BACKGROUND: Myocardial contraction fraction (MCF)-the ratio of left ventricular stroke volume to myocardial volume-is a volumetric measure of myocardial shortening that distinguishes between pathologic and physiologic hypertrophy. In this post-hoc analysis of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial, we investigated the prognostic value of MCF and its association with heterogeneity of treatment effect in heart failure with preserved ejection fraction (HFpEF). METHODS: TOPCAT randomized patients with HFpEF to spironolactone or placebo. Patients with echocardiography data allowing for the calculation of MCF were included. The primary outcome was a composite of all-cause mortality, HF hospitalization, myocardial infarction, and stroke. RESULTS: 588 patients (median age 72.0 [63.0-79.3] years
49.1 % female) were included. Median MCF was 27.0 % (21.8-32.8 %) for the overall group and was not different in the spironolactone and placebo groups. Over a median follow-up of 3.0 (1.9-4.5) years, MCF below median was associated with a worse prognosis (p = 0.003). On multivariable regression analysis (HR, 95 % CI), only New York Heart Association class (1.47, 1.14-1.91, p = 0.003) and MCF (0.76, 0.64-0.90, p = 0.001) were associated with the composite outcome. In this subset, spironolactone as compared to placebo was not associated with improved outcomes, but stratifying by MCF showed differential outcomes to spironolactone therapy (p = 0.010). CONCLUSIONS: Among patients with HFpEF enrolled in TOPCAT, reduced MCF was independently associated with worse outcomes. Larger prospectively designed studies are needed to further assess the role of MCF in patients with HFpEF.