{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T03:52:27Z","timestamp":1777002747626,"version":"3.51.4"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,4,9]]},"abstract":"\n Background<\/jats:title>\n \n Concurrent presence of aortic stenosis and aortic regurgitation is termed mixed aortic valve disease (\n MAVD<\/jats:styled-content>\n ). Although multiple articles have addressed patients with \u201cisolated\u201d aortic stenosis or aortic regurgitation, the natural history, impact, and outcomes of\n MAVD<\/jats:styled-content>\n are not well defined. Here, we evaluate long\u2010term outcomes in patients with\n MAVD<\/jats:styled-content>\n and cardiovascular adaptations to chronic\n MAVD<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n This observational cohort study evaluated 862 adult patients (56.8% male) with preserved left ventricular ejection fraction and at least moderate aortic regurgitation and moderate aortic stenosis. Primary outcome was all\u2010cause mortality. Subgroup analysis was based on treatment modality (aortic valve replacement [\n AVR<\/jats:styled-content>\n ] versus medical management). A regression analysis of longitudinal echocardiographic parameters was performed to assess the natural history of\n MAVD<\/jats:styled-content>\n . Mean age was 68\u00b115\u00a0years, and mean left ventricular ejection fraction was 58\u00b15%. At 4.6\u00a0years (25th\u201375th percentile range, 1.0\u20138.7), 58.6% of patients underwent an\n AVR<\/jats:styled-content>\n and 48.8% patients died. In both unadjusted and adjusted Cox survival analysis,\n AVR<\/jats:styled-content>\n was associated with improved survival (hazard ratio, 0.41; 95%\n CI<\/jats:styled-content>\n , 0.34\u20130.51,\n P<\/jats:italic>\n <0.001). Impact of\n AVR<\/jats:styled-content>\n persisted when stratifying the cohort by symptom status and baseline aortic valve area (log rank,\n P<\/jats:italic>\n <0.001 for both) and after propensity\u2010score matching (hazard ratio, 0.40; 95%\n CI<\/jats:styled-content>\n , 0.32\u20130.50;\n P<\/jats:italic>\n <0.001). In the longitudinal analysis, there were statistically significant changes over time in aortic valve peak gradient (\n P<\/jats:italic>\n <0.001) and aortic valve area (\n P<\/jats:italic>\n <0.001) and only mild increases in left ventricular end\u2010diastolic (\n P<\/jats:italic>\n <0.007) and \u2010systolic (\n P<\/jats:italic>\n <0.001) volumes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n MAVD<\/jats:styled-content>\n confers a high risk of all\u2010cause mortality. However,\n AVR<\/jats:styled-content>\n significantly reduces this risk independent of aortic valve area, symptom status, and after controlling for confounding variables.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.014591","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T09:00:28Z","timestamp":1585040428000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":37,"title":["Long\u2010Term Outcomes in Patients With Mixed Aortic Valve Disease and Preserved Left Ventricular Ejection Fraction"],"prefix":"10.1161","volume":"9","author":[{"given":"Nicolas","family":"Isaza","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milind Y.","family":"Desai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samir R.","family":"Kapadia","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amar","family":"Krishnaswamy","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. Leonardo","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Grimm","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julijana Z.","family":"Conic","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihito","family":"Saijo","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric E.","family":"Roselli","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Marc","family":"Gillinov","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas R.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars G.","family":"Svensson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian P.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5692-2299","authenticated-orcid":false,"given":"Zoran B.","family":"Popovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"},{"name":"Department of Thoracic and Cardiovascular Surgery Sydell and Arnold Miller Family Heart & Vascular Institute Cleveland Clinic Foundation Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2010.212282"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/cir.0000000000000031"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000503"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2014.04.013"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2017.02.009"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.02.536"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2014.10.003"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0894-7317(03)00335-3"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2012.04.052"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020363010465"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.509"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.11.070"},{"key":"e_1_3_1_14_2","volume-title":"Applied Longitudinal Analysis","author":"Fitzmaurice GM","year":"2004","unstructured":"Fitzmaurice GM, Laird NM, Ware JH. 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