{"id":"3398e1549f94","type":"article","url":"https://hartvaat.nl/2026/05/05/reduce-mfa-dzhk25-trial-naar-antifibrotische-therapie-tegen-myocardfibrose-na-ta/","title":"Reduce-MFA DZHK25: trial naar antifibrotische therapie tegen myocardfibrose na TAVI — opzet en achtergrond","title_en":"","category":"hartfalen","category_label":"Hartfalen","professions":["cardioloog"],"tags":["dapa-hf"],"journal":"ESC heart failure","doi":"10.1093/eschf/xvag083","source_url":"https://doi.org/10.1093/eschf/xvag083","authors":["Miriam Puls","Elisabeth M Zeisberg","Marius Placzek","Bo E Beuthner","Christoph F Jacob","Kristin E Steinhaus","Torben Lange","Ralf Tostmann","Moritz Schnelle","Andreas Schuster","Gerd Hasenfuß","Tim Friede"],"significance":5,"published":"2026-06-28","source_date":"2026-05-05","image":"","kennis":["https://hartvaat.nl/kennis/hartfalen/cardiale-remodellering/","https://hartvaat.nl/kennis/diagnostiek/cardiale-mri/"],"congress":"","summary_en":"Trial design of the German Reduce-MFA DZHK25 trial: prospective, multicenter, randomised, open-label study with blinded outcome assessment (PROBE design) in patients with severe aortic stenosis and high baseline myocardial fibrosis undergoing TAVI. Only patients with cardiac MRI ECV ≥25.9% (independent mortality predictor) are randomised to 3 arms: (i) standard care, (ii) + spironolactone, (iii) + spironolactone + low-dose dihydralazine (epigenetic reactivation of anti-fibrotic genes), for 12 months. Primary outcome is fibrosis regression by CMR-T1 mapping (ECV-derived LV matrix volume); secondary outcomes include reverse remodelling, KCCQ, 6MWT, NT-proBNP, NYHA class, mortality, and cardiac hospitalisations. Enrolment is complete with 384 screened and 153 randomised. Results may open a new adjuvant treatment route after TAVI for patients with high fibrotic burden.","created":"2026-07-03T10:33:08Z","updated":"2026-07-03T13:32:02Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Studie-opzet van de Duitse Reduce-MFA DZHK25-trial: prospectieve, multicenter, gerandomiseerde, open-label studie met geblindeerde uitkomstbeoordeling (PROBE-design) bij patiënten met ernstige aortastenose en een hoog uitgangsniveau aan myocardiale fibrose, die TAVI ondergaan. Alleen patiënten met cardiale MRI-ECV ≥25,9% (onafhankelijke voorspeller van mortaliteit) worden gerandomiseerd in 3 armen: (i) standaardzorg, (ii) +spironolacton, (iii) +spironolacton +laaggedoseerd dihydralazine (epigenetische reactivering van antifibrotische genen), gedurende 12 maanden. Primaire uitkomst is fibrose-regressie via CMR-T1-mapping (ECV-afgeleid LV-matrix-volume); secundaire uitkomsten omvatten reverse remodeling, KCCQ, 6MWT, NT-proBNP, NYHA-klasse, mortaliteit en hartopnames. Inclusie afgerond met 384 gescreend en 153 gerandomiseerd. De resultaten kunnen een nieuwe adjuvante behandelroute na TAVI openen voor patiënten met hoge fibroselast.","abstract_original":"AIMS: 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. METHODS: 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%) ≥ 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. CONCLUSIONS: The study findings have the potential to inform the development of a novel adjuvant therapy to improve the prognosis of specific AS patients."}