{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:26:52Z","timestamp":1791646012855,"version":"4.3.4"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,1,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Spironolactone may have prognostic benefit in selected patients with heart failure with preserved ejection fraction. This study assessed the myocardial tissue effects of spironolactone in heart failure with 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              A 1:1 randomized controlled study of 6\u00a0months of spironolactone versus control in heart failure with preserved ejection fraction. The primary outcome was change in myocardial extracellular volume fraction by cardiovascular magnetic resonance as a surrogate of diffuse fibrosis. Of 55 randomized patients, 40 (20 women; age, 75.2\u00b15.9\u00a0years) completed follow\u2010up (19 treatment, 21 control). A significant change in extracellular volume over the study period was not seen (treatment, 28.7\u00b13.7% versus 27.7\u00b13.4% [\n              <jats:italic>P<\/jats:italic>\n              =0.14]; controls, 27.6\u00b13.4% versus 28.3\u00b14.4% [\n              <jats:italic>P<\/jats:italic>\n              =0.14]); however, the rate of extracellular volume expansion was decreased by spironolactone (\u22121.0\u00b12.4% versus 0.8\u00b12.2%). Indexed left ventricular mass decreased with treatment (104.4\u00b126.6 versus 94.0\u00b120.6\u00a0g\/m\n              <jats:sup>2<\/jats:sup>\n              ;\n              <jats:italic>P<\/jats:italic>\n              =0.001) but not in controls (101.4\u00b129.4 versus 104.0\u00b132.8\u00a0g\/m\n              <jats:sup>2<\/jats:sup>\n              ;\n              <jats:italic>P<\/jats:italic>\n              =0.111). Extracellular mass decreased by 13.8% (15.1\u00b14.8 versus 13.0\u00b13.4\u00a0g\/m\n              <jats:sup>2<\/jats:sup>\n              ;\n              <jats:italic>P<\/jats:italic>\n              =0.003), and cellular mass decreased by 8.3% (37.6\u00b110.0 versus 34.3\u00b17.9\u00a0g\/m\n              <jats:sup>2<\/jats:sup>\n              ;\n              <jats:italic>P<\/jats:italic>\n              =0.001) with spironolactone, but was static in controls.\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 did not lead to significant change in extracellular volume. However, spironolactone did decrease rate of extracellular expansion, with a decrease in the mass of both cellular and extracellular myocardial compartments. These data point to the mechanism of action of spironolactone in heart failure with preserved ejection fraction, including a direct tissue effect with a reduction in rate of myocardial fibrosis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.118.011521","type":"journal-article","created":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T10:00:29Z","timestamp":1576749629000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Myocardial Effects of Aldosterone Antagonism in Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1161","volume":"9","author":[{"given":"Adam K.","family":"McDiarmid","sequence":"first","affiliation":[{"name":"Multidisciplinary Cardiovascular Research Centre and Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds United Kingdom"},{"name":"Department of Cardiology Freeman Hospital Newcastle\u2010upon\u2010Tyne United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter P.","family":"Swoboda","sequence":"additional","affiliation":[{"name":"Multidisciplinary Cardiovascular Research Centre and Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bara","family":"Erhayiem","sequence":"additional","affiliation":[{"name":"Multidisciplinary Cardiovascular Research Centre and Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina A.","family":"Bounford","sequence":"additional","affiliation":[{"name":"Leeds Teaching Hospitals NHS Trust Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Bijsterveld","sequence":"additional","affiliation":[{"name":"Multidisciplinary Cardiovascular Research Centre and Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Tyndall","sequence":"additional","affiliation":[{"name":"Leeds Teaching Hospitals NHS Trust Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham J.","family":"Fent","sequence":"additional","affiliation":[{"name":"Multidisciplinary Cardiovascular Research Centre and Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Garg","sequence":"additional","affiliation":[{"name":"Multidisciplinary Cardiovascular Research Centre and Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E.","family":"Dobson","sequence":"additional","affiliation":[{"name":"Multidisciplinary Cardiovascular Research Centre and Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarique A.","family":"Musa","sequence":"additional","affiliation":[{"name":"Multidisciplinary Cardiovascular Research Centre and Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R. J.","family":"Foley","sequence":"additional","affiliation":[{"name":"Multidisciplinary Cardiovascular Research Centre and Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus K.","family":"Witte","sequence":"additional","affiliation":[{"name":"Multidisciplinary Cardiovascular Research Centre and Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Kearney","sequence":"additional","affiliation":[{"name":"Multidisciplinary Cardiovascular Research Centre and Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Greenwood","sequence":"additional","affiliation":[{"name":"Multidisciplinary Cardiovascular Research Centre and Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Plein","sequence":"additional","affiliation":[{"name":"Multidisciplinary Cardiovascular Research Centre and Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw128"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq426"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehl250"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805450"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090555"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.013255"},{"key":"e_1_3_2_8_2","first-page":"181","article-title":"Spironolactone for heart failure with preserved ejection fraction","volume":"371","author":"Pfeffer MA","year":"2014","unstructured":"Pfeffer MA, Pitt B, McKinlay SM. 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