{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:36:33Z","timestamp":1784698593377,"version":"3.55.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T00:00:00Z","timestamp":1648339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","award":["TNE\u201018CVD04"],"award-info":[{"award-number":["TNE\u201018CVD04"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01\u2010HL148050"],"award-info":[{"award-number":["R01\u2010HL148050"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01\u2010HL148565"],"award-info":[{"award-number":["R01\u2010HL148565"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01\u2010HL142711"],"award-info":[{"award-number":["R01\u2010HL142711"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01\u2010HL155915"],"award-info":[{"award-number":["R01\u2010HL155915"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01\u2010HL139865"],"award-info":[{"award-number":["R01\u2010HL139865"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35\u2010GM124836"],"award-info":[{"award-number":["R35\u2010GM124836"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32\u2010GM007280"],"award-info":[{"award-number":["T32\u2010GM007280"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Individuals with supranormal left ventricular ejection fraction (snLVEF; LVEF &gt;70%) have increased mortality. However, the genetic and phenotypic profile of snLVEF remains unknown. This study aimed to determine the relationship of both snLVEF genetic risk and phenotype with survival and underdiagnosed heart failure (HF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      A snLVEF genetic risk score (GRS) was applied and cases of snLVEF were identified in 486\u2009754 individuals across two population\u2010based cohorts (Bio\n                      <jats:italic>Me<\/jats:italic>\n                      Biobank and UK Biobank). The snLVEF GRS and phenotype were evaluated for association with survival, as well as HF diagnosis, markers, symptoms, and medications. Of 486\u2009754 participants, the median age was 58\u2009years, 20\u2009069 (4.1%) died, and 10\u2009088 (2.1%) had diagnosed HF. Both snLVEF GRS (hazard ratio [HR]\u00a01.1 for top 10% vs. bottom 10% GRS;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.002) and phenotype (HR\u00a01.4;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.003) were associated with increased all\u2010cause mortality. Both snLVEF GRS and phenotype were associated with reduced HF diagnosis (odds ratio [OR]\u00a00.97 and OR\u00a00.63, respectively; both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u22640.002). However, the snLVEF GRS and phenotype were both associated with elevated brain natriuretic peptide (BNP) levels (146 and 185\u2009pg\/ml increase, respectively;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;0.001), including 268 out of 455 (59%) individuals with snLVEF phenotype who had BNP &gt;100\u2009pg\/ml. Among 476\u2009666 participants without HF diagnoses, snLVEF GRS and phenotype were associated with increased HF symptoms (e.g. exertional dyspnoea OR\u00a01.4 and OR\u00a01.3;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;0.003) and HF medications (e.g. loop diuretic OR\u00a01.2 and OR\u00a01.03;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;0.02). Associations were consistent in hypertensive individuals without cardiac comorbidities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Genetic predisposition to and presence of snLVEF are associated with decreased survival and underdiagnosed HF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2482","type":"journal-article","created":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T09:19:47Z","timestamp":1647076787000},"page":"2118-2127","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Genetic and phenotypic profiling of supranormal ejection fraction reveals decreased survival and underdiagnosed heart failure"],"prefix":"10.1093","volume":"24","author":[{"given":"Iain S.","family":"Forrest","sequence":"first","affiliation":[{"name":"The Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai  New York NY USA"},{"name":"Medical Scientist Training Program Icahn School of Medicine at Mount Sinai  New York NY USA"},{"name":"The Bio<i>Me<\/i> Phenomics Center Icahn School of Medicine at Mount Sinai  New York NY USA"},{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghislain","family":"Rocheleau","sequence":"additional","affiliation":[{"name":"The Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai  New York NY USA"},{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shantanu","family":"Bafna","sequence":"additional","affiliation":[{"name":"The Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai  New York NY USA"},{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Argulian","sequence":"additional","affiliation":[{"name":"Mount Sinai Heart Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagat","family":"Narula","sequence":"additional","affiliation":[{"name":"Mount Sinai Heart Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Natarajan","sequence":"additional","affiliation":[{"name":"Program in Medical and Population Genetics and Cardiovascular Disease Initiative Broad Institute of Massachusetts Institute of Technology and Harvard  Cambridge MA USA"},{"name":"Cardiovascular Research Center Massachusetts General Hospital, Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Do","sequence":"additional","affiliation":[{"name":"The Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai  New York NY USA"},{"name":"The Bio<i>Me<\/i> Phenomics Center Icahn School of Medicine at Mount Sinai  New York NY USA"},{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai  New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz550"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-020-04892-x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311059"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2017-311506"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2017.04.012"},{"key":"e_1_2_5_7_1","first-page":"326","article-title":"Heritability of left ventricular structure and function in Caucasian families","volume":"12","author":"Jin Y","year":"2011","journal-title":"Eur J Echocardiogr"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15823-7"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14213-y"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.03.512"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1735"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00870-7"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq340"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.023188"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.035774"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/pubmed\/fdv155"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab067"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24220"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020233"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr105"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2016.00021"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2015.09.010"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602543103"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.2333"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.05.043"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a040501"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107038"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv338"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejechocard\/jeq069"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1532-429X-18-S1-P31"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.2482","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejhf.2482","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.2482","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T12:16:08Z","timestamp":1767701768000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ejhf.2482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,27]]},"references-count":30,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1002\/ejhf.2482"],"URL":"https:\/\/doi.org\/10.1002\/ejhf.2482","archive":["Portico"],"relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,27]]},"assertion":[{"value":"2021-11-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}