Mechanistic Specificity of Capillary Leak Indices: Validation in Heart Failure as a Negative Control
Jonathan Popham, Farah Yasmin, Niranjana Ramani, Kevin Okifo, Veena Rao, Jeffrey Testani, F. Perry Wilson, Ioannis Koutroulis, Richard W. PierceObjective:
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.