Efficacy of empagliflozin in heart failure with preserved ejection fraction according to the presence of echocardiographic features of diastolic dysfunction in the EMPEROR-Preserved trial

AIMS: To define the impact of diastolic dysfunction (DD) on the response to empagliflozin treatment in patients with heart failure with preserved ejection fraction. METHODS AND RESULTS: Diastolic dysfunction was defined by left atrial volume index ≥34 ml/m2, the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular tissue velocity (E/e) ≥ 13 or left ventricular mass index >115 (males) or >95 (females). We created three categories of increasing DD (0, 1, or ≥2 DD criteria at baseline) to describe the effect of DD on response to empagliflozin therapy and adverse effects. Of 5988 patients in the EMPEROR-Preserved trial, 3766 (63%) had no documented baseline DD, 1619 (27%) had one, and 603 (10%) had two or more measures. Baseline DD was associated with sex, race, ethnicity, and region and was more common with lower heart rate, DBP, body weight, and eGFR. Despite baseline DD not being significantly associated with the primary endpoint of hospitalization for heart failure or cardiovascular death within the placebo group, a progressive treatment effect across the three DD categories was seen (trend test P-value .0014), with estimated hazard ratios of empagliflozin vs placebo of 0.91 (none present), 0.64 (1 present), and 0.49 (≥2). A significant treatment-by-subgroup trend test was also observed for the total number of hospitalizations for heart failure. Both Kansas City Cardiomyopathy Questionnaire Clinical Summary Score improvement at week 52 and safety profile were consistent across DD categories. CONCLUSION: Baseline detection of echocardiographic DD predicted improved clinical response to empagliflozin in a graded fashion, but the reasons cannot be reliably determined from this analysis.