{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T12:08:20Z","timestamp":1779278900589,"version":"3.51.4"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010447","name":"DZHK","doi-asserted-by":"publisher","award":["81X1300121"],"award-info":[{"award-number":["81X1300121"]}],"id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["CRC 1002, D1"],"award-info":[{"award-number":["CRC 1002, D1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Myocardial fibrosis (MF) represents a key player in transition to heart failure in aortic stenosis (AS), and AS patients with high baseline MF are at increased risk to die within 12 months after transcatheter aortic valve implantation (TAVI). Therefore, the objective of the Reduce-MFA DZHK25 trial is to assess the impact of anti-fibrotic therapy on regression of AS-induced MF after TAVI in patients with high baseline fibrotic burden. Key secondary objectives include reverse LV remodelling, symptomatic improvement, and reduction of mortality and cardiac hospitalizations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Reduce-MFA represents a national, prospective, randomized, parallel group, controlled, open-label interventional multi-centre trial with blinded outcome assessment (PROBE design) enrolling patients with severe AS scheduled for TAVI. The anti-fibrotic principles employed are spironolactone and low-dose dihydralazine (epigenetic reactivation of anti-fibrotic genes). Baseline burden and course of MF are assessed by cardiac MRI (CMR). Since CMR-derived extracellular volume fraction (ECV%) \u2265 25.9% emerged as independent mortality predictor, only patients above this cut-off are randomized into three parallel groups: (i) Standard of Care alone, (ii) + spironolactone, (iii) + spironolactone + low-dose dihydralazine, each for 12 months. To assess MF regression, CMR is repeated after 12 months. MF is assessed by quantification of the ECV-derived LV matrix volume using T1 mapping. Additionally, measures of heart failure (Kansas City Cardiomyopathies Quality of Life Questionnaire, 6MWT, NT-proBNP, NYHA class) and reverse cardiac remodelling are evaluated at 6 and 12 months. Mortality and cardiac hospitalizations are recorded. The recruitment was recently completed with 384 enrolled and 153 randomized patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study findings have the potential to inform the development of a novel adjuvant therapy to improve the prognosis of specific AS patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eschf\/xvag083","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:40:47Z","timestamp":1778067647000},"source":"Crossref","is-referenced-by-count":0,"title":["Effect of anti-fibrotic therapy on regression of myocardial fibrosis after TAVI: design and rationale of the Reduce-MFA DZHK25 trial"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5540-1264","authenticated-orcid":false,"given":"Miriam","family":"Puls","sequence":"first","affiliation":[{"name":"Department of 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Robert-Koch-Stra\u00dfe 40, G\u00f6ttingen 37075 ,","place":["Germany"]},{"name":"Department of Medical Statistics, University Medical Centre G\u00f6ttingen , G\u00f6ttingen 37073 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo E","family":"Beuthner","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Centre G\u00f6ttingen , Robert-Koch-Stra\u00dfe 40, G\u00f6ttingen 37075 ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK), partner site Lower Saxony , Robert-Koch-Stra\u00dfe 40, G\u00f6ttingen 37075 ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph F","family":"Jacob","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Centre G\u00f6ttingen , Robert-Koch-Stra\u00dfe 40, G\u00f6ttingen 37075 ,","place":["Germany"]},{"name":"German Centre for Cardiovascular 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