Introduction: Lung volume reduction with endobronchial valves (EBV) can significantly improve functional outcomes in patients with advanced emphysema and severe hyperinflation. The extent and spatial distribution pattern of emphysema shows considerable heterogeneity within the lungs which might affect response to EBV treatment. 

Objectives: To study the effect of emphysema heterogeneity on change in clinical outcomes after EBV treatment. 

Methods: Data were collected from patients who received EBV treatment between 2016 and 2020 and completed the 6-month follow-up visit. We assessed the association between the heterogeneity index, absolute difference in destruction between the target and ipsilateral lobe, and relative change in FEV₁, residual volume (RV), Saint George?s respiratory questionnaire (SGRQ), and 6-minute walk distance (6MWD). 

Results: In total, 197 patients were included. Heterogeneity index was significantly associated with improvements in FEV₁ (?=0.27), RV (?=?0.31), SGRQ (?=?0.26), and 6MWD (?=0.20). The majority of patients, independent of heterogeneity index, showed clinically meaningful improvements based on minimal important difference values.

Conclusions: Heterogeneity index influences the degree of improvement after EBV treatment where a more heterogeneous distribution translates to larger improvements. However, a more homogeneous distribution generally also resulted in significant improvements. Therefore, emphysema heterogeneity alone should not be used as a decisive patient selection criterium but should be weight in the context of all other relevant patient and target lobe characteristics. As a consequence, strict cut-off values for heterogeneity seem redundant.