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Canadian Journal of Cardiology

Sex and Race Differences in the Pathophysiology, Diagnosis, Treatment, and Outcomes of Valvular Heart Diseases

  • Marie-Ange Fleury
    Affiliations
    Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada
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  • Marie-Annick Clavel
    Correspondence
    ∗ Corresponding author: Dr Marie-Annick Clavel, Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Sainte-Foy, Québec City, Québec G1V 4G5, Canada. Tel: +1-418-656-8711 ext: 2678; fax: +1-418-656-4918
    Affiliations
    Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada
    Search for articles by this author
Published:February 10, 2021DOI:https://doi.org/10.1016/j.cjca.2021.02.003

      Abstract

      Valvular heart diseases have long been considered to be similar in men and women and across races/ethnicities. Recently, studies have demonstrated major differences between sexes. Unfortunately, studies on valvular heart diseases, as on other cardiovascular diseases, are mostly performed in Caucasian men or in cohorts with a vast majority of Caucasian men. Therefore, our knowledge on valvular diseases in women and non-Caucasians remains limited. Nevertheless, aortic stenosis has been shown to be almost as prevalent in women as in men, and less prevalent in African Americans. Men appear to have a more calcified aortic valve lesion, and women tend to have a more fibrosed one. Primary mitral regurgitation is more frequent in women who have more rheumatic and Barlow etiologies, whereas men have more fibroelastic deficiency and posterior leaflet prolapse/flail. Left ventricular remodelling due to valvular heart diseases is sex related in terms of geometry and probably also in composition of the tissue. Outcomes seem to be worse in women after surgical interventions and better than or equivalent to men after transcatheter ones. Regarding other valvular heart diseases, very few studies are available: Aortic regurgitation is more frequent in men, isolated tricuspid regurgitation more frequent in women. Rheumatic valve diseases are more frequent in women and are mostly represented by mitral and aortic stenoses. Many other sex/gender- and race/ethnic-specific studies are still needed in epidemiology, pathophysiology, presentation, management, and outcomes. This review aims to report the available data on sex differences and race specificities in valvular heart diseases, with a primary focus on aortic stenosis and mitral regurgitation.

      Résumé

      Les cardiopathies valvulaires ont longtemps été considérées comme étant similaires chez les hommes et les femmes, de même que chez l’ensemble des races/origines ethniques. Récemment, des études ont montré qu’il existe des différences majeures entre les sexes. Malheureusement, les études sur les cardiopathies valvulaires, -comme celles sur les autres maladies cardiovasculaires, sont pour la plupart menées chez des hommes blancs ou dans des cohortes comptant une vaste majorité d’hommes blancs. Nos connaissances sur les valvulopathies chez les femmes et les personnes non blanches demeurent donc limitées. Néanmoins, la prévalence de sténose aortique est presque identique chez les femmes et les hommes, et est plus faible chez les Afro-Américains. Les lésions de la valve aortique sont plus calcifiées chez les hommes, et sont plus fibrosées chez les femmes. L'insuffisance mitrale s’observe plus souvent chez les femmes, pour lesquelles les étiologies les plus fréquentes sont une atteinte rhumatismale ou la maladie de Barlow, tandis que les hommes présentent plus souvent une déficience fibroélastique avec prolapsus/éversion du feuillet postérieur. Le remodelage ventriculaire gauche dû aux cardiopathies valvulaires est lié au sexe en ce qui a trait à la géométrie et, probablement, aussi à la composition des tissus. Par rapport aux hommes, les femmes semblent avoir un devenir plus défavorable après des interventions chirurgicales alors qu'il est supérieur ou équivalent après des interventions par voie transcathéter. Il y a très peu d’études sur les autres cardiopathies valvulaires : l'insuffisance aortique est plus fréquente chez les hommes et l'insuffisance tricuspide isolée est plus fréquente chez les femmes. Les valvulopathies rhumatismales sont plus fréquentes chez les femmes et se manifestent surtout par des sténoses mitrales et aortiques. De nombreuses autres études doivent encore être menées, en fonction du sexe/genre et de la race/l’origine ethnique, sur l’épidémiologie, la physiopathologie, les premiers signes ou symptômes, la prise en charge et les issues. Cette revue vise à présenter les données dont on dispose sur les différences entre les sexes et les caractéristiques propres à la race chez les patients atteints de cardiopathies valvulaires, plus particulièrement de sténose aortique et d'insuffisance mitrale.
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      References

        • Maganti K.
        • Rigolin V.H.
        • Sarano M.E.
        • Bonow R.O.
        Valvular heart disease: diagnosis and management.
        Mayo Clin Proc. 2010; 85: 483-500
        • Go A.S.
        • Mozaffarian D.
        • Roger V.L.
        • et al.
        Heart disease and stroke statistics—2013 update: a report from the American Heart Association.
        Circulation. 2013; 127: e6-e245
        • Iung B.
        • Vahanian A.
        Epidemiology of valvular heart disease in the adult.
        Nat Rev Cardiol. 2011; 8: 162-172
        • Norris C.M.
        • Yip C.Y.Y.
        • Nerenberg K.A.
        • et al.
        State of the science in women’s cardiovascular disease: A Canadian perspective on the influence of sex and gender.
        J Am Heart Assoc. 2020; 9e015634
        • Nattel S.
        • Pilote L.
        Sex as a key variable in predicting cardiovascular outcomes: rapidly evolving knowledge but much more needed.
        Can J Cardiol. 2020; 36: 1-3
        • Lancet T.
        Cardiology’s problem women.
        Lancet. 2019; 393: 959
        • Humphries K.H.
        • Izadnegahdar M.
        • Sedlak T.
        • et al.
        Sex differences in cardiovascular disease—impact on care and outcomes.
        Front Neuroendocrinol. 2017; 46: 46-70
        • Pelletier R.
        • Khan N.A.
        • Cox J.
        • et al.
        Sex versus gender-related characteristics: which predicts outcome after acute coronary syndrome in the young?.
        J Am Coll Cardiol. 2016; 67: 127-135
        • Kaplan J.B.
        • Bennett T.
        Use of race and ethnicity in biomedical publication.
        JAMA. 2003; 289: 2709-2716
        • Martinsson A.
        • Li X.
        • Andersson C.
        • et al.
        Temporal trends in the incidence and prognosis of aortic stenosis: a nationwide study of the Swedish population.
        Circulation. 2015; 131: 988-994
        • Osnabrugge R.L.
        • Mylotte D.
        • Head S.J.
        • et al.
        Aortic stenosis in the elderly: disease prevalence and number of candidates for transcatheter aortic valve replacement: a meta-analysis and modeling study.
        J Am Coll Cardiol. 2013; 62: 1002-1012
        • Andell P.
        • Li X.
        • Martinsson A.
        • et al.
        Epidemiology of valvular heart disease in a swedish nationwide hospital-based register study.
        Heart. 2017; 103: 1696-1703
        • Clavel M.A.
        • Iung B.
        • Pibarot P.
        A nationwide contemporary epidemiological portrait of valvular heart diseases.
        Heart. 2017; 103: 1660-1662
        • Toyofuku M.
        • Taniguchi T.
        • Morimoto T.
        • et al.
        Sex differences in severe aortic stenosis—clinical presentation and mortality.
        Circ J. 2017; 81: 1213-1221
        • Ward C.
        Clinical significance of the bicuspid aortic valve.
        Heart. 2000; 83: 81-85
        • Tutar E.
        • Ekici F.
        • Atalay S.
        • Nacar N.
        The prevalence of bicuspid aortic valve in newborns by echocardiographic screening.
        Am Heart J. 2005; 150: 513-515
        • Fedak P.W.
        • Verma S.
        • David T.E.
        • et al.
        Clinical and pathophysiological implications of a bicuspid aortic valve.
        Circulation. 2002; 106: 900-904
        • McKellar S.H.
        • Michelena H.I.
        • Li Z.
        • Schaff H.V.
        • Sundt III, T.M.
        Long-term risk of aortic events following aortic valve replacement in patients with bicuspid aortic valves.
        Am J Cardiol. 2010; 106: 1626-1633
        • Kong W.K.
        • Regeer M.V.
        • Ng A.C.
        • et al.
        Sex differences in phenotypes of bicuspid aortic valve and aortopathy: insights from a large multicenter, international registry.
        Circ Cardiovasc Imaging. 2017; : 10
        • Cripe L.
        • Andelfinger G.
        • Martin L.J.
        • Shooner K.
        • Benson D.W.
        Bicuspid aortic valve is heritable.
        J Am Coll Cardiol. 2004; 44: 138-143
        • Glick B.N.
        • Roberts W.C.
        Congenitally bicuspid aortic valve in multiple family members.
        Am J Cardiol. 1994; 73: 400-404
        • Robledo-Carmona J.
        • Rodríguez-Bailón I.
        • Carrasco-Chinchilla F.
        • et al.
        Hereditary patterns of bicuspid aortic valve in a hundred families.
        Int J Cardiol. 2013; 168: 3443-3449
        • Sievers H.H.
        • Schmidtke C.
        A classification system for the bicuspid aortic valve from 304 surgical specimens.
        J Thorac Cardiovasc Surg. 2007; 133: 1226-1233
        • Michelena H.I.
        • Suri R.M.
        • 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; 5e004211
        • Michelena H.I.
        • Khanna A.D.
        • Mahoney D.
        • et al.
        Incidence of aortic complications in patients with bicuspid aortic valves.
        JAMA. 2011; 306: 1104-1112
        • Tzemos N.
        • Therrien J.
        • Yip J.
        • et al.
        Outcomes in adults with bicuspid aortic valves.
        JAMA. 2008; 300: 1317-1325
        • Ren X.
        • Li F.
        • Wang C.
        • et al.
        Age- and sex-related aortic valve dysfunction and aortopathy difference in patients with bicuspid aortic valve.
        Int Heart J. 2019; 60: 637-642
        • Andrei A.C.
        • Yadlapati A.
        • Malaisrie S.C.
        • et al.
        Comparison of outcomes and presentation in men-versus-women with bicuspid aortic valves undergoing aortic valve replacement.
        Am J Cardiol. 2015; 116: 250-255
        • Harrison O.J.
        • Visan A.C.
        • Moorjani N.
        • et al.
        Defective NOTCH signaling drives increased vascular smooth muscle cell apoptosis and contractile differentiation in bicuspid aortic valve aortopathy: a review of the evidence and future directions.
        Trends Cardiovasc Med. 2019; 29: 61-68
        • Lee A.
        • Wei S.
        • Schwertani A.
        A Notch more: molecular players in bicuspid aortic valve disease.
        J Mol Cell Cardiol. 2019; 134: 62-68
        • Gould R.A.
        • Aziz H.
        • Woods C.E.
        • et al.
        ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm.
        Nat Genet. 2019; 51: 42-50
        • Bravo-Jaimes K.
        • Prakash S.K.
        Genetics in bicuspid aortic valve disease: where are we?.
        Prog Cardiovasc Dis. 2020; 63: 398-406
        • Dargis N.
        • Lamontagne M.
        • Gaudreault N.
        • et al.
        Identification of gender-specific genetic variants in patients with bicuspid aortic valve.
        Am J Cardiol. 2016; 117: 420-426
        • Aggarwal S.R.
        • Clavel M.A.
        • 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
        • Clavel M.A.
        • 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
        • Pawade T.
        • Clavel M.A.
        • Tribouilloy C.
        • et al.
        Computed tomography aortic valve calcium scoring in patients with aortic stenosis.
        Circ Cardiovasc Imaging. 2018; 11e007146
        • Baumgartner H.
        • Falk V.
        • Bax J.J.
        • et al.
        2017 ESC/EACTS guidelines for the management of valvular heart disease: the Task Force for 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. 2017; 38: 2739-2791
        • Clavel M.A.
        • 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
        • Tastet L.
        • Enriquez-Sarano M.
        • Capoulade R.
        • et al.
        Impact of aortic valve calcification and sex on hemodynamic progression and clinical outcomes in AS.
        J Am Coll Cardiol. 2017; 69: 2096-2098
        • Cote N.
        • Clavel M.A.
        Sex differences in the pathophysiology, diagnosis, and management of aortic stenosis.
        Cardiol Clin. 2020; 38: 129-138
        • Dweck M.R.
        • Boon N.A.
        • Newby D.E.
        Calcific aortic stenosis: a disease of the valve and the myocardium.
        J Am Coll Cardiol. 2012; 60: 1854-1863
        • Akahori H.
        • Tsujino T.
        • Masuyama T.
        • Ishihara M.
        Mechanisms of aortic stenosis.
        J Cardiol. 2018; 71: 215-220
        • Voisine M.
        • Hervault M.
        • Shen M.
        • et al.
        Age, sex, and valve phenotype differences in fibro-calcific remodeling of calcified aortic valve.
        J Am Heart Assoc. 2020; 9e015610
        • 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
        • McCoy C.M.
        • Nicholas D.Q.
        • Masters K.S.
        Sex-related differences in gene expression by porcine aortic valvular interstitial cells.
        PLoS One. 2012; 7e39980
        • Masjedi S.
        • Lei Y.
        • Patel J.
        • Ferdous Z.
        Sex-related differences in matrix remodeling and early osteogenic markers in aortic valvular interstitial cells.
        Heart Vessels. 2017; 32: 217-228
        • Parra-Izquierdo I.
        • Castanos-Mollor I.
        • Lopez 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; 38: 2148-2159
        • Dahl J.S.
        • Magne J.
        • Pellikka P.A.
        • Donal E.
        • Marwick T.H.
        Assessment of subclinical left ventricular dysfunction in aortic stenosis.
        JACC Cardiovasc Imaging. 2019; 12: 163-171
        • Carroll J.D.
        • Carroll E.P.
        • Feldman T.
        • et al.
        Sex-associated differences in left ventricular function in aortic stenosis of the elderly.
        Circulation. 1992; 86: 1099-1107
        • Treibel T.A.
        • Kozor R.
        • Fontana M.
        • et al.
        Sex dimorphism in the myocardial response to aortic stenosis.
        JACC Cardiovasc Imaging. 2018; 11: 962-973
        • Lee J.M.
        • Park S.J.
        • Lee S.P.
        • et al.
        Gender difference in ventricular response to aortic stenosis: insight from cardiovascular magnetic resonance.
        PLoS One. 2015; 10e0121684
        • Capoulade R.
        • Clavel M.A.
        • Le Ven F.
        • et al.
        Impact of left ventricular remodelling patterns on outcomes in patients with aortic stenosis.
        Eur Heart J Cardiovasc Imaging. 2017; 18: 1378-1387
        • 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
        • 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. 2020; 13: 699-711
        • Elmariah S.
        Patterns of left ventricular remodeling in aortic stenosis: therapeutic implications.
        Curr Treat Options Cardiovasc Med. 2015; 17: 391
        • Ugander M.
        • Oki A.J.
        • Hsu L.Y.
        • et al.
        Extracellular volume imaging by magnetic resonance imaging provides insights into overt and sub-clinical myocardial pathology.
        Eur Heart J. 2012; 33: 1268-1278
        • Dumesnil J.G.
        • Shoucri R.M.
        Effect of the geometry of the left ventricle on the calculation of ejection fraction.
        Circulation. 1982; 65: 91-98
        • Clavel M.A.
        • Dumesnil J.G.
        • Capoulade R.
        • et al.
        Outcome of patients with aortic stenosis, small valve area and low-flow, low-gradient despite preserved left ventricular ejection fraction.
        J Am Coll Cardiol. 2012; 60: 1259-1267
        • Lee S.P.
        • Kim Y.J.
        • Kim J.H.
        • et al.
        Deterioration of myocardial function in paradoxical low-flow severe aortic stenosis: two-dimensional strain analysis.
        J Am Soc Echocardiogr. 2011; 24: 976-983
        • Vollema E.M.
        • Sugimoto T.
        • Shen M.
        • et al.
        Association of left ventricular global longitudinal strain with asymptomatic severe aortic stenosis natural course and prognostic value.
        JAMA Cardiol. 2018; 3: 839-847
        • Clavel M.A.
        • Pibarot P.
        • Dumesnil J.G.
        Paradoxical low flow aortic valve stenosis: incidence, evaluation, and clinical significance.
        Curr Cardiol Rep. 2014; 16: 431
        • Guzzetti E.
        • Poulin A.
        • Annabi M.S.
        • et al.
        Transvalvular flow, sex, and survival after valve replacement surgery in patients with severe aortic stenosis.
        J Am Coll Cardiol. 2020; 75: 1897-1909
        • Lang R.M.
        • Badano L.P.
        • 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
        • Hayward C.S.
        • Kalnins W.V.
        • Kelly R.P.
        Gender-related differences in left ventricular chamber function.
        Cardiovasc Res. 2001; 49: 340-350
        • Clavel M.A.
        • Fuchs C.
        • Burwash I.G.
        • et al.
        Predictors of outcomes in low-flow, low-gradient aortic stenosis: results of the multicenter TOPAS study.
        Circulation. 2008; 118: S234-S242
        • 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; 6e006370
        • Lee R.
        • Li S.
        • Rankin J.S.
        • et al.
        Fifteen-year outcome trends for valve surgery in North America.
        Ann Thorac Surg. 2011; 91: 677-684
        • Dobson L.E.
        • Fairbairn T.A.
        • Musa T.A.
        • 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
        • Fuchs C.
        • Mascherbauer J.
        • Rosenhek R.
        • et al.
        Gender differences in clinical presentation and surgical outcome of aortic stenosis.
        Heart. 2010; 96: 539-545
        • Barreto-Filho J.A.
        • Wang Y.
        • Dodson J.A.
        • et al.
        Trends in aortic valve replacement for elderly patients in the United States, 1999-2011.
        JAMA. 2013; 310: 2078-2085
        • Brown J.M.
        • O’Brien S.M.
        • Wu C.
        • et al.
        Isolated aortic valve replacement in North America comprising 108,687 patients in 10 years: changes in risks, valve types, and outcomes in the Society of Thoracic Surgeons National Database.
        J Thorac Cardiovasc Surg. 2009; 137: 82-90
        • Singh A.
        • Musa T.A.
        • Treibel T.A.
        • et al.
        Sex differences in left ventricular remodelling, myocardial fibrosis and mortality after aortic valve replacement.
        Heart. 2019; 105: 1818-1824
        • Pighi M.
        • Piazza N.
        • Martucci G.
        • et al.
        Sex-specific determinants of outcomes after transcatheter aortic valve replacement.
        Circ Cardiovasc Qual Outcomes. 2019; 12e005363
        • Saad M.
        • Nairooz R.
        • Pothineni N.V.K.
        • et al.
        Long-term outcomes with transcatheter aortic valve replacement in women compared with men: evidence from a meta-analysis.
        JACC Cardiovasc Interv. 2018; 11: 24-35
        • Kodali S.
        • Williams M.R.
        • Doshi D.
        • et al.
        Sex-specific differences at presentation and outcomes among patients undergoing transcatheter aortic valve replacement: a cohort study.
        Ann Intern Med. 2016; 164: 377-384
        • Czarnecki A.
        • Qiu F.
        • Koh M.
        • et al.
        Clinical outcomes after trans-catheter aortic valve replacement in men and women in Ontario, Canada.
        Catheter Cardiovasc Interv. 2017; 90: 486-494
        • Lindman B.R.
        • Piana R.N.
        What does sex have to do with transcatheter aortic valve replacement?.
        JACC Cardiovasc Interv. 2018; 11: 21-23
        • Fish R.D.
        Transcatheter aortic valve replacement: what really matters for women?.
        Tex Heart Inst J. 2018; 45: 236-237
        • Humphries K.H.
        • Toggweiler S.
        • Rodés-Cabau J.
        • et al.
        Sex differences in mortality after transcatheter aortic valve replacement for severe aortic stenosis.
        J Am Coll Cardiol. 2012; 60: 882-886
        • Patel D.K.
        • Green K.D.
        • Fudim M.
        • et al.
        Racial differences in the prevalence of severe aortic stenosis.
        J Am Heart Assoc. 2014; 3e000879
        • Beydoun H.A.
        • Beydoun M.A.
        • Liang H.
        • et al.
        Sex, race, and socioeconomic disparities in patients with aortic stenosis (from a nationwide inpatient sample).
        Am J Cardiol. 2016; 118: 860-865
        • Chandra S.
        • Lang R.M.
        • Nicolarsen J.
        • et al.
        Bicuspid aortic valve: inter-racial difference in frequency and aortic dimensions.
        JACC Cardiovasc Imaging. 2012; 5: 981-989
        • Novaro G.M.
        • Houghtaling P.L.
        • Gillinov A.M.
        • Blackstone E.H.
        • Asher C.R.
        Prevalence of mitral valve prolapse and congenital bicuspid aortic valves in black and white patients undergoing cardiac valve operations.
        Am J Cardiol. 2013; 111: 898-901
        • Liu F.
        • Yang Y.N.
        • Xie X.
        • et al.
        Prevalence of congenital heart disease in Xinjiang multi-ethnic region of China.
        PLoS One. 2015; 10e0133961
        • Jilaihawi H.
        • Wu Y.
        • Yang Y.
        • et al.
        Morphological characteristics of severe aortic stenosis in China: imaging corelab observations from the first Chinese transcatheter aortic valve trial.
        Catheter Cardiovasc Interv. 2015; 85: 752-761
        • Li Y.
        • Wei X.
        • Zhao Z.
        • et al.
        Prevalence and complications of bicuspid aortic valve in Chinese according to echocardiographic database.
        Am J Cardiol. 2017; 120: 287-291
        • Kong W.K.F.
        • Regeer M.V.
        • Poh K.K.
        • et al.
        Inter-ethnic differences in valve morphology, valvular dysfunction, and aortopathy between Asian and European patients with bicuspid aortic valve.
        Eur Heart J. 2018; 39: 1308-1313
        • Tay E.L.W.
        • Ngiam J.N.
        • Kong W.K.
        • Poh K.K.
        Management of severe aortic stenosis: the Singapore and Asian perspective.
        Singapore Med J. 2018; 59: 452-454
        • Hernandez-Suarez D.F.
        • Ranka S.
        • Villablanca P.
        • et al.
        Racial/ethnic disparities in patients undergoing transcatheter aortic valve replacement: insights from the healthcare cost and utilization project’s national inpatient sample.
        Cardiovasc Revasc Med. 2019; 20: 546-552
        • Alkhouli M.
        • Holmes D.R.
        • Carroll J.D.
        • et al.
        Racial disparities in the utilization and outcomes of TAVR: TVT registry report.
        JACC Cardiovasc Interv. 2019; 12: 936-948
        • Alqahtani F.
        • Aljohani S.
        • Amin A.H.
        • et al.
        Effect of race on the incidence of aortic stenosis and outcomes of aortic valve replacement in the United States.
        Mayo Clin Proc. 2018; 93: 607-617
        • Taylor N.E.
        • O’Brien S.
        • Edwards F.H.
        • Peterson E.D.
        • Bridges C.R.
        Relationship between race and mortality and morbidity after valve replacement surgery.
        Circulation. 2005; 111: 1305-1312
        • Vahanian A.
        • Iung B.
        Mitral regurgitation. Timing of surgery or interventional treatment.
        Herz. 2016; 41: 3-9
        • Dziadzko V.
        • Clavel M.A.
        • Dziadzko M.
        • et al.
        Outcome and undertreatment of mitral regurgitation: a community cohort study.
        Lancet. 2018; 391: 960-969
        • Dziadzko V.
        • Enriquez-Sarano M.
        Isolated mitral regurgitation in the population: prevalence and outcomes.
        J Am Coll Cardiol. 2016; 67: 2188
        • Nishimura R.A.
        • Otto C.M.
        • Bonow R.O.
        • et al.
        2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2014; 63: 2438-2488
        • Nitsche C.
        • Koschutnik M.
        • Kammerlander A.
        • Hengstenberg C.
        • Mascherbauer J.
        Gender-specific differences in valvular heart disease.
        Wien Klin Wochenschr. 2020; 132: 61-68
        • Beaudoin J.
        • Handschumacher M.D.
        • Zeng X.
        • et al.
        Mitral valve enlargement in chronic aortic regurgitation as a compensatory mechanism to prevent functional mitral regurgitation in the dilated left ventricle.
        J Am Coll Cardiol. 2013; 61: 1809-1816
        • Avierinos J.F.
        • Inamo J.
        • Grigioni F.
        • et al.
        Sex differences in morphology and outcomes of mitral valve prolapse.
        Ann Intern Med. 2008; 149: 787-795
        • Mantovani F.
        • Clavel M.A.
        • Michelena H.I.
        • et al.
        Comprehensive imaging in women with organic mitral regurgitation: implications for clinical outcome.
        JACC Cardiovasc Imaging. 2016; 9: 388-396
        • Vakamudi S.
        • Jellis C.
        • Mick S.
        • et al.
        Sex differences in the etiology of surgical mitral valve disease.
        Circulation. 2018; 138: 1749-1751
        • Seeburger J.
        • Eifert S.
        • Pfannmüller B.
        • et al.
        Gender differences in mitral valve surgery.
        Thorac Cardiovasc Surg. 2013; 61: 42-46
        • Kislitsina O.N.
        • Zareba K.M.
        • Bonow R.O.
        • et al.
        Is mitral valve disease treated differently in men and women?.
        Eur J Prev Cardiol. 2019; 26: 1433-1443
        • Monteagudo Ruiz J.M.
        • Galderisi M.
        • Buonauro A.
        • et al.
        Overview of mitral regurgitation in Europe: results from the European Registry of Mitral Regurgitation (EuMiClip).
        Eur Heart J Cardiovasc Imaging. 2018; 19: 503-507
        • Dziadzko V.
        • Dziadzko M.
        • Medina-Inojosa J.R.
        • et al.
        Causes and mechanisms of isolated mitral regurgitation in the community: clinical context and outcome.
        Eur Heart J. 2019; 40: 2194-2202
        • Amigoni M.
        • Meris A.
        • Thune J.J.
        • et al.
        Mitral regurgitation in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both: prognostic significance and relation to ventricular size and function.
        Eur Heart J. 2007; 28: 326-333
        • Kataria R.
        • Friedman A.
        • Wiesenfeld E.
        • Latib M.A.
        • Jorde U.P.
        Sex differences in functional mitral regurgitation [abstract].
        Circulation. 2019; 140: A14028
        • LaPar D.J.
        • Likosky D.S.
        • Zhang M.
        • et al.
        Development of a risk prediction model and clinical risk score for isolated tricuspid valve surgery.
        Ann Thorac Surg. 2018; 106: 129-136
        • McNeely C.
        • Vassileva C.
        Mitral valve surgery in women: another target for eradicating sex inequality.
        Circ Cardiovasc Qual Outcomes. 2016; 9: S94-S96
        • Vassileva C.M.
        • Stelle L.M.
        • Markwell S.
        • Boley T.
        • Hazelrigg S.
        Sex differences in procedure selection and outcomes of patients undergoing mitral valve surgery.
        Heart Surg Forum. 2011; 14: E276-E282
        • Gammie J.S.
        • Sheng S.
        • Griffith B.P.
        • et al.
        Trends in mitral valve surgery in the United States: results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database.
        Ann Thorac Surg. 2009; 87: 1431-1437
        • Suri R.M.
        • Clavel M.A.
        • Schaff H.V.
        • et al.
        Effect of recurrent mitral regurgitation following degenerative mitral valve repair: long-term analysis of competing outcomes.
        J Am Coll Cardiol. 2016; 67: 488-498
        • Giustino G.
        • Overbey J.
        • Taylor D.
        • et al.
        Sex-based differences in outcomes after mitral valve surgery for severe ischemic mitral regurgitation: from the Cardiothoracic Surgical Trials Network.
        JACC Heart Fail. 2019; 7: 481-490
        • Werner N.
        • Puls M.
        • Baldus S.
        • et al.
        Gender-related differences in patients undergoing transcatheter mitral valve interventions in clinical practice: 1-year results from the German TRAMI registry.
        Catheter Cardiovasc Interv. 2020; 95: 819-829
        • Paulus M.G.
        • Meindl C.
        • Böhm L.
        • et al.
        Predictors of functional improvement in the short term after MitraClip implantation in patients with secondary mitral regurgitation.
        PLoS One. 2020; 15e0232817
        • Estévez-Loureiro R.
        • Settergren M.
        • Winter R.
        • et al.
        Effect of gender on results of percutaneous edge-to-edge mitral valve repair with MitraClip system.
        Am J Cardiol. 2015; 116: 275-279
        • Attizzani G.F.
        • Ohno Y.
        • Capodanno D.
        • et al.
        Gender-related clinical and echocardiographic outcomes at 30-day and 12-month follow up after MitraClip implantation in the GRASP registry.
        Catheter Cardiovasc Interv. 2015; 85: 889-897
        • Stone G.W.
        • Lindenfeld J.
        • Abraham W.T.
        • et al.
        Transcatheter mitral-valve repair in patients with heart failure.
        N Engl J Med. 2018; 379: 2307-2318
        • DiGiorgi P.L.
        • Baumann F.G.
        • O’Leary A.M.
        • et al.
        Mitral valve disease presentation and surgical outcome in African-American patients compared with white patients.
        Ann Thorac Surg. 2008; 85: 89-93
        • Hoyler M.M.
        • Feng T.R.
        • Ma X.
        • et al.
        Insurance status and socioeconomic factors affect early mortality after cardiac valve surgery.
        J Cardiothorac Vasc Anesth. 2020; 34: 3234-3242
        • DiGiorgi P.L.
        • Baumann F.G.
        • O’Leary A.M.
        • et al.
        Differences in mitral valve disease presentation and surgical treatment outcome between Hispanic and non-Hispanic patients.
        Ethn Dis. 2008; 18: 306-310
        • Vassileva C.M.
        • Markwell S.
        • Boley T.
        • Hazelrigg S.
        Impact of race on mitral procedure selection and short-term outcomes of patients undergoing mitral valve surgery.
        Heart Surg Forum. 2011; 14: E221-E226
        • Mentias A.
        • Feng K.
        • Alashi A.
        • et al.
        Long-term outcomes in patients with aortic regurgitation and preserved left ventricular ejection fraction.
        J Am Coll Cardiol. 2016; 68: 2144-2153
        • Nishimura R.A.
        • Otto C.M.
        • Bonow R.O.
        • et al.
        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 Practice Guidelines.
        J Am Coll Cardiol. 2014; 63: e57-e185
        • Walsh-Wilkinson E.
        • Drolet M.C.
        • Arsenault M.
        • Couet J.
        Sex differences in the evolution of left ventricle remodeling in rats with severe volume overload.
        BMC Cardiovasc Disord. 2020; 20: 51
        • Alashi A.
        • Khullar T.
        • Mentias A.
        • et al.
        Long-term outcomes after aortic valve surgery in patients with asymptomatic chronic aortic regurgitation and preserved LVEF: impact of baseline and follow-up global longitudinal strain.
        JACC Cardiovasc Imaging. 2020; 13: 12-21
        • Sambola A.
        • Tornos P.
        • Ferreira-Gonzalez I.
        • Evangelista A.
        Prognostic value of preoperative indexed end-systolic left ventricle diameter in the outcome after surgery in patients with chronic aortic regurgitation.
        Am Heart J. 2008; 155: 1114-1120
        • Turina J.
        • Milincic J.
        • Seifert B.
        • Turina M.
        Valve replacement in chronic aortic regurgitation. True predictors of survival after extended follow-up.
        Circulation. 1998; 98: 100-106
        • Yang L.T.
        • Michelena H.I.
        • Scott C.G.
        • et al.
        Outcomes in chronic hemodynamically significant aortic regurgitation and limitations of current guidelines.
        J Am Coll Cardiol. 2019; 73: 1741-1752
        • Topilsky Y.
        Tricuspid valve regurgitation: epidemiology and pathophysiology.
        Minerva Cardioangiol. 2018; 66: 673-679
        • Kazum S.S.
        • Sagie A.
        • Shochat T.
        • et al.
        Prevalence, echocardiographic correlations, and clinical outcome of tricuspid regurgitation in patients with significant left ventricular dysfunction.
        Am J Med. 2019; 132: 81-87
        • Singh J.P.
        • Evans J.C.
        • Levy D.
        • et al.
        Prevalence and clinical determinants of mitral, tricuspid and aortic regurgitation.
        Am J Cardiol. 1999; 83: 897-902
        • Chandrashekar P.
        • Fender E.A.
        • Zack C.J.
        • et al.
        Sex-stratified analysis of national trends and outcomes in isolated tricuspid valve surgery.
        Open Heart. 2018; 5e000719
        • Taramasso M.
        • Benfari G.
        • van der Bijl P.
        • et al.
        Transcatheter versus medical treatment of patients with symptomatic severe tricuspid regurgitation.
        J Am Coll Cardiol. 2019; 74: 2998-3008
        • Mulla S.
        • Asuka E.
        • Siddiqui W.J.
        Tricuspid regurgitation. Updated July 27, 2020. Treasure Island, FL: StatPearls Publishing.
        (Available at:)
        • Katzenellenbogen J.M.
        • Ralph A.P.
        • Wyber R.
        • Carapetis J.R.
        Rheumatic heart disease: infectious disease origin, chronic care approach.
        BMC Health Serv Res. 2017; 17: 793
        • Watkins D.A.
        • Johnson C.O.
        • Colquhoun S.M.
        • et al.
        Global, regional, and national burden of rheumatic heart disease, 1990-2015.
        N Engl J Med. 2017; 377: 713-722
        • Gordon J.
        • Kirlew M.
        • Schreiber Y.
        • et al.
        Acute rheumatic fever in First Nations communities in northwestern Ontario: Social determinants of health “bite the heart.
        Can Fam Physician. 2015; 61: 881-886
        • Anthony J.
        • Osman A.
        • Sani M.U.
        Valvular heart disease in pregnancy.
        Cardiovasc J Afr. 2016; 27: 111-118
        • Lumsden R.H.
        • Akwanalo C.
        • Chepkwony S.
        • et al.
        Clinical and geographic patterns of rheumatic heart disease in outpatients attending cardiology clinic in western Kenya.
        Int J Cardiol. 2016; 223: 228-235
        • Vakamudi S.
        • Wu Y.
        • Jellis C.
        • et al.
        Gender differences in the etiology of mitral valve disease.
        J Am Coll Cardiol. 2017; 69: 1972
        • Zuhlke L.
        • Engel M.E.
        • Karthikeyan G.
        • et al.
        Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study).
        Eur Heart J. 2015; 36 (1115-22a)
        • Xiao F.
        • Zheng R.
        • Yang D.
        • et al.
        Sex-dependent aortic valve pathology in patients with rheumatic heart disease.
        PLoS One. 2017; 12e0180230
        • Bernal J.M.
        • Pontón A.
        • Diaz B.
        • et al.
        Surgery for rheumatic tricuspid valve disease: a 30-year experience.
        J Thorac Cardiovasc Surg. 2008; 136: 476-481
        • El-Eshmawi A.
        • Alexis S.L.
        • Sengupta A.
        • et al.
        Surgical management of mitral annular calcification.
        Curr Opin Cardiol. 2020; 35: 107-115
        • Willens H.J.
        • Chirinos J.A.
        • Gómez-Marin O.
        • Hare J.M.
        • de Marchena E.
        Prevalence of mitral annulus calcification in African Americans: comparison with non-Hispanic whites and Hispanics.
        Ethn Dis. 2008; 18: 48-52
        • Abramowitz Y.
        • Jilaihawi H.
        • Chakravarty T.
        • Mack M.J.
        • Makkar R.R.
        Mitral annulus calcification.
        J Am Coll Cardiol. 2015; 66: 1934-1941
        • Mehta P.K.
        • Wei J.
        • Wenger N.K.
        Ischemic heart disease in women: a focus on risk factors.
        Trends Cardiovasc Med. 2015; 25: 140-151