Key Points
- In patients with severe aortic stenosis undergoing TAVI and high baseline myocardial fibrosis, anti-fibrotic therapy improved regression of myocardial fibrosis compared with TAVI alone.
- The primary hierarchical endpoint was not met in the intention-to-treat analysis but was significant in the as-treated population.
- Anti-fibrotic therapy significantly improved quality of life, with consistent trends toward reduced cardiac hospitalizations.
- The intervention was safe, though associated with expected changes in renal function and potassium levels.
Myocardial fibrosis is a key driver of adverse cardiac remodeling and heart failure progression in patients with severe aortic stenosis (AS), and its persistence after transcatheter aortic valve implantation (TAVI) has been associated with worse outcomes. However, whether targeted anti-fibrotic therapy can reverse myocardial fibrosis and improve clinical outcomes after TAVI has remained uncertain.
During an Investigative Horizons session at the American College of Cardiology 2026, Dr. Miriam Puls of the University Medical Center Göttingen, Germany, presented results from the Reduce-MFA DZHK25 trial evaluating anti-fibrotic therapy in patients with AS and high myocardial fibrotic burden following TAVI.
Reduce-MFA (NCT05230901) was an investigator-initiated, multicenter, randomized controlled trial enrolling patients aged >60 years with severe symptomatic AS undergoing TAVI and elevated myocardial fibrosis, defined by extracellular volume (ECV ≥25.9%) on cardiac MRI. Participants were randomized to TAVI alone (control) or TAVI plus anti-fibrotic therapy consisting of spironolactone alone or spironolactone in combination with dihydralazine for 12 months. The primary endpoint was a hierarchical composite of all-cause mortality and reduction in left ventricular (LV) matrix volume (a surrogate for diffuse myocardial fibrosis) at 12 months.
In the modified intention-to-treat (mITT) population, the primary endpoint was not significantly different between groups (win ratio 1.40; 95% CI 0.86–2.26; p=0.18). However, in the as-treated population, the primary endpoint reached statistical significance (win ratio 1.64; 95% CI 1.01–2.67; p=0.047), suggesting a treatment effect among patients adherent to therapy. Quantitatively, regression of myocardial fibrosis was greater in the treatment group, with LV matrix volume reductions of approximately −14.9% (mITT) and −15.8% (as-treated) compared with −4.0% and −2.6%, respectively, in the control arm.
While cardiovascular mortality did not differ significantly between groups (HR ~0.90; p=0.87), and reductions in cardiac hospitalizations did not reach statistical significance, there was a consistent potential signal toward benefit. Importantly, anti-fibrotic therapy resulted in significant improvements in quality of life, with KCCQ overall summary scores improving by +18.1 points vs. +5.4 points in controls (p=0.02).
Similarly, the secondary hierarchical clinical benefit endpoint, which included cardiovascular mortality, hospitalizations, quality of life, and functional capacity, was not significant in mITT but reached significance in the as-treated population (win ratio 1.60; p=0.03). Subgroup analyses suggested that patients with more advanced disease (NYHA class III) and women may derive greater benefit from anti-fibrotic therapy. The therapy was generally safe. There were no significant differences in systolic blood pressure, though expected changes were observed in renal function (decline in eGFR) and potassium levels (increase), consistent with mineralocorticoid receptor antagonist use.
“These findings suggest that anti-fibrotic therapy may represent a promising strategy to reverse myocardial remodeling and improve patient-centered outcomes after TAVI,” the investigators concluded, emphasizing the need for larger trials to confirm clinical benefit.