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

Abstract

To evaluate the mechanistic specificity of capillary leak clinical indices by testing their performance in a heart failure population as a negative control. Retrospective observational study. Tertiary-care academic medical center. Adults with chronic heart failure (both stable outpatients and those with acute decompensation) undergoing clinically indicated blood volume analysis. None. 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. 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.