Impact of myocardial fibrosis on cardiovascular structure, function and functional status in heart failure with preserved ejection fraction

Myocardial fibrosis, measured using cardiovascular magnetic resonance extracellular volume (ECV), is associated with adverse outcome in heart failure with preserved ejection fraction but the mechanisms by which myocardial fibrosis exerts this deleterious effect are unclear. We performed mediation analyses of data from the PIROUETTE (The Pirfenidone in Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction) trial to determine whether myocardial fibrotic regression causes changes in cardiovascular function and functional status following antifibrotic therapy. Regression of myocardial fibrosis correlated with improvements in 6-minute walk test and KCCQ clinical summary score. The only outcome variable that demonstrated a treatment effect was an increase in left ventricular ejection fraction (LVEF). The estimated average causal mediation effects of myocardial ECV, absolute myocardial extracellular matrix volume and absolute myocardial cellular volume on LVEF were 6.1%, 21.5%, and 13.7% respectively, none of which were significant and therefore not mediated by myocardial fibrosis. (PIROUETTE; NCT02932566).