Changes in cardiac structure and function are associated with health‐related quality of life in heart failure patients with reduced ejection fraction: Results from the EVALUATE ‐ HF trial

Abstract Aims This analysis aims to investigate the relationship between changes in cardiac structure and function and changes in health‐related quality of life in patients with heart failure with reduced ejection fraction (HFrEF). Methods and results The association between echocardiographic measures and Kansas City Cardiomyopathy Questionnaire (KCCQ)‐12 scores was examined in HFrEF patients of the EVALUATE‐HF trial who were randomized to sacubitril‐valsartan or enalapril for 12 weeks followed by 12 weeks of open‐label sacubitril‐valsartan for both groups. We used linear regression models adjusted for age, sex, treatment assignment at randomization, baseline KCCQ‐12 score, baseline echo measurements, and other clinical variables. Among 406 patients (median age 67 years; 25% women), the KCCQ‐12 overall summary score (KCCQ‐12‐OSS) improved by +9 points (95% confidence interval +7 to +11 points) over 24 weeks. Increases in mitral e′ velocities correlated with KCCQ‐12‐OSS improvement (+2.5 and +2.3 points per standard deviation [SD] increase in septal and lateral e′ velocities, respectively, p < 0.05 for each). Decreases in septal E/e′ ratio and left atrial volume index (LAVi) also correlated with KCCQ‐12‐OSS improvement (+3.2 and +2.0 points per SD decrease in septal E/e′ ratio and LAVi, respectively, p < 0.05 for each). Changes in left ventricular size, ejection fraction, longitudinal strain, and right ventricular function were not associated with changes in KCCQ‐12‐OSS. Similar associations were observed for other KCCQ‐12 domains. Conclusions In the EVALUATE‐HF trial, increases in mitral e′ velocities and decreases in septal E/e′ ratio and LAVi were associated with improved KCCQ‐12 scores over 24 weeks, after adjusting for treatment assignment. These findings suggest that reductions in left ventricular filling pressures and left atrial size are closely coupled with improved physical function and quality of life in HFrEF patients, which may provide insights into the early benefits of sacubitril‐valsartan. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02874794.