed Web of Science ®Google Scholar
• Clavel MA, Pibarot P, Messika-Zeitoun D, et al. Impact of aortic valve calcification, as measured by MDCT, on survival in patients with aortic stenosis: results of an international registry study. J Am Coll Cardiol. 2014;64:1202–1213.
   PubMed Web of Science ®Google Scholar
• Pawade T, Clavel MA, Tribouilloy C, et al. Computed tomography aortic valve calcium scoring in patients with aortic stenosis. Circ Cardiovasc Imaging. 2018 Mar;11(3):e007146.
   PubMed Web of Science ®Google Scholar
• Ortlepp JR, Hoffmann R, Ohme F, et al. The vitamin D receptor genotype predisposes to the development of calcific aortic valve stenosis. Heart. 2001;85:635–638.
   PubMed Web of Science ®Google Scholar
• Jian B, Narula N, Li QY, et al. Progression of aortic valve stenosis: TGF-β1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis. Ann Thorac Surg. 2003;75:457–465.
   PubMed Web of Science ®Google Scholar
• Parra-Izquierdo I, Castaños-Mollor I, López J, et al. Calcification induced by type i interferon in human aortic valve interstitial cells is larger in males and blunted by a janus kinase inhibitor. Arterioscler Thromb Vasc Biol. 2018 Sep;38(9):2148–2159.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• de Simone G, Izzo R, Chinali M, et al. Does information on systolic and diastolic function improve prediction of a cardiovascular event by left ventricular hypertrophy in arterial hypertension? Hypertension. 2010;56:99–104.
   PubMed Web of Science ®Google Scholar
• Seiler C, Jenni R. Severe aortic stenosis without left ventricular hypertrophy: prevalence, predictors, and short-term follow up after aortic valve replacement. Heart. 1996;76:250–255.
   PubMed Web of Science ®Google Scholar
• Maceira AM, Prasad SK, Khan M, et al. Normalized left ventricular systolic and diastolic function by steady state free precession cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2006;8:417–426.
   PubMed Web of Science ®Google Scholar
• Treibel TA, Kozor R, Fontana M, et al. Sex dimorphism in the myocardial response to aortic stenosis. JACC Cardiovasc Imaging. 2018;11:962–973.
   PubMed Web of Science ®Google Scholar
• Dweck MR, Joshi S, Murigu T, et al. Left ventricular remodeling and hypertrophy in patients with aortic stenosis: insights from cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2012;14:50.
   PubMed Web of Science ®Google Scholar
• Kwiecinski J, Chin CWL, Everett RJ, et al. Adverse prognosis associated with asymmetric myocardial thickening in aortic stenosis. Eur Heart J Cardiovasc Imaging. 2018;19:347–356.
   PubMed Web of Science ®Google Scholar
• Singh A, Musa TA, Treibel TA, et al. Sex differences in left ventricular remodelling, myocardial fibrosis and mortality after aortic valve replacement. Heart. 2019 Aug 29;105:1818–1824. pii: heartjnl-2019-314987.
   Web of Science ®Google Scholar
• Petrov G, Regitz-Zagrosek V, Lehmkuhl E, et al. Regression of myocardial hypertrophy after aortic valve replacement: faster in women? Circulation. 2010;122(suppl):S23–S28.
   PubMedGoogle Scholar
• Saeed S, Mancia G, Rajani R, et al. Sex-differences in aortic stenosis: effect on functional capacity and prognosis. Int J Cardiol. 2019 Nov 28. pii: S0167-5273(19)34571-1. doi: 10.1016/j.ijcard.2019.11.136. [Epub ahead of print].
   Google Scholar
• Nguyen V, Mathieu T, Melissopoulou M, et al. Sex differences in the progression of aortic stenosis and prognostic implication: the COFRASA-GENERAC study. JACC Cardiovasc Imaging. 2016;9:499–501.
   PubMed Web of Science ®Google Scholar
• Tastet L, Kwiecinski J, Pibarot P, et al. Sex-related differences in the extent of myocardial fibrosis in patients with aortic valve stenosis. JACC Cardiovasc Imaging. 2019 Aug 14. pii: S1936-878X(19)30596-0 Epub ahead of print. DOI:10.1016/j.jcmg.2019.06.014.
   PubMedGoogle Scholar
• Singh A, Chan DCS, Greenwood JP, et al. Symptom onset in aortic stenosis: relation to sex differences in left ventricular remodeling. JACC Cardiovasc Imaging. 2019;12:96–105.
   PubMed Web of Science ®Google Scholar
• Lee JM, Park SJ, Lee SP, et al. Gender difference in ventricular response to aortic stenosis: insight from cardiovascular magnetic resonance. PLoS One. 2015;10:e0121684.
   PubMed Web of Science ®Google Scholar
• Petrov G, Dworatzek E, Schulze TM, et al. Maladaptive remodeling is associated with impaired survival in women but not in men after aortic valve replacement. JACC Cardiovasc Imaging. 2014;7:1073–1080.
   PubMed Web of Science ®Google Scholar
• Cramariuc D, Rogge BP, Lønnebakken MT, et al. Sex differences in cardiovascular outcome during progression of aortic valve stenosis. Heart. 2015;101:209–214.
   PubMed Web of Science ®Google Scholar
• Villar AV, Llano M, Cobo M, et al. Gender differences of echocardiographic and gene expression patterns in human pressure overload left ventricular hypertrophy. J Mol Cell Cardiol. 2009;46:526–535.
   PubMed Web of Science ®Google Scholar
• Chaker Z, Badhwar V, Alqahtani F, et al. Sex differences in the utilization and outcomes of surgical aortic valve replacement for severe aortic stenosis. J Am Heart Assoc. 2017 Sep 21;6(9):e006370.
   PubMed Web of Science ®Google Scholar
• Fuchs C, Mascherbauer J, Rosenhek R, et al. Gender differences in clinical presentation and surgical outcome of aortic stenosis. Heart. 2010;96:539–545.
   PubMed Web of Science ®Google Scholar
• Yousif N, Obeid S, Binder R, et al. Impact of gender on outcomes after transcatheter aortic valve implantation. J Geriatric Cardiol. 2018;15:394–400.
   Web of Science ®Google Scholar
• Toyofuku M, Taniguchi T, Morimoto T, et al. CURRENT AS registry investigators. Sex differences in severe aortic stenosis - clinical presentation and mortality. Circ J. 2017;81:1213–1221.
   PubMed Web of Science ®Google Scholar
• Chandrasekhar J, Dangas G, Yu J, et al. Sex-based differences in outcomes with transcatheter aortic valve therapy: TVT registry from 2011 to 2014. J Am Coll Cardiol. 2016;68:2733–2744.
   PubMedGoogle Scholar
• Buja P, Napodano M, Tamburino C, et al. Italian multicenter corevalve registry investigators. Comparison of variables in men versus women undergoing transcatheter aortic valve implantation for severe aortic stenosis (from Italian multicenter corevalve registry). Am J Cardiol. 2013;111:88–93.
   PubMed Web of Science ®Google Scholar
• Kararigas G, Dworatzek E, Petrov G, et al. Sex dependent regulation of fibrosis and inflammation in human left ventricular remodelling under pressure overload. Eur J Heart Fail. 2014;16:1160–1167.
   PubMed Web of Science ®Google Scholar
• Dobson LE, Fairbairn TA, Musa TA, et al. Sex related differences in left ventricular remodeling in severe aortic stenosis and reverse remodeling after aortic valve replacement: a cardiovascular magnetic resonance study. Am Heart J. 2016;175:101–111.
   PubMed Web of Science ®Google Scholar
• Capoulade R, Clavel MA, Le Ven F, et al. Impact of left ventricular remodelling patterns on outcomes in patients with aortic stenosis. Eur Heart J Cardiovasc Imaging. 2017 Dec 1;18(12):1378–1387.
   PubMed Web of Science ®Google Scholar
• Saeed S, Gerdts E. Managing complications of hypertension in aortic valve stenosis patients. Expert Rev Cardiovasc Ther. 2018;16:897–907.
   PubMed Web of Science ®Google Scholar
• Carabello BA. The relationship of left ventricular geometry and hypertrophy to left ventricular function in valvular heart disease. J Heart Valve Dis. 1995;4(Suppl 2):S132–9.
   PubMedGoogle Scholar
• Morris JJ, Schaff HV, Mullany CJ, et al. Gender differences in left ventricular functional response to aortic valve replacement. Circulation. 1994;90:II183–9.
   PubMed Web of Science ®Google Scholar
• Aurigemma GP, Silver KH, McLaughlin M, et al. Impact of chamber geometry and gender on left ventricular systolic function in patients > 60 years of age with aortic stenosis. Am J Cardiol. 1994;74:794–798.
   PubMed Web of Science ®Google Scholar
• Villari B, Campbell SE, Schneider J, et al. Sex-dependent differences in left ventricular function and structure in chronic pressure overload. Eur Heart J. 1995;16:1410–1419.
   PubMed Web of Science ®Google Scholar
• Douglas PS, Otto CM, Mickel MC, et al. Gender differences in left ventricle geometry and function in patients undergoing balloon dilatation of the aortic valve for isolated aortic stenosis: NHLBI balloon valvuloplasty registry. Br Heart J. 1995;73:548–554.
   PubMedGoogle Scholar
• Everett RJ, Clavel MA, Pibarot P, et al. Timing of intervention in aortic stenosis: a review of current and future strategies. Heart. 2018 Dec;104(24):2067–2076.
   PubMed Web of Science ®Google Scholar
• 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 Jun;11(6):e007451.
   PubMed Web of Science ®Google Scholar
• Saeed S, Senior R, Chahal NS, et al. Lower transaortic flow rate is associated with increased mortality in aortic valve stenosis. JACC Cardiovasc Imaging. 2017;10:912–920.
   PubMed Web of Science ®Google Scholar
• Hachicha Z, Dumesnil JG, Bogaty P, et al. Paradoxical low-flow, low-gradient severe aortic stenosis despite preserved ejection fraction is associated with higher afterload and reduced survival. Circulation. 2007;115(22):2856–2864.
   Web of Science ®Google Scholar
• Tan YQ, Ngiam JN, Kong WK, et al. Prevalence, clinical and echocardiographic characteristics of various flow and gradient patterns in mild or moderate aortic stenosis with normal left ventricular ejection fraction. Int J Cardiol. 2016;221:1107–1115.
   PubMed Web of Science ®Google Scholar
• Lee SP, Lee W, Lee JM, et al. Assessment of diffuse myocardial fibrosis by using MR imaging in asymptomatic patients with aortic stenosis. Radiology. 2015;274:359–369.
   PubMed Web of Science ®Google Scholar
• Dweck MR, Joshi S, Murigu T, et al. Midwall fibrosis is an independent predictor of mortality in patients with aortic stenosis. J Am Coll Cardiol. 2011;58:1271–1279.
   PubMed Web of Science ®Google Scholar
• Weidemann F, Herrmann S, Störk S, et al. Impact of myocardial fibrosis in patients with symptomatic severe aortic stenosis. Circulation. 2009;120:577–584.
   PubMed Web of Science ®Google Scholar
• Azevedo CF, Nigri M, Higuchi ML, et al. Prognostic significance of myocardial fibrosis quantification by histopathology and magnetic resonance imaging in patients with severe aortic valve disease. J Am Coll Cardiol. 2010;56:278–287.
   PubMed Web of Science ®Google Scholar
• Barone-Rochette G, Piérard S, de Ravenstein DMC, et al. Prognostic significance of LGE by CMR in aortic stenosis patients undergoing valve replacement. J Am Coll Cardiol. 2014;64:144–154.
   PubMed Web of Science ®Google Scholar
• Ng ACT, Prihadi EA, Antoni ML, et al. Left ventricular global longitudinal strain is predictive of all-cause mortality independent of aortic stenosis severity and ejection fraction. Eur Heart J Cardiovasc Imaging. 2018;19:859–867.
   PubMed Web of Science ®Google Scholar
• Weinberg EO, Thienelt CD, Katz SE, et al. Gender differences in molecular remodeling in pressure overload hypertrophy. J Am Coll Cardiol. 1999;34:264–273.
   PubMed Web of Science ®Google Scholar
• Montalvo C, Villar AV, Merino D, et al. Androgens contribute to sex differences in myocardial remodeling under pressure overload by a mechanism involving TGF-β. PLoS One. 2012;7:e35635.
   PubMed Web of Science ®Google Scholar
• Liu CY, Liu YC, Wu C, et al. Evaluation of age-related interstitial myocardial fibrosis with cardiac magnetic resonance contrast-enhanced T1 mapping: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2013;62:1280–1287.
   PubMed Web of Science ®Google Scholar
• Freeman RV, Otto CM. Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies. Circulation. 2005;111:3316–3326.
   PubMed Web of Science ®Google Scholar
• Stewart BF, Siscovick D, Lind BK, et al. Clinical factors associated with calcific aortic valve disease: cardiovascular health study. J Am Coll Cardiol. 1997;29:630–634.
   PubMed Web of Science ®Google Scholar
• Saeed S, Rajani R, Seifert R, et al. Exercise testing in asymptomatic patients with moderate or severe aortic stenosis. Heart. 2018;104:1836–1842.
   PubMed Web of Science ®Google Scholar
• Saeed S, Vamvakidou A, Seifert R, et al. The impact of aortic valve replacement on survival in patients with normal flow low gradient severe aortic stenosis: a propensity-matched comparison. Eur Heart J Cardiovasc Imaging. 2019 Oct 1;20(10):1094–1101.
   PubMed Web of Science ®Google Scholar
• McKellar SH, Michelena HI, Li Z, et al. Long-term risk of aortic events following aortic valve replacement in patients with bicuspid aortic valves. Am J Cardiol. 2010;106:1626–1633.
   PubMed Web of Science ®Google Scholar
• Eveborn GW, Schirmer H, Heggelund G, et al. The evolving epidemiology of valvular aortic stenosis. Tromso Study Heart. 2013;99:396–400.
   PubMed Web of Science ®Google Scholar
• Lauten A, Figulla HR, Mollmann H, et al. TAVI for low-flow, low-gradient severe aortic stenosis with preserved or reduced ejection fraction: a subgroup analysis from the German Aortic Valve Registry (GARY). EuroIntervention. 2014;10:850–859.
   PubMed Web of Science ®Google Scholar
• Pilgrim T, Englberger L, Rothenbuhler M, et al. Long-term outcome of elderly patients with severe aortic stenosis as a function of treatment modality. Heart. 2015;101:30–36.
   PubMed Web of Science ®Google Scholar
• Buchanan GL, Chieffo A, Montorfano M, et al. The role of sex on VARC outcomes following transcatheter aortic valve implantation with both edwards SAPIEN™ and medtronic corevalve revalving system® devices: the milan registry. EuroIntervention. 2011;7:556–563.
   PubMed Web of Science ®Google Scholar
• Chandrasekhar J, Dangas G, Mehran R. Valvular heart disease in women, differential remodeling, and response to new therapies. Curr Treat Options Cardiovasc Med. 2017 Sep 11;19(9):74.
   PubMedGoogle Scholar
• O’Connor SA, Morice MC, Gilard M, et al. Revisiting sex equality with transcatheter aortic valve replacement outcomes. A collaborative, patient-level meta-analysis of 11,310 patients. J Am Coll Cardiol. 2015;66:221–228.
   PubMed Web of Science ®Google Scholar
• Rossi P, Frances Y, Kingwell BA, et al. Gender differences in artery wall biomechanical properties throughout life. J Hypertens. 2011;29:1023–1033.
   PubMed Web of Science ®Google Scholar
• Pibarot P, Dumesnil JG. Assessment of aortic stenosis severity: check the valve but don’t forget the arteries! Heart. 2007;93:780–782.
   PubMed Web of Science ®Google Scholar
• Kamath AR, Pai RG. Risk factors for progression of calcific aortic stenosis and potential therapeutic targets. Int J Angiol. 2008;17:63–70.
   PubMedGoogle Scholar
• O’Ben KD. Pathogenesis of calcific aortic valve disease: a disease process comes of age (and a good deal more). Arterioscler Thromb Vasc Biol. 2006;26:1721–1728.
   PubMed Web of Science ®Google Scholar
• Nishimura RA, Otto CM, Bonow RO, et al. AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol. 2017;70:252–289.
   PubMed Web of Science ®Google Scholar
• Baumgartner H, Falk V, Bax JJ, et al. ESC scientific document group. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J. 2017;38:2739–2791.
   PubMed Web of Science ®Google Scholar
• Kong WK, Regeer MV, Ng AC, et al. Sex differences in phenotypes of bicuspid aortic valve and aortopathy: insights from a large multicenter, international registry. Circ Cardiovasc Imaging. 2017 Mar;10(3):e005155.
   PubMed Web of Science ®Google Scholar
• Roman MJ, Pugh NL, Bavaria JE, et al. Abstract 12308: aortic aneurysm associated with bicuspid aortic valve: relation to gender, hemodynamics, and valve morphology: the NHLBI gentac registry. Circulation. 2015;132:A12308.
   Web of Science ®Google Scholar
• Michelena HI, Suri RM, Katan O, et al. Sex differences and survival in adults with bicuspid aortic valves: verification in 3 contemporary echocardiographic cohorts. J Am Heart Assoc. 2016;5:e004211.
   PubMed Web of Science ®Google Scholar
• Thomassen HK, Cioffi G, Gerdts E, et al. Echocardiographic aortic valve calcification and outcomes in women and men with aortic stenosis. Heart. 2017;103:1619–1624.
   PubMed Web of Science ®Google Scholar
• Legget ME, Kuusisto J, Healy NL, et al. Gender differences in left ventricular function at rest and with exercise in asymptomatic aortic stenosis. Am Heart J. 1996;131:94–100.
   PubMed Web of Science ®Google Scholar
• Lund O, Nielsen TT, Emmertsen K, et al. Mortality and worsening of prognostic profile during waiting time for valve replacement in aortic stenosis. Thorac Cardiovasc Surg. 1996;44:289e95.
   Web of Science ®Google Scholar
• Rosenhek R, Binder T, Porenta G, et al. Predictors of outcome in severe, asymptomatic aortic stenosis. N Engl J Med. 2000;343:611e7.
   Web of Science ®Google Scholar
• Das P, Rimington H, Chambers J. Exercise testing to stratify risk in aortic stenosis. Eur Heart J. 2005;26:1309–1313.
   PubMed Web of Science ®Google Scholar
• Redfors B, Pibarot P, Gillam LD, et al. Stress Testing in Asymptomatic Aortic Stenosis. Circulation. 2017;135:1956–1976.
   PubMed Web of Science ®Google Scholar
• Cowell SJ, Newby DE, Prescott RJ, et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med. 2005;352:2389–2397.
   PubMed Web of Science ®Google Scholar
• Rossebo AB, Pedersen TR, Boman K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008;359:1343–1356.
   PubMed Web of Science ®Google Scholar
• Chan KL, Teo K, Dumesnil JG, et al. Effect of lipid lowering with rosuvastatin on progression of aortic stenosis. Results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial. Circulation. 2010;121:306–314.
   PubMed Web of Science ®Google Scholar
• Daniec M, Dziewierz A, Sorysz D, et al. Sex-related differences in outcomes after percutaneous balloon aortic valvuloplasty. J Invasive Cardiol. 2017;29:188–194.
   PubMed Web of Science ®Google Scholar
• Saeed S, Scalise F, Chambers JB, et al. Hypertension in aortic stenosis: A focused review and recommendations for clinical practice. J Hypertens. 2020. In press. doi:10.1097/HJH.0000000000002426.
   PubMedGoogle Scholar
• Rodriguez-Gabella T, Catalá P, Muñoz-García AJ, et al. Renin-angiotensin system inhibition following transcatheter aortic valve replacement. J Am Coll Cardiol. 2019;74:631–641.
   PubMed Web of Science ®Google Scholar
• Lindman BR, Stewart WJ, Pibarot P, et al. Early regression of severe left ventricular hypertrophy after transcatheter aortic valve replacement is associated with decreased hospitalizations. JACC Cardiovasc Interv. 2014 Jun;7:662–673.
   PubMed Web of Science ®Google Scholar
• Kamperidis V, Joyce E, Debonnaire P, et al. Left ventricular functional recovery and remodeling in low-flow low-gradient severe aortic stenosis after transcatheter aortic valve implantation. J Am Soc Echocardiogr. 2014;27:817–825.
   PubMed Web of Science ®Google Scholar
• Stangl V, Baldenhofer G, Knebel F, et al. Impact of gender on three-month outcome and left ventricular remodeling after transfemoral transcatheter aortic valve implantation. Am J Cardiol. 2012;110:884–890.
   PubMed Web of Science ®Google Scholar
• Pibarot P, Magne J, Leipsic J, et al. Imaging for predicting and assessing prosthesis-patient mismatch after aortic valve replacement. J Am Coll Cardiol Img. 2019;12:149–162.
   Google Scholar
• Tasca G, Brunelli F, Cirillo M, et al. Impact of valve prosthesis-patient mismatch on left ventricular mass regression following aortic valve replacement. Ann Thorac Surg. 2005;79:505–510.
   PubMed Web of Science ®Google Scholar
• Naoum C, Blanke P, Dvir D, et al. clinical outcomes and imaging findings in women undergoing TAVR. JACC Cardiovasc Imaging. 2016;9:483–493.
   PubMed Web of Science ®Google Scholar
• Mohty D, Boulogne C, Magne J, et al. Prevalence and long-term outcome of aortic prosthesis-patient mismatch in patients with paradoxical low-flow severe aortic stenosis. Circulation. 2014;130:S25–31.
   PubMed Web of Science ®Google Scholar
• Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364:2187–2198.
   PubMed Web of Science ®Google Scholar
• Leon MB, Smith CR, Mack MJ, et al. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2016;374:1609–1620.
   PubMed Web of Science ®Google Scholar
• Popma JJ, Deeb GM, Yakubov SJ. Evolut low risk trial investigators. Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients. N Engl J Med. 2019;380:1706–1715.
   PubMed Web of Science ®Google Scholar
• Al-Lamee R, Broyd C, Parker J, et al. Influence of gender on clinical outcomes following transcatheter aortic valve implantation from the UK transcatheter aortic valve implantation registry and the National Institute for Cardiovascular Outcomes Research. Am J Cardiol. 2014;113:522–528.
   PubMed Web of Science ®Google Scholar
• Zhao ZG, Liao YB, Peng Y, et al. Sex-related differences in outcomes after transcatheter aortic valve implantation: a systematic review and meta-analysis. Circ Cardiovasc Interventions. 2013;6:543–551.
   PubMed Web of Science ®Google Scholar
• Conrotto F, D’Ascenzo F, Presbitero P, et al. Effect of gender after transcatheter aortic valve implantation. Ann Thorac Surg. 2015;99:809–816.
   PubMed Web of Science ®Google Scholar
• Skelding KA, Yakubov SJ, Kleiman NS, et al. Transcatheter aortic valve replacement versus surgery in women at high risk for surgical aortic valve replacement (from the corevalve US high risk pivotal trial). Am J Cardiol. 2016;118:560–566.
   PubMed Web of Science ®Google Scholar
• Ferrante G, Pagnotta P, Petronio AS, et al. Sex differences in postprocedural aortic regurgitation and mid-term mortality after transcatheter aortic valve implantation. Catheter Cardiovasc Interv. 2014;84:264–271.
   PubMed Web of Science ®Google Scholar
• Qian Z, Lancellotti P, Vannan MA. Aortic root calcium burden and post-transcatheter aortic valve implantation paravalvular leak: can’t live without it, can’t live with it. Eur Heart J Cardiovasc Imaging. 2017;18:654–656.
   PubMed Web of Science ®Google Scholar
• Abdel-Wahab M, Mehilli J, Frerker C, et al. Comparison of balloon-expandable vs self-expandable valves in patients undergoing transcatheter aortic valve replacement. JAMA. 2014;311:1503.
   PubMed Web of Science ®Google Scholar
• Leon MB, Smith CR, Mack M, et al. PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363:1597–1607.
   PubMed Web of Science ®Google Scholar
• Moat NE, Ludman P, de Belder MA, et al. Long-term outcomes after transcatheter aortic valve implantation in high-risk patients with severe aortic stenosis: the U.K. TAVI (United Kingdom transcatheter aortic valve implantation) registry. J Am Coll Cardiol. 2011;58:2130–2138.
   PubMed Web of Science ®Google Scholar
• Gilard M, Eltchaninoff H, Iung B, et al. FRANCE 2 investigators. Registry of transcatheter aortic-valve implantation in high-risk patients. N Engl J Med. 2012;366:1705–1715.
   PubMed Web of Science ®Google Scholar
• Assmann P, Kievit P, van der Wulp K, et al. Frailty is associated with delirium and mortality after transcatheter aortic valve implantation. Open Heart. 2016 Dec 12;3(2):e000478.
   PubMed Web of Science ®Google Scholar
• Skaar E, Eide LSP, Norekvål TM, et al. A novel geriatric assessment frailty score predicts 2-year mortality after transcatheter aortic valve implantation. Eur Heart J Qual Care Clin Outcomes. 2019 Apr 1;5(2):153–160.
   PubMed Web of Science ®Google Scholar
• Eide LS, Ranhoff AH, Fridlund B, et al. Comparison of frequency, risk factors, and time course of postoperative delirium in octogenarians after transcatheter aortic valve implantation versus surgical aortic valve replacement. Am J Cardiol. 2015 Mar 15;115(6):802–809.
   PubMed Web of Science ®Google Scholar
• Johnson BD, Shaw LJ, Buchthal SD, et al. Prognosis in women with myocardial ischemia in the absence of obstructive coronary disease: results from the national institutes of health-national heart, lung, and blood institute-sponsored Women’s Ischemia Syndrome Evaluation (WISE). Circulation. 2004;109:2993–2999.
   PubMed Web of Science ®Google Scholar
• Stenström I, Maaniitty T, Uusitalo V, et al. Frequency and angiographic characteristics of coronary microvascular dysfunction in stable angina: a hybrid imaging study. Eur Heart J Cardiovasc Imaging. 2017;18:1206–1213.
   PubMed Web of Science ®Google Scholar
• Bahlmann E, Cramariuc D, Gerdts E, et al. Impact of pressure recovery on echocardiographic assessment of asymptomatic aortic stenosis: a SEAS substudy. JACC Cardiovasc Imaging. 2010;3:555–562.
   PubMed Web of Science ®Google Scholar
• Nagata Y, Takeuchi M, Wu VC, et al. Prognostic value of LV deformation parameters using 2D and 3D speckle-tracking echocardiography in asymptomatic patients with severe aortic stenosis and preserved LV ejection fraction. JACC Cardiovasc Imaging. 2015;8:235–245.
   PubMed Web of Science ®Google Scholar
• Mor-Avi V, Sugeng L, Weinert L, et al. Fast measurement of left ventricular mass with real-time three-dimensional echocardiography: comparison with magnetic resonance imaging. Circulation. 2004;110:1814–1818.
   PubMed Web of Science ®Google Scholar
• Lang RM, Badano LP, Tsang W, et al. EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography. J Am Soc Echocardiogr. 2012;25:3–46.
   PubMed Web of Science ®Google Scholar