Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis

Abstract Background Left ventricular (LV) hypertrophy, a key process in human cardiac disease, results from cellular (hypertrophy) and extracellular matrix expansion (interstitial fibrosis). Objectives This study sought to investigate whether human myocardial interstitial fibrosis in aortic stenosis (AS) is plastic and can regress. Methods Patients with symptomatic, severe AS (n = 181; aortic valve area index 0.4 ± 0.1 cm 2 /m 2 ) were assessed pre–aortic valve replacement (AVR) by echocardiography (AS severity, diastology), cardiovascular magnetic resonance (CMR) (for volumes, function, and focal or diffuse fibrosis), biomarkers (N-terminal pro–B-type natriuretic peptide and high-sensitivity troponin T), and the 6-min walk test. CMR was used to measure the extracellular volume fraction (ECV), thereby deriving matrix volume (LV mass × ECV) and cell volume (LV mass × [1 − ECV]). Biopsy excluded occult bystander disease. Assessment was repeated at 1 year post-AVR. Results At 1 year post-AVR in 116 pacemaker-free survivors (age 70 ± 10 years; 54% male), mean valve gradient had improved (48 ± 16 mm Hg to 12 ± 6 mm Hg; p  2 to 71 ± 19 g/m 2 ; p  2 to 21 ± 7 ml/m 2 ; p  2 to 50 ± 13 ml/m 2 ; p  Conclusions Post-AVR, focal fibrosis does not resolve, but diffuse fibrosis and myocardial cellular hypertrophy regress. Regression is accompanied by structural and functional improvements suggesting that human diffuse fibrosis is plastic, measurable by CMR and a potential therapeutic target. (Regression of Myocardial Fibrosis After Aortic Valve Replacement; NCT02174471)