{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:25:52Z","timestamp":1788999952689,"version":"build-2803163510"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,7,7]]},"abstract":"\n Background<\/jats:title>\n \n Heart failure with preserved ejection fraction (\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n ) is an increasingly prevalent form of heart failure, representing half of the total burden of heart failure. We hypothesised that modulation of the phosphodiesterase type 3\/cyclic\n AMP<\/jats:styled-content>\n using a novel oral formulation of milrinone might exert favorable effects\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n via pulmonary and systemic vasodilation and enhancement of ventricular relaxation. We assessed the safety and efficacy of oral milrinone on quality of life and functional outcomes in patients with\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n The Mil\n HFPEF<\/jats:styled-content>\n (Extended Release Oral Milrinone for the Treatment of Heart Failure With Preserved Ejection Fraction) study was a randomized, double\u2010blind, placebo\u2010controlled pilot study in 23 patients with symptomatic\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n . Efficacy end points included changes from baseline in Kansas City Cardiomyopathy Questionnaire summary score and 6\u2010minute walk distance. The primary safety end point was the development of clinically significant arrhythmia. The Kansas City Cardiomyopathy Questionnaire score improved significantly in milrinone\u2010treated patients compared with placebo (+10\u00b113 versus \u22123\u00b115;\n P<\/jats:italic>\n =0.046). Six\u2010minute walk distance also tended to improve in the treatment group compared with placebo (+22 [\u22128 to 49] versus \u221247 [\u221297 to 12];\n P<\/jats:italic>\n =0.092). Heart rate (\u22121\u00b15 versus \u22122\u00b19\u00a0bpm;\n P<\/jats:italic>\n =0.9) and systolic blood pressure (\u22123\u00b118 versus +1\u00b112\u00a0mm\u00a0Hg;\n P<\/jats:italic>\n =0.57) were unchanged. Early filling velocity\/early mitral annular velocity (\u22120.3\u00b13.0 versus \u22121.9\u00b14.8;\n P<\/jats:italic>\n =0.38) was unchanged. One patient in the placebo arm was hospitalized for heart failure. Holter monitoring did not demonstrate evidence of a proarrhythmic effect of milrinone.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n In this novel pilot study, extended release oral\u00a0milrinone was well tolerated and\u00a0associated with improved quality of life in patients with\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n . Further longer\u2010term studies are warranted to establish the role of this therapeutic approach in\u00a0\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Registration<\/jats:title>\n \n URL<\/jats:styled-content>\n :\n https:\/\/www.anzctr.org.au\/<\/jats:ext-link>\n ; Unique identifier:\n ACTRN<\/jats:styled-content>\n 12616000619448.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.015026","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T10:14:37Z","timestamp":1592475277000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":39,"title":["Extended\u2010Release Oral Milrinone for the Treatment of Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1161","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0146-6588","authenticated-orcid":false,"given":"Shane","family":"Nanayakkara","sequence":"first","affiliation":[{"name":"Department of Cardiology Alfred Hospital Melbourne Australia"},{"name":"Heart Failure Research Group Baker Heart and Diabetes Institute Melbourne Australia"},{"name":"Faculty of Medicine, Nursing and Health Sciences Monash University Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Byrne","sequence":"additional","affiliation":[{"name":"Heart Failure Research Group Baker Heart and Diabetes Institute Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Cardiology Alfred Hospital Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaye","family":"Carter","sequence":"additional","affiliation":[{"name":"Department of Cardiology Alfred Hospital Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliza","family":"Dean","sequence":"additional","affiliation":[{"name":"Department of Cardiology Alfred Hospital Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Kaye","sequence":"additional","affiliation":[{"name":"Department of Cardiology Alfred Hospital Melbourne Australia"},{"name":"Heart Failure Research Group Baker Heart and Diabetes Institute Melbourne Australia"},{"name":"Faculty of Medicine, Nursing and Health Sciences Monash University Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32520-5"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.09.052"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.147"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.115.002729"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.03.539"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2018.02.006"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2009.11.007"},{"key":"e_1_3_2_9_2","first-page":"375","article-title":"Echocardiographic assessment of pressure volume relations in heart failure and valvular heart disease: using imaging to understand physiology","volume":"59","author":"Green P","year":"2011","unstructured":"Green P, Kodali S, Leon MB, Maurer MS. 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Eur J Heart Fail. 2017;2:92\u201397.","journal-title":"Eur J Heart Fail"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2012.05.014"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.04.040"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002530"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.119.015026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:36:02Z","timestamp":1715600162000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.119.015026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,7]]},"references-count":26,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2020,7,7]]}},"alternative-id":["10.1161\/JAHA.119.015026"],"URL":"https:\/\/doi.org\/10.1161\/jaha.119.015026","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,7]]},"assertion":[{"value":"2020-10-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e015026"}}