Mechanistic Specificity of Capillary Leak Indices: Validation in Heart Failure as a Negative Control.

OBJECTIVE: To evaluate the mechanistic specificity of capillary leak clinical indices by testing their performance in a heart failure population as a negative control. DESIGN: Retrospective observational study. SETTING: Tertiary-care academic medical center. PATIENTS: Adults with chronic heart failure (both stable outpatients and those with acute decompensation) undergoing clinically indicated blood volume analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical capillary leak indices, Sequential Organ Failure Assessment score, Capillary Leak Index, Vascular Leak Index, and Hematocrit-Albumin Difference, were calculated and compared with the transcapillary escape rate of albumin (TERalb) by Spearman correlation. Across analyses, indices showed weak or absent correlation with TERalb, indicating a lack of mechanistic specificity outside acute inflammatory illness. CONCLUSIONS: Clinical capillary leak indices do not accurately reflect true capillary permeability in a cohort of patients with chronic and acute-on-chronic heart failure, suggesting that they should be interpreted as context-dependent markers rather than as general measures of endothelial permeability.