Combined Prognostic Value of Cardiac Magnetic Resonance–Derived Myocardial Extracellular Volume and the Fibrosis‐4 Index in Patients With Heart Failure With Preserved Ejection Fraction

Background Heart failure with preserved ejection fraction is increasingly recognized as a multisystem metabolic–inflammatory syndrome. We investigated the comparative and complementary prognostic value of cardiac magnetic resonance–derived extracellular volume fraction (ECV) and the Fibrosis‐4 index for predicting adverse cardiovascular outcomes in patients with heart failure with preserved ejection fraction. Methods Between 2017 and 2019, 250 patients with heart failure with preserved ejection fraction underwent assessment of myocardial ECV by cardiac magnetic resonance and hepatic fibrosis using the Fibrosis‐4 index. The primary outcome was a composite of cardiovascular death or heart failure hospitalization. Multivariable Cox regression and discrimination analyses were performed to evaluate prognostic performance. Results During a median follow‐up of 1190 days, 75 patients (30.0%) experienced the primary outcome. Both ECV (hazard ratio [HR], 1.13 [95% CI, 1.08–1.17]; P <0.001) and the Fibrosis‐4 index (HR, 1.12 [95% CI, 1.02–1.22]; P =0.015) independently predicted the primary outcome. Patients with concomitantly elevated ECV and Fibrosis‐4 index had a markedly increased risk of adverse events compared with those with low values of both markers. ECV‐based models demonstrated superior discrimination compared with Fibrosis‐4–based models (concordance index, 0.732 versus 0.663; P =0.011). Addition of ECV to the Fibrosis‐4 model significantly improved discrimination, whereas addition of the Fibrosis‐4 index to the ECV model improved reclassification (continuous net reclassification improvement and integrated discrimination improvement) but not discrimination. Conclusions Both myocardial ECV and the Fibrosis‐4 index independently predict adverse cardiovascular outcomes in heart failure with preserved ejection fraction. Although ECV provides greater prognostic discrimination, combined assessment of ECV and the Fibrosis‐4 index identifies a subgroup at particularly high risk and may provide complementary information for risk stratification.