{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:13:41Z","timestamp":1793146421883,"version":"4.5.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,9,15]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Patients with permanent atrial fibrillation have poor outcomes, exercise capacity, and quality of life even on optimal anticoagulation. Based on mechanistic and observational data, we tested whether the mineralocorticoid receptor antagonist spironolactone can improve exercise capacity, E\/e' ratio, and quality of life in patients with permanent atrial fibrillation and preserved ejection fraction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The double\u2010masked, placebo\u2010controlled IMPRESS\u2010AF (Improved Exercise Tolerance in Heart Failure With Preserved Ejection Fraction by Spironolactone on Myocardial Fibrosis in Atrial Fibrillation) trial (NCT02673463) randomized 250 stable patients with permanent atrial fibrillation and preserved left ventricular ejection fraction to spironolactone 25\u00a0mg daily or placebo. Patients were followed for 2\u00a0years. The primary efficacy outcome was peak oxygen consumption on cardiopulmonary exercise testing at 2\u00a0years. Secondary end points included 6\u2010minute walk distance, E\/e' ratio, quality of life, and hospital admissions. Spironolactone therapy did not improve peak oxygen consumption at 2\u00a0years (14.0\u00a0mL\/min per kg [SD, 5.4]) compared with placebo (14.5 [5.1], adjusted treatment effect, \u22120.28; 95% CI, \u22121.27 to 0.71];\n                      <jats:italic>P<\/jats:italic>\n                      =0.58). The findings were consistent across all sensitivity analyses. There were no differences in the 6\u2010minute walking distance (adjusted treatment effect, \u22128.47\u00a0m; \u221231.9 to 14.9;\n                      <jats:italic>P<\/jats:italic>\n                      =0.48), E\/e\u2019 ratio (adjusted treatment effect, \u22120.68; \u22121.52 to 0.17,\n                      <jats:italic>P<\/jats:italic>\n                      =0.12), or quality of life (\n                      <jats:italic>P<\/jats:italic>\n                      =0.74 for EuroQol\u20105 Dimensions, 5\u2010level version quality of life questionnaire and\n                      <jats:italic>P<\/jats:italic>\n                      =0.84 for Minnesota Living with Heart Failure). At least 1 hospitalization occurred in 15% of patients in the spironolactone group and 23% in the placebo group (\n                      <jats:italic>P<\/jats:italic>\n                      =0.15). Estimated glomerular filtration rate was reduced by 6\u00a0mL\/min in the spironolactone group with &lt;1\u2010unit reduction in controls (\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001). Systolic blood pressure was reduced by 7.2\u00a0mm\u00a0Hg (95% CI, 2.2\u201312.3) in the spironolactone group versus placebo (\n                      <jats:italic>P<\/jats:italic>\n                      =0.005).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Spironolactone therapy does not improve exercise capacity, E\/e' ratio, or quality of life in patients with chronic atrial fibrillation and preserved ejection fraction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      UTL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrial.gov\">https:\/\/www.clini\u200bcaltr\u200bial.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT02673463. EudraCT number 2014\u2010003702\u201033.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.119.016239","type":"journal-article","created":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T07:32:06Z","timestamp":1599723126000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["Spironolactone in Atrial Fibrillation With Preserved Cardiac Fraction: The\u00a0IMPRESS\u2010AF Trial"],"prefix":"10.1161","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2429-6980","authenticated-orcid":false,"given":"Eduard","family":"Shantsila","sequence":"first","affiliation":[{"name":"North Worcestershire VTS St Helens and Knowsley Teaching Hospitals NHS Trust Prescot Merseyside United Kingdom"},{"name":"Institute of Cardiovascular Sciences University of Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhan","family":"Shahid","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences University of Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhong","family":"Sun","sequence":"additional","affiliation":[{"name":"Birmingham Clinical Trials Unit Institute of Applied Health Research University of Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Deeks","sequence":"additional","affiliation":[{"name":"Birmingham Clinical Trials Unit Institute of Applied Health Research University of Birmingham United Kingdom"},{"name":"NIHR Birmingham Biomedical Research Centre University of Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Calvert","sequence":"additional","affiliation":[{"name":"NIHR Birmingham Biomedical Research Centre University of Birmingham United Kingdom"},{"name":"Centre for Patient Reported Outcomes Research (CPROR) Institute of Applied Health Research University of Birmingham United Kingdom"},{"name":"National Institute for Health Research (NIHR) Applied Research Centre West Midlands University of Birmingham United Kingdom"},{"name":"National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre University of Birmingham United Kingdom"},{"name":"Birmingham Health Partners Centre for Regulatory Science and Innovation University of Birmingham United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7851-9222","authenticated-orcid":false,"given":"James P.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Department of Physiology Faculty of Medical and Health Sciences University of Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulus","family":"Kirchhof","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences University of Birmingham United Kingdom"},{"name":"University Hospitals Birmingham NHS Foundation Trust Birmingham United Kingdom"},{"name":"Sandwell and West Birmingham Hospitals NHS Trust Birmingham United Kingdom"},{"name":"University Heart and Vascular Center UKE Hamburg Hamburg Germany"},{"name":"German Center for Cardiovascular Research (DZHK), partner site Hamburg\/Kiel\/L\u00fcbeck Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paramjit S.","family":"Gill","sequence":"additional","affiliation":[{"name":"Academic Unit of Primary Care Warwick Medical School University of Warwick Coventry United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7566-1626","authenticated-orcid":false,"given":"Gregory Y. 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