{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T20:33:32Z","timestamp":1790454812267,"version":"4.1.0"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Patients with heart failure (HF) and preserved left ventricular ejection fraction comprise a heterogeneous group including some with mildly reduced EF. We hypothesized that mode of death differs by EF in ambulatory patients with HF and preserved left ventricular ejection fraction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor\u2013Neprilysin Inhibitor With Angiotensin-Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction) compared clinical outcomes in 4796 patients with chronic HF and EF \u226545% randomly assigned to sacubitril\/valsartan or valsartan. We examined the mode of death in relation to baseline EF in logistic regression models and the effect of randomized treatment on cause-specific death in Cox regression models. Nonlinear relationships with continuous EF were modelled using quadratic and cubic terms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Of 691 deaths during the trial, 416 (60%) were ascribed to cardiovascular, 220 (32%) to noncardiovascular, and 55 (8%) to unknown causes. Of cardiovascular deaths, 154 (37%) were due to sudden death, 118 (28%) were due to HF, 35 (8%) to stroke, 27 (6%) to myocardial infarction, and 82 (20%) to other cardiovascular causes. Rates of all-cause, cardiovascular, and sudden death were higher in those with lower left ventricular ejection fraction (all\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001), while rates of non-cardiovascular death were greater in patients with higher EF. Sacubitril\/valsartan did not reduce overall death, cardiovascular death, or sudden death compared with valsartan, irrespective of baseline EF (all\n              <jats:italic>P<\/jats:italic>\n              for interaction &gt;0.30).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Among patients with HF and preserved left ventricular ejection fraction enrolled in PARAGON-HF, the proportion of cardiovascular and sudden death were higher in those with lower left ventricular EF, and the proportion of noncardiovascular death rose with EF. Regardless of EF, sacubitril\/valsartan did not reduce death from any cause compared with valsartan.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT01920711.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.121.008597","type":"journal-article","created":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T18:41:22Z","timestamp":1637606482000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":38,"title":["Mode of Death in Patients With Heart Failure and Preserved Ejection Fraction: Insights From PARAGON-HF Trial"],"prefix":"10.1161","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct01920711","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8224-5121","authenticated-orcid":true,"given":"Akshay S.","family":"Desai","sequence":"first","affiliation":[{"name":"Cardiovascular Division (A.S.D., M.V., B.L.C., E.B., P.F., M.A.P., S.D.S.), Brigham and Women\u2019s Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muthiah","family":"Vaduganathan","sequence":"additional","affiliation":[{"name":"Cardiovascular Division (A.S.D., M.V., B.L.C., E.B., P.F., M.A.P., S.D.S.), Brigham and Women\u2019s Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Cleland","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics, Institute of Health and Wellbeing and British Heart Foundation Centre of Research Excellence, University of Glasgow, United Kingdom (J.G.C.)."},{"name":"National Heart and Lung Institute, Imperial College, London, United Kingdom (J.G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Division (A.S.D., M.V., B.L.C., E.B., P.F., M.A.P., S.D.S.), Brigham and Women\u2019s Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8224-5121","authenticated-orcid":true,"given":"Ebrahim","family":"Barkoudah","sequence":"additional","affiliation":[{"name":"Cardiovascular Division (A.S.D., M.V., B.L.C., E.B., P.F., M.A.P., S.D.S.), Brigham and Women\u2019s Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Finn","sequence":"additional","affiliation":[{"name":"Cardiovascular Division (A.S.D., M.V., B.L.C., E.B., P.F., M.A.P., S.D.S.), Brigham and Women\u2019s Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0299-0533","authenticated-orcid":true,"given":"Finnian R.","family":"McCausland","sequence":"additional","affiliation":[{"name":"Renal Division (F.R.M.), Brigham and Women\u2019s Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8169-8628","authenticated-orcid":true,"given":"Mehmet B.","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Dokuz Eylul University, Izmir, Turkey (M.B.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Lefkowitz","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals, East Hanover, NJ (M.L., V.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Shi","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals, East Hanover, NJ (M.L., V.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Cardiovascular Division (A.S.D., M.V., B.L.C., E.B., P.F., M.A.P., S.D.S.), Brigham and Women\u2019s Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division (A.S.D., M.V., B.L.C., E.B., P.F., M.A.P., S.D.S.), Brigham and Women\u2019s Hospital, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hft062"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.10.078"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz550"},{"key":"e_1_3_2_5_2","unstructured":"Novartic Public Affairs. 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